Treatment Of Bladder Tumors Research Articles

Abstract 1903: Enhanced antitumor effect of coincident combination intravesical MMC plus BCG therapy in an orthotopic bladder cancer model

Abstract Introduction and Objective: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is currently the most successful adjuvant agent for the treatment and/or prophylaxis of superficial bladder tumors. However, superficial bladder tumors recur in 60 to 70% of all cases, and 30 % of these recurrent tumors present with a higher grade with invasive properties. We evaluated the combination of intravesical MMC plus BCG treatment against bladder tumors in a model of orthotopic murine bladder cancer. Methods: An orthotopic murine bladder cancer model was established using the simple instillation of 1 × 106 MBT-2 cells into the lumen of the bladder of a female C3H/HeN mouse through a urethral catheter. To assess the antitumoral effect of MMC, intravesical MMC therapy was administered at various dose-escalating concentrations: 0μg (control: PBS), 25μg, 50μg, 100μg, and 200μg, (n = 8 for each group; a total of 5 groups). Next, a comparative evaluation of tumor growth in a control group(PBS), a MCC-alone group, a BCG-alone group(100μg), and a combined MMC plus BCG (100μg) group were performed (n= 8 for each group; a total of 4 groups). Intravesical therapy was administered at 3-day intervals starting on day 5 and repeated 5 times. On day 60 after the initial implantation of the MBT-2 cells, all the surviving mice were sacrificed and necropsied. To evaluate macrophage infiltration in the tumor and the proliferative activity among the different groups, immunohistochemical staining analysis of the tumor cells utilizing CD68 and Ki-67 was performed in animal model. Results: In the MMC groups of 8 mice each treated with a dose of 0μg (survival; 26.4 ± 3.2 days), 25μg (34.8 ± 7.0 days) and 50μg (40.0 ± 13.2 days), 0, 0 and 2 of the mice failed to develop tumor and survived, respectively. In both the 100μg (17.3 ± 2.8 days) and 200μg (11.9 ± 3.0 days) groups, all eight mice died from adverse events. A significant survival advantage was observed in the combined MMC (50μg) plus BCG (100μg) group (51.5 ± 8.1 days), compared with that in the BCG-alone group (33.4 ± 16.8 days; p = 0.03) and the MMC-alone group (39.5 ± 13.5 days; p = 0.04). BCG significantly suppressed while MMC increased macrophage infiltration in the tumors, compared with in the control groups. The Ki-67 expression level, which is regarded as a proliferation index was significantly lower in the combined MMC (50μg) plus BCG (100μg) group (31.1 ± 5.2%) than in the BCG-alone group (50.9 ± 4.1%; p <0.001) and the MCC-alone group (39.2 ± 2.5%; p <0.05). Conclusion: Combining BCG plus MMC treatment decreased the tumor appearance rate, improved the survival period and reduced the proliferation rate in tumors, as compared with BCG-alone and MMC-alone treatment, possibly providing a greater therapeutic benefit over either agent alone. Immunochemotherapy with a combination of intravesical MMC plus BCG may be a promising alternative treatment for bladder tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1903.

Clinical observation on 2 micron laser for non-muscle-invasive bladder tumor treatment: single-center experience

To evaluate the efficacy and safety of 2 micron continuous wave laser resection of non-muscle-invasive bladder tumor (NMIBT) compared with holmium laser resection of bladder tumor (HoLRBT) and standard transurethral resection of bladder tumor (TURBT). Since April 2006 to August 2007, 97 patients with NMIBT were retrospectively collected in this study. All of them were classified into 3 groups, which were treated with 2 micron continuous wave laser resection, holmium laser resection and TURBT, respectively. The preoperative, intraoperative and postoperative clinical data were recorded and compared using SAS 6.12 statistical software. There were no differences with the preoperative characteristics among the three groups, except the diameter of the tumors. The maximum diameter of the tumors in 2 micron laser group was larger than the other two groups (P < 0.05). Two micron laser group was associated with less hemoglobin decrease compared with TURBT group (P < 0.05). All of the patients were followed and the recurrence rate of the three groups indicated no statistical significance (P > 0.05). In conclusion, 2 micron continuous wave laser resection of non-muscle-invasive bladder tumor is a safe and reliable treatment. With the distinguished hemostasis, it is an available optional treatment.

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

BackgroundPhotodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period.ResultsOur results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux.ConclusionThe combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors.

Safe Handling of Cytotoxic Agents: A Team Approach

The use of cytotoxic medications has become increasingly prevalent in the OR for the treatment of bladder tumors. Perioperative nursing staff members in the day surgery unit, OR, and postanesthesia care unit at St Mary's General Hospital, Kitchener, Ontario, Canada, expressed concern about their lack of knowledge in the safe handling of cytotoxic medications and contaminated wastes. Facility educators recognized this as an area of risk for the hospital and a learning need for staff members. As a result, they formed a committee with members representing nursing, pharmacy, infection control, occupational health, and environmental safety to develop a policy and protocol for the safe use of cytotoxic medications.

Fluorescence cystoscopy in the diagnostics and treatment of bladder tumors.

Fluorescence cystoscopy in the diagnostics and treatment of bladder tumors.

Histopathologic analysis of 2 micron continuous wave laser for the partial cystectomy of bladder urothelial carcinoma

To observe the histopathologic characteristics of 2 micron continuous wave laser transurethral partial cystectomy for the treatment of bladder tumor. A total of 54 patients with 65 bladder tumors underwent 2 micron laser via transurethral by caudal or surface anesthesia from October 2007 to December 2008. It included 41 male and 13 female cases, and the age ranged from 27 to 81 years old with a mean of (66.2 +/- 12.4) years old. The operation evaporated and exsected the wall of urinary bladder, including tumor, submucosa and all muscular layers. Specimens were sent for pathology examination. The histomorphologic changes of raw surfaces were observed 1 week, 1 month, 3 months, 6 months and 1 year postoperation by cystoscopic and pathologic examinations. All the patients tolerated in the operation. Clinical stages of the tumor: T1 for 42 cases, T2 for 12 cases. All cases were followed-up for 1 to 14 months, with a mean of 8.5 months. Tumor recurrences were found in 2 cases, no one had recurrence in situ. The tumor, submucosa and all muscular layers can be resected completely by 2 micron continuous wave laser transurethral partial cystectomy. Pathologic staging can be judged correctly. The umbilication raw surface were infiltrated by fibrous connective tissue and chronic inflammatory cells 1 week postoperation. The umbilication changed shallow and transitional epithelial cells began to cover it 1 month postoperation. The umbilication disappeared and transitional epithelial cells cover the raw surface 3 months postoperation. There was no difference between the raw surface and normal bladder mucosa. 2 micron continuous wave laser for the treatment of bladder tumor can get the same clinical result as partial cystectomy. The pathologic staging can be judged correctly by the specimens.

Traitement par instillations vésicales de BCG et mitomycine C dans les tumeurs de vessie n’infiltrant pas le muscle : enquête de pratique de l’Afu auprès des urologues français

To survey the French urologists in order to evaluate their practice of BCG and mitomycin C instillations in the treatment of non muscle invasive bladder tumours (NMIBT). The survey was performed in 2008 on French urologists registered by the French Urological Association (AFU), using online self-administered questionnaires. One hundred and fifty-six urologists answered the questionnaire. The majority of responders reported indications for bladder instillations that were closed to the AFU recommendations, but for 25% of the respondents, indications were far away from the recommendations. Seventy-nine percent of respondents said that first line plus maintenance BCG therapy was more efficient than first line alone. However, many of the respondents reported that maintenance BCG therapy was not well accepted by patients (46%), was not easy to organize (28%), and was not well tolerated by patients (56%). Eighty-eight percent of respondents said using ofloxacin to prevent BCG adverse effects, but the protocol they were using was not clearly defined. Definition of BCG therapy failure given by respondents was close to the AFU one, but the way to manage it was heterogeneous. Responses of the 156 urologists who took part in this survey should help to evaluate French urologists attitude toward bladder instillations in the treatment of NMIBT. Although they were not so far from the AFU recommendations, urologists' practices of instillations appeared to be heterogeneous. Some points requiring clarification were highlighted in this study.

Donor CD4 T Cells Are Critical in Allogeneic Stem Cell Transplantation against Murine Solid Tumor

Nonmyeloablative allogeneic stem cell transplantation (SCT) has been used for various malignancies, although detailed mechanisms of antitumor effects remain unclear. We showed that a nonmyeloablative allogeneic SCT regimen, which consists of mixed chimerism induced by an injection of donor spleen and bone marrow cells followed by cyclophosphamide treatment and a donor lymphocyte infusion (DLI), exerted antitumor effects on established murine bladder tumor, MBT-2. An expansion of donor CD4 T cells accompanied by transient but vigorous IFN-gamma production was detected shortly after DLI. In vivo neutralization of IFN-gamma or depletion of CD4 T cells from DLI abolished the antitumor effects, indicating an indispensable role of donor CD4 T cells producing IFN-gamma. Donor as well as host CD8 T cells accumulated in the tumor region with time. Importantly, depletion of CD8 T cells from DLI did not reverse the suppression of tumor growth, indicating that CD4 T cells play a more essential role in mediating early antitumor effects. Furthermore, tumor-specific response of host CD8 T cells was suggested. These results not only provide the first evidence of nonmyeloablative allogeneic SCT for the treatment of bladder tumor but also elucidate detailed mechanisms of antitumor effects provoked by DLI.

Transurethral Partial Cystectomy With Continuous Wave Laser for Bladder Carcinoma

To our knowledge we established a new technique to vaporize and incise the full-thickness bladder wall and peel off the entire muscular layers with a 2 microm continuous wave laser to treat bladder carcinoma. Nine patients were treated transurethrally with a 2 microm laser under sacral block. This 2 microm laser was used to incise the full-thickness bladder wall around the tumors. The entire bladder wall was peeled between the detrusor muscle layer and outer connective tissues. Tumors with full-thickness detrusor muscle layers at the base were removed together and sent for pathological examination. Intraoperative hemorrhage and postoperative complications were observed, and pathological staging and postoperative followup were performed. All operations were successful. Mean +/- SD operative time was 8.7 +/- 2.6 minutes (range 7 to 15) per patient. Perioperative blood loss was minimal. There was no obturator nerve reflection and no hemorrhage was detected after surgery. Bladder perforation occurred in 1 case. Pathological stage of the tumors was T1 and T2a. Patients were followed for 6 to 9 months postoperatively with no recurrence at the resection site. This series included highly selected patients treated by a single high volume surgeon. To our knowledge this is the first report of a 2 microm laser used to treat bladder carcinoma. It can be applied to precisely vaporize and incise the full-thickness bladder wall and peel it between detrusor muscle layers and outer loose connective tissues, thus completing partial cystectomy for bladder carcinoma.

Bladder cancer: new TUR techniques

Transurethral resection of bladder tumours (TURBT) using a wire loop remains the gold-standard treatment for bladder tumours, but it is associated with unacceptably high early recurrence rates after first resection. Improvements to standard resection techniques and a range of optical and technological advances offer exciting possibilities for improving outcomes. Early second resection has been shown to reduce recurrence rates, and increase response to intravesical chemotherapy and/or immunotherapy. It should be considered in most high-risk non-muscle invasive cancers (T1; G3; multifocal) being managed by bladder conservation. Newer energy sources, such as laser, may facilitate day case management of bladder tumours using local anaesthesia in select groups of patients. The novel technique of photodynamic diagnosis improves tumour detection, and quality of resection, and is likely to become the standard for initial tumour management. The traditional 'incise and scatter' resection technique goes against all oncological surgical principles. En-bloc resection of tumours would be far preferable and demands further development and evaluation. The technique of TURBT needs to evolve to allow first-time clearance of disease and low recurrence rates.

Updates in intravesical electromotive drug administration® of mitomycin-C for non-muscle invasive bladder cancer

Electromotive drug administration (EMDA) increases the local drug efficacy by controlling and enhancing transmembranous transport into tissue. EMDA of intravesical mitomycin-C (MMC) has been used for treatment of non-muscle invasive bladder cancer (NMIBC) for about a decade on the basis of laboratory studies that demonstrated an enhanced administration rate of MMC into all bladder wall layers after EMDA compared to standard instillation/passive diffusion (PD). Higher MMC concentrations might have a clinical impact since EMDA was associated with lower recurrence rates than PD in randomized studies. Further data suggest that EMDA/MMC is at least equivalent to BCG in treatment of high-risk bladder tumours. In addition, BCG combined with EMDA/MMC as well as preoperative EMDA/MMC are new therapeutic strategies with promising preliminary results in terms of higher remission rates and longer remission times. In summary, these findings suggest that EMDA for MMC delivery in the bladder could be a major therapeutic breakthrough in the treatment of NMIBC.

Initial experience of partial cystectomy in treatment of bladder tumor by 2 microm continuous wave laser

To analyze the clinical characteristics of partial cystectomy in treatment of bladder tumor by 2 microm continuous wave laser. A total of 18 patients with 21 bladder tumors treated by 2 microm laser via transurethral under sacral block. The diameters of tumors were between 1-3 cm. In the operation, we vaporized and cut whole wall of bladder, dissected the muscular layers from connective tissue, and sent them for pathology inspection. We reviewed these following variables: operation time, blood loss, complications during and after the operation, pathology staging of the tumor and follow-up visit. All the patients were tolerated in the operation. The mean operative time was (7.4 +/- 3.3) min (range, 5-12 min). Blood loss in the operation was minimal. No patient experienced an obturator nerve reflection or a hemorrhage after the operation. One case has urine leakage. The pathology staging of the tumors were as follows: T1 stage 15 cases, total 18 tumors; and T2 stage 3 cases, total 3 tumors. The followup periods were between 3 to 6 months, and the mean period was 4.5 months. There was no recurrence in situ. The 2 microm laser not only can vaporize and cut the wall of bladder finely, but also can dissect the muscular layers from connective tissue efficiently. So it can be partial cystectomy in the treatment of bladder tumor.

La terapia fotodinámica en urología: Mecanismos de acción biológicos y patológicos

Photodynamic Therapy (FDT) is a minimally invasive therapeutic modality extraordinarily useful. In urology, FDT is very useful and may be applied through endoscopes or directly, with excellent results obtained for the diagnosis and treatment of bladder tumors, in the treatment of prostate cancer and its recurrences, and in the treatment of dermatological premalignant lesions and carcinomas of the penis. FDT is founded on the use of photosensitizing products which selectively accumulate in tumor tissues. The irradiation of these tissues with a proper wavelength light (generally in the red region of the visible spectrum lambda > or = 600 nm) produces the formation of oxygen reactive species with cytotoxic effects leading to selective death of neoplastic cells, and tumor regression. The main advantage of FDT is the restriction of cellular damage to the irradiation area, with the associated decrease of secondary effects on healthy tissues near the tumor, on the contrary to what happen with other conventional therapies for some tumors of the urinary tract. Moreover, FDT may be used in combination with radiotherapy and chemotherapy.

Chronic Mycobacterium Infection of First Dorsal Web Space After Accidental Bacilli Calmette-Guérin Injection in a Health Worker: Case Report

We present a case of inoculation of the first dorsal web space by a nurse practitioner who accidentally stuck herself while preparing Bacilli Calmette-Guérin vaccine for treatment of bladder tumor. We report the evolution and management of this resistant chronic Mycobacterium infection that ultimately required use of a vacuum wound management system followed by a microvascular free tissue transfer.

Continuous wave laser of 2 microm for bladder tumor treatment

To analyze the clinical characteristics of 2 microm continuous wave laser vaporization resection for the treatment of bladder tumors. A total of 56 patients with 68 bladder tumors underwent 2 microm laser vaporization resection via a transurethral cystoscope under caudal anesthesia. In the operation, the wall of the urinary bladder was vaporized and cut, the muscular layers were removed, and then the specimens were sent for pathological inspection separately. The following variables were recorded: operation time, blood loss, complications during and after the operation, pathology staging of the tumors, and follow-up visit time. All patients endured the operation. The mean surgery time was 8.8 +/- 3.3 minutes (range, 4 to 15 minutes). Blood loss was minimal, no patient experienced an obturator nerve reflection, or a hemorrhage after the operation. The pathology staging of the tumors were as follows: 40 cases (total 47 tumors) were T1 stage; 16 cases (total 21 tumors) were T2 stage. The follow-up periods were between 12 to 17 months, and the mean period was 14.5 months. Tumor recurrences were found in 3 cases, and one patients suffered two recurrences, the total recurrence rate was 5.3%. There was no primary recurrence. The 2 microm continuous wave laser is a new, safe and efficacious method for the treatment of bladder tumors. Because the 2 microm laser can vaporize and cut the muscular layers of the bladder finely, it can not only treat superficial bladder tumors efficiently, but also treat some types of invasive tumors of the bladder.

Gene therapy in bladder cancer

Gene therapy remains a promising therapy for controlling cancer. Bladder cancer is a particularly interesting tumor system for consideration of a gene therapy approach based on several factors, including the ability to access the tumor in a relatively noninvasive fashion. Several gene therapy strategies have been studied in the treatment of bladder tumors. In this review, an update of the recent outcomes of viral-based gene therapy for bladder cancer is discussed. Several preclinical in-vitro and in-vivo studies have demonstrated the feasibility of intravesical viral-mediated gene therapy. Recent studies have introduced additional viral systems as useful vectors for transfection of the bladder and associated tumor. Advances in targeting techniques have improved transgene delivery to the bladder. Additionally, a variety of therapeutic strategies, including gene corrective treatment, gene-directed enzyme prodrug therapy, and immunomodulation have been recently investigated with positive findings. Viral-based gene therapy for bladder cancer remains an intriguing potential future therapy for bladder cancer. Additional advances in gene delivery and the establishment of novel vector safety will be required to move this therapeutic option out of the laboratory and into the clinical setting.

BCGite du gland post-BCGthérapie intravésicale

BCG therapy is an effective adjuvant treatment for superficial bladder tumors. Therapy involves intravesical instillation of live attenuated Calmette-Guérin bacilli. BCG infection of the glans is a rare local complication associated with this treatment, two cases of which are reported below.Case 1: A 77-year-old man presented relapsing urothelial bladder carcinoma treated by endoscopic resection and BCG therapy. One week after the seventh instillation, severe balanitis developed. Three months later, examination revealed massive painful perimeatal ulceration with yellowish papules in the peripheral regions. Histology revealed epithelioid giant-cell granulomas. Ziehl-Neelsen staining was positive. Slow cure of the lesions was achieved within 12months using double antitubercular antibiotic therapy. Case 2: In a 61-year-old man receiving BCG therapy for relapsing bladder carcinoma in situ, the sixth instillation was considered traumatic since it was highly painful. One week later, papular nodules appeared on the glans with a sclerosing lesion of the balanopreputial sac, dark purple perimeatal papules and a mass beneath the mucosa of the glans. Antibiotic treatment comprising ofloxacin followed by rifampicin for two months proved ineffective. Histology revealed granulomatous dermal lesions with eosinophilic necrosis. Triple antitubercular antibiotic therapy was initiated.The first reported case of BCG infection of the glans in patients undergoing intravesical BCG therapy was published in 1992. Since then, there have been nine other reports. There is no stereotypical clinical presentation. In most cases, an infiltrated erythematosus plaque is seen together with yellowish papules in certain patients. Diagnosis is based upon history and histological examination.

Use of Bipolar Energy for Transurethral Resection of Superficial Bladder Tumors: Long-Term Results

To evaluate the long-term efficacy and safety of transurethral resection of bladder tumor (TURBT) with bipolar plasmakinetic energy. We reviewed the records of 121 patients with superficial transitional cell carcinoma of the bladder treated at our institute. Bipolar TURBT with plasmakinetic energy was performed for diagnostic and therapeutic purposes in all patients. Resected tissue was examined by a pathologist who recorded the number of tumors, tumor size, tumor shape, location, grade, invasion of the muscularis propria, and presence of muscular invasion. The operating time, length of hospital stay, blood loss, and intraoperative and postoperative complications were recorded by a urologist. Follow-up was 3 to 5.5 years after operation. The median age of the patients was 61 years; 41 patients had multiple tumors and 80 had single tumors. The mean tumor size was 1.9 cm in diameter. The tumor was located in the lateral wall of the bladder in 67 patients. The mean operative time was (25 +/- 16) minutes and the mean postoperative hospitalization period was 3 days. Three (2.5%) patients had hematuria requiring blood transfusion and 2 (1.7%) patients had bladder perforation. Adductor contraction was noted in 6 patients (4.9%), and urethral strictures occurred in 5 patients (4.1%). Transurethral resection of bladder tumors with bipolar plasmakinetic energy is safe and effective in the treatment of superficial bladder tumors.

Place de la cystectomie radicale par voie laparoscopique dans le traitement des carcinomes urothéliaux infiltrants de vessie

Radical cystectomy is the reference treatment for recurrent superficial or invasive bladder tumours. The most standardized incision is midline infra-umbilical laparotomy. The first laparoscopic cystectomy was performed in 1992 in a patient with neurogenic bladder and several teams have subsequently described this incision for the treatment of bladder tumours. The advantages of laparoscopy have been reported in terms of morbidity and earlier return to daily activities. The current oncological results of this incision are difficult to compare with those of conventional open surgery due to the insufficient follow-up. However, published series have not reported any significant difference in the intermediate term. Until convincing results become available, it therefore appears legitimate to allow teams skilled in laparoscopy to demonstrate the oncological efficacy of this approach. At the present time, the reference treatment for invasive bladder cancer remains open cystectomy.

POS-02.43: Laser treatment of superficial bladder tumors

Laser advantages in superficial bladder tumors (SBT) are especially represented by non contact tumoral vaporization with homogenous coagulation of the tumor and blood vessels (less than 0.5 mm.). Our goal was to analyze the particularities and results of Nd:YAG laser used in a selected series of patients with SBT.