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

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

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

Plasmacytoid transitional cell carcinoma of the urinary bladder

A case of rare plasmacytoid transitional cell carcinoma of the urinary bladder in a 60-year old man is described. The presence of end-stage disease did not allow for any efficacious therapy. Immunohistochemistry showed the tumor cells to be reactive for epithelial markers and syndecan-1 (CD138)

Percutaneous nephrostomy in patients with tumors of advanced stage: Treatment dilemmas and impact on clinical course and quality of life

Objectives: The purpose of this study was to evaluate the outcome, in respect to safety, survival, and quality of life (QoL), after performance of percutaneous nephrostomy in patients with obstructive nephropathy caused by various types of advanced malignancy. Patients and Methods: A cohort of 270 patients with established nephropathy because of advanced pelvic or nonpelvic tumors was evaluated. A decision to obtain percutaneous access was made; primary stenting had either failed or was not feasible because of complicated anatomy. Patients were divided in equal groups by type of malignancy ( 54 patients each). In addition, each malignancy group was further divided in two equal subgroups by tumor burden ( 27 patients each). Correlations were made with respect to renal function outcome, overall survival after the procedure, and QoL differences both before and after the procedure. Results: No serious complications, such as severe bleeding or sepsis, were experienced because of the procedure. Statistical analysis showed no significant differences in survival among patients with different types of cancer. Only patients with prostate (P < 0.0365) and colorectal (P < 0.0307) cancer with lower tumor burden had significantly longer survival when compared with patients with large tumor burden. Regarding QoL scores, only patients with prostate cancer in the subgroup with low tumor burden demonstrated a positive statistically significant difference ( P < 0.001). Conclusions: Despite the fact that percutaneous nephrostomy has shown good safety characteristics and beneficial impact on renal function, only patients with specific cancers most likely to respond to ongoing palliative therapy or with cancers that progress slowly by nature may statistically benefit from the procedure. This questions the universal application of this procedure for all types and stages of advanced malignancy

Is there a learning curve for photodynamic diagnosis of bladder cancer with hexaminolevulinate hydrochloride?

Introduction: To assess the learning curve for fluorescence cystoscopy using hexaminolevulinate hydrochloride (HAL) in patients with bladder cancer. Material and methods: Fifty patients underwent bladder instillation with HAL. Two senior residents inspected separately the bladder using white light cystoscopy, followed by fluorescence cystoscopy and mapped the lesions. An experienced with photodynamic diagnosis (PDD) urologist also performed both cystoscopies, mapped, resected or cold biopsied suspect lesions under the supervision of another experienced urologist. To evaluate the learning curve, patients were divided into five subgroups, including group 1 (patients 1-10), group 2 (11-20), group 3 (21-30), group 4(31-40) and group 5(41-50). The kappa statistics was calculated to assess interobserver agreement between the physicians and the false positive rates of urologists and residents were also compared. Results: Histologically verified tumors were diagnosed in 103 of 142 lesions identified by PDD. The interobserver agreement between urologists and residents was moderate, moderate, good, excellent, and excellent for group 1, 2, 3, 4, and 5, respectively. Both residents had increased false positive rates compared to urologists in all subgroups of patients but this difference did not reach statistical significance. In addition, false positive rate of residents was declining as the number of procedures was increasing. Conclusions: Our data suggest that 20 cases of HAL PDD are required to achieve a good interobserver agreement between inexperienced and experienced operator, and excellent agreement is achieved after 30 cases. The false positive rate of inexperienced operators was comparable to the experts and showed a gradual decrease