Expression of Neutral Endopeptidase, Endothelin-1, and Nuclear Factor Kappa B in Prostate Cancer: Interrelations and Associations with Prostate-Specific Antigen Recurrence after Radical Prostatectomy

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods. 70 patients with early-stage PC were treated with RP and their tumor samples were evaluated for expression of NEP, endothelin-1 (ET-1) and NFκB (p65). Time to PSA recurrence was correlated with the examined parameters and combined with preoperative PSA level, Gleason score, pathological TNM (pT) stage, and surgical margin (SM) assessment. Results and Limitations. Membranous expression of NEP (P < 0.001), cytoplasmic ET-1 (P = 0.002), and cytoplasmic NFκB (P < 0.001) were correlated with time to PSA relapse. NEP was associated with ET-1 (P < 0.001) and NFκB (P < 0.001). ET-1 was also correlated with NFκB (P < 0.001). NEP expression (P = 0.017), pT stage (P = 0.013), and SMs (P = 0.036) were independent predictors of time to PSA recurrence. Conclusions. There seems to be a clinical model of NEP/NPs and NFκB pathways interconnection, with their constituents following inverse patterns of expression in accordance with their biological roles and molecular interrelations

Lithotrites and Postoperative Fever: Does Lithotrite Type Matter? Results from the Clinical Research Office of the Endourological Society Percutaneous Nephrolithotomy Global Study

Objective: To compare the risks of fever from different lithotrites after percutaneous nephrolithotomy (PNL). Materials and Methods: The Clinical Research Office of the Endourological Society (CROES) PNL database is a prospective, multi-institutional, international PNL registry. Of 5,803 total patients, 4,968 received preoperative antibiotics, were supplied with complete information and included in this analysis. The lithotrites assessed included no fragmentation, ultrasonic, laser, pneumatic and combination ultrasonic/pneumatic. Risk of fever was estimated using multivariate logistic regression with adjustment for diabetes, steroid use, a history of positive urine culture, the presence of stag horn calculi or preoperative nephrostomy, stone burden and lithotrite. Results: The overall fever rate was 10%. Pneumatic lithotrites were used in 43% of the cohort, followed by ultrasonic (24%), combination ultrasonic/pneumatic (17.3%), no fragmentation (8.4%) and laser (7.3%). Fever rates were no different between patients who underwent no or any fragmentation (p = 0.117), nor among patients when stratified by lithotrite (p = 0.429). On multivariate analysis, fragmentation was not significantly associated with fever [Odds Ratio (OR) 1.17, p = 0.413], while diabetes (OR 1.32, p = 0.048), positive urine culture (OR 2.08, p = 0.128). Conclusions: Risk of post-PNL fever was not significantly different among the various lithotrites used in the CROES PNL study. Copyright (C) 2013 S. Karger AG, Base

Sexual dysfunction in newly diagnosed multiple sclerosis women

Objectives The aim of the study was to evaluate female sexuality in a selective population of newly diagnosed multiple sclerosis (MS) women. Materials and methods In this clinic-based study, 63 newly diagnosed consecutive women affected by definite MS were admitted. Disability and depression were evaluated with the expanded disability status scale (EDSS) and Beck depression inventory, respectively. Sexual function was evaluated with the female sexual function index (FSFI). A group of 61 healthy female volunteers with the same baseline characteristics were used as controls. Postmenopausal women and patients with other major concomitant neurological, endocrinological, vascular, gynecological, psychiatric disorders, use of medicines that can cause female sexual dysfunction (FSD) and disease-modifying drugs were excluded from the study. Results All the evaluated patients were ambulant with no major neurological impairment (mean EDSS score 2.5, range 0-3.5). None of the patients were considered clinically depressed, but some of them were sad or worried. According to the sexual history and FSFI scores, sexual dysfunction was diagnosed in 22 (34.9%) out of the 63 patients and in 13 (21.31%) out of the 61 healthy females (P > 0.05). Conclusions In the newly diagnosed MS patients, FSD represent an important issue even though disability and other concomitant disorders affecting sexual function were excluded

Extracorporeal shock-wave lithotripsy and garlic consumption: a lesson to learn

The first case of a kidney haematoma after extracorporeal shock-wave lithotripsy (SWL) in a patient with nephrolithiasis who was taking aged garlic extraction is reported. Patient was treated conservatively without the need of any intervention. Urologists should be aware that herbal products including garlic, ginkgo, and ginseng have been associated with potential increased bleeding. The present case emphasises the need to specifically seek out a history of herbal use in presurgical patients. It is suggested that herbal medications should be discontinued up to 15 days prior to urologic surgery or SWL to minimise the risk of complications

Endothelin-1 overexpression: a potential biomarker of unfavorable prognosis in non-metastatic muscle-invasive bladder cancer

Endothelin-1 (ET-1) is a multifunctional peptide exerting its effects via receptors A and B. ET-1 and its receptors, endothelin axis (ET axis), play a promoting role in cancer biology. Alterations of proteins of ET axis have been detected in non-metastatic muscle-invasive bladder cancer (NMMIBC). The objective of this study is to investigate the potential role of ET-1 tumor expression as a biomarker of prognosis, compared to other prognostic parameters (epidemiologic and pathologic), in NMMIBC. We prospectively included 40 consecutive, primary, high-grade NMMIBC patients. Tumor specimens after initial transurethral resection were stained immunohistochemically for ET-1. The ET-1 evaluation of expression was based on staining intensity (SI) of ET-1. SI was classified according to an arbitrary four-tiered scale (negative = 0, mild = 1, moderate = 2, strong = 3). Epidemiologic and pathologic parameters were analyzed, using univariate and multivariate statistics, for disease progression, progression-free survival (PFS), and overall survival (OS). ET-1 overexpression (SI = 3) was the unique parameter which associated significantly, both in univariate (log-rank test, p = 0.033) and multivariate (Cox regression analysis, p = 0.045, HR = 4.849, 95 % CI: 1.039-22.624) analysis, with an increased hazard ratio of progression. ET-1 overexpression (SI = 3) was also the unique parameter which associated, marginally significantly in univariate analysis (log-rank test, p = 0.056) and highly significantly in multivariate analysis (Cox regression analysis, p = 0.005, HR = 7.001, 95 % CI: 1.782-27.501), with an increased hazard ratio of death. Overexpression of ET-1 may be a potential biomarker of unfavorable prognosis in NMMIBC patients

CD10 Is Inversely Associated with Nuclear Factor-Kappa B and Predicts Biochemical Recurrence after Radical Prostatectomy

Introduction: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-kappa B (NF-kappa B) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC. Patients and Methods: The immunohistochemical expression of CD10 and NF-kappa B in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure. Results: CD10 expression was inversely associated with NF-kappa B expression (p < 0.001), stage (p = 0.03) and grade (p = 0.003), whereas NF-kappa B was directly related with stage (p = 0.006) and grade (p = 0.002). The median time to PSA failure was 56 months. CD10 and NF-kappa B were directly (p < 0.001) and inversely (p < 0.001) correlated with biochemical recurrence-free survival, respectively. CD10 expression (p = 0.022) and stage (p = 0.018) were independently associated with time to biochemical recurrence. Conclusion: Low CD10 expression is an adverse prognostic factor for biochemical relapse after RP in localized PC, which is also associated with high NF-kappa B expression. Decreased CD10 expression which would lead to increased neuropeptide signaling and NF-kappa B activity may be present in a subset of early PCs. Copyright (C) 2012 S. Karger AG, Base