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UROLOGY Key advances ■ Encouraging results have been obtained from studies of targeted therapies in bladder cancer, 1 laying the groundwork for future investigation in this area ■ The reporting of a second randomized phase III trial of neoadjuvant chemotherapy 3 confirms a survival advantage for patients with muscleinvasive bladder cancer ■ A 20-gene expression model has been developed 5 that can identify patients, before cystectomy, at high risk of lymph node involvement ■ Evidence suggests a number of chromatin remodeling genes are involved in bladder cancer, 6 representing a novel area for future investigation ■ The immunohistochemical assessment of p53 is not a useful marker of prognosis or predictive of response to chemotherapy 9 invasion. Conceivably, with further validation, patients at high risk of node-positive disease could be identified using this algorithm and then strongly encouraged to undergo neoadjuvant chemotherapy before definitive treatment. Whole-exome sequencing of paired tumoral and peripheral blood samples was recently performed in a small set of patients with bladder cancer, in an attempt to identify prognostic biomarkers. 6 The initial findings from this cohort were then tested in a larger cohort of 88 patients. Several previously defined mutations were observed (in TP53, RB1 and HRAS), as well as a number of novel mutations. Of these, UTX was the most commonly mutated gene, identified in 21% of tested individuals, with 17 nonsense, 5 missense and 1 synonymous mutation noted when combining the discovery and validation screens. Of particular note, eight of the newly identified mutated genes were related to chromatin remodeling, suggesting a potential area for bladder cancer investigation. Interestingly, mutations in chromatin remodeling genes have been commonly found in several other cancer types, suggesting a fundamental contribution to carcinogenesis. Results of retrospective studies have suggested that p53 is both a marker of prognosis 7 and potentially predictive of response to cytotoxic chemotherapy. 8 However, the results of a much anticipated phase III trial testing p53 as a biomarker in patients after radical cystectomy were somewhat disappointing. 9 Notably, these patients had early stage disease (pT1–2 N0 M0), and based on current pathologic risk stratification they would frequently not receive adjuvant chemo therapy. Patients whose tumors were negative for p53 overexpression—with
Aging Study (MMAS) and the multinational Men’s Attitudes to Life Events and Sexuality (MALES), revealed that 21% and 25% of men reported improvement, over 7 and 3 years of follow-up, respectively. 2 Worsening of ED was reported by 51% and 28% of men in MMAS and MALES, respectively. As might be expected, the proportion of men reporting progression increased with age, and men younger than 50 years were more likely to experience improvement than worsening. The age-specific rates of progression were higher in MMAS than in MALES, which might be explained by the fact that the MMAS population is older or that there was a longer period of follow-up in MMAS than MALES. Only a small proportion of men (14% in MMAS and 28% in MALES) reported use of phospho diesterase type 5 (PDE5) inhibitors, which is not uncommon in population- based studies. Furthermore, most patients were recruited before the commercialization of PDE5 inhibitors. Although this study reported several pertinent findings, there are problems associated with combining data from several longitudinal studies, including the difference in follow- up duration between studies. Moreover, self-reported outcomes might not represent formal diagnosis of a condition, and the lack of access to PDE5 inhibitors or other erectogenic agents may further restrict the generalization of this study. A novel treatment for men with vasculogenic ED was reported in 2011: extracorporeal shock wave therapy (ESWT). In contrast to high-intensity ESWT, which is commonly used to treat urolithiasis and orthopedic conditions, a low-intensity protocol (LI-ESWT) has previously been shown to improve the hemodynamics of many organs via an improvement in vascular supply and endothelial function. Neovascularization is mediated by the nonenzymatic production of physiologic levels of nitric oxide, activa tion of intracellular signaling pathways, and increased expression of vascular endothelial growth factor and its receptor. This year, Gruenwald et al. 3 reported that penile LI-ESWT (two treatment sessions per week for 3 weeks in 29 patients) can improve erectile function and penile hemodynamics. The mean IIEF-ED scores increased from 8.8 ± 1 at baseline to 12.3 ± 1 at 1-month follow-up (P = 0.035). At 2 months, while patients were on active PDE5 inhibitor treatment, the IIEF-ED further increased to 18.8 ± 1 (P
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January 2012 KEY ADVANCES IN MEDICI
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Cover image: Hippocrates of Cos ref
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CARDIOLOGY ACUTE CORONARY SYNDROMES
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5. Alexander, J. H. et al. Apixaban
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9. Lip, G. Y. H. et al. Bleeding ri
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HYPERTENSION IN 2011 New insights
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9. Bibbins-Domingo, K. et al. Proje
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CLINICAL ONCOLOGY OVARIAN CANCER IN
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malignancy and, until recently, doc
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in CLL. Four cases were analyzed an
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of patients. 1,2 The phase III BRIM
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metastasis has provided a new speci
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ENDOCRINOLOGY THYROID DISEASE IN PR
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gene that encodes steroid 11β-hydr
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using the Rotterdam cri teria (two
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(HNF-4α), a crucial regulator of g
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Page 49 and 50: (ADPKD) detach from renal tubules a
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Page 59 and 60: STROKE IN 2011 Major advances acros
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Page 67 and 68: Key advances ■ Early‑onset refr
Page 69 and 70: RHEUMATOLOGY RA IN 2011 Advances in
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Page 73 and 74: Genetic predisposition Subphenotype
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Page 81 and 82: UROLOGY PROSTATE CANCER IN 2011 Red
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