Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokine

The effects of obesity and diet on prostate cancer risk

Prostate cancer is nowadays the most common malignancy in males of the western world, but little is as yet known regarding the causes of initiation and progression of this disease. To explain the geographical variations in the incidence of clinical prostate cancer, the changes in its prevalence in migrants moving from countries with a low prostate cancer incidence to those with a high incidence, and the lack of international variation in the prevalence of microfocal or latent prostatic tumors, environmental factors have been implicated. Obesity, western-type diet, increased total energy and saturated animal fat intake have all been suspected as potential risks. In contrast, consumption of vegetables and soy products and intake of certain vitamins and micronutrients, such as vitamins E and D, lycopene and selenium, may exert a protective effect. The hypothesis that dietary changes might affect the development of prostate cancer is strengthened by the fact that of all mammals almost only humans and dogs (at a much lower rate) get prostate cancer. Both have dramatically altered their diets during the last 15,000 years of their evolution, while other primates and mammals in which the disease is absent, made no significant changes. Case-control and cohort studies have failed to find a consistent association between prostate cancer risk and body mass index, dietary fat, total energy intake or other life-style changes. The conflicting results of past and recent trials are perhaps due to methodological and statistical limitations, measurement errors, different questionnaires, heterogeneity of prostate cancer patients, unsuspected biases and the retrospective nature of these investigations. Nevertheless, pending more extensive, well-controlled prospective studies, dietary and life-style changes should be advised, based on reduced morbidity and mortality from cardiovascular disease, the number 1 cause of death in western countries, and the number 1 or 2 cause of death in patients diagnosed with prostate cancer

Complicated urinary tract infections

The term complicated urinary tract infection is usually used to convey an infection that occurs in a patient with a structural or functional abnormality impeding urine flow, or in a host with altered defences. The distinction between complicated and uncomplicated infections is important because, when complicating factors are present, antimicrobial resistance is more common and the response to therapy is often disappointing, even with agents active against the causative microbial pathogen. In addition, severe complications frequently occur which may lead to urosepsis, renal scarring or even end-stage disease. Drug treatment of complicated urinary tract infections often must be complemented with endoscopic and/or surgical intervention. Only a few well designed treatment studies have been published acid therefore sources for definitive therapeutic guidelines remain inadequate. g 2000 Elsevier Science B.V. and International Society of Chemotherapy. Ail rights reserved

Intravesical therapy of superficial bladder cancer

Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and/or immunotherapy is administered in an effort to enhance the efficacy of surgery alone. The initial tumor stage and grade, the multifocality of this cancer and the history of previous recurrences remain the determinant factors in survival. It is important to decide exactly which patients are at risk, and, therefore, do need treatment. Knowledge of the natural history of the disease will facilitate this decision making, although the natural history of TCC is largely unpredictable owing to tumor heterogeneity. Several cytotoxic and immune modifying agents have been used intravesically in different treatment schedules. However, despite their effectiveness, no consensus exists about the optimal antineoplastic regimen. The selection of the latter is a subject of continuous investigation. Intravesical treatment with cytotoxic drugs has been demonstrated to achieve an acceptable reduction in short- and intermediate-term recurrence rates, but has no proven ability in preventing disease progression to muscle-invasive cancer or prolonging survival. On the other hand, bacillus Calmette-Guerin (BCG) currently appears to be the most effective agent for intravesical use, especially in patients with high grade and stage neoplasms but the optimum strain, dosage and duration schedule have not been determined. Clinical trials have shown that BCG provides long-term protection from tumor recurrence, while there is evidence that it may favorably alter the progression rate of the disease with prolongation of survival. Toxicity of intravesical chemo- and immunotherapy still remains a major problem and attempts at reducing the dosage, and, thus, toxicity without affecting efficacy are underway. This review endeavors to present updated information on intravesical chemotherapy in treating superficial bladder cancer, the expanding role of intravesical immunotherapy, the recent work comparing various immunotherapeutic regimens with chemotherapeutic intravesical therapies, and the progress made towards achieving optimal treatment regimens