Resection Of Bladder Cancer Research Articles

MP-04.14 Endoscopic Resection of Bladder Cancer in Patients Receiving Double Platelet Antiaggregant Therapy

MP-04.14 Endoscopic Resection of Bladder Cancer in Patients Receiving Double Platelet Antiaggregant Therapy

Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE

Objectives Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. Material and methods Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. Results A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. Conclusions Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD.

Abstract 4861: Identification of premalignant bladder markers using DNA microarray analysis of the UPII-SV40Tag model for invasive bladder UCC

Abstract Urothelial cell carcinoma of the bladder (UCC) ranks 5th in incidence of all cancers in the developed world, yet the mechanisms of its origin and progression remain poorly understood. A few urine-based tests for screening and surveillance are commercially available for bladder cancer, but there are no reliable non-invasive methods for detecting premalignant UCC. In order to determine molecular mechanisms involved in early UCC development and to identify new biomarkers for detection, diagnosis and prognosis of UCC, a transgenic mouse model for invasive bladder cancer (UPII-SV40Tag mice) was analyzed by DNA microarray technology. Genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild type (WT) littermates at 3, 6, 20 and 30 weeks of age were identified. The ages selected correspond to premalignant, carcinoma in-situ, and early and later stage papillary UCC, respectively. Approximately 1,900 unique genes were differentially expressed (≥ 3-fold difference at one or more time points) between WT and UPII-SV40Tag urothelium during the time course of tumor development. A high proportion of cell cycle regulatory genes and proliferation signaling genes were more strongly expressed in the UPII-SV40Tag bladder urothelium. Several of the genes upregulated and downregulated in UPII-SV40Tag urothelium were tested as biomarkers for premalignancy, including autocrine motility factor (AMFR), hyaluronan-mediated motility receptor (Hmmr), proliferating cell nuclear antigen (PCNA), Rac GTPase activating protein 1 (RacGAP1), superoxide dismutase 3 (SOD3), collagen 1a2 (Col1a2), and others. These tests were performed by analyzing urine samples from a recently completed Phase II, randomized, placebo controlled chemoprevention trial (N01 CN85186, PI: A. Sabichi) that was designed to test whether celecoxib can prevent recurrence in patients successfully treated by transurethral resection (TUR) for non-muscle invasive bladder cancer. Positive markers, Hmmr and RacGAP1, and a negative marker, Col1a2, have been identified in patient urine samples that show promise for detecting UCC recurrence. We are currently attempting to determine the biological function of Hmmr, and RacGAP1 in bladder premalignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4861. doi:10.1158/1538-7445.AM2011-4861

Narrow band imaging-assisted transurethral resection for non-muscle invasive bladder cancer significantly reduces residual tumour rate

PurposeTo investigate whether narrow band imaging (NBI)-assisted transurethral resection (TUR) (NBI-TUR) has an impact on non-muscle invasive bladder cancer (NMIBC) residual tumour rate compared to white light (WL)-assisted TUR (WL-TUR).MethodsPatients with NMIBC treated with either NBI- or WL-TUR were compared in a frequency-matched index-control setting. During NBI-TUR, all suspicious lesions identified by either WL or NBI were resected. Index patients (NBI-TUR, n = 40) were prospectively recruited and control patients (WL-TUR, n = 120) were retrospectively collected, whilst being blinded for their first follow-up (fFU)-status. Non-radical TUR cases, patients without evidence of urothelial carcinoma in the pathology specimen and those with isolated carcinoma in situ or muscle invasive disease were excluded. Matching was based on the risk of tumour recurrence defined by (a) the EORTC risk score for recurrence and (b) the administration or not of one single chemotherapeutic intravesical instillation immediately after TUR. All patients underwent routine follow-up with WL cystoscopy supplemented with cytology at 3 months or re-TUR in selected cases. The residual tumour rates at fFU (RR-fFU) of patients with NMIBC submitted to either NBI- or WL-TUR were compared.ResultsBaseline patient and tumour characteristics were comparable between groups. The RR-fFU for WL- and NBI-TUR was 30.5% (36 out of 118 patients) and 15.0% (6 out of 40 patients), respectively (OR: 2.7, one-sided 95% CI: 1.2–6.1; P = 0.03).ConclusionNBI-TUR decreases residual tumour rate significantly when compared to a matched cohort of WL-TUR.

Endoscopic resection of bladder cancer in patients receiving double platelet antiaggregant therapy

Approximately 5% of patients who have undergone coronary artery stenting require noncardiac surgery within a year of their cardiac intervention. European cardiological guidelines and recommendations from the U.S. Food and Drug Administration on platelet antiaggregant therapy following coronary artery stenting are for dual treatment with acetylsalicylic acid and clopidogrel, which should be continued for at least 12 months. The aim of this study was to evaluate the clinical course in patients receiving double platelet antiaggregant therapy who underwent transurethral resection of bladder cancer. Between September 2007 and April 2010, twelve patients receiving double antithrombotic therapy (clopidogrel+acetylsalicylic acid) underwent transurethral resection of bladder cancer. In two cases the operation was "urgent". The mean age of the patients was 71.25 years (range, 52-83 years). In nine cases the bladder cancer was newly diagnosed. The patients' preoperative mean hemoglobin concentration was 11.4 g/dl (range=5.2-13.4 g/dl), and on the first postoperative day it was 10.2 g/dl (range=9.6-12.6 g/dl). The mean duration of the intervention was 32 min (range=20-60 min). There were no cardiac complications in either the perioperative or the postoperative period. No patient required reintervention for hemostatic purposes. Three episodes of clot-related acute urinary retention occurred after removal of the bladder catheter, all of which were resolved with replacement of the catheter without needing reintervention. Despite the high number of complications related to cardiac problems that suspension of these drugs causes, this urological intervention, carried out during dual antithrombotic therapy, was feasible and without major complications. Given the high proportion of complications due to clot-related urinary retention, it is advisable to leave the urinary catheter in place for a longer period.

Quel traitement d’entretien par instillations endovésicales de BCG pour les tumeurs de vessie n’infiltrant pas le muscle ?

Intravesical Bacillus Calmette-Guerin (BCG) is the standard treatment after transurethral resection for intermediate or high-risk non muscle-invasive bladder cancer. The objective is to prevent tumor recurrence and progression with muscle invasion. To improve immunotherapy efficacy, an induction course followed by maintenance BCG cycles is strongly recommended. The SWOG schedule is today considered as the gold standard, consist of three weekly instillations of BCG at 3 and 6 months, and every 6 months for 3 years. However, less than 20% of the patients are able to complete the 3-year maintenance-dosing schedule because of BCG side effects. Prophylactic ofloxacin could lead to a reduction of 18.5% of grade II and III toxicity. Alternative schedules have been currently evaluated to improve the tolerance of maintenance treatment with endo-vesical instillations of BCG. Thus, low dose BCG during maintenance therapy does not appear to affect the recurrence-free survival and/or the risk of tumor progression. In contrast, the optimal number of instillations of BCG maintenance therapy remains to be defined.

Disease-Free Survival at 2 or 3 Years Correlates With 5-Year Overall Survival of Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival. We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic. Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival. Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.

Is Repeat Transurethral Resection Effective and Necessary in Patients with T1 Bladder Carcinoma?

Introduction: We investigated the efficacy and necessity of repeat transurethral resection (Re-TUR) in T1 bladder cancer. Patients and Methods: From September 2004 to September 2009, 62 patients with pathologically confirmed T1 bladder tumours were investigated. Re-TUR was routinely performed within 3–6 weeks following the initial resection. The pathological results of the Re-TUR were reviewed, and the risk of recurrence was investigated. Results: Of the 62 patients who underwent Re-TUR, 22 had a residual tumour pathologically. Visible residual tumours were detected in 9 patients (14.5%). The risk of having a residual tumour was directly correlated with the diameter of the initial tumour in T1 tumours (p = 0.007). Conclusions: Upstaging to T2 of the disease led to radical cystectomy in 11.29% of the patients in our series. Re-TUR should be routinely performed on all patients, especially on patients with high-grade tumours and with tumour diameters greater than 3 cm in T1 bladder cancer.

The Role of Tumor-Free Status in Repeat Resection Before Intravesical Bacillus Calmette-Guerin for High Grade Ta, T1 and CIS Bladder Cancer

We evaluated the outcome of repeat transurethral bladder tumor resection for high risk nonmuscle invasive bladder cancer before induction and maintenance bacillus Calmette-Guerin. Included in the study were 151 consecutive patients with a mean age of 68.6 years (range 32 to 86) with primary high grade, nonmuscle invasive (Ta, T1 or CIS) bladder cancer. All patients underwent repeat transurethral bladder tumor resection and were shown by repeat resection to be tumor-free or have residual tumor before bacillus Calmette-Guerin. The bacillus Calmette-Guerin response was evaluated by disease recurrence and progression. A total of 70 tumor-free patients and 47 with residual tumor received bacillus Calmette-Guerin induction and maintenance therapy after repeat transurethral bladder tumor resection, of whom 84 (71.8%) were disease-free during followup. In the tumor-free group 11.4% of tumors recurred compared with 27.7% in the residual tumor group (p <0.05). Progression was noted in 5.7% of tumor-free cases vs 17.0% of residual tumor cases (p <0.05). Time to recurrence was significantly less in the residual tumor group than in the tumor-free group (17.8 vs 23.9 months, p <0.001). Tumor-free status at repeat transurethral bladder tumor resection improves the bacillus Calmette-Guerin response rate and delays tumor recurrence. During followup recurrence in residual tumor-free patients develop more likely as low grade lesions than in patients with residual tumor at repeat transurethral bladder tumor resection.

Variability of treatment selection among surgeons for patients with cT1 urothelial carcinoma

To report the heterogeneity in the treatment of patients with cT1 urothelial carcinoma by different surgeons, and to report outcomes in patients with and without bacillus Calmette-Guérin (BCG) treatment. We retrospectively reviewed 396 patients who had undergone a re-staging transurethral resection (TUR) for cT1 bladder cancer. We assessed both differences in the treatment by surgeon, and the association of early treatment with BCG with recurrence, progression and bladder cancer-specific death. Muscle was captured in the re-staging TUR specimen in a median of 76% of patients (range 50-94 when stratified by surgeon). On multivariable analysis there was significant heterogeneity among surgeons in the use of early cystectomy (P < 0.001), deferred cystectomy (P < 0.001), and BCG (P= 0.014). However, there was no significant heterogeneity between surgeons in clinical outcome for recurrence (P= 0.9) and overall survival (P= 0.3). Among 288 patients placed on surveillance, the 5-year probability (95% confidence interval) of freedom from recurrence was 45 (36-54)% for those receiving and 54 (44-62)% for those not receiving early BCG. On multivariable analysis, early BCG was not significantly associated with recurrence (P= 0.14). The cumulative incidence of progression was ≈10% for both groups, and the cumulative incidence of bladder cancer-specific death was ≈7% for both groups. The cumulative incidence of deferred cystectomy before progression was 14% for those receiving and 15% for those not receiving early BCG. There is a significant variability among surgeons in the management of patients with T1 disease. The similar outcome for the BCG-treated and -untreated patients in our study is most likely confounded by patient selection.

Reply

The intent of our article was not to describe in detail the technique of accomplishing a complete endoscopic resection of all bladder tumors, as I have coauthored chapters 1 Shelfo S.W. Brady J.D. Soloway M.S. Transurethral resection of bladder cancer: the mainstay of treatment. Atlas Urol Clin North Am. 1997; 5: 1-14 Google Scholar , 2 Dudak S.D. Soloway M.S. Video resection techniques in the diagnosis and management of bladder tumors. in: McGuire E.J. Bloom D. Catalona W.J. Advances in Urology. Vol 9. Mosby-Year Book, Chicago, IL1996: 11-23 Google Scholar addressing some of the excellent points indicated by Dr Herr in his editorial comments. Rather this article aimed to stress that, for a variety of reasons, a high percentage of patients with Ta and T1 bladder tumors do not undergo a complete resection. One would have to assume, possibly incorrectly, that a urologist performing a TUR of bladder tumors would try to remove all tumors. The fact that macroscopic tumor remains in the bladder within 4 weeks before resection indicates that this procedure is not easily performed. This might be because tumors are located in a region of the bladder that is difficult to visualize, the bladder is thin and the surgeon is concerned about perforation, or the equipment is substandard and does not allow a successful procedure. Attention to detail is required. Among the requirements for success in the outcome of patients with Ta−T1 bladder tumors is accurate staging as well as removal of all evident tumor before proceeding with intravesical therapy, or a bladder preservation strategy for T2 tumors. In either case, there is agreement that the results are far better when all tumors have been eradicated before embarking on prophylaxis or treatment. As Dr Herr correctly emphasizes, the guideline for a reTUR for high grade T1 and for some high grade Ta tumors is to help ensure accuracy in staging. A 3 month delay in the proper management of high grade bladder cancer can be catastrophic. Editorial CommentUrologyVol. 75Issue 2PreviewThe aim of transurethral resection (TUR) is to resect all nonmuscle-invasive bladder tumors, but surgery as currently practiced fails in a significant proportion of patient's resection. Incomplete TURs are partly due to the number, size, location, and extent of bladder neoplasm, and in part due to the lack of experience, skill, and diligence of the surgeon.1 Confirming these observations, the authors provide guidelines to improve the quality of TUR of bladder tumors. Their recommendations are too general and lacking in detail, however, to be useful in individual cases. Full-Text PDF

Two instillations of epirubicin as prophylaxis for recurrence after transurethral resection of Ta and T1 transitional cell bladder cancer: a prospective, randomized controlled study

Although transurethral resection (TUR) is the standard treatment for non-muscle-invasive bladder tumors, 40-80% of tumors recur in spite of complete resection. To evaluate the efficacy, dose effectiveness and safety of early short-duration intravesical instillation therapy using epirubicin (EPI) administered immediately after TUR and on the next day following TUR. Between 1995 and 2001, 303 patients with Ta and T1 non-muscle-invasive bladder carcinoma were enrolled in this study. Patients were randomized into three groups. Group A patients were treated with two intravesical infusions of EPI 20 mg/40 ml saline immediately after TUR and within 24 h. Group B patients were treated with EPI 50 mg/100 ml on the same schedule as group A. Group C patients were treated by TUR alone as a control group. The primary endpoint was a duration to the first recurrence. Of the 303 patients, 79 in Group A, 84 in Group B, and 77 in Group C could be evaluated for recurrence. Median follow-up was 44 months. Median recurrence-free survival durations for Groups A, B, and C were 24, 38, and 13 months, respectively. The difference between Groups B and C was statistically significant (p = 0.04). Adverse reactions related to instillation were observed in about 30% of the patients. These reactions included micturition pain and frequency. These toxicities were mild and transient. Intravesical instillation of EPI 50 mg twice within 24 h after TUR was effective as prophylactic therapy for non-muscle-invasive bladder cancer with tolerable toxicity problems.

膀胱癌術後結腸転移を認めた1例

症例は70歳代の男性．膀胱癌および肺転移に対して術前化学療法を施行後，経尿道的膀胱腫瘍切除術を施行した．その後外来にて経過観察中，手術から約8カ月後の腹部CT検査にて左総腸骨動脈周囲リンパ節の腫大，および上行結腸に腫瘤陰影が認められた．さらに大腸内視鏡検査にて上行結腸に1型の腫瘍を認めた．上行結腸腫瘍に対し，結腸右半切除術を行い，同時に左総腸骨動脈周囲のリンパ節を摘出した．病理組織検査の結果，上行結腸の腫瘍，左総腸骨動脈周囲リンパ節ともに膀胱癌の転移と診断された．転移性大腸癌は非常に稀であり，若干の文献的考察を加えて報告する．

Comparing the Safety and Efficiency of Conventional Monopolar, Plasmakinetic, and Holmium Laser Transurethral Resection of Primary Non-muscle Invasive Bladder Cancer

To compare the safety and efficiency of conventional monopolar, plasmakinetic and holmium laser transurethral resection of bladder tumor (CM-TURBT, PK-TURBT and HoL-TURBT) while managing primary non-muscle invasive bladder cancer. From 2005 to 2009, 173 patients with primary non-muscle invasive bladder cancer underwent endoscopic surgery. Among them, 51 patients underwent CM-TURBT, 58 patients underwent PK-TURBT, and 64 patients underwent HoL-TURBT. All patients were divided into three risk groups (low, intermediate, and high) based on the European Association of Urology guidelines and prognostic factors of recurrence. Clinical data, included preoperative, operative, and postoperative management and follow-up, were recorded. Patient demographics and tumor characteristics in all three groups were compared before surgery. There was no significant difference in operative duration among the three groups. Compared with the CM-TURBT group, both PK-TURBT and HoL-TURBT groups had less intraoperative and postoperative complications, including obturator nerve reflex, bladder perforation, as well as bleeding and postoperative bladder irritation. There were no significant differences among the three groups in the transfusion rate and occurrence of urethral strictures. Patients in the PK-TURBT and HoL-TURBT groups had less catheterization and hospitalization time than those in the CM-TURBT group, and there were no significant differences in each risk subgroup as well as the overall recurrence rate among the CM-TURBT, PK-TURBT and HoL-TURBT groups. Both PK-TURBT and HoL-TURBT might prove to be preferable alternatives to CM-TURBT management of non-muscle invasive bladder cancer. PK-TURBT and HoL-TURBT, however, did not demonstrate an obvious advantage over CM-TURBT in tumor recurrence rate.

Biopsies of the normal-appearing urothelium in primary bladder cancer

Aim:The aim of the study was to determine the incidence of "positive" findings in biopsies of the normal-appearing urothelium near primary cancer and their influence on therapeutic decisions.Materials and Methods:Between January 2001 and October 2008, in 230 patients with primary bladder cancer during initial resection of tumor, we also performed random biopsy of surrounding normal-appearing urothelium. We analyzed retrospectively the number and type of positive biopsy findings and their impact on further treatment.Results:There were 40% of patients (92/230) whose normal-appearing urothelium biopsy revealed pathological findings such as tumor tissue, Tis, and dysplasia. In 24.4% of patients, the stage of the primary tumor was Ta (32/131), in 50% it was T1 stage (30/61), and in 79% T2 stage (30/38). When we assessed the grade of malignancy, we found 18% of biopsies with G1 tumors (16/88), 33% with G2 tumors (19/59), and 69% with G3 tumors (57/83). Tumor tissue that was found in the normal-appearing urothelium in biopsy specimens in 13% of patients was in stage Ta (17/131), in 16% it was T1 stage (10/61), and in 39% of patients, the tumor was in T2 stage (15/38). Pathological findings of random biopsies were crucial in changing therapeutical decisions in 4.6% (9/192) of patients.Conclusion:Biopsy of the normal-appearing urothelial tissue is easy to perform and may help in identifying patients with high risk of disease progression and recurrence. Based on our results and results from the literature we recommend this simple tool as part of the routine management during transurethral resection of primary bladder cancer.

The Efficacy of the EORTC Scoring System and Risk Tables for the Prediction of Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer after Intravesical Bacillus Calmette-Guerin Instillation

PurposeThe European Organization for Research and Treatment of Cancer (EORTC) scoring system and risk table were introduced in the 2008 European Association of Urology guidelines on TaT1 bladder cancer. We compared the recurrence and progression rate between EORTC risk tables and author's patients who underwent transurethral resection of bladder cancer (TURB) following intravesical Bacillus Calmette-Guerin (BCG) instillation.Materials and MethodsThe medical records of 251 patients who underwent TURB and were diagnosed with non-muscle-invasive bladder cancer from l993 to 2007 were analyzed. The patients were divided into 2 groups: the recurrence group and the progression group. According to the EORTC scoring system, the patients in each group were categorized in terms of number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and pathologic grade and the scores were summed. According to the summed scores, the recurrence group and the progression group were divided into 3 subgroups: low, intermediate, and high risk, respectively. The recurrence rate and progression rate of each group were compared with the EORTC risk tables.ResultsThe recurrence rate and progression rate were almost similar to the EORTC risk tables. However, the recurrence rate was low in the intermediate-risk group.ConclusionsClinical utilization of the EORTC scoring system and risk tables is very effective in predicting the recurrence and progression of non-muscle-invasive bladder cancer and in selecting treatment.

Efficacy of bladder-preserving therapy for patients with t3b, t4a, and t4b transitional cell carcinoma of the bladder.

PurposeRadical cystectomy has been the most widely used method in the treatment of bladder cancer, but it is limited by major problems. Therefore, we investigated the results of bladder-preserving treatment in patients with T3b, T4a, and T4b transitional carcinoma of the bladder who underwent transurethral resection of bladder cancer and subsequent administration of chemotherapy.Materials and MethodsOf all patients who were diagnosed with bladder cancer and underwent bladder-preserving treatment between January 2001 and August 2008, 78 patients with at least 12 months of follow-up data were enrolled in this study. All patients received gemcitabine (1,000 mg/m2) and cisplatin (70 mg/m2) once per month postoperatively for a total of 6 months and completed a follow-up visit every 3 months. The patient survival rate and prognostic factors (age, tumor size, differentiation, number of lesions, stage, and presence of hydronephrosis) were assessed. The Kaplan-Meier method was used to analyze survival rate, and Cox multiple regression analysis was used for prognostic factors.ResultsThe mean patient age was 68.32±8.6 years, the mean duration of follow-up was 54.70±32.8 months, and the median duration of follow-up was 49.0 months. The 5-year survival rate was 66.2%. Single lesions were found in 28 cases (35.9%), and multiple lesions were found in 50 cases (64.1%). Stage T3b lesions were identified in 56 cases (71.8%), stage T4a lesions were identified in 16 cases (20.5%), and stage T4b lesions were identified in 6 cases (7.7%). Tumor size was less than 4 cm in 4 cases (59.0%) and greater than 4 cm in 32 (41.0%). Hydronephrosis was present in 21 cases (26.9%). In the 5-year survival analysis, prognostic factors significantly influencing survival rate were T-stage of the tumor and absence of hydronephrosis and complete regression after treatment (p<0.05). Multivariate analysis revealed that tumor stage and the absence of hydronephrosis were statistically significant prognostic indicators.ConclusionsIn patients with T3b, T4a, and T4b transitional carcinoma of the bladder, bladder preservation may prevent a decrease in quality of life. Also, our findings suggest that this approach could be considered a primary treatment option for patients with T3b stage tumors without evidence of hydronephrosis.

Testing for urinary hyaluronate improves detection and grading of transitional cell carcinoma

Objective The purpose of this study is to establish a method for the diagnosis and grading of transitional cell carcinoma (TCC), which is responsible for 90% of bladder tumors, using a recently developed ultrasensitive assay for the measurement of hyaluronan (HA). Materials and methods Urine samples were collected prior to surgery (cystoscopy, transurethral resection for bladder cancer (TURBT), and cystectomy) in 350 patients. After the procedure, pathologic examination revealed that 160 patients had TCC. HA was measured directly in the urine by a noncompetitive enzyme-linked immunosorbent assay (ELISA)-like fluorometric assay. Using the receiver operator characteristic curve (ROC), t-test, Dunn test, Kruskal-Wallis test, and Mann-Whitney test, we evaluated the differences between groups (those with TCC vs. those without TCC). Results By analyzing the ROC curve, we chose a urinary HA cutoff value of 13.0 μg/l for indicating risk of TCC. Using the value this of 13.0 μg/l, we found that this test had an overall sensitivity of 82.3% and an overall specificity of 81.2%. The positive predictive value of this assay was 78.9%, the negative predictive negative value was 84.2%, and the predictive accuracy was 81.7%. Logistic regression analysis revealed that every 1 μg/l increase in HA increased a patient's likelihood of having TCC by 3.9%. The sensitivity of this test to detect superficial tumors was 76.6%, whereas its sensitivity for detecting invasive tumors was 94.6%. The urinary HA excretion of patients with TCC, classified according to the TNM staging system and the World Health Organization (WHO) grading system, were compared, and a significant difference was observed between the HA levels of patients with superficial tumors compared with invasive tumors ( P = 0.005) as well as between patients with low- vs. high-grade carcinomas ( P < 0.001). Patients with urinary HA levels >35 μg/l had a 4.63 times increased risk of having an aggressive, invasive, high grade tumor ( P = 0.005). Conclusions Our results support the postulate that urinary HA may be used as a tumor marker to aid in the diagnosis and grading of TCC. Additionally, more invasive tumors produce and release more HA in urine than superficial tumors, thus higher HA levels indicate more aggressive disease.

Disseminated bacille Calmette–Guérin infection in two patients with CD8+ T-cell lymphopenia

To the Editors: Intravesical bacille Calmette–Guerin (BCG) therapy is an effective treatment for high-risk superficial bladder cancer. A nonspecific immune response is expected after instillation of BCG, an alive but attenuated strain of Mycobacterium bovis . Disseminated BCG disease is a rare but well known complication of this therapy. It occurs in approximately 1% of cases 1. Severe complications could occur with hepatitis and pneumonitis but bone marrow involvement is exceptional. There are limited data on factors associated with the risk of BCG infection. The role of CD4+ T-cells in controlling mycobacteria infection is well established and the susceptibility of HIV-infected individuals for tuberculosis is an argument for this 2. Nevertheless, CD8+ T-cells play a significant role in this control, in particular secreting interferon (IFN)-γ and killing infected cells given their cytotoxic potential 3. Furthermore, experimental studies have shown that CD8+ T-cells play an important role in the early control of mycobacteria infection in older mice 4, suggesting that this may be occurring in elderly people. The present study describes two disseminated BCG infections, including bone marrow involvement, in elderly patients. Severe CD8+ T-cell depletion was found in the two patients, which illustrates the importance of CD8+ T-cells in the early control of mycobacterial infection in humans. The first patient was a 74-yr-old male, admitted in our department for fever and chills. He had concomitant weight loss of 6 kg and intense fatigue over the last 15 days. 3 months earlier he had undergone a trans-urethral resection for superficial bladder cancer. Treatment was completed by weekly instillation of BCG. A few days after the second instillation, the patient noted gradual onset of fever. 3 weeks after the onset of fever, he was referred to our hospital. Clinical examination gave no conclusive results but the biological results showed elevated C-reactive protein …

UP-3.040: Mistletoe Extract as an Adjuvant Therapy after Resection of Superficial Bladder Cancer: Prospective Clinical Randomized Study

UP-3.040: Mistletoe Extract as an Adjuvant Therapy after Resection of Superficial Bladder Cancer: Prospective Clinical Randomized Study