[Correlation of genetic and cytogenetic alterations in pathological aggressiveness urothelial carcinoma of the bladder: Performance of BCA-1, a mini-array comparative genomic hybridisation-based test]. / Corrélation des altérations génétiques à l'agressivité anatomo-pathologique des carcinomes urothéliaux de la vessie : performance du test BCA-1.

INTRODUCTION: Urothelial carcinomas are the fourth leading cause of cancer in humans. Their incidence is increasing by more than 50% in 25 years. The superficial forms (70% cases) require a close active surveillance to identify frequent recurrences and progression to invasive stage. Our main goal was to identify prognostic molecular markers for bladder cancer that could be used alone or in combination in routine clinical practice. In this aim, we evaluated the capability of the BCA-oligo test based on a CGH array to correctly classify tumoral grade/stage. METHOD: Urinary DNA was extracted from 81 patients with superficial bladder cancer and has been hybridized on the BCA-oligo array. The results from the molecular analysis were correlated with the tumoral grade and stage. RESULTS: Several chromosomal alterations were significantly more frequent in tumors of higher grade and more advanced stage. A significant association was observed between a high grade and the presence of one of these alterations: loss on 6p, gain on 8q or 13q, loss or gain on 9q or 11q, with an odds ratio of 6.91 (95% CI=2.20-21.64; P=0.0009). Moreover, a significant association was found between a more advanced stage (pT1) and the presence of one of these alterations: loss on 6p, gain on 8q, loss or gain on 5p, with an odds ratio of 15.2 (95% CI=3.71-62.58; P=0.0002). CONCLUSION: Our results showed that molecular analyses of superficial bladder cancers based on urinary DNA and the BCA-oligo test could be used as prognostic factor for the tumor evolution, allowing then a more adapted clinical management.

Biomarkers in Rheumatoid Arthritis, what is new?

UNLABELLED: Rheumatoid arthritis (RA) is a chronic inflammatory disease with autoimmune pathogenesis. It affects mainly small joints (of the hands and feet) and has many systemic manifestations. Studying biomarkers in rheumatology intensely appeared from the need to understand the mechanisms underlying some rheumatic diseases. Discovering new biomarkers with key roles in various stages of evolution, remains a subject of interest for RA. Currently, according to the EULAR 2010 criteria, the rheumatoid factor (RF) and the anti-cyclic citrullinated peptide (anti-CCP) are used for RA diagnosis. Since 2010, new biomarkers were discovered and proved useful in identifying RA in early stages. For a more rigorous management of these cases, one of the key steps in the evolution of patients with RA is to recognize and distinguish the more aggressive forms of the disease through prognostic biomarkers. "Treat to target" recommends the use of 3 composite scores to monitor the evolution of the disease: disease activity score (DAS 28), simple disease activity index (SDAI) and clinical disease activity index (CDAI), but, a new test was developed which better monitors the disease activity. The introduction of biological therapies has revolutionized the treatment of RA. Despite these advances, 20-40% of the patients are declared nonresponders to at least one of the therapies. The patient exposure to the potential side effects and high costs requires the discovery of a biomarker that could identify those who can benefit from the pretreatment of a certain therapy. ABBREVIATIONS: RA = rheumatoid arthritis, RF = rheumatoid factor, DAS 28 = disease activity score, SDAI = simple disease activity index, CDAI = clinical disease activity index, ACR = American College of Rheumatology, EULAR = European League against Rheumatism, anti-CCP = antibodies against cyclic citrullinated proteins, anti-MCV = mutated citrullinated vimentin antibodies, anti-CarP = antibodies against carbamylated proteins, MBDA = multi biomarker disease activity test, COMP = cartilage oligomeric matrix protein, ADAs = antidrug antibodies, CDA = clinical disease activity index, SDAI = simplified disease activity index, ESR = erythrocyte sedimentation rate, CRP = C reactive protein, SAA = serum amyloid A, VCAM-1 = vascular cell adhesion molecule-1, IL-6 = interleukin-6, TNF-R1 = tumor necrosis factor receptor 1, EGF = epidermal growth factor, VEGF-A = vascular endothelial growth factor A.

The efficiency of biologic therapy in a group of patients with rheumatoid arthritis.

OBJECTIVES: The following study aims to evaluate the monotherapy with biologic agents: Infliximab (IFX), Etanercept (ETA), Adalimumab (ADA) and Rituximab (RTX) in patients diagnosed with rheumatoid arthritis (RA). METHODS: To achieve these objectives, the database of "Dr. I. Cantacuzino" Clinical Hospital, Department of Internal Medicine and Rheumatology, was used. The study was retrospective and descriptive, covering 168 patients with RA, followed for 12 months, from January 2012 to January 2013. Admission criteria for the study were the following: patients diagnosed with RA according to ACR 1987/ EULAR 2010 criteria, disease activity score (DAS 28)> 5.1, positive inflammation tests, presence of RA refractory to classic remitting treatment administered at least 6 months prior to the initiation of biological therapy, on patients treated with RTX. They were considered non-responders after 6 months of treatment with anti tumor necrosis factor alpha (anti-TNF) and decided to switch agents with anti CD-20. RESULTS: Comparing values between any two points in time (baseline - 6 months -12 months) for any type of therapy, there were significant decreases in the values of erythrocyte sedimentation rate (ESR), reactive C protein (CRP) and disease activity score (DAS 28). There were no significant differences between therapies regarding ESR at 6 months (p = 0.070, ANOVA) and 12 months (p = 0.375, Kruskal-Wallis), significant differences were regarding CRP at 6 and 12 months (p = 0.000, Kruskal-Wallis) and DAS 28 at 6 months (p = 0.000, Kruskal- Wallis) and 12 months (p = 0.018, Kruskal-Wallis). CONCLUSION: All 4 therapies have proven efficient, prognostic markers decreasing gradually at 6 and 12 months.

[Mini-sling for management of stress urinary incontinence in women: a literature review]. / Mini-bandelettes pour le traitement de l'incontinence urinaire d'effort féminine : revue de la littérature.

AIM: To conduct a review about the use of single incision mini-slings (SIMS) to manage non-neurogenic stress urinary incontinence in women. METHODS: Literature search in Pubmed/MEdline database until june 2013. TVT-Secur™ was excluded because this device is not anymore marketed. RESULTS: Ajust™ and Mini-Arc™ were the two main SIMS evaluated in the literature. Studies about Mini-Arc™ generated heterogeneous results, with a success rate between 44% and 91% after 1 year. Ajust™ was the most promising device with 80% efficacy after mid-term follow-up. All evaluated SIMS had a low rate of immediate complications. Two randomized controlled trials comparing SIMS and traditional mid-urethral slings were identified, as well as one meta-analysis; they all concluded to non-superiority or inferiority for the mini-sling versus traditional slings. CONCLUSION: Due to short follow-up, limited evidence and heterogeneous data, SIMS are not yet standard of care and further research is warranted.

[Salvage therapy with artificial urinary sphincter after Advance™ male sling failure for post-prostatectomy incontinence: a first clinical experience]. / Thérapie de sauvetage par implantation d'un sphincter artificiel urinaire après échec de bandelette Advance™ pour incontinence urinaire après prostatectomie : une expérience monocentrique.

OBJECTIVES: To assess the clinical outcome following artificial urinary sphincter (AUS) implantation after failure of Advance™ sub-urethral male sling for post-prostatectomy incontinence (PPI). METHODS: A prospective evaluation was conducted about consecutive patients who received an AUS after failure of Advance™ therapy in one tertiary reference center. Evaluation included medical history, pad use and operative data (duration, cuff size, technical difficulties). Follow-up was scheduled at 1, 6, 12 months and yearly thereafter. Clinical outcome was evaluated by pad use, patient global impression of improvement (PGI-I) scale and assessment of side effects. Cure was defined as no pad usage. RESULTS: Twelve patients were included in this evaluation. Median follow-up was 20 months (12-43). No patient was lost to follow-up. Four patients had a history of radiation therapy and all patients had mild or moderate PPI with previous failed Advance™ surgery. Median (range) operative time was 47 minutes (40-60). No technical problem occurred during AUS implantation. Hospital stay duration and catheterization duration were respectively 2 days and 24 hours in all but one case. At last follow-up, 10/12 patients (83%) were cured and fully satisfied. Two were improved, wearing only one pad per day. Postoperative complications were noted in two cases (17%) (one case of cutaneous erosion and one case of superficial iliac wound infection). CONCLUSIONS: AUS implantation is feasible in patients who have undergone Advance™ male sling implantation. Mid-term results of this procedure are comparable to those obtained after first line AUS implantation.

[Predictive value of the penile cuff-test for the assessment of bladder outlet obstruction in men]. / Valeur prédictive du cuff-test dans le diagnostic de l'obstruction sous-vésicale chez l'homme.

PURPOSE: To assess the diagnostic performances and the acceptability of the penile cuff test (PCT) which is a non invasive method for the evaluation of bladder outlet obstruction (BOO), in comparison with the pressure flow study (PFS), the actual gold-standard. MATERIAL: Monocentric prospective study comparing the following subsets: "obstructed", "not obstructed" or "equivocal", deduced from PFS vs PCT, in 30 consecutive patients presenting with lower urinary tract symptoms. For the PCT, a cuff placed around the penis inflated automatically during the micturition, until flow rate interruption. The interruption cuff pressure revealed the isovolumetric bladder pressure (Pcuff-int). The data collected - Pcuff-int and maximum flow rate - were automatically reported on ICS modified nomogram. RESULTS: With the PFS, 11 patients (39%) were classified "obstructed", six patients (22%) "non-obstructed" and 11 patients (39%) "equivocal". In 61% cases, the patient was classified in the same category by both techniques. The "obstructed positive predictive value" of the PCT was 82% and the "non-obstructed-equivocal negative predictive value" was 88%. The median acceptability visual analogic scale score was 1/10 (0-3) for the PCT whereas it was 5/10 (2-10) for the PFS. This difference was statistically significant (p=0.004). CONCLUSION: The PCT was a reliable non-invasive tool for the diagnosis of BOO in male, in comparison with PFS. The predictive values of the PCT were relevant and its tolerance was better than PFS.

[Prospective evaluation of intrasphincteric injections of autologous muscular cells in patients with stress urinary incontinence following radical prostatectomy]. / Évaluation prospective du traitement de l'incontinence urinaire post-prostatectomie par injections intrasphinctériennes de cellules musculaires autologues.

PURPOSE: Cell therapy for urinary incontinence management has been experienced in animals with encouraging results, but studies in human beings are lacking. Our primary objective was to assess the safety of intrasphincteric injections of autologous muscular cells in patients with postprostatectomy incontinence (PPI). Secondary objectives focused on complications efficacy. METHODS: We conducted an open, prospective study in a single center on 12 patients presenting PPI. Patients underwent intrasphincteric injections of autologous muscular cells isolated from a biopsy of deltoid muscle. The primary endpoint was the Q(max) variation at the three month visit in order to assess potential bladder outlet obstruction. Secondary endpoints assessed side effects and efficacy parameters based on symptoms, quality of life score, voiding diary, pad-test, and urethral pressure profile at one, two, three, six and 12 months after injection. RESULTS: No immediate complication occurred and no significant variation was noted on Q(max). The only side effects possibly product-related were three cases of urinary tract infection treated by antibiotics. An acceptable safety and tolerability of the procedure whatever the injected dose of muscular cells was demonstrated. Results on efficacy after one year were heterogeneous, with 4/12 patients describing reduced urine leakage episodes, 1/12 patient presenting increased maximal closure pressure, and 8/12 patients showing improvement on pad-test. CONCLUSIONS: Cell therapy consisting of intrasphincteric injections of autologous muscular cells in patients with PPI was a feasible and safe procedure. The results point out that some subjects may positively respond to this procedure, but clinical efficacy remains to be confirmed.

[Initial experience combinating transobturator male sling and penile implant after radical prostatectomy]. / Chirurgie combinée par bandelette transobturatrice Advance et prothèse pénienne après prostatectomie totale: une première expérience.

PURPOSE: Stress urinary incontinence (SUI) and erectile dysfunction (ED) are two major complications following radical prostatectomy (RP). In case of failure of medical treatment, Advance™ retrourethral male sling and penile implant are validated options to manage respectively SUI and ED. Our goal was to assess the feasibility and results of the combination of these two devices. PATIENTS AND METHODS: Four patients were treated for SUI and DE following RP in our institution by retrourethral sling and penile prosthesis, after failure of medical management. Each patient was preoperatively evaluated by age, complete medical history, ASA score, endoscopy, pad-test, and urodynamics. The first two patients were implanted with the two devices in a two-stage procedure: retrourethral sling then penile prosthesis for one, and penile prosthesis then retrourethral sling for the other. The two other patients underwent a one-stage procedure: one received the two devices, and the other had retrourethral sling implantation and replacement of a penile prosthesis. Post-operative follow-up was focused on complications and efficacy (evaluated by pad use and PGI-I questionnaire for continence, and patient auto-evaluation for sexual function). RESULTS: No perioperative complication occurred. After a minimum of 6 months follow-up, all the four patients were pad-free with no leakage reported, feeling very much better after the procedure according to the PGI-I. The four patients were fully satisfied of the penile implant device. CONCLUSIONS: According to our initial experience, surgery combining the transobturator Advance male sling and a penile prosthesis is feasible, successively or simultaneously, and leads to excellent functional results with no complications.

HLA-C locus and genetic susceptibility to psoriatic arthritis in Romanian population.

We determined the distribution of human leukocyte antigen-C (HLA-C) allelic groups in a cohort of psoriatic arthritis (PsA) patients and a control population of Romanian ethnicity. A nominal association of HLA-C*06 with susceptibility to PsA was observed [P = 0.014, p(corr) > 0.05, odds ratio (OR) 2.1, 95% confidence interval (CI) 1.08-4.46]. When subanalyzing data according to PsA clinical phenotypes, association was noticed between HLA-C*06 and PsA with psoriasis onset before 40 years (p(corr) = 0.013, OR 3.7, 95% CI 1.58-9). This first report from Romania confirmed the association of HLA-C*06 with type I psoriasis in PsA patients. Other study findings, such as the relationship between HLA-C*06 and spondylitis or the protective effect of HLA-C*07 for the polyarthritis clinical phenotype of PsA, are of preliminary character and require verification.

Genetic susceptibility to urinary incontinence: implication of polymorphisms of androgen and oestrogen pathways.

PURPOSE: Although existence of genetic factors predisposing to urinary incontinence in women is widely admitted, precise molecular and genetic variations implicated are still unknown. Given the established influence of steroids metabolism in incontinence, we studied the correlation between polymorphisms of genes of oestrogen/androgen pathways and urinary incontinence in women, in order to raise evidence of genetic susceptibility. METHODS: A case-control study included 121 cases and 66 controls. Age, familial history of incontinence, gynaecologic history and age of menopause were collected. Patients were classified into three groups: control, urge urinary incontinence (UUI), stress urinary incontinence (SUI). Genetic polymorphisms were determined after amplification by PCR for the following genes: CYP-19, CYP17, androgen receptor (AR) and oestrogen receptor (ESR-1). Statistical analysis was performed to study correlation between genotype and presence of a subtype of incontinence. RESULTS: A total of 187 patients were analysed: 66 were controls, 30 presented UUI and 107 presented SUI. Patients presenting incontinence had significantly more often familial history of incontinence than controls. AR polymorphism (combination of 2 alleles containing more than 21 CAG repeats) is significantly associated with UUI (P = 0.02). Polymorphisms of ESR-1, CYP17 and CYP19 were not associated with any subtype of urinary incontinence. CONCLUSIONS: This study shows that AR polymorphism is linked to genetic susceptibility to urinary incontinence. This result suggests that this disease is partly gene-related and encourages larger studies to explore the genetics factors of urinary incontinence.

Distribution of HLA-B27 in Romanian spondyloarthritides patients.

The analysis of 310 Romanian spondyloarthritides patients confirmed the association of the HLA-B27 marker with the susceptibility to different diseases of this group. For ankylosing spondylitis, the HLA-B27 frequency in Romanian patients (72.1%) was similar to that found in several regions in the Mediterranean area.

[Management of premature ejaculation in adults]. / Prise en charge de l'éjaculation prématurée chez le sujet adulte.

Premature ejaculation is a very frequent form of sexual dysfunction characterized by loss of control of ejaculation, inducing performance anxiety and, consequently, impaired quality of life of patients and their partners. The pathophysiology of this symptom is often both psychogenic and organic. The various organic causes must be systematically investigated. Several drug treatments are used with varying degrees of efficacy and their adverse effects must be taken into account when choosing a molecule. Psychological management is an essential complement to drug treatment.

[Contribution of VLPP (Valsalva leak point pressure) in the urodynamic assessment]. / Apport du VLPP dans l'examen urodynamique.

The Valsalva leak point pressure (VLPP) is fully part of urologic assessment. Several factors can influence it: the patient's position, the bladder volume, the presence or absence of the urethral catheter, and the way of observing the leakage (direct visualisation or video-urodynamics). Sometimes VLPP is not feasible because patients cannot push strong enough. Nevertheless, a standardisation of the methodology has been suggested by the Société internationale francaphone d'urodynamique (SIFUD). Values below 60 cmH2O should be considered suggestive for sphincter insufficiency. Conversely, the diagnosis of urethral sphincter insufficiency should rely on the tripod: clinical examination (low urethral mobility), low closure pressure and low VLPP.

[Bladder involvement in scleroderma: report of 3 cases]. / Atteinte vésicale dans la sclérodermie: à propos de 3 cas.

Lower urinary tract involvement is the common manifestation of systemic sclerosis. It may represent a troublesome disturbance affecting the quality of life in systemic sclerosis patients. We report three patients with progressive systemic sclerosis who manifested pathologic abnormalities in the urinary bladder. The first patient manifested a recurrent macroscopic hematuria requiring transfusions. Both other patients developed functional and urodynamic abnormalities. With a review of the literature on this involvement of the bladder in systemic sclerosis we try to more understand urinary symptoms and urodynamics features of vesical involvement in systemic sclerosis patients.

Tension-free vaginal tape: why an unusual concept is so successful.

The surgical treatment of female stress urinary incontinence has been dramatically changed during the last 5 years, after Ulmsten introduced the tension-free vaginal tape procedure. This technique is based on a series of experimental investigations of the urethral closure mechanisms in women. The procedure is easy to learn, could be performed on an outpatient basis, and is recognized as a minimally invasive surgery. Despite these arguments, the most probable reason for its present success is the reproducibility of the results in the various published series. The success rate is estimated at between 85 and 95% for correction of genuine stress urinary incontinence. However, longer follow-up will be necessary to confirm these preliminary results, and probably to determine what are the most valuable prognostic factors.