Superficial Transitional Cell Carcinoma Research Articles

TRANSURETHRAL BLADDER BIOPSY AFTER POST INTRAVESICAL BCG THERAPY FOR SUPERFICIAL BLADDER CANCER PATIENTS

This study evaluated the role of routine biopsy from the site of previously resected superficialbladder tumor three months following resection and intravesical BCG therapy in the presenceof negative urine cytology and cystoscopy. Thirty-two patients (21males and 11 females)with high-risk superficial transitional cell carcinoma (TCC) of the bladder were followed prospectively.All patients received a single six weeks course of intravesical Bacillus Chalmette-Guerin (BCG). Three months following resection, urine cytology was done. Cystoscopy wasthen performed and a routine biopsy from the previous resection site was taken. All patientsincluded in the study had negative urine cytology and cystoscopy at the time of biopsy. Four(12.5%) patients were having TCC although they had negative urine cytology and cystoscopyat the time of biopsy. The histological recurrence was corresponded to T1G1 in two patientsand T1G2 in the other two patients and the pathology after BCG treatment for the four patientswas the same as before instillation. There were no statistically significant differences betweenpatients with positive and negative biopsies with regard to the stage and grade of the tumor beforeresection, or the number of resected lesions.

Recurrence rate of superficial bladder cancer with intravesical BCG and mitomycin.

Objective: To compare the recurrence rate of superficial transitional cell carcinoma of urinary bladder using intravesical BCG and Mitomycin-C. Study Design: Randomized Controlled Trial. Setting: Urology Department, Teaching DHQ Hospital, Gujranwala. Period: November 2018, to Sep, 2019. Material & Methods: Was carried out on total 270 patients, admitted with suspicion of urothelial tumors. They were grouped in Group A and B, comprising 135 in each group. Group A received BCG and Group B received Mtiomycin-C intravesically following TUR-BT. Results: Out of 270 patients male to female ratio was 3:1. Age range of patients was between 30 to 70 years with mean of 50.0± 13.1 and 552.3 ± 12.9 years in Group A and B respectively. Recurrence was noted in 05.38% and 15.38% patients in Group A and B respectively. Regarding side effects pyrexia was associated with BCG in 27.40% patients which were self-limited in 26.66% cases however required anti-tuberculosis therapy for six months in 0.74%. Whereas only 06.67% patients receiving Mitomycin had pyrexia. Dysuria occurred in 74% and frequency in 68% patients who received BCG. Whereas Dysuria occurred in 20% and frequency in 36.29% patients who received Mitomycin-C. However genital skin rash was more common (08.14%) in Mitomycin group than BCG. Conclusion: Keeping in mind less recurrence rate and bearable toxicity, it is concluded that BCG is superior to Mitomycin. This study suggests long term follow up is required to establish recurrence in the management of superficial bladder cancer.

The Incidence and Management of Urethral Stricture in Bladder Carcinoma

Background: Urethral stricture disease is one of the oldest and most difficult maladies known to the urologist. While references to the disease and its treatment date back to the writings of the Hindus, Egyptians, and Greeks. Objective: To elicit the incidence of urethral strictures, their severity and management in patients with superficial bladder tumor. Patients and Methods: From January 2018 to January 2020, we followed 98 patients admitted and treated at Baquba Teaching Hospital urology unit for having bladder carcinoma. Theywere all male subjects, their age range from 38-76y with a mean 56.8y. They were required to have a cystoscopically and histologically proven superficial transitional cell carcinoma of the bladder to be enrolled in this study (invasive tumors were excluded). For all the patients and after having the cystoscopic diagnosis ,transurethral resection of the tumor done and in most of them this is followed by six week courses of intravesical chemotherapy (either mitomycin or doxorubicin according to the availability). Intravesical Doxorubicin used in 13 cases (56.5%), Mitomycin C in 6 cases (26.1%) and 3 patients (13.0%) received both drugs (through multiple courses).while 1 patient (4.3%) received no chemotherapy. Thirteen strictures (56.5%) were managed by optical urethrotomy while 10 cases (43.5%) were mild strictures and opened just by introducing the cystoscope. Results: During the period of the study, a total of 23 urethral strictures were identified in the 98 male patients with superficial bladder tumor enrolled in this study, which constitutes an incidence of 23.5% all were diagnosed by the follow -up check cystoscopies . Patient age ranged from 38-75 years with a mean age 59.30+- 10.58 . Among those patients with urethral stricture ,14 patients had also B.P.H (60.9%), but only 7 patients (30.4%) had a history of retention of urine . The urethral stricture was bulbar in all patients and it was mild stricture in 10 cases (43.5%), moderate in 6 cases (26.1%) and severe in 7 cases (30.4%) . Prior to the diagnosis of stricture , 13 patients had been subjected to a single check cystoscopy (56.5%) ,6 patients (26.1%) had twice , while 4 patients (17.4%) had 3 or more cystoscopies prior to the occurence of stricture . Regarding intravesical chemotherapy prior to the occurance of stricture ,4 patients (17.4%) received 1-3 sessions , 10 patients (43.5%) received 4-6 sessions and 9 patients (39.1%) received more than 6 sessions . Intravesical Doxorubicin used in 13 cases (56.5%), Mitomycin C in 6 cases (26.1%) and 3 patients (13.0%) received both drugs (through multiple courses).while 1 patient (4.3%) received no chemotherapy. Thirteen strictures (56.5%) were managed by optical urethrotomy while 10 cases (43.5%) were mild strictures and opened just by introducing the cystoscope. Conclusion: Urethra stricture in patients with bladder carcinoma may be a substantial source of preventable morbidity, implementing a nursing education program may significantly decrease the incidence of stricture. Keywords: bladder carcinoma; urethral stricture; Baquba Teaching Hospital

Adjuvant Intravesical Chemotherapy in the Management of Superficial Transitional Cell Carcinoma of Urinary Bladder Following Transurethral Resection of Bladder Tumor- Result of Single Dose and Multiple doses of Mitomycin C

Background: Bladder cancer is the second most common cancer of the genitourinary tract. Mitomycin C has been commonly used in a perioperative fashion delivered intravesically immediately after TURBT
 Objective: To compare the results of post TURBT immediate single dose and multidose regimen of Mitomycin C therapy in the management of superficial transitional cell carcinoma of the urinary bladder.
 Method: The present prospective and comparative interventional study was conducted in the Department of Urology, National Institute of Kidney Diseases and Urology, Sher-E-Bangla Nagar, Dhaka from January 2015 to December 2016. Patients of superficial bladder cancer (tumor size ≤3 cm, number ≤3, grade I, II) were randomly included in the 2 groups. The sample size was seventy four (74). Thirty (30) patients were in each group and fourteen (14) were excluded from the study. In MMC single dose group (Group A), single dose of MMC 40mg/ 40ml was started immediately within 24 hours of TURBT. In MMC multi-dose group (Group B) 1st instillation of chemotherapy was started immediately within 24 hours of TURBT and additional instillation (5 instillations) were given as OPD basis and was continued weekly for 5 weeks. Follow-up was done on 3rd, 6th, 12th month of initial TURBT.
 Results: In this study mean age was 61.8±13.7 years in group A and 62.7±13.6 years in group B. Male was found 25 (83.3%) in group A and 26 (86.7%) in group B. Female was found 5 (16.7%) in group A and 4 (13.3%) in group B. Mean size of the tumor was found 2.13±0.78 cm in group A and 2.05±0.84 cm in group B. Mean number of tumor was found 1.8±0.8 in group A and 1.9±0.7 in group B. Tumor grade I was found 23 (76.7%) in group A and 25 (83.3%) in group B. Tumor status Ta of superficial bladder was found 25 (83.3%) in group A and 26 (86.7%) group B. Tumor status T1 of superficial bladder was found 5(16.7%) in group A and 4 (13.3%) group B. Five (16.7%) patients was found recurred in group A and 4 (13.3%) in group B at 6th month follow up. At 12th month follow up, 6 (20.0%) patients was found recurred in group A and 5 (16.7%) in group B. Side effect was found in 2 (6.7%) patients in group B and not found in group A.
 Conclusion: MMC single dose was similar to MMC multi-dose regimen with insignificant difference among the two.
 Bangladesh Journal of Urology, Vol. 23, No. 1, January 2020 p.62-66

A Comparative Study Between Single Dose & Multiple Doses of Mitomycin-C in the Management of Transitional Cell Carcinoma of Urinary Bladder

Objectives: To find out the efficacy of post TURBT immediate single dose adjuvant intravesical Mitomycin C therapy in comparison with multi-dose regimen of Mitomycin C therapy in the management of superficial transitional cell carcinoma of the urinary bladder.
 Methods: Total 76 patients of bladder mass were included in the study who had undergone transurethral resection followed by immediate single instillation of Mitomycin C. After availability of histopathological examination report of resected tumor, those fulfill the selection criteria were randomized into two groups. One group (Group A) was the odd numbers of the patients who already received immediate single intravesical instillation of Mitomycin C and another group (Group B) even number of the patients who received single dose of intravesical instillation of Mitomycin C immediately with additional 5 instillations (1 week interval for 5 weeks) and in whom prospective follow-up could be completed within next 12 months
 Results: The effect of single intravesical instillation of 40 mg of Mitomycin C (Group A) within 24 hours of TURBT with that of multiple doses (six doses) of Mitomycin C (Group B) in similar dose was insignificant.
 Conclusion: The efficacy of MMC single dose was similar to MMC multi-dose regimen with insignificant difference of side effect among the two groups (0% versus 6.25%).
 Bangladesh Journal of Urology, Vol. 20, No. 2, July 2017 p.74-77

Tuberculous spondylitis following intravesical bcg-instillation in the treatment of transitional cell carcinoma: Case report and systematic review

ObjectivesTuberculous spondylitis (TS), also known as Pott’s disease (PD), is a form of tuberculosis in which the vertebral column is affected. Since the first description by Katz et al. in 1992, it became clear that Bacillus Calmette-Guérin (BCG) instillations in the treatment of superficial transitional cell carcinoma (TCC) form a plausible way in which PD is introduced. Nowadays, BCG forms the most effective treatment modality for superficial TCC. The incidence of other than minor complications have been estimated under five per cent. Here we report a case of TS after BCG-instillation in the treatment of TCC. Furthermore, all available literature concerning this topic was gathered into a systematic review. The primary objective was to create an overview of all available literature concerning TS after intravesical BCG-instillations, with an emphasis on the neurosurgical approach of these patients, forming a scaffold at which future case reports can be compared. As a secondary objective, we tried to raise the awareness concerning this very rare complication of intravesical BCG-instillation as a possible cause of low back pain (LBP). Patients and MethodsWe performed a systematic review, in which patients who developed TS after intravesical BCG-therapy in the treatment of TCC, were examined. A total of twenty-three articles (twenty-four cases) obtained from MEDLINE were included. Search terms included: “tuberculous spondylitis”, “Pott’s disease”, “vertebral osteomyelitis”, “intravesical”, “Bacillus Calmette-Guérin” and “transitional cell carcinoma”. Additional studies were identified by checking reference lists. Furthermore, we present a case concerning one of our own patients who consulted our Neurosurgical department with a similar clinical presentation. This systematic review is in conformity with the PRISMA-guidelines. The case report is in accordance with the CARE statement guidelines. ResultsResults are based on twenty-five cases (twenty-four cases extracted from previous literature and our case report). All included articles are case reports written in English. Publication year and recruitment time varies from 1992 to 2018. Mean age at clinical presentation varies from 35 to 94 years old (mean 74). All patients were male. Surgery was performed in 17 out of 25 cases (68%). A posterior approach was performed in seven cases (41%), zero anterior approaches (0%), a combined approach in five cases (29%) and not specified in five cases (29%). All patients received intravesical BCG-instillation in the treatment of TCC, ranging from one month to twelve years before clinical presentation (mean 26). Radiographic abnormalities were seen in thoracic vertebral segments in thirteen cases (52%), eleven cases in lumbar segments (44%), one at the thoracolumbar transition level (4%) and not in cervical vertebral segments. ConclusionAlthough very rare, TS should be part of the differential diagnosis in patients with LBP, even years after BCG-instillation for TCC. It mostly affects elderly men and involves the thoracolumbar spine through hematogenous spread via Batson’s plexus. Antitubercular therapy remains the mainstay in the treatment of TS. A posterior surgical approach, with debridement and stabilization, should be preferred when surgical intervention seems necessary. To our knowledge, this systematic review forms one of the first comprehensive reviews evaluating neurosurgical intervention for PD following intravesical BCG-therapy in the treatment of TCC.

Transurethral en bloc resection of non-muscle invasive bladder cancer with holmium:YAG laser in pediatric patients: cases series and review of literatures

Urothelial bladder carcinoma frequently occurs in adults over 60 years of age; yet it affects only 0.1–0.4% of patients before the first 2 decades of life. We present two cases of transitional cell carcinoma in two young patients treated with holmium:YAG laser to demonstrate the effectiveness of this technique in pediatrics. Case study 1 During a routine abdomen ultrasound, a 14-year-old female showed a endoluminal formation about 10 × 6 × 10 mm of size, in the left paramedian site. There was an absence of meaningful vascular signs during color-Doppler. Physical examination and laboratory exams were all normal. Case study 2 A 12-year-old female presented with acute macroscopic haematuria. No other symptoms were associated. Bladder ultrasound revealed an irregular 15 mm intravesical endophytic lesion in the posterior-superior area. In both cases, treatment commenced with an en bloc enucleation. For the resections, a 272 µm holmium:YAG fiber laser was used through the 12 Ch cystoscopy working channel with an energy of 0.8–1 J/pulse and a frequency of 8–10 Hz. There was no haematuria after the procedure and the transurethral catheter remained for 12 h. The histological diagnosis was papillary urothelial neoplasm of low malignant potential. Cystoscopy was performed 3 and 9 months after the surgery and an ultrasound every 6 months, which all came back normal. The follow-up continued for each patient with a cystoscopy once a year, according to EAU guidelines. Based on the findings, holmium:YAG laser is a good alternative to treat superficial transitional cell carcinoma in pediatric patients.

A TALE OF TWO MYCOBACTERIA: SCROTAL TB IN THE SETTING OF INTRAVESICAL BACILLUS CALMETTE–GUÉRIN TREATMENT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Extra-pulmonary TB represents 10-15% of tuberculosis infections. Urogenital tuberculosis is a small and rare subset of these infections [1]. On the other hand, disseminated Mycobacterium bovis infections have been reported in the setting of intravesical Bacillus Calmette–Guérin (BCG) treatments [2,3]. We present a patient with symptoms of epididymo-orchitis with cavitary lung disease on imaging, whose suspicion was high for disseminated M. bovis based on previous BCG treatments, but was found to have necrotizing scrotal granulomas, positive for M. tuberculosis (MTB) with PCR. CASE PRESENTATION: A 72-year-old man with a past medical history of chronic obstructive pulmonary disease and urothelial cancer presented with symptoms of epididymitis after failed outpatient treatment. He completed his intravesical BCG treatments for urothelial cancer 1 week ago. CT of the pelvis was notable for left scrotal collection consistent with an abscess, with concerns for a necrotizing infection. CT Lung showed a thick-walled cavitary lesion in the right lower lobe, suspicious for malignancy. He underwent surgical exploration of the scrotum, which revealed his left scrotum infiltrated with pockets of infected tissue. He subsequently underwent left orchiectomy without complication. Pathology returned positive for confluent necrotizing granulomas involving primarily the epididymis and surrounding para-testicular soft tissue with a positive acid-fast bacterial smear. Based on his multiple courses of intravesical BCG instillations, it was presumed to be M. bovis; however, PCR for MTB strain was positive, prompting the initiation of the RIPE therapy. DISCUSSION: Intravesical BCG treatments have been associated with rare, disseminated M. bovis infections, most commonly affecting the lung [4,5]. Despite the high suspicion of this rare complication given the history of BCG treatments, the diagnosis of extrapulmonary tuberculosis, presenting with necrotizing granulomas in epididymis was confirmed with PCR. Unfortunately, in this case, high suspicion for a different Mycobacterium spp hindered diagnostic clarity and initiation of therapy. With MTB PCR and its high specificity, the correct Mycobacterium was identified, and treatment was promptly started [8,9]. CONCLUSIONS: Hematogenous spread of MTB to urogenital structures rare, and therefore, often overlooked as a diagnosis [6]. Utilization of PCR technology should hasten the diagnosis of urogenital MTB, and therefore, reduces the risk of urogenital organ destruction and subsequent infertility. Reference #1: Das A, Batabyal S, Bhattacharjee S, Sengupta A. A rare case of isolated testicular tuberculosis and review of literature. J Family Med Prim Care. 2016;5(2):468-470. Reference #2: Elzein F, Albogami N, Saad M, El tayeb N, Alghamdi A, Elyamany G. Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder. Clin Med Insights Case Rep. 2016;9:71-3. Reference #3: Nadasy KA, Patel RS, Emmett M, et al. Four cases of disseminated Mycobacterium bovis infection following intravesical BCG instillation for treatment of bladder carcinoma. South Med J. 2008;101(1):91-5. DISCLOSURES: no disclosure on file for Christian Castaneda; No relevant relationships by Rammohan Gumpeni, source=Web Response No relevant relationships by Christina Jee Ah Rhee, source=Web Response No relevant relationships by Joon Ha Woo, source=Web Response

Increased Incidence of Lung Cancer Among Patients With Superficial Transitional Cell Carcinoma: A Potential Risk Cohort for Lung Cancer Screening

BackgroundSmoking is a major risk factor for lung cancer (LC) and transitional cell carcinoma of the bladder (TCC). Current recommendations for LC screening do not include TCC as a risk factor for determining screening eligibility. In this study we aimed to evaluate whether TCC patients constitute a population who might benefit from LC screening. Patients and MethodsThe Surveillance, Epidemiology, and End Results 18 database was used to determine the incidence, standardized incidence ratio (SIR), and the average time to diagnosis of LC in patients with localized TCC of the bladder (American Joint Committee on Cancer, sixth edition, stages 0-1). ResultsOn the basis of 91,606 patients with localized TCC, The SIR for LC in men was 1.89 (95% confidence interval [CI], 1.8-1.97), significantly different from the risk for all solid tumors. The SIR for LC in women was 2.43 (95% CI, 2.22-2.65), significantly higher than for men. The 5-year incidence of LC was 3.2%, and the 10-year incidence was 5.94%. The average time to diagnosis of LC was 3.4 years, with >80% of LC cases occurring within 5 years of TCC diagnosis. ConclusionPatients with localized TCC have a higher incidence of LC than the general population. The risk is significantly increased among women compared with men. Considering this increased risk, patients with early stage TCC might stand to benefit from LC screening. Additional differences were noted between male and female TCC patients, which bear further study.

Combined urine Cytology and Cystoscopy can detect recurrence of superficial transitional cell carcinoma of the urinary bladder.

The study was aimed to evaluate the accuracy of combined urine cytology and cystoscopy for the detection of recurrence of superficial transitional cell carcinoma of the urinary bladder without bladder biopsy. Total 60 patients of superficial TCC of urinary bladder were selected of these 48 were male and 12 were female with age were between 41 to 80 years (mean age- 63.15 years).Urine cytology was done for all patients .Then cystoscopy done with targeted biopsy taken from any apparently visible growth in the bladder and systematic biopsy were taken where there was no growth. Reports of the cytology and cystoscopy were compared with the histopathology reports.It was found that 18 patients were cytology positive (false positive 2) and 42 patients were cytology negative (false negative 10) with sensitivity 61.5% and specificity 94%. During cystoscopy 24 patients were found recurrent growth in the bladder (false positive 3) and 36 patients were negative (false negative 5) with sensitivity 80.7% and specificity 91%. But when combined urine cytology and cystoscopic findings evaluated, the sensitivity and specificity were found 100% and 91% respectively.So, combined urine cytology and cystoscopy can be used for the detection of recurrence of superficial TCC. Key Ward- Urine Cytology, Cystoscopy, Bladder Biopsy

Pulmonary Metastasis Due to Superficial Transitional Cell Carcinoma of Urinary Bladder, A Rare Case Report and Literature Review

Pulmonary Metastasis Due to Superficial Transitional Cell Carcinoma of Urinary Bladder, A Rare Case Report and Literature Review

INTRA-VESICAL BCG INDUCED GRANULOMATOUS HEPATITIS AND DISSEMINATED KOCH’S: OUR EXPERIENCE

Bacille Calmette-Guerin (BCG) vaccine, developed by Calmette and Guerin at Institute Pasteur (Lille, France), is a live-attenuated Mycobacterium bovis strain. There are many therapeutic uses of the species have been described, Intravesical BCG has been established as an effective treatment of superficial bladder cancer. A 66-year old gentleman with newly diagnosed superficial high-grade papillary transitional cell carcinoma involving lamina propria (T1) of the bladder underwent 3 cycles of intravesical BCG. First 2 cycles were uneventful and tolerated well. After 3rd BCG cycle, patient developed granulomatous hepatitis with disseminated Koch's. BCG-induced sepsis after intra-vesical instillation for bladder cancer is a rare complication. Pathophysiology remains largely unknown, but BCG’s low virulence suggests that immunological hypersensitivity reaction probably plays a role. There have been no prospective studies to evaluate the optimal treatment for BCG infection. Keywords: Bacille Calmette-Guerin (BCG), Mycobacterium bovis strain, granulomatous hepatitis.

Miliary Tuberculosis that Developed after Intravesical Bacillus Calmette-Guerin Therapy.

As a treatment for superficial transitional cell carcinoma, Bacillus Calmette-Guerin (BCG) intravesical instillation can rarely cause unpredictable systemic side effects. We describe a patient admitted due to continuous pyrexia and general fatigue. He was previously treated with intravesical BCG. Laboratory data indicated a hepatic disorder, and chest computed tomography revealed extensive bilateral miliary nodules. Transbronchial lung biopsy specimens showed several small noncaseating granulomas. The diagnosis was unsolved on the basis of acid fast staining, polymerase chain reaction and microbiological cultures, so we considered the possibility of BCG side effect-induced granuloma. Two months after treatment with antituberculous agents and corticosteroids, his clinical symptoms were improved.

FACTORS ASSOCIATED WITH TUMOR RECURRENCE IN STAGE 1 BLADDER TRANSITIONAL CELL CARCINOMA IN SARDJITO HOSPITAL YOGYAKARTA

Objective: This study is assigned to evaluate factors associated with tumor recurrence in patients with superficial transitional cell carcinoma (TCC) of bladder in Sardjito General Hospital Yogyakarta. Material & methods:A prospective observational study design is conducted to evaluate patients with T1 TCC of bladder between 2011 and 2012. Inclusion criteria was patients with T1 TCC of bladder from pathological report. The independent variables are ages, hemoglobin, albumin, creatinine level, urine cytology, tumor grade, tumor diameter, number of tumor, and intravesical chemotherapy. The outcome measure is tumor recurrence during cystoscopy at 3, 6, 9, and 12 month after first resection. This study used chi-square and logistic regression analysis as statistical methods with p < 0.05 and a = 5% are considered significant. All analyses were performed with SPSS statistical software, version 20.0. Result: Sixty-two patients were participated in this study with mean age 60.62 ± 12.15 years. There were 32 patients (51.6%) who had tumour recurrence during first year that need to be resected. Of these patients, 9 patients (14.5%) had tumour recurrence more than one time during first year. In multivariate analysis, factors associated with tumour recurrence were tumour grade (p = 0.041, CI = 0.008-0.908), number of tumor (p = 0.003, CI = 0.003-0.293), and intravesical chemotherapy (p = 0.022, CI = 0.015-0.719). Conclusion: Degree of tumor differentiation, number of tumor and intravesical chemotherapy are factors affecting recurrence of stage 1 transitional cell carcinoma of the bladder.

Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer

More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins-SLC3A2, STMN1, and TAGLN2-in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant overexpression in individual bladder cancer tissues and urine specimens, and thus represents a potential biomarker for noninvasive screening for bladder cancer. Our findings highlight the value of bladder tissue proteome in providing valuable information for future validation studies of potential biomarkers in urothelial carcinoma.

Reply by Authors

No AccessJournal of UrologyAdult Urology1 Nov 2015Reply by Authors View All Author Informationhttps://doi.org/10.1016/j.juro.2015.05.108AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 194(5), p. 1208 References 1 : Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. J Clin Oncol2003; 21: 4270. Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 194Issue 5November 2015Page: 1208 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement PDF downloadLoading ...

C.29C>T polymorphism in the transforming growth factor-β1 (TGFB1) gene correlates with increased risk of urinary bladder cancer

TGF-β1 is a pleiotropic cytokine, which plays a dual role in tumor development. In the early stages, it inhibits the growth of tumor while in the late stages of carcinoma, it promotes tumor growth. The purpose of this study was to analyze the distribution of the TGFB1 gene polymorphisms between cases and controls so as to assess their correlation with bladder cancer risk. This study included 237 cases of urinary bladder cancer and 290 age matched controls from the same ethnic background. Three polymorphisms in the TGFB1 gene, c.29C>T (rs-1800470), c.74G>C (rs-1800471) and +140A>G (rs-13447341), were analyzed by direct DNA sequencing. Statistical analyses revealed no significant differences in the demographical data, except that the frequencies of smokers and non-vegetarians were higher in the cases. Eighty percent of the bladder cancer patients had superficial transitional cell carcinoma, and 53.16% and 26.31% of the patients were in grade I and grade II, respectively. We found that c.29C>T substitution increased the risk of bladder cancer significantly and recessive model of analysis was the best fitted model (p=0.004; OR=1.72 95% CI 1.18–2.50). A significantly higher risk in the recessive form was also suggested by co-dominant analysis showing that the homozygous form (TT) was a significant risk factor in comparison to CC and CT genotypes. The other two polymorphisms, c.74G>C (p=0.18, OR=0.67 95% CI 0.37–1.21) and +140A>G (p=0.416, OR=0.77 95% CI 0.41–1.45) did not affect the risk of urinary bladder cancer. In conclusion, we found that the TGFB1 c.29C>T substitution increases the risk of bladder cancer significantly while c.74G>C and +140A>G polymorphisms do not affect the risk.

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.

Analysis of Japanese Patients Treated with or without Long-Term Epirubicin Plus Ara-C Intravesical Instillation Therapy for Low-Grade Superficial Bladder Cancer.

The high incidence of tumor recurrence following transurethral resection (TUR) represents a major problem encountered in the management of bladder cancer. This study examined the efficacy of intravesical chemotherapy in superficial bladder cancer. We retrospectively analyzed 90 Japanese cases with low-grade superficial transitional cell carcinoma (stage T1, grades 1 and 2) who were rendered tumor-free by TURBT (TUR of bladder tumor) and who thereafter were treated with or without intravesical chemotherapy. Among them, instillation was terminated in 2 patients due to adverse effects (severe but reversible chemical cystitis). Remaining 88 patients were divided into 2 groups according to therapy: the TURBT-only group (n = 46), defined as patients treated with TURBT alone, and the Instillation group (n = 42), defined as patients treated with weekly intravesical instillation therapies using epirubicin plus Ara-C. Recurrence-free rate was significantly higher in the Instillation group than in the TURBT-only group (p = 0.02, HR = 0.457). The 5-year recurrence-free rate was 58.5% for the Instillation group and 38.6% for the TURBT-only group. Our instillation schedule represents the most intensive regimen among previously reported therapies and resulted in a 54.3% decrease in incidence of tumor recurrence. We believe that the results of this study could provide useful information on management of bladder cancer.

Abstract 2226: Loss of STAG2 in bladder cancer

Abstract Bladder cancer (BC), 90% of which have transitional cell histology, is the fourth most common malignancy in the US. Transitional cell carcinoma (TCC), which occurs predominantly in men and whose incidence appears to be increasing, occurs most frequently as superficial disease which, while prone to recurrence, is not life threatening. However, TCC which invades the muscle layer of the bladder (stage T2-T4) is lethal in ∼50% of individuals. Stage T2-T4 TCC is present at initial diagnosis in ∼30% of patients and superficial TCC progresses to T2-T4 disease 20% of the time. We sequenced whole exomes of 28 muscle-invasive bladder tumors and performed an additional screen of over 200 genes in 119 additional TCCs. We found frequent alterations (10%) in STAG2, a gene encoding a subunit of the cohesin complex, which regulates the sister chromatids segregation process. Most mutations identified on STAG2 were nonsense, missense or frameshift. Genetic disruption of the sister chromatid segregation process leads to aneuploidy, which is one of the hallmarks of cancer. Based on recently published studies, however, it is uncertain whether a loss of STAG2 causes aneuploidy or not. In this study we sought to elucidate the role of STAG2 loss of expression in bladder tumorigenesis. We have analyzed the expression of STAG2 in 14 urothelial cell lines at both mRNA and protein levels by means of q-PCR and western blots, respectively. We found that STAG2 expression was lost in 2 of the 14 urothelial cell lines (HB-CLS-2 and UM-UC-3) analyzed. We chose SV-HUC (immortalized normal urothelium cells) along with two bladder cancer cell lines that had high expression of STAG2 (HB-CLS-1 and TCC-SUP) to study effects of STAG2 loss by transient knockdown. Knockdown of STAG2 in SV-HUC, TCC-SUP and HB-CLS-1 cells did not affect proliferation. Cell cycle analysis on TCC-SUP cells revealed that STAG2 knockdown resulted in a lower percentage of cells in the G0/G1 phase in comparison to the scrambled control. Taken together, these data suggest that STAG2 has a role in modifying DNA content but not proliferation. Our ongoing studies utilizing bladder cancer tissue microarray (TMAs) and copy number variation (CNV) array will help to clarify the consequences of STAG2 loss in bladder cancer. Citation Format: Nithya Krishnan, Anna Woloszynska-Read, Jianmin Wang, Song Liu, Carl Morrison, Khurshid Guru, Evelyn Smit, Donald Trump, Candace Johnson. Loss of STAG2 in bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2226. doi:10.1158/1538-7445.AM2014-2226