Radical Prostatectomy: Hospital volumes and surgical volumes – does practice make perfect?

<p>Abstract</p> <p>Background</p> <p>Between the years 1993 and 2003, more than 140,000 men underwent radical prostatectomy (RP), thus making RP one of the most common treatment options for localized prostate cancer in the United States.</p> <p>Discussion</p> <p>Localized prostate cancer treated by RP is one of the more challenging procedures performed by urologic surgeons. Studies suggest a definite learning curve in performing this procedure with optimal results noted after performing >500 RPs. But is surgical volume everything? How do hospital volumes of RP weigh in? Could fellowship training in RP reduce the critical volume needed to reach an 'experienced' level?</p> <p>Summary</p> <p>As we continue to glean data as to how to optimize outcomes after RP, we must not only consider surgeon and hospital volumes of RP, but also consider training of the individual surgeon.</p

Expression of SMARCD1 interacts with age in association with asthma control on inhaled corticosteroid therapy.

BackgroundGlobal gene expression levels are known to be highly dependent upon gross demographic features including age, yet identification of age-related genomic indicators has yet to be comprehensively undertaken in a disease and treatment-specific context.MethodsWe used gene expression data from CD4+ lymphocytes in the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE), an open-access collection of subjects participating in genetic studies of asthma with available gene expression data. Replication population participants were Puerto Rico islanders recruited as part of the ongoing Genes environments &amp; Admixture in Latino Americans (GALA II), who provided nasal brushings for transcript sequencing. The main outcome measure was chronic asthma control as derived by questionnaires. Genomic associations were performed using regression of chronic asthma control score on gene expression with age in years as a covariate, including a multiplicative interaction term for gene expression times age.ResultsThe SMARCD1 gene (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1) interacted with age to influence chronic asthma control on inhaled corticosteroids, with a doubling of expression leading to an increase of 1.3 units of chronic asthma control per year (95% CI [0.86, 1.74], p = 6 × 10- 9), suggesting worsening asthma control with increasing age. This result replicated in GALA II (p = 3.8 × 10- 8). Cellular assays confirmed the role of SMARCD1 in glucocorticoid response in airway epithelial cells.ConclusionFocusing on age-dependent factors may help identify novel indicators of asthma medication response. Age appears to modulate the effect of SMARCD1 on asthma control with inhaled corticosteroids

Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer

<p>Abstract</p> <p>Background</p> <p>Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including cancers of the prostate. Over the past several years, our group has been studying how mycoplasmas could possibly initiate and propagate cancers of the prostate. Specifically, <it>Mycoplasma hyorhinis </it>encoded protein p37 was found to promote invasion of prostate cancer cells and cause changes in growth, morphology and gene expression of these cells to a more aggressive phenotype. Moreover, we found that chronic exposure of benign human prostate cells to <it>M. hyorhinis </it>resulted in significant phenotypic and karyotypic changes that ultimately resulted in the malignant transformation of the benign cells. In this study, we set out to investigate another potential link between mycoplasma and human prostate cancer.</p> <p>Methods</p> <p>We report the incidence of men with prostate cancer and benign prostatic hyperplasia (BPH) being seropositive for <it>M. hyorhinis</it>. Antibodies to <it>M. hyorhinis </it>were surveyed by a novel indirect enzyme-linked immunosorbent assay (ELISA) in serum samples collected from men presenting to an outpatient Urology clinic for BPH (N = 105) or prostate cancer (N = 114) from 2006-2009.</p> <p>Results</p> <p>A seropositive rate of 36% in men with BPH and 52% in men with prostate cancer was reported, thus leading us to speculate a possible connection between <it>M. hyorhinis </it>exposure with prostate cancer.</p> <p>Conclusions</p> <p>These results further support a potential exacerbating role for mycoplasma in the development of prostate cancer.</p

Persistent Exposure to Mycoplasma Induces Malignant Transformation of Human Prostate Cells

Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1) was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis

Anchorage-independent growth.

<p>BPH-1 cells infected with <i>M. genitalium</i> (Mg) or <i>M. hyorhinis</i> (Mh) were tested for the ability to grow in soft agar. Persistent infection for 19 weeks with either mycoplasma induced anchorage-independent growth of BPH-1 cells. The PC-3 prostate cancer cell line was used as a positive control. (10 micrometer scale bar  = 2 mm)</p

Growth of BPH-1 xenograft tumors.

<p>Growth of BPH-1 xenograft tumors.</p

Molecular analysis of human BPH-1 xenograft tumors grown in nude male mice.

<p>Tumors generated by mycoplasma infection in BPH-1 cells did not have a typical adenocarcinoma appearance, but a more squamoid appearance (H&E). In addition, uninfected BPH-1 cells from passage 19 grown subcutaneously in nude mice were less angiogenic (CD34) and harbored more leukocytes (CD45) than did xenograft tumors from BPH-1 cells infected with <i>M. hyorhinis</i> or <i>M. genitalium</i>. Only mycoplasma infected BPH-1 cells formed xenograft tumors. Expression of markers of malignancy (CD44v9 and Ki-67) were revealed using immunohistochemistry. (10 micrometer scale bar  = 2 mm)</p

Cytogenetic analysis of mycoplasma infected BPH-1 cells.

<p>Metaphase chromosomal complement was revealed by spectral karyotyping (SKY) and counter-staining with DAPI. Representative metaphase cells after SKY classification are shown. A, uninfected BPH-1 cells. B, BPH-1 cells after 19 weeks <i>M. hyorhinis</i> infection. Composite for each chromosome shows, left to right, inverted DAPI-stained image, and spectral imaging color representation. Chromosome number is shown below image groupings, numbers alongside the derivative chromosomes indicate the origin of the translocated material. <i>M. hyorhinis</i> exposed BPH-1 cells were noted to harbor trisomy of chromosomes 1, 2, 6, 7, 15–18, and 21, in addition to loss of chromosome 13.</p

<i>In vitro</i> invasion and migration.

<p>BPH-1 cells with and without <i>M. genitalium</i> (Mg) or <i>M. hyorhinis</i> (Mh) infection were tested for migration (A) and invasion (B) potential at weeks 7 and 19 post-infection. Both <i>M. genitalium</i> and <i>M. hyorhinis</i> infected BPH-1 cells had increased migration and invasion rates at week 19. Data presented are means of triplicates, and the error bars represent the standard error of the mean. *, p<0.05 versus no mycoplasma control (M-).</p