T1 Transitional Cell Carcinoma Research Articles

INCIDENTAL BLADDER MELANOSIS WITH CHRONIC CYSTITIS

Abstract Introduction/Objective Melanosis is a black or brown discoloration due to melanin deposition in the skin or on the mucosa of body organs such as conjunctiva, lips, mouth, genitalia, colon, and rectum. For example, melanosis coli is associated with chronic laxative use. However, melanosis on the bladder mucosa is an extremely rare, incidental, and benign finding which is commonly associated with bladder cancer or melanoma. We report an unusual case of incidental bladder melanosis with chronic cystitis in a patient diagnosed with bladder cancer. Methods/Case Report A 77-year-old male current smoker presented for a follow-up of recurrent bladder cancer (high-grade T1 Transitional Cell Carcinoma, TCC) diagnosed in 2016 with currently no symptoms. His past medical history included high blood pressure, papillary thyroid carcinoma status post thyroid lobectomy, and Type 2 diabetes mellitus. He had completed two cycles of treatment of Bacillus Calmette-Guerin (BCG) and BCG/Interferon for 6 weeks each. He had multiple transurethral bladder resections and biopsies in the past which revealed invasive high- grade papillary urothelial carcinoma, not invading muscularis propria. A recent computerized tomography scan of the abdomen and pelvis revealed diffuse bladder wall thickening and trabeculation along the dome and posterior urinary bladder. His lab workup including urinalysis, complete blood count, and chemistry were within normal limits. This time, the patient underwent urinary bladder midline and back wall cystoscopic biopsies and transurethral resection of the right lateral wall. The biopsies showed mild chronic cystitis with melanosis, however, the resection showed non- invasive high-grade papillary urothelial carcinoma. Results (if a Case Study enter NA) NA Conclusion Bladder melanosis has been reported less than 25 times in the literature worldwide. The etiology of melanosis is still unknown. No specific symptoms or treatment guidelines have been established for bladder melanosis so far due to decreased number of cases reported and therefore, reduced follow-up surveillance. Nonetheless, the general behavior of bladder melanosis alone seems to be benign. To the best of our knowledge, this is the first report of bladder melanosis with chronic cystitis. Further studies are required to establish the association of bladder melanosis with chronic cystitis and to probe its clinicopathologic course, and implications.

Robot-assisted ipsilateral partial nephrectomy with distal ureterectomy for synchronous renal and ureteric tumors—a case report

BackgroundIpsilateral synchronous renal and ureteric tumor is uncommon. Nephron sparing surgery is the standard for small renal masses. Ureteric tumors can be selectively managed with nephron sparing surgery, especially in renal dysfunction. This case report details the management of double malignancy by nephron sparing surgery with robot-assisted approach.Case reportA 63-year-old gentleman with diabetes presented with history of intermittent gross hematuria for 2 weeks. He was clinically normal. On evaluation, he had grade 4 renal dysfunction (Se. creatinine 4.5 mg%) with mild proteinuria. Magnetic resonance imaging revealed right renal upper polar Bosniak III lesion and right hydroureteronephrosis due to 2 cm ureteric tumor near the vessel crossing. Renogram showed overall GFR of 22 ml/min with 31% (6 ml/min) contribution from the right side. He underwent robot-assisted right partial nephrectomy with distal ureterectomy and Boari flap ureteric reimplantation. Histopathology revealed margins free T2 clear cell carcinoma (kidney) and high-grade T3 transitional cell carcinoma (ureter). His nadir creatinine at 1 year follow-up was 3.3 mg% and no recurrence on MRI, cystoscopy, and ureteroscopy at 1 year.ConclusionMinimally invasive nephron sparing surgery is feasible and reasonable option with satisfactory oncological control even in ipsilateral synchronous renal and ureteric tumors in selected patients with renal dysfunction.

Lymph node expression of cytokeratin 7 and 20 in extended lymph node dissection with radical cystectomy for muscle-invasive disease: value in pathologic staging, treatment strategies, and outcomes

Background Precise staging of lymph node (LN) status is an important clinicopathological prognostic parameter following radical cystectomy. Aim The aim was to assess tumor recurrence in patients with T2 transitional cell carcinoma undergoing radical cystectomy with extended pelvic lymphadenectomy. Patients and methods A total of 80 patients underwent bilateral extended lymphadenectomy during radical cystectomy that reached up to the aortic bifurcation and sentinal LN. This was a multicenter study among Urology Departments of Ain Shams University Hospital, Theodor Bilharz Research Institute, and Saint Louis University Hospital. Comparison was based on classification of patients into two groups: cytokeratin 7 and 20 (CK7 and CK20) positive and negative. Results In this study, the authors used both CK7 and CK20 for evaluating the metastatic and micrometastatic burdens in LNs, and these markers were correlated with the primary bladder and its nodal metastases. After displaying the results, we evaluated the markers as follows: CK7 sensitivity is 100%, whereas specificity is 65% and showed 48.8% positive predictive value and 100% negative predictive value, with overall accuracy of 73.8%. CK20 has a sensitivity of 100%, whereas specificity is 65% and showed 48.8% positive predictive value and 100% negative predictive value, with overall accuracy of 73.8%. Conclusion The use of molecular markers provides a better and proper nodal staging but what is thought to be a disadvantage is the exaggerated sensitivity sometimes gives false-positive results.

Accelerated Hypofractionated Radiation Therapy for Elderly Frail Bladder Cancer Patients Unfit for Surgery or Chemotherapy.

The main purpose of this study was to report treatment outcomes of definitive image-guided accelerated hypofractionated radiation therapy for elderly patients with muscle-invasive bladder cancer unsuitable for surgery or trimodality therapy. Patients with confirmed muscle-invasive or high-risk T1 transitional cell carcinoma of the bladder, stage T1-T4aN0M0, who underwent transurethral resection of bladder tumor were irradiated with 45 Gy in 15 fractions. Comorbidity was assessed by Charlson Comorbidity Index. Cystoscopy, cytology, and computerised tomography imaging were used to evaluate treatment outcomes. Seventeen patients with a median age of 87 (range, 81 to 95) years and age-adjusted Charlson Comorbidity Index ≥3 were included. Transurethral resection of bladder tumor was incomplete in 65%. Radiation technique evolved from 3-dimensional conformal radiotherapy (3D CRT, 47%) to volumetric modulated arc therapy (VMAT, 53%). Ninety-four percent completed radiotherapy, with a median time of 20 days. The median follow-up was 65.3 months. Complete local response at 3-month cystoscopy was 69%. Six patients developed a local recurrence (35%), and 2 patients developed distant metastases (11.7%). Overall survival at 1 year was 47% and 23% at 2 years. Cancer-specific survival at 1 and 2 years were 85% and 63%, respectively. Acute grade 3 gastrointestinal or genitourinary toxicities were 6% and 24%, respectively. No grade 4 toxicity was documented. Diarrhea of any grade occurred in 35% of patients treated with 3D CRT, but in none of the patients treated with VMAT (P=0.002). Accelerated hypofractionated radiotherapy alone provides good local control in elderly patients unfit for chemoradiotherapy. Contemporary radiation techniques such as VMAT were associated with reduced bowel toxicity compared with 3D CRT.

Accelerated Hypo-Fractionated Radiation Therapy for Elderly Frail Bladder Cancer Patients Unfit for Surgery or Chemotherapy

Frail elderly patients with potentially curable muscle-invasive bladder cancer are often unsuitable candidates for surgery or tri-modality therapy as they are unfit for chemotherapy and unable to complete a six-week course of radiotherapy. We hypothesized that accelerated hypofractionated radiotherapy, as a single modality, would improve outcomes for this population of patients. Patients with confirmed muscle-invasive or high-risk T1 transitional cell carcinoma of the bladder, stage T1-T4aN0M0, who underwent transurethral resection of bladder tumor (TURBT) and were not suitable for cystectomy or chemotherapy were eligible for this retrospective analysis. All patients were treated with curative intent to a dose of 45 Gy in 15 fractions. Comorbidity burden was assessed by Charlson Comorbidity Index (CCI). Weekly symptom assessment and physical examination was performed during treatment, followed by cystoscopy and cytology sample commencing at a mean of 3 months after completion of treatment. Cystoscopy, cytology, and computed tomography imaging were used to evaluate treatment outcome. Endpoints for this study included local control and complete local response (stable or absence of bladder tumor) as well as overall, disease-free, and cancer-specific survival analyzed by the Kaplan-Meier method. Seventeen patients with a median age of 87 (range, 81-95 years), mostly male (82%) and age-adjusted CCI >3 were included during 2010 to 2015. Pre-treatment staging was T2N0 in 76% of patients and hydronephrosis was evident in 47% of patients. TURBT was considered incomplete in 65% of patients. Radiation therapy technique has evolved over the years from 3-D CRT (47%) to VMAT (53%). Almost all patients (94%) completed radiotherapy, with a median treatment time of twenty days. Median follow-up was 10.6 months. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in 6% and 24%, respectively. No grade 4 toxicity was documented. Acute/late Diarrhea of any grade occurred in 29% of patients treated with 3-D technique, but in none of the patients treated with VMAT (p=0.002). Local control within the bladder was achieved in 69% of patients evaluated by cystoscopy or imaging, and complete local response was 69% of patients who underwent cystoscopy. Overall survival at 1 year was 45%, and cancer-specific survival at 1 and 2 years were 85% and 70%, respectively. Of the surviving patients at the end of follow-up, 80% were without evident of disease and 60% had a functioning bladder. Accelerated hypo-fractionated radiotherapy alone provides excellent local control in elderly patients unfit for concomitant chemoradiotherapy. Contemporary radiation techniques such as VMAT were associated with reduced bowel toxicity compared with 3-D CRT.

A Novel Presentation of Bladder Mass: Self-palpation by a Patient With Cystocele

This case describes diagnosis of a T2 transitional cell carcinoma in an 89-year-old woman with known cystocele and urinary retention managed with clean intermittent self-catheterization. While self-catheterizing, the patient noted a palpable mass in her cystocele. She eventually pursued urologic evaluation of this mass, which ultimately led to her diagnosis. This is the first reported case of transitional cell carcinoma being found on self-examination by palpating a cystocele.

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.

MP88-19 URINARY MICROBIOME PATTERNS APPEARS TO BE CORRELATIVE TO INTRAVESICAL RECURRENCE OF NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2016MP88-19 URINARY MICROBIOME PATTERNS APPEARS TO BE CORRELATIVE TO INTRAVESICAL RECURRENCE OF NON-MUSCLE INVASIVE BLADDER CANCER Yige Bao, Hassan Razvi, Gregory Gloor, Gregor Reid, John Denstedt, and Jeremy Burton Yige BaoYige Bao More articles by this author , Hassan RazviHassan Razvi More articles by this author , Gregory GloorGregory Gloor More articles by this author , Gregor ReidGregor Reid More articles by this author , John DenstedtJohn Denstedt More articles by this author , and Jeremy BurtonJeremy Burton More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2437AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Several studies have recently reported association between various urinary conditions. The objective of this study was to describe the urinary microbiome among bladder cancer patients, observe longitudinal urinary microbiome changes during surgery and chemotherapy, and identify microbiome patterns that are associated with frequent bladder cancer recurrences. METHODS After optimising urine sample collection, storage and processing methods for microbiome analysis, we carried out a prospective, multicenter cohort study, recruiting patients with newly diagnosed Ta, T1 or CIS transitional cell carcinoma of the bladder who underwent transurethral resection with or without intravesical instillation. Urine samples were collected at multiple time points before and after surgery as the patients were followed up for recurrence. Routine urine culture, enhanced culture, qPCR quantification and V4 16S rRNA gene sequencing were performed on urine samples for microbiome analysis. Urine samples were also analysed from gender and age-matched healthy volunteer controls. RESULTS To eliminate “background” 16S rRNA amplification we found it necessary to collect at least 20 ml of urine and store the pellet in -80 °C. We also needed to treat samples with PMA to bind any contaminating environmental DNA present. Ninety-nine patients were recruited from two medical centers and followed up for up to three years. When compared to healthy individuals, bladder cancer patients had urinary microbiome with increased alpha (within sample) diversity with a decreased proportion of “typically” commensal species. Healthy individuals generally maintained a stable urinary microbiome during the longitudinal follow up, while cancer patients’ urinary microbiome were disrupted during periods following surgery and subsequent chemotherapy, though often a restored community profile was observed in the follow up. A common urinary microbiome pattern was identified among patients with frequent recurrences compared to patients with no recurrence. CONCLUSIONS The urinary microbiome maybe indicative of likely recurrence among non-muscle invasive bladder cancer patients © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1136 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yige Bao More articles by this author Hassan Razvi More articles by this author Gregory Gloor More articles by this author Gregor Reid More articles by this author John Denstedt More articles by this author Jeremy Burton More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of Adjuvant Intravesical Bacillus Calmette-Guérin Treatment on Patients with High-Grade T1 Bladder Cancer

Purpose: To evaluate the impact of adjuvant intravesical bacillus Calmette-Guérin (BCG) treatment in patients with high-grade transitional cell carcinoma of bladder. Patients and Methods: A total of 207 consecutive patients who underwent transurethral resection for high-grade T1 transitional cell carcinoma of bladder at our institution between January 1, 2005 and December 31, 2012. Of those patients, 77 underwent early cystectomy without BCG instillation and were excluded from the analysis. The overall survival and cancer-specific mortality were compared in 2 different therapy options groups (group of patients who received adjuvant BCG instillation vs. the group of patients who did not receive BCG therapy). Overall mortality was estimated by the Kaplan-Meier method, univariate comparisons were made with the log rank test. The cumulative incidence of deaths from bladder cancer (BC) was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study the combined effects of the variables on BC-specific mortality. Results: The 5-year overall survival in patients with BCG instillation vs. patients who did not receive BCG therapy was 74 vs. 28% (p = 0.0016). In the univariate analysis, the adjuvant intravesical BCG treatment was associated with decreased cancer-specific mortality (p = 0.0062). In the multivariable analysis, the age and the BCG instillation were independent factors of overall survival (hazard ratio 0.26, 95% CI 0.15-0.46, p < 0.0001) and cancer-specific mortality (hazard ratio 0.29, 95% CI 0.12-0.71, p = 0.0067). Conclusion: Dispensing from adjuvant intravesical BCG treatment is associated with increased overall- and disease-specific mortality in patients with T1 high-grade transitional cell carcinoma of bladder. This observation confirms that adjuvant BCG instillation is a crucial part of treatment in this patient population.

G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma.

G9a has been reported to highly express in bladder transitional cell carcinoma (TCC) and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incorporation assay and colony formation assay. G9a inhibition induced autophagy like morphology as determined by transmission electron microscope and LC-3 fluorescence assay. In addition, autophagy flux was induced by G9a inhibition in TCC cells, as determined by p62 turnover assay and LC-3 turnover assay. The autophagy induced positively contributed to the inhibition of cell proliferation because the growth attenuation capacity of G9a inhibition was reversed by autophagy inhibitors 3-MA. Mechanically, AMPK/mTOR pathway was identified to be involved in the regulation of G9a inhibition induced autophagy. Intensively activating mTOR by Rheb overexpression attenuated autophagy and autophagic cell death induced by G9a inhibition. In addition, pre-inhibiting AMPK by Compound C attenuated autophagy together with the anti-proliferation effect induced by G9a inhibition while pre-activating AMPK by AICAR enhanced them. In conclusion, our results indicate that G9a inhibition induces autophagy through activating AMPK/mTOR pathway and the autophagy induced positively contributes to the inhibition of cell proliferation in TCC cells. These findings shed some light on the functional role of G9a in cell metabolism and suggest that G9a might be a therapeutic target in bladder TCC in the future.

The Effect of Restaging Transurethral Resection on Recurrence and Progression Rates in Patients with Nonmuscle Invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guérin

We determined whether restaging resection before initiating induction intravesical bacillus Calmette-Guérin improves the recurrence-free rate in patients with high risk nonmuscle invasive bladder cancer. We retrospectively analyzed data on 1,021 patients treated at our institution with intravesical bacillus Calmette-Guérin for nonmuscle invasive high risk bladder cancer. All patients underwent a second resection except those already receiving bacillus Calmette-Guérin at the time of initial consultation and those who refused restaging resection. All patients were assessed every 3 to 12 months for a minimum of 5 years. Univariate and multivariate regression was used to identify predictors of 5-year recurrence. Restaging transurethral resection was performed in 894 patients (87.5%). At restaging resection viable tumor was found in 496 patients (55.5%). At 3 months patients with a single resection had a 44.3% recurrence rate compared to 9.6% in those with restaging resection (p <0.01). On multivariate analysis a single transurethral resection was the only predictor of recurrence at 5 years (OR 2.1, 95% CI 1.3-3.3, p = 0.01). Time to recurrence in patients with a single resection was significantly shorter than in those with restaging resection (median 22 vs 36 months, p <0.001). Failure to repeat resection before initiating intravesical bacillus Calmette-Guérin therapy for high risk nonmuscle invasive bladder cancer significantly increases the risk of recurrence. Therefore, we believe that restaging resection should be performed before initiating bacillus Calmette-Guérin therapy in all patients with high risk nonmuscle invasive bladder cancer.

Time between First and Second Transurethral Resection of Bladder Tumors in Patients with High-Grade T1 Tumors: Is It a Risk Factor for Residual Tumor Detection?

Purpose: We evaluated the risk factors for residual tumor detection after transurethral resection of bladder tumors (TURBT) in patients with newly diagnosed high-grade T1 transitional cell carcinoma of the bladder. Patients and Methods: Overall 132 patients underwent TURBT for primary bladder tumors and were diagnosed as high-grade T1 bladder cancer. Patients with incomplete resections were excluded from the study. Clinical and pathologic characteristics of the patients were compared and multivariate analysis was performed to determine independent prognostic factors. Results: Residual tumor was demonstrated in 57 (43.1%) of the patients. The residual tumor rate was significantly lower in patients with solitary tumors, tumors <3 cm in diameter, muscle presence in the initial TURBT pathologic sample and treated by an expert surgeon. In patients with solitary bladder tumors, tumors at the dome and posterior wall of the bladder exhibited higher rates of residual tumor (p < 0.0001). The time elapsed between first and second TURBT was significantly shorter in patients without residual tumor compared to patients with residual tumor at second TURBT (32.6 ± 9.1 vs. 39.3 ± 10.9 days, respectively, p = 0.001). Multivariate analysis demonstrated that time elapsed between first and second TURBT is the most important parameter for residual tumor detection. Conclusion: Our study revealed that multiple tumors, tumors >3 cm in size, absence of detrusor muscle in the initial TURBT specimen, TURBT performed by trainees and finally, as a new finding, prolonged interval between first and second TURBT are independent predictors for residual tumor detection in patients with high-grade T1 tumors.

390 ROLE OF KI-67 PROLIFERATION MARKER IN PREDICTING RECURRENCE OF HIGH GRADE TA & T1 BLADDER TRANSITIONAL CELL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Natural History, Markers & Pathophysiology1 Apr 2013390 ROLE OF KI-67 PROLIFERATION MARKER IN PREDICTING RECURRENCE OF HIGH GRADE TA & T1 BLADDER TRANSITIONAL CELL CARCINOMA Mohamed Abdallah, Ahmed Abdelhalim, Hala Said, Tarek Abdelbakey, Nancy Assad, and Abdelaliem Eldorey Mohamed AbdallahMohamed Abdallah Quesna, Egypt More articles by this author , Ahmed AbdelhalimAhmed Abdelhalim Shibin Elkom, Macedonia More articles by this author , Hala SaidHala Said shibin elkom, Egypt More articles by this author , Tarek AbdelbakeyTarek Abdelbakey shibin elkom, Egypt More articles by this author , Nancy AssadNancy Assad shibin elkom, Egypt More articles by this author , and Abdelaliem EldoreyAbdelaliem Eldorey shibin elkom, Egypt More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1779AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ki-67, an established proliferation marker expressed in G1, S, G2, M phases of cell cycle. We previously found an association between Ki-67 index & urothelial tumor grade, muscle invasion & positive lymph nodes. In this study, we focused on high grade non-muscle invasive urothelial tumor to predict recurrence after complete TURBT with 1 year follow up. This can aid decision of urologist either to follow up or to schedule his patient for radical cystectomy. METHODS 87 patients with high grade non-muscle invasive TCC did complete TURBT with immediate intravesical instillation of Epirubicin® 50 mg, Ki-67 index was estimated using purified rabbit polyclonal antibody raised against the C-terminal fragment of the human Ki67 nuclear antigen (Lab vision, USA). Intravesical immunotherapy by instillation of BCG & follow up cystoscopy & immunohistochemical determination of Ki-67 index at 3, 6, 9 & 12 months. RESULTS The Age of the patients (Range, Mean ± SD)45-60, 56.72 ± 4.81. The gender (Male%, Female%)86.1, 13.9.The Ki-67 index was(Range, Median)30-90,70.The table shows the recurrence rates. CONCLUSIONS The higher the Ki-67 index, the higher the probability of recurrence of high grade Ta & T1 transitional cell carcinoma of bladder with 56% recurrence with Ki-67 index 81-90% at 1 year follow up. New recurrence at 3 months 6 months 9 months 12 months total Ki-67 index 30-40% (N=15) 0 (0%) 0 (0%) 0 (0%) 2 (13.33%) 2 (13.33%) Ki-67 index 41-60% (N=21) 0 (0%) 0 (0%) 4 (19.05%) 4 (19.05%) 8 (38.1%) Ki-67 index 61-80% (N=26) 1 (3.85%) 1 (3.85%) 4 (15.38%) 4 (30.77%) 10 (38.46%) Ki-67 index 81-90% (N=25) 2 (8.0%) 4 (16%) 2 (8.0%) 6 (24.0%) 14 (56.0%) Overall recurrence at 1 year 34 (39.08%) © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e158 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Abdallah Quesna, Egypt More articles by this author Ahmed Abdelhalim Shibin Elkom, Macedonia More articles by this author Hala Said shibin elkom, Egypt More articles by this author Tarek Abdelbakey shibin elkom, Egypt More articles by this author Nancy Assad shibin elkom, Egypt More articles by this author Abdelaliem Eldorey shibin elkom, Egypt More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1769 UPDATED RESULTS OF THE COMBINED PHASE I/II TRIAL OF INTRAVESICAL NANOPARTICLE ALBUMIN-BOUND PACLITAXEL IN THE TREATMENT OF BCG REFRACTORY NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Superficial II1 Apr 20121769 UPDATED RESULTS OF THE COMBINED PHASE I/II TRIAL OF INTRAVESICAL NANOPARTICLE ALBUMIN-BOUND PACLITAXEL IN THE TREATMENT OF BCG REFRACTORY NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA James M. McKiernan, Dara D. Holder, Max Kates, Gina M. Badalato, Lamont J. Barlow, Arindam RoyChoudhury, Daniel Petrylak, and Mitchell C. Benson James M. McKiernanJames M. McKiernan New York, NY More articles by this author , Dara D. HolderDara D. Holder New York, NY More articles by this author , Max KatesMax Kates New York, NY More articles by this author , Gina M. BadalatoGina M. Badalato New York, NY More articles by this author , Lamont J. BarlowLamont J. Barlow New York, NY More articles by this author , Arindam RoyChoudhuryArindam RoyChoudhury New York, NY More articles by this author , Daniel PetrylakDaniel Petrylak New York, NY More articles by this author , and Mitchell C. BensonMitchell C. Benson New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1786AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Up to 50% of patients treated with intravesical agents for non-muscle invasive bladder cancer (NMIBC) will recur. Response rates to current second-line intravesical therapies average less than 20%. For these high risk patients, novel agents are necessary. Nanoparticle albumin-bound (nab-) paclitaxel has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy trials.It is therefore an appropriate candidate for further investigation as an intravesical agent. Results of the Phase I trial demonstrated minimal toxicity and systemic absorption during dose escalation. We now report the results of the ongoing Phase II trial. METHODS In January 2010, accrual began for the IRB approved phase II trial investigating the use of (nab-) paclitaxel for BCG refractory NMIBC. Inclusion criteria included patients with recurrent high grade (HG) Ta, T1, and Tis transitional cell carcinoma who failed at least one prior regimen of BCG. In accordance with the dosing determinations from Phase I data, 500mg of nab-paclitaxel was administered in six weekly intravesical instillations . The primary endpoint was response rate. Efficacy was evaluated by cystoscopy, biopsy, cytology, and imaging. If there was no evidence of disease, patients could elect to undergo maintenance treatment at 3, 6, 12, 18, 24 and 36 mos. Safety and toxicity profiles were monitored throughout. RESULTS As of November 1st 2011, nineteen of the targeted 29 patients had been enrolled. Three patients were withdrawn from the study: one due to non-study related pneumonia and sepsis; one withdrew consent; and one had a grade II urinary tract infection (UTI). Three patients (16%) had no evidence of disease at their initial post-treatment cystoscopy and became eligible for maintenance therapy. To date, these patients were free of disease at 5, 18 and 21 months following enrollment. Of the 16 patients who did not respond, no patient had progression of their disease. Local grade 1 toxicities were observed in 10/19 (52%) of patients, with UTIs being the most common. There was only 1 grade II complication, a Pseudomonas aeruginosa UTI. CONCLUSIONS Intravesical nab-paclitaxel has minimal toxicity and a 16% response rate in patients with non-muscle invasive disease and previous BCG failure. Completion of accrual is expected in April 2012. Long-term follow-up and quality of life will be reported at that time. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e714 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information James M. McKiernan New York, NY More articles by this author Dara D. Holder New York, NY More articles by this author Max Kates New York, NY More articles by this author Gina M. Badalato New York, NY More articles by this author Lamont J. Barlow New York, NY More articles by this author Arindam RoyChoudhury New York, NY More articles by this author Daniel Petrylak New York, NY More articles by this author Mitchell C. Benson New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prognostic Significance of Substaging according to the Depth of Lamina Propria Invasion in Primary T1 Transitional Cell Carcinoma of the Bladder

PurposeTo evaluate the prognostic significance of the depth of lamina propria invasion in primary T1 transitional cell carcinoma (TCC) of the bladder.Materials and MethodsWe retrospectively reviewed the medical records of 183 patients with primary T1 TCC of the bladder who had undergone transurethral resection (TUR) at our institution. Substaging was defined according to the depth of lamina propria invasion as follows: T1a, superficial invasion of lamina propria; T1b, invasion into the muscularis mucosa (MM); T1c, invasion beyond the MM but not to the muscularis propria. The prognostic significance of various clinicopathological variables for recurrence and progression was analyzed.ResultsOf the 183 patients, substaging was T1a in 119, T1b in 57, and T1c in 7 patients. The recurrence rate was 32.8% for T1a and 40.6% for T1b/c, but there was no significant difference between the two groups. The progression rate was significantly different between the two groups: 5.8% in T1a and 21.9% in T1b/c (p=0.003). The cancer-specific mortality rate was also significantly different: 4.2% in T1a and 14.0% in T1b/c (p=0.036). In the univariate analysis, microscopic tumor architecture was the only significant prognostic factor for recurrence. In the univariate and multivariate analysis concerning progression, depth of lamina propria invasion and concomitant carcinoma in situ were significant prognostic factors.ConclusionsSubstaging according to the depth of lamina propria invasion in primary T1 TCC of the bladder was an independent prognostic factor for progression. This suggests that substaging would be helpful for guiding decisions about adjuvant therapies and follow-up strategies.

A Phase I Trial of Intravesical Nanoparticle Albumin-Bound Paclitaxel in the Treatment of Bacillus Calmette-Guérin Refractory Nonmuscle Invasive Bladder Cancer

Up to 50% of patients treated with intravesical agents for high grade nonmuscle invasive bladder cancer will have disease recurrence. Response rates to current second line intravesical therapies are low and for these high risk patients novel agents are necessary. Our previously completed phase I trial showed docetaxel was a safe agent for intravesical use. Nanoparticle albumin-bound paclitaxel (Abraxane®, ABI-007) has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy. Thus, we assessed the dose limiting toxicity and maximum deliverable dose of intravesical nanoparticle albumin-bound paclitaxel. Inclusion criteria for this institutional review board approved phase I trial were recurrent high grade Ta, T1 and Tis transitional cell carcinoma of the bladder for which at least 1 prior standard intravesical regimen failed. Six weekly instillations of nanoparticle albumin-bound paclitaxel were administered with a modified Fibonacci dose escalation model used until the maximum deliverable dose was achieved. The primary end point was dose limiting toxicity and the secondary end point was response rate. A total of 18 patients were enrolled in the study. One patient demonstrated measurable systemic absorption after 1 infusion. Grade 1 local toxicities were experienced by 10 (56%) patients with dysuria being the most common, and no grade 2, 3 or 4 drug related local toxicities were encountered. Of the 18 patients 5 (28%) had no evidence of disease at posttreatment evaluation. Intravesical nanoparticle albumin-bound paclitaxel exhibited minimal toxicity and systemic absorption in the first human intravesical phase I trial to our knowledge. A larger phase II study has begun to formally evaluate the activity of this regimen.

Risk stratification of local-regional failure in bladder cancer after radical cystectomy.

e15045 Background: Patients with stage ≥T2 transitional cell carcinoma (TCC) of the bladder are typically treated with radical cystectomy (RC) + pelvic node dissection (PND) +/- chemotherapy. Adjuvant radiation therapy (RT) has no clearly defined role, although local-regional failure (LF) following RC remains a significant problem. Adjuvant RT could potentially reduce LF, but the morbidity reported in the past for such RT discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest in adjuvant RT. Identifying subgroups with differing LF risk could facilitate patient selection for adjuvant RT protocols. Methods: From 1990 - 2008, 442 patients with TCC of the bladder were followed after RC + PND +/- chemotherapy at the Hospital of the University of Pennsylvania. 132 (30%) received neoadjuvant or adjuvant chemotherapy. LF was scored as any failure within the pelvis before or within 3 months of distant failure. Univariate, multivariate Cox regression, and recursive partitioning analyses (RPA) were performed to identify subgroups with differing LF risk. Results: On univariate analysis, stage ≥pT3, nodes removed (<10 vs. ≥10), positive margins, positive nodes (pN+), node density, hydronephrosis, lymphovascular invasion, mixed histology disease and type of surgical diversion were significant predictors of LF, while chemotherapy, gender, race and BMI were not. Age at surgery was a marginal predictor of LF. On multivariate analysis, stage ≥pT3, nodes removed (<10 vs. ≥10), positive margins, pN+ and age were significant independent predictors of LF with hazard ratios of 3.36, 2.98, 2.08, 1.84, 1.04(per yr), respectively (p <0.05 for all variables). Different cut points and definitions were explored for pT stage, pN status, number of nodes removed and chemotherapy status, but none improved the regression models. RPA identified 3 patient subgroups with significantly different LF risk (logrank/p<0.01): low (<pT3), intermediate (≥pT3 + >10 nodes), and high (≥pT3 + <10 nodes) with 5 yr LF rates of 11%, 31% and 73%. Conclusions: The risk of LF after RC varies significantly among different subgroups of TCC patients. This risk stratification model could facilitate patient selection in future trials.

1846 COMPARATIVE SURVIVAL FOLLOWING DIFFERENT TREATMENT MODALITIES FOR STAGE T2- MUSCLE INVASIVE BLADDER CANCER IN OCTOGENARIANS- A POPULATION BASED STUDY

You have accessJournal of UrologyBladder Cancer: Invasive1 Apr 20111846 COMPARATIVE SURVIVAL FOLLOWING DIFFERENT TREATMENT MODALITIES FOR STAGE T2- MUSCLE INVASIVE BLADDER CANCER IN OCTOGENARIANS- A POPULATION BASED STUDY Naveen Pokala, Piyush Agarwal, Ravi P. Kiran, Sumit De, Emil Kheterpal, James Peabody, and Mani Menon Naveen PokalaNaveen Pokala Detroit, MI More articles by this author , Piyush AgarwalPiyush Agarwal Detroit, MI More articles by this author , Ravi P. KiranRavi P. Kiran Cleveland, OH More articles by this author , Sumit DeSumit De Detroit, MI More articles by this author , Emil KheterpalEmil Kheterpal Detroit, MI More articles by this author , James PeabodyJames Peabody Detroit, MI More articles by this author , and Mani MenonMani Menon Detroit, MI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1879AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Introduction: Anticipated higher operative risk and higher incidence of co-morbidities in octogenarians may influence urologists in opting for less aggressive modalities of treatment. This population-based study analyzes and compares survival after different modalities of treatment in patients with stage T2 muscle invasive bladder cancer in octogenarians. METHODS Patients that were 80 years or older diagnosed with T2 muscle invasive transitional cell bladder cancer (TCC) between 1988 and 2008 were identified from the SEER 17 database and included in the study. Patients were studied for demographics, stage at presentation, treatment modality and overall and cancer-specific survival. Patients with other histology, incomplete data, diagnosed at autopsy, distant disease, Ta, T1, T3 and T4 stages were excluded. Appropriate statistical methods were used. RESULTS 3232 patients met inclusion criteria, the mean age was 85.5± 4.3 years, 38.2% (N=1234) were female, 90.6% were white, 5.1% were black and 4.3% belonged to other races. 6 % were T2a (n=195), 8.4% were T2 b ( n=270), and 85.6% were T2 NOS. The nodal status at diagnosis was N0 (n=1323), N1 (n=17), N2 (n=11) and N3 (n=1). 2216 patients underwent endoscopic procedures alone, 108 underwent partial cystectomy, 2 patients underwent pelvic extenteration, 2 patients underwent exploratory laparotomy, 156 underwent radical cystectomy, 733 patients underwent RT and 15 patients underwent total cystectomy. The median and mean overall (OS) and cancer specific survival (CSS) following endoscopic procedure, partial cystectomy, total cystectomy, radical cystectomy and endoscopic resection with RT is shown in Table 1. Table 1. Median and mean overall survival in months Primary procedure Median OS Mean OS Median CSS Mean CSS Endoscopic procedure 11 27.1 11 33.6 TURBT and RT 14 30.5 13 30.7 Radical Cystectomy 40 60.8 59 86.1 Partial Cystectomy 37 57.5 54 78.5 Cystectomy 39 59.2 30 45.4 Whole Group 13 30.7 13 38.4 There was no significant difference noted in the age, gender or, T stage between the different Treatment groups. On multivariate analysis the age at diagnosis, T stage, N stage and treatment modality was a predictor of overall and cancer specific survival. CONCLUSIONS Cystectomy (partial or radical) offers a significant survival advantage over endoscopic resection or endoscopic resection followed by radiation to patients over 80 years of age with T2 transitional cell carcinoma of the bladder and should be offered as the treatment of choice to Octogenarians with stage T2 TCC of the bladder. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e740-e741 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naveen Pokala Detroit, MI More articles by this author Piyush Agarwal Detroit, MI More articles by this author Ravi P. Kiran Cleveland, OH More articles by this author Sumit De Detroit, MI More articles by this author Emil Kheterpal Detroit, MI More articles by this author James Peabody Detroit, MI More articles by this author Mani Menon Detroit, MI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Intravesical bacille Calmette–Guérin-induced multiorgan failure after treatment for transitional cell carcinoma

Intravesical bacille Calmette-Guérin (BCG) has been safely used to treat stage Ta and T1 bladder carcinoma since 1976. This report presents the case of a 56-year-old man who presented with multiorgan failure after bacille Calmette-Guérin (BCG) treatment for stage T1 transitional cell carcinoma of the bladder. On admission the patient was jaundiced, had inflammatory infiltrates on chest radiography and required dialysis for renal failure. He had a persisting fever of unknown origin and elevated cholestatic liver function tests, which prompted a liver biopsy.This demonstrated hypersensitivity hepatic granuloma but no organism was identified. He responded well to steroid and antimycobacterial treatment. A small percentage of BCG-treated patients suffer hypersensitivity side-effects (pneumonitis, hepatitis or interstitial nephritis). This complication most commonly follows a traumatic installation. Mycobacteriumbovis is rarely cultured or identified using polymerase chain reaction techniques, and the diagnosis is based on histological findings of granuloma.

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

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