PURPOSE: We wanted to determine the safety and efficacy 1 year after intravesical keyhole-limpet hemocyanin (KLH) therapy for the patients suffering with superficial transitional cell carcinoma. MATERIALS AND METHODS: A total of 60 patients with bladder cancer who had undergone transurethral resection were treated with a one-year protocol (once a week for 6 weeks and 12 further treatments every 4 weeks) of KLH 20mg. The local and systemic safety and efficacy were evaluated. RESULTS: In terms of the safety of KLH, 4 patients (6.7%) reported dizziness and slight fever, and 2 (3.3%) experienced urgency. The remaining 54 patients (90.0%) did not report any local side effects during the treatment period. In terms of efficacy, recurrence developed in 32 patients (53.3%) at a mean of 4.5 months after transurethral resection; 28 patients (46.7%) were disease free after 14 months. The univariate analysis showed a greater level of efficacy in the patients suffering with bacille Calmette-Gu rin (BCG)-refractory disease (p=0.0150). No significant differences were found between the low, the intermediate-risk and the high-risk patients in terms of efficacy. CONCLUSIONS: The results of this study have confirmed the good tolerability of intravesical KLH and better efficacy in the BCG-refractory patients. However, in terms of overall efficacy, intravesical KLH therapy had no superiority over that of other intravesical treatments in terms of the overall efficacy.
Carcinoma, Transitional Cell* ; Dizziness ; Fever ; Hemocyanin* ; Humans ; Prospective Studies* ; Recurrence ; Urinary Bladder Neoplasms

Purpose: The antitumor activity and toxicity of keyhole limpet hemocyanin (KLH) on bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) were investigated. Materials and Methods: Sixty 6 to 8-week-old female C3H2 mice were divided into three groups. Bladder carcinomas were induced by the addition of 0.05% BBN to the drinking water for 8 weeks. Group A received an intravesical instillation of 0.25ml KLH-free buffer, Group B received 0.5mg KLH in 0.1ml buffer subcutaneously and Group C received an intravesical instillation of 2mug KLH in 0.25ml buffer twice weekly for 8 weeks (day 15 to day 70). On day 91, all the animals were sacrificed. The tumor incidence, bladder weight and toxicity were evaluated. Results: The incidences of cancer in groups A, B and C were 80, 40 and 60%, respectively. The incidence of cancer was significantly reduced in group B compared to group A (p<0.05). The average bladder weights were 93.63+/-17.746, 71.5+/-7.540 and 77.5+/-9.530mg in groups A, B and C, respectively. The bladder weights in groups B and C were significantly reduced compared to group A (p<0.05). There was no liver, kidney or bone marrow toxicities in groups B and C. Conclusions: These results suggest that KLH act as an effective and safe immunotherapeutic agent for bladder cancer. Prospective randomized clinical trials should be used to evaluate the role of KLH as an immunotherapeutic agent in the prophylaxis of recurrent bladder cancer.
Administration, Intravesical ; Animals ; Bone Marrow ; Drinking Water ; Female ; Hemocyanin* ; Humans ; Immunotherapy ; Incidence ; Kidney ; Liver ; Mice* ; Models, Animal ; Urinary Bladder Neoplasms ; Urinary Bladder* ; Weights and Measures

BACKGROUND AND OBJECTIVES: Local immune response, one of the pathogenesis of middle ear effusion (MEE) is associated with the development and persistence of effusion in the middle ear cavity and inflammatory mediators play a major role in the production of MEE. The purpose of this study was to determine the effects of TNF-alpha antagonist and oxatomide on the outcome of immune mediated otitis media with effusion (OME) in rats. MATERIALS AND METHOD: Otitis media was induced by injecting KLH (Keyhole lympet hemocyanin) transtympanically 7 days after systemic immunization. Phosphate-buffered saline solution was used as control. Other groups were pretreated with TNF-alpha antagonist (soluble TNF receptor type I, sTNF RI) or oxatomide respectively before transtympanic injection of KLH. Seventy-two hours after the transtympanic injection, temporal bones in each group were examined histopathologically and vascular permeability of the middle ear mucosa was measured by the Evans blue vital dye technique. RESULTS: In the KLH, sTNF RI and oxatomide groups, MEE was developed in 83%, 0%, 66% of the ears, respectively. The oxatomide group and sTNF RI group showed significant decrease in inflammation, mucosal thickening and vascular permeability as compared with KLH group and those parameters of sTNF RI group showed lower values than those of oxatomide group. CONCLUSION: Transtympanic administration of sTNF RI and oxatomide appears to suppress the development of immune mediated OME. In terms of inhibiting MEE, sTNF RI was more effective than oxatomide. This study suggests that TNF-alpha antagonist and oxatomide may have a adjunctive role in the treatment and prevention of otitis media with effusion.
Animals ; Capillary Permeability ; Ear ; Ear, Middle ; Evans Blue ; Hemocyanin ; Immunization ; Inflammation ; Leukotriene Antagonists ; Mucous Membrane ; Otitis Media with Effusion* ; Otitis Media* ; Otitis* ; Rats ; Receptors, Tumor Necrosis Factor ; Sodium Chloride ; Temporal Bone ; Tumor Necrosis Factor-alpha*