Intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been used for treating bladder cancer for 3 decades. However, BCG therapy is ineffective in approximately 30–40% of cases. Since evidence supports the T helper type 1 (Th1) response to be essential in BCG-induced tumor destruction, studies have focused on enhancing BCG induction of Th1 immune responses. Although BCG in combination with Th1 cytokines (e.g., interferon-α) has demonstrated improved efficacy, combination therapy requires multiple applications and a large quantity of cytokines. On the other hand, genetic manipulation of BCG to secrete Th1 cytokines continues to be pursued with considerable interest. To date, a number of recombinant BCG (rBCG) strains capable of secreting functional Th1 cytokines have been developed and demonstrated to be superior to BCG. This paper discusses current rBCG research, concerns, and future directions with an intention to inspire the development of this very promising immunotherapeutic modality for bladder cancer.

Anti-interleukin-10 receptor 1 mAb enhanced the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity. A humanized form of this mAb warrants future investigation for bacillus Calmette-Guérin treatment of bladder cancer.

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Previous studies have linked oxidative stress and nephrolithiasis. Animal studies have demonstrated that pomegranate juice may play a role in preventing stone formation. We examined differences between recurrent stone formers (RSFs) and non-stone formers (NSFs) regarding oxidative stress and the effect of pomegranate administration on risk factors for nephrolithiasis. RSFs were recruited prospectively and matched to a group of NSFs. Subjects submitted urine and blood samples prior to and after receiving pomegranate polyphenol extract (1,000 mg) for 90 days. Serum and urine samples were analyzed for stone risk and oxidative stress. Thirty subjects completed the study. RSFs had significantly higher levels of oxidative stress at baseline as measured by urinary 8-hydroxy-deoxyguanosine (p < 0.0001), 2.2'-azobis (2-amidinopropane) hydrochloride-induced serum lipid peroxidation [increased levels of lipid peroxides (p = 0.0002), and thiobarbituric acid reactive substances (p = 0.002)], but not by serum paraoxonase1 (PON1) arylesterase activity (p > 0.99), or by highly sensitive C-reactive protein (p > 0.99). Following pomegranate supplementation, there was a 10 % increase in PON1 activity in RSFs (p = 0.007), which correlated with a trend toward decreasing values of supersaturation of calcium oxalate (SSCaOx; p = 0.05). RSFs have markedly higher levels of oxidative stress than NSFs. While the ability to prevent stone formation through supplementation cannot be determined in this pilot study, supplementation with pomegranate extract does not increase the risk of stones and may confer some benefit in lowering SSCaOX in those patients with increased PON-1 levels following supplementation, confirming findings of previous animal models.

Men's health issues have increasingly gained attention not only in the mass media, but also among most health-care providers. The diagnosis and treatment of male-related health problems, unfortunately, can lead to complications and error-related injuries resulting in claims of medical malpractice. This review article will look at the most common claims relating to complications and injuries in the management of men's health issues. Reviews of the literature over the past three decades using multiple search engines including PubMed were utilized. The most pertinent articles were selected on the basis of their relevance to men's health issues, complications and medico-legal ramifications. An evaluation of the literature reveals that although the number of claims against urologists has not increased over the past several decades, indemnity payments have continued to rise significantly. Claims can be divided into those relating to diagnosis and those relating to treatment. Providers of men's health care may become involved in claims of medical malpractice at some time during their careers. Patients' care can result in complications and injuries, most of which do not lead to claims. Certain areas of men's health lead to more claims than others. The keys to prevention and management of those claims are good communication, informed consent and documentation.

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Introduction: Induction of Th1 immunity is required for effective intravesical BCG immunotherapy of bladder cancer. IL-10 down-regulates the Th1 response and is associated with BCG failure. We previously demonstrated that blocking IL-10 receptor (IL-10R) by systemic administration of anti-IL-10R1 mAb enhanced intravesical BCG (living Pasteur strain) treatment of bladder cancer in an orthotopic mouse model. Here we investigated the effect of anti-IL-10R1 mAb on clinically used BCG (lyophilized TICE strain) for induction of anti-bladder cancer immunity. Methods: Splenocytes were incubated with BCG alone or plus control IgG or ant-IL-10R1 mAb for 24 hours, followed by ELISA analysis of IFN-γ production. Bladder RNA was extracted after 6 treatments (twice weekly) with intravesical (i.b.) BCG plus intraperitoneal (i.p.) control IgG or anti-IL-10R1 mAb, followed by qPCR analysis of IFN-γ mRNA expression. Three groups of 20 mice were inoculated with luciferase-expressing MB49 bladder cancer cells and treated with i.b. PBS plus i.p. PBS (Group 1), i.b. BCG plus i.p. control IgG (Group 2), or i.b. BCG plus i.p. anti-IL-10R1 mAb (Group 3) 2x/wk for 6 total treatments. Mice were monitored weekly using IVIS luminescence and followed for 76 days. A bioluminesence cutoff of 5X104 p/s was used to establish the presence of bladder cancer. At animal death bladders were collected, weighed and processed for histological analysis. In suspected cases of metastatic disease the affected organs were also collected for histological analysis. Results: BCG plus anti-IL-10R1 mAb induced increased IFN-γ production by splenocytes in a dose-dependent manner. BCG plus anti-IL-10R1 mAb substantially increased IFN-γ mRNA. Eleven, 17 and 9 mice from Groups 1, 2 and 3, respectively, developed bladder cancer. One mouse in Group 2 and 2 mice in Group 3 showed cancer regression. 36%, 53% and 0% of Groups 1, 2 and 3 developed metastatic bladder cancer, respectively (p=0.020). While bladder weights for the groups were different, the differences did not reach statistical significance. Conclusions: Anti-IL-10R1 mAb enhances BCG-induced Th1 immune responses both in vitro and in vivo. Intravesical BCG plus anti-IL-10R1 mAb shows statistical significance in preventing metastasis of bladder cancer in an orthotopic bladder tumor mouse model. Anti-IL-10R1 mAb may prove useful in clinical practice for the prevention of metastatic bladder cancer in high-risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5390. doi:1538-7445.AM2012-5390