Therapy For Bladder Carcinoma Research Articles

Reactive Arthritis after BCG Therapy in Bladder Carcinoma

Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from nonaggressive and usually noninvasive tumors that recur and require long-term invasive follow-up to aggressive and invasive tumors with high disease-specific mortality. Bacillus Calmette Guerin (BCG) intravesical immunotherapy, a vaccine derived from attenuated Mycobacterium strains - Bovis is one of the most effective bladder cancer therapies currently available. Reactive arthritis has occurred in between 0.5% and 1% of bladder cancer patients treated with intravesical BCG immunotherapy. Here, we present a 66-year-old man diagnosed with urothelial carcinoma undergoing intravesical BCG therapy with high-grade fever and polyarthralgia.

Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells.

Background & Objective:Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma. Methods:The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated.Results:A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis. Conclusion:The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.

A Mycobacterium bovis Mycotic Abdominal Aortic Aneurysm Resulting From Bladder Cancer Treatment, Resection, and Reconstruction With a Cryopreserved Aortic Graft

Mycotic abdominal aortic aneurysms (AAAs) are a clinical challenge for vascular surgeons due to their critical location, surrounding inflammation, risk of rupture, and danger of reinfection following treatment. We present a case of Mycobacterium bovis AAA in a 69-year-old male after treatment with intravesicular bacillus Calmette-Guérin (BCG) therapy for bladder carcinoma. The classical approach for mycotic AAA entails extra-anatomic reconstruction followed by resection with oversewing of the proximal and distal aortic stumps. Alternative in-line reconstruction options have also been advocated. This case illustrates a technically straightforward, durable, in-line repair within an infected field utilizing cryopreserved aortic allograft.

Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non‐specific immunostimulatory effects

Hemocyanins, which boost the immune system of mammals, have been used as carrier-adjuvants to promote Ab production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified oxidized Concholepas concholepas hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox-CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox-CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly through macropinocytosis. During this process, Ox-CCH remained inside endosome-like structures for a longer period. Mouse immunization experiments demonstrated that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH showed a significant antitumor effect in the B16F10 melanoma model similar to that produced by CCH, inducing IFN-γ secretion. Together, these data demonstrate that the aldehydes formed by the periodate oxidation of sugar moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory carrier effects.

176. AdCD40L Immunogene Therapy for Bladder Carcinoma – A Phase I/IIa Trial

176. AdCD40L Immunogene Therapy for Bladder Carcinoma – A Phase I/IIa Trial

Role of anti-Her-2 therapy in bladder carcinoma

Bladder cancer, in its advanced stage, has very few therapeutic strategies with proven efficacy. Platinum-combination chemotherapy can be considered a standard for first-line therapy, but after progression there is no standard therapy, and the prognosis is very poor. The development of targeted therapies in the last few years has significantly changed the prognosis of a wide variety of tumors. In bladder cancer, there is no targeted therapy currently approved for its use in advanced disease. There is evidence that Her-2 amplification and/or overexpression is seen in bladder cancer, and may influence prognosis. Anti-Her-2 drugs, such as trastuzumab or lapatinib, are under investigation in urothelial neoplasms, but there is no phase III trial that has evaluated their use in bladder cancer. We review the published evidence about Her-2 determination, its influence on bladder carcinoma prognosis, the clinical development of anti-Her-2-targeted therapies, and the possible future research directions involving this pathway in bladder cancer.

AdCD40L Immunogene Therapy for Bladder Carcinoma

AdCD40L Immunogene Therapy for Bladder Carcinoma

RECURRENCE AND PROGRESSION OF STAGE T1, GRADE 3 TRANSITIONAL CELL CARCINOMA OF THE BLADDER FOLLOWING INTRAVESICAL IMMUNOTHERAPY WITH BACILLUS CALMETTE-GUERIN

We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.

LOW DOSE BACILLUS CALMETTE-GUERIN FOR CARCINOMA IN SITU OF THE BLADDER: LONG-TERM RESULTS

Bacillus Calmette-Guerin (BCG) is standard treatment for carcinoma in situ of the bladder. However, its long-term effectiveness is still debated. From January 1987 to January 1995, 70 consecutive patients with primary or secondary carcinoma in situ with or without concomitant solitary or multifocal papillary tumor were treated with weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after histological diagnosis. An additional induction course was given to patients with relapse. Tumor-free patients were given a maintenance course of monthly instillations for 12 months. At the end of induction course 1, 56 of the 70 patients (80%) were tumor-free. Of 14 patients given induction course 2, 9 had a complete response (64.2%). A total of 65 patients (92.8%) were disease-free after 1 or 2 courses and given the maintenance course. Median followup for disease-free patients was 74 months (range 17 to 134). Subsequently 50 patients (71.4%) were disease-free, 12 (17.1%) had recurrence and 8 (11.4%) had progression. Mean time was 18 months (range 6 to 69) to treatment failure and 13 months (range 7 to 53) to progression. Of the patients 1 died of disease and 10 of other causes. Crude survival was 84.2%, disease specific mortality 1.4% and nondisease specific mortality 14.2%. The risk of treatment failure was significantly greater for carcinoma in situ associated with stage T1 papillary tumor (p = 0.0001) or severe dysplasia (p = 0.0005), and the risk of disease progression was significantly greater for carcinoma in situ associated with stage T1 papillary tumor (p = 0.0001). The drug was well tolerated with few side effects. Intravesical BCG is the best available conservative therapy for patients with carcinoma in situ of the bladder. Low dose BCG is similarly effective, with a lower incidence of side effects and long lasting positive outcome.

Original Articles: Bladder Cancer: A New Approach Using Local Combined Microwave Hyperthermia and Chemotherapy in Superficial Transitional Bladder Carcinoma Treatment

For some time hyperthermia, alone or in combination with radiotherapy or chemotherapy, has proved to be a promising method for treating several kinds of solid tumors. After intensive laboratory investigations a new device, based on a microwave source delivering local bladder hyperthermia together with intravesical mitomycin C chemotherapy has been clinically tested as a neoadjuvant approach in 44 patients suffering from superficial cancer of the bladder. The combined approach was administered on an outpatient basis without major complications and with acceptable local toxicity. Endoscopic and histological evaluations proved that combined local hyperthermia and chemotherapy can induce necrosis of transitional tumors. The overall response rate was 90.8%, with 70.4% complete and 20.4% partial, leaving 4 patients (9.2%) nonrespondent. Clinical and histological evaluations have confirmed the feasibility and safety of this combined treatment. Further multicentric studies have been initiated.

Transrectal ultrasound appearance of granulomatous prostatitis.

Granulomatous prostatitis is an uncommon condition that can masquerade as prostatic carcinoma on both digital rectal exam and prostate ultrasound. It occurs most often after acute urinary tract infection, transurethral prostate resection, or needle biopsy. It can be seen in systemic granulomatous diseases and after intravesical bacillus Calmette-Guerin (BCG) therapy for bladder carcinoma. In some cases it is idiopathic. Six patients who underwent transrectal ultrasound of the prostate and subsequent transrectal ultrasound-guided biopsy had histologic diagnosis of granulomatous prostatitis. One patient was undergoing BCG therapy for bladder cancer. Two patients had recent urinary tract infections. The other three patients had no known predisposing conditions. Sonographically, the glands were enlarged in five patients, with multiple large and small hypoechoic zones throughout the peripheral, transition, and central zones. The appearance was similar to that seen in diffuse prostatic carcinoma. In one patient, a solitary hypoechoic lesion in the peripheral zone, indistinguishable from carcinoma, was present. Granulomatous prostatitis should be considered in the differential diagnosis of focal and diffuse abnormality with prostatic ultrasound.

Laser Treatment of Bladder Carcinoma and Genital Condylomata

The lasers most amenable to urologic surgery are the CO2, argon, and neodymium:YAG lasers. An understanding of the characteristics of these lasers is essential to the choice of the proper laser for the individual urologic condition to be treated. The relative advantages and disadvantages of all modes of therapy for bladder carcinoma and condylomata are discussed.

Therapy of bladder carcinoma. Long-term results of a retrospective study of 214 cases.

Two hundred and fourteen bladder carcinomas were evaluated retrospectively after reclassification of histological specimens according to UICC. Follow-up time was 7 years or longer. Large size but not multiplicity of the primary tumour indicated a poor prognosis. Local infiltration, even if superficial and restricted to the lamina propria, worsened prognosis as well as high grade of the tumour. Late deaths in the present series were generally explained by a progression in stage in patients with high grade tumours at initial assessment. Therefore a close longterm follow-up should be performed in these patients.

Vesico-Ureteric Reflux in Connection with Supervoltage Therapy for Bladder Carcinoma

Vesico-Ureteric Reflux in Connection with Supervoltage Therapy for Bladder Carcinoma

Evaluation of radiation therapy of bladder carcinoma.

Evaluation of radiation therapy of bladder carcinoma.