Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA(11a) and hMENA Delta v6, in early NSCLC. The epithelial hMENA(11a) isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENA Delta v6. Enforced expression of hMENA Delta v6 or hMENA(11a) increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA(11a) were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA(11a) was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA(11a) expression fared significantly better (P <= 0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk

Role of surgery in treatment of locally advanced prostate cancer

The proportion of prostate cancer diagnosed at localized stages increased from 56.7% to 74. 0% between 1973 and 1993 ("stage migration"). A corresponding increase in the number of radical prostatectomies performed each year was also noted. Nomograms are mathematical algorithms derived from statistical models that are used to predict outcomes for an individual patient, or for groups of patients. In fact, careful pre-operative patient and tumor selection before radical prostatectomy is mandatory. Locally advanced prostate cancer is defined as tumor that has extended clinically beyond the prostatic capsule, with invasion of the pericapsular tissue, apex, bladder neck or seminal vescicle, but without lymph node involvement or distant metastasis. It is estimated that 12-15% of prostate cancer are stage T3. Overstaging or understaging of this cancer is common. Correct staging of clinical T3 disease is even more difficult and both overstaging pT2 and understaging pT4 or pN+ are common. The goals of treatment for T3 tumors are to cure the disease, prolong survival or metastasis-free survival and improve the quality of life. The authors reviewed the most important studies, investigated radical prostatectomy as monotherapy for locally advanced prostate cancer and the integration of surgery with hormonal treatment. The EAU guidelines on prostate cancer state that radical prostatectomy in locally advanced disease is an option for selected patients with small T3, PSA 10 years. Ten to 15% of clinical T3 are overstaged as pT2. This may lead to the possibility of curing these patients with surgery as the monotherapy. The increased use of nomograms and increased knowledge of recognized prognostic factors could lead to the selection of a large number of patients, often with a long life expectancy, who could benefit from surgical treatment

Cavernous body reduction in four patients with erectile dysfunction due to insufficient venous occlusion and a deficit of elastic fibers in the tunica albugínea

INTRODUCTION: The corpora cavernosa are cylindrical vessels containing fluid under pressure. Thus, if cavernous wall resistance decreases, the radius increases and internal pressure decreases (LaPlace's law). We reasoned that if we decrease the corpus cavernosum radius, by excising a strip from each tunica albuginea, intracavernous pressure would increase during erection. MATERIALS AND METHODS: We treated with this procedure, four patients (mean age 41.5) with long-standing erectile dysfunction due to veno-occlusive dysfunction, non-responders to phosphodiesterase-5 inhibitors and intracavernous PGE1 injection. RESULTS: Two months post-surgery, intracavernous PGE1 (40 mcg) induced a satisfactory erection in two patients and a 45% and 58% tumescence in the other two. PGE1 responders also responded to 100 mg sildenafil. After 100 mg sildenafil and 20 mg tadalafil, the two non-responders had erections that enabled penetration but were short lasting. CONCLUSION: The procedure described could be more effective than cavernous revascularization operations. The results seem to confirm the mathematical assumptions