Gender-specific differences in muscle-invasive bladder cancer: the concept of sex steroid sensitivity

Purpose

To describe the role of sex steroid-dependent growth of muscle-invasive bladder cancer (MIBC) and the role of single-nucleotide polymorphisms (SNP) located on chromosome 8q24 as a molecular explanation for gender-specific differences in the incidence and outcome of MIBC.

Methods

A detailed, non-systematic analysis was performed for articles and reviews investigating the role of sex steroids in the development and progression of MIBC between 2000 and 2012.

Results

Localized MIBCs overexpress the androgen receptor (AR), whereas in lymph node-positive stages, loss of AR expression has been found. High-risk SNPs of genes on chromosome 8q24, that is, the rs2294008 of prostate stem cell antigen (PSCA) gene, have been linked with increased susceptibility for MIBC. The PSCA gene possesses an androgen-responsive element (ARE) in its promoter region. Recent studies suggest that loss of AR responsiveness to the PSCA promoter may result in the induction of an androgen-independent mechanism, that is, the insulin-like growth factor-binding protein 2 signalling pathway—a key event in the development of hormone-independent prostate cancer—and this may increase the metastatic potential. In females, it can be hypothesized that due to the altered androgen levels, these mechanisms may be initiated earlier during tumor progression in females and result in inferior survival compared to males.

Conclusion

Muscle-invasive bladder cancer (MIBC) is a sex steroid-dependent tumor. AREs in the promoter region of high-risk genes may drive tumor progression and result in loss of androgen responsiveness, which eventually leads to the activation of androgen-independent processes forming the metastatic potential. The determination of the AR status in cystectomy specimens additionally offers new adjuvant approaches after cystectomy.     

Primäre monosymptomatische Enuresis

Nocturnal enuresis is one of the most common problems in childhood. In this article a standardized terminology for basic diagnostics additionally to extended diagnostics will be presented. Depending on the findings a specialized therapy can be performed. Besides drug therapy with antidiuretic hormone (ADH) sleep arousal devices can be used and the combination of both approaches also shows excellent results. At the end of therapy a protracted withdrawal shows better results than abrupt cessation.     

Multimodal treatment of esophageal cancer

Background

The treatment of localized esophageal cancer has been debated controversially over the past decades. Neoadjuvant treatment was used empirically, but evidence was limited due to the lack of high-quality confirmatory studies. Meanwhile, data have become much clearer due to recently published well-conducted randomized controlled trials and meta-analyses.

Methods

Neoadjuvant and perioperative platinum fluoropyrimidine-based combination chemotherapy has now an established role in the treatment of stage II and stage III esophageal adenocarcinoma and cancer of the esophago-gastric junction. Neoadjuvant chemoradiation is now the standard of care for treating stage II and stage III esophageal squamous cell cancer and can also be considered for treating esophageal adenocarcinoma.

Results

Patients with esophageal squamous cell cancer treated with definitive chemoradiation achieve comparable long-term survival compared with surgery. Short-term mortality is less with chemoradiation alone, but local tumor control is significantly better with surgery.

Conclusion

This expert review article outlines current data and literature and delineates recommendable treatment guidelines for localized esophageal cancer.     

Cell-Based Therapy for the Deficient Urinary Sphincter

When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.     

The prognostic role of pre-cystectomy hemoglobin levels in patients with invasive bladder cancer

Purpose

To determine whether pre-treatment hemoglobin (Hb) levels in patients with bladder cancer impact on oncological outcomes after radical cystectomy (RC).

Methods

A consecutive, contemporary series of 246 patients undergoing RC and pelvic lymph node dissection for bladder cancer. Decreased Hb level was defined as ≤12 g/dL. The Kaplan–Meier method was used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). The Fisher exact/Chi-square test was used to investigate differences between both groups. Uni- and multivariable Cox regression analysis addressed risk factors for recurrence, cancer-specific death and overall death. The median follow-up was 30 months (2–116).

Results

Of the 246 patients, 182 (74 %) had normal (>12 g/dL) and 64 decreased (≤12 g/dL) preoperative Hb (26 %). In univariable analysis, decreased Hb was associated with increased age, extravesical disease, hydronephrosis (all p < 0.001), node-positive disease and positive resection margins (both p = 0.01). Subanalyzed for patients with organ-confined disease (defined as ≤pT2bN0R0; N = 109), the 3-year RFS, CSS and OS was significantly lower in patients with decreased (34.9, 35.5 and 19.8 %) compared to normal Hb level (69.7, 86.3 and 77.6 %; p = 0.01/p = 0.002/p < 0.001). In multivariable analysis, RFS, CSS and OS were significantly lower in patients with decreased Hb (p = 0.007, p = 0.001 and p = 0.002), pathologically locally advanced tumor (≥pT3a; p = 0.023, p = 0.036 and p = 0.065) and nodal stage (p < 0.001, p = 0.006 and p = 0.001) and positive soft tissue surgical margins (p = 0.040, p = 0.004 and 0.012).

Conclusions

Pre-cystectomy Hb levels are associated with adverse histopathologic characteristics and provide additional prognostic information especially for patients with pathologically localized bladder cancer.

     

Associations of serum 25-hydroxyvitamin D level with incidence of lung cancer and histologic types in Norwegian adults: a case-cohort analysis of the HUNT study

Previous prospective studies have shown inconsistent associations between serum 25-hydroxyvitamin D [25(OH)D] level and lung cancer incidence. The aim of the present study was to explore the associations of serum 25(OH)D levels with incidence of lung cancer overall and different histologic types. We performed a population-based prospective case-cohort study including 696 incident lung cancer cases and 5804 individuals in a subcohort who participated in the second survey of the Nord-Trøndelag Health Study in Norway. Cox proportional hazards regression models counting for the case-cohort design were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) for lung cancer overall or histologic types in relation to serum 25(OH)D levels. Compared with the fourth season-specific quartile of 25(OH)D (median 68.0 nmol/L), lower 25(OH)D levels were not associated with the incidence of overall, small or squamous cell lung cancer. However, the risk of adenocarcinoma was lower in the second and third quartiles (median 39.9 and 51.5 nmol/L) compared with the fourth quartile, with HRs of 0.63 (95% CI 0.41–0.98) and 0.58 (0.38–0.88), respectively. The associations of lower levels of 25(OH)D with a reduced risk of adenocarcinoma were only observed in the overweight/obese subjects [HRs for second and third quartiles: 0.40 (0.22–0.72) and 0.50 (0.27–0.92)] but not in the normal weight subjects [HRs: 0.95 (0.52–1.75) and 0.60 (0.32–1.10)]. Serum 25(OH)D levels were not associated with the risk of lung cancer in general. The observation that lower 25(OH)D levels were associated with a lower risk of adenocarcinoma should be interpreted with caution.