First-line treatment in senior adults with metastatic castration-resistant prostate cancer: A prospective international registry.

AIMS: To compare the efficacy and tolerability of taxane and nontaxane therapy in senior adults with chemonaïve metastatic castration-resistant prostate cancer (mCRPC), and examine the effect of patient health status on outcomes. PATIENTS AND METHODS: Between 2009 and 2011, 333 patients aged≥70 years with mCRPC were enrolled in a prospective international registry. Patients were categorized as having received taxane-based or nontaxane therapy, and classified as fit, vulnerable, frail, or terminal, according to investigator judgement or International Society of Geriatric Oncology guidelines. Efficacy measures included overall survival (OS) and progression-free survival. Grade 3/4 toxicities were recorded. Predictors of OS were identified using multivariate Cox regression. RESULTS: The proportions of fit/vulnerable/frail patients were 65%/14%/17% (International Society of Geriatric Oncology), and 39%/43%/17% (investigator). In single-factor analyses, taxane therapy improved OS (hazard ratio [95%CI] = 0.53 [0.30-0.93]; P = 0.027) and progression-free survival (hazard ratio [95% CI] = 0.55 [0.40-0.76]; P<0.001) vs. nontaxane therapy. Patients with frailty also benefited from taxane therapy (adapted regimen in 52%). In multivariate analysis, taxanes improved OS even with poor prognostic factors present (P = 0.017); age was unrelated to prognosis. Taxane therapy was well tolerated; most common grade 3/4 toxicities (taxane vs. nontaxane) were fatigue (17% vs. 4%), nausea/vomiting (14% vs. 5%) and neutropenia (10% vs. 1%). CONCLUSIONS: The results of this nonrandomized, observational study suggest that first-line taxane therapy may benefit senior adults with mCRPC more than alternative therapies. Treatment decisions should not be based on chronological age.

[Impact of alfuzosin 10 mg once daily on quality of life in Tunisian patients with lower urinary symptoms suggestive of benign prostatic hyperplasia]. / Impact de l'alfuzosine lp 10 mg sur la qualite de vie chez les patients avec troubles urinaires du bas appareil suggestifs d'une hypertrophie benigne de la prostate.

BACKGROUND: Incidence of benign prostatic hyperplasia (BPH), one of the most common conditions affecting adult men, increases dramatically after the age of 50. The various symptoms of BPH, which include lower urinary tract symptoms (LUTS), can adversely affect quality of life (QoL) and sexuality and 1-Blockers are the most frequently prescribed oral medications as first-line treatment. AIM: The objectives of this study try to evaluate QoL and sexuality in patients requiring treatment by Alfuzosin 10mg once daily according to physician decision in current practice and to identify patient's profile treated with Alfuzosin 10 mg under daily practice conditions by Tunisian urologists. METHODS: 730 patients presenting a symptomatic BPH were enrolled in this study by 40 urologists. The impact of treatment on patient's QoL and sexual dysfunction were checked at every visit before treatment and at 3 and 6 months using "International Prostate symptoms score" (IPSS) and "Male Sexual Health Questionnaire - Ejaculatory Dysfunction" (MSHQ - EJD) questionnaire. RESULTS: BPH affect Qol and near half of the patients reported sexual disorders. The treatment compliance to Alfuzosin was very good with a regular intake in 92% of the cases. Quality of life significantly improves during visits: the global IPSS score decreases from 18.8 at baseline to 9.5 at 6 months. The same favorable evolution was observed with the bother score which decreases from 4.0 at baseline to 1.6 at 6 months, and with MSHQ - EJD score which increases from 10.5 at first visit to 11.4 at 6 months. CONCLUSION: Alfuzosin 10 mg administered for 6 months provides a marked improvement in patients presenting symptomatic BPH not only on LUTS but also in QoL and sexual disorders.

PSMA-PSA clones controlled by full Akt phosphorylation (T308+,S473+) recapitulate molecular features of human prostate cancer.

BACKGROUND: (PSMA+,PSA+) and (PSMA+,PSA-) are the two most individual clones that we have previously identified during prostate cancer (PC) progression. However, molecular signatures associated with these distinct PSMA-PSA prostate clones and their specific correlation with disease outcome is yet to be defined. AIM: Since Akt is a major pathway involved in the critical activating events that leads to malignant form of the disease, we studied the involvement of full Akt activation (T308+,S473+) connected with serum PSA levels, tissue PSMA expression and angiogenic activity on the emergence of (PSMA+,PSA+) and (PSMA+,PSA-) PC clones. METHODS: The study was carried out in 6 normal prostate, 25 benign prostate hyperplasia (BPH) and 23 (PC). Immunohistochemical analysis was performed to study the expression of PSMA, PSA, pAkt(T308), pAkt(S473) and CD34 in prostate tissues. The evaluation of angiogenesis was made by CD34 immune marker. Serum levels of PSA were assayed by Immulite autoanalyser. RESULTS: The most relevant result showed that, among PC patients with pAkt (T308+,S473+) profile, patients that exhibit the (PSMA+,PSA+) clone have .higher serum PSA levels, tissue PSMA expression and angiogenic activity than those with (PSMA+,PSA-) clone. Although have the same (PSMA+,PSA+) prostate clone, BPH patients have distinct molecular-biological features compared to PC patients among pAkt (T308+,S473+) profile. In fact, among patients with maximal Akt activation, the (PSMA+,PSA+) PC clone is characterized by higher serum PSA levels, tissue PSMA production and intensive angiogenic activity than (PSMA+,PSA+) BPH clone. CONCLUSION: These findings emphasize the potential role of the full Akt activation (T308+,S473+) in expansion of several PSMA-PSA prostate clones capable of driving both human PC initiation as well as progression to a metastatic phenotype. Pinpoint patients according to PSMA-PSA clones could recapitulate the histological and molecular features of human PC and may offer a novel approach for controlling metastasis.

Evolution and prognosis of bladder papillomatosis managed by endoscopic resection and endovesical BCG therapy : about 24 cases.

BACKGROUND: Bladder papillomatosis is a diffuse tumor proliferation even up almost all of the bladder mucosa. We analyzed prognosis of this rare entity after conservative treatment. METHODS: We retrospectively analyzed epidemiological, clinical, therapeutic and evolutive data in 24 patients with newly diagnosed bladder transitional cell carcinoma papillomatosis. All patients underwent a complete endoscopic transurethral resection (TUR) with curative intent. A second look was performed within 30 days. The intravesical therapy regimen consisted on weekly instillations for 6 weeks, and then monthly for 6 months. If the tumor recurred without muscle invasion, TUR was repeated with a second intravesical BCGtherapy regimen. Parameters investigated included age, gender, risk factors, cystoscopic findings (aspect, multiplicity and location of bladder lesion), tumor stage, tumor grade, recurrences and progression times from diagnosis to last follow up. RESULTS: The mean age of the patients at initial diagnosis was 64,9±6,1 years. They were males in 23 cases. Initial cancer staging was as follow: pTa (n=6) and pT1 (n=18). The recurring tumors were reported in 17 patients (70,8%). They were stage Ta in 5 patients and stage T1 in 12. The median interval of time between the initial TUR and the first recurrence was 10,3 months. Six patients remain tumor free. From the 17 recurrences, 6 patients developed progression with muscle invasion in 4 of them. Radical cystectomy with ileal conduit was performed in 3 patients and one patient died before radical treatment. Univariate analysis didn't reveal any prognostic factor: age (p=0,7), tumor location and aspect (p= 0,7 and p= 0,5 respectively), tumor stage (p=0,7) and grade (p=0,09). CONCLUSION: TCC bladder papillomatosis is a rare entity. TUR with intravesical BCG therapy may be indicated as a first option despite correct follow up. Radical cystectomy should be considered in cases of recurrent or non-resectable tumours.

Cellular distribution and heterogeneity of Psa and Psma expression in normal, hyperplasia and human prostate cancer.

BACKGROUND: As promising targets for in vivo diagnostic,prognostic and therapeutic approaches, the distribution and staining pattern of prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA) in tumors are of significant interest. AIMS: To compare the cellular distribution and heterogeneity of PSA and PSMA expression in normal prostate (NP), benign prostatic hyperplasia (BPH) and primary prostatic tumors and to analyze their relation with the angiogenic activity according to Gleason grade (low, medium and high) in primary PC. METHODS: The study was carried out in 6 NP, 44 BPH and 39 PC. Immunohistochemical analysis was performed. Monoclonal antibodies 3E6 and ER-PR8 were used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis was made by CD34 immune marker. RESULTS: In our study we noticed differences in the intracellular localization of the PSMA immunostaining which seem to be related to the normal and pathological context. A significant number of primary tumors presented with apical pattern of PSMA (28/39); whereas a relevant part of NP samples and BPH samples showed cytoplasmic localization (4/6 and 30/44,respectively) in luminal epithelial cells. Compared to PSMA, PSA was preferentially localized in cytoplasmic compartment in all type of prostate. A direct correlation between histological grade, PSMA expression and angiogenic activity could be demonstrated in primary PC. CONCLUSIONS: Simultaneous stains with PSA and PSMA in individual prostate tissue will greatly improve the detection rate and identify a high risk PC that could progress to metastatic phenotype. Our findings clearly support the feasibility but also direct the potential of PSMA-targeted in vivo therapeutic approaches in PC patients rather than PSA especially those with poorly differentiated adenocarcinoma.

[Endoscopic realignment versus delayed urethroplasty in the management of post traumatic urethral disruption : report of 30 cases]. / Le réalignement endoscopique versus urétrorraphie terminoterminale tardive dans le traitement des ruptures post-traumatiques de l'urètre : Notre expérience à propos de 30 cas.

BACKGROUND: Post traumatic posterior urethral disruption is a common condition, its treatment is controversial. AIM: To assess the long term results of endoscopic realignment compared with delayed urethroplasty, in the management of post traumatic urethral disruption. METHODS: Between February 2002 and March 2009, 30 patients have been operated for post traumatic posterior urethral disruption. 20 have had a primary endoscopic realignment and 10 have had delayed urethroplasty. Analysis of the results took into consideration, the quality of micturition, the continence and the erectile function. results: Median follow-up was 21 months, good results were recorded in 13 patients among the group of realignment (65%). 0f the failure cases (7), 3 underwent urethroplasty and 4 were managed by endoscopic treatment. Endoscopic realignment could avoid open surgery in 17 patients (85%). Among the 10 patients that underwent urethroplasty, 7 patients had good results (70%). No patient had urinary incontinence. A post operative erectile dysfunction was noted in one patient from the realignment group and two other patients from the urethroplasty group. CONCLUSION: The endoscopic urethral realignment could be used as a primary therapeutic management of post traumatic urethral disruption. It could be recommended for recent trauma, between one and two weeks, and for patients that can support exaggerated lithotomy position. Endoscopic realignment is an effective safe therapeutic mean that does not contraindicate a second-line urethroplasty.

[Fournier's gangrene : what are the prognostic factors? Our experience with 40 patients].

BACKGROUND: Fournier's gangrene (FG) is a serious, extensive fulminant infection of the genitals and perineum. Indeed, despite antibiotics and aggressive debridement, the mortality rate of FG remains high. AIM: Through our experience, we intent to identify effective factors in the survival of patients with FG and we try to determine how the Fournier's gangrene severity index score (FGSIS) is accurate. METHODS: Between 1995 and 2010, 40 patients with Fournier's gangrene were treated in our institution. All of them were treated with broad spectrum triple antimicrobial therapy, broad debridement and exhaustive cleaning. Then they underwent skin grafts or delayed closure as needed. Data were collected on demographics, medical history, predisposing factors of FG, etiological infection agents, admission signs and symptoms, physical examination, admission laboratory studies and bacteriology. Timing and degree of surgical debridement as well as outcomes were also reviewed. The extent of disease was calculated from body surface area nomograms. RESULTS: All the 40 patients included in this study were males; their mean age was 52,75 years (21-75 years). Twelve patients (30%) had FG secondary to anorectal pathological conditions. No etiologic factors of FG were found in 6 patients (15%). Diabetes mellitus as predisposing factor was found in 13 patients (32.5%). The mean hospital stay was 8.72 days (range, 3 to 30). All the patients underwent surgical debridement. Orchidectomy was done in 7 cases (17.5%). Skin grafts were applied to 6 patients (15%) and the remaining wounds, once cleaned, were approximated. The overall mortality rate was 17.5% (7 patients) due to severe metabolic acidosis in relation to diabetic decompensation and sepsis. We individualized two groups: those who died (n = 7) and those who survived (n = 33). We evaluated the admission laboratory parameters that are significantly correlated with outcome included hematocrit (p=0.003) and serum sodium (p=0.05). The extent of body surface area involved among patients who died was not found significantly different statistically between the two groups (4.07% and 3,14%, p=0,4). The mean FGSIS (without counting bicarbonate serum level) for survivors was 9.1 compared with 6,8 for nonsurvivors (p=0.16). CONCLUSION: FG is a rapidly progressive, fulminant infection's condition. Hematocrit and serum sodium levels were found to be the only prognostic factors. It doesn't seem that the FGSIS has a prognostic value.

Testicular cancer patterns in Tunisian men : diagnosis problems, pathological types and prognosis. About 41 patients.

AIM: To analyze the testicular cancer (TCa) incidence, diagnosis aspects, pathologic grade, stage, and survival in Tunisian men. METHODS: We studied all patients who had histopathologically confirmed TCa treated in La Rabta University-Hospital between 1991 and 2010. Baseline demographic data included age at diagnosis, year of diagnosis, clinical symptoms, stage at diagnosis, histologic type, management strategies and survival were analyzed. RESULTS: The incidence of TCa among Tunisians is very low; we collected only 41 cases over a period of 20 years with an average incidence of 2 new cases per year. Peak age incidence was 30-49 years. Testicular swelling was the principal complaint in 25 patients. 58.5% of tumours were rightsided and 39% were left-sided. There was bilateral involvement in only one case. The mean interval between onset of symptoms and presentation was 16.5 months (1-120). Most patients presented at stages T2 and T3 (63.4% and 26.8% respectively). Treatment consisted of radical orchidectomy in all patients and cisplatin-based chemotherapy and radiotherapy in respectively 11 and 12 patients (association in 5 patients). One patient with a tumour in an intra-abdominal testis underwent laparotomy. The most common histological types were seminomas (n=20) and mixed germ cell (n=8). Three patients died within 48 months, while half were lost to follow-up. CONCLUSIONS: The incidence of TCas in Tunisia remains low. Late presentation and treatment are major challenges to management. Better health funding and education regarding testicular self examination is essential.

[The role of bisphosphonate in the treatment of bone metastases from prostate cancer]. / Apport des bisphosphonates dans la prise en charge des métastases osseuses du cancer de la prostate.

BACKGROUND: Bone metastasis is very frequent in prostate cancer. It is a turning point that marks the severity of the disease. Before metastasis become symptomatic, treatment preventing bone events should be indicated. AIM: To evaluate the role of bisphosphonate in the treatment of bone metastases from prostate cancer. METHODS: A review of literature. RESULTS: Bisphosphonates play a very important role to prevent bone mass loss and to reduce bone complication events. CONCLUSION: Bisphosphonates are recommended as preventive treatment at the time of diagnosis of bone metastatic prostate cancer.

[Bellini renal cell carcinoma : diagnosis and treatment. A report of 7 cases]. / Carcinome à cellules rénales de Bellini : diagnostic et traitement A propos de 7 cas.

BACKGROUND: The Bellini collecting duct carcinoma (CDC) is a very rare form of renal cell carcinoma (1%) associated with an extremely poor prognosis. AIM: To study clinical and radiological characteristics of CDC. METHODS: From 1993 to 2002, 7 patients with CDC were treated at our institution. The diagnosis of CDC was made by a nephrectomy specimen in all cases. Demographic, clinical, pathological and survival data were gathered. RESULTS: They were five men and two women with an average age of 63 years. Lumbar pain and hematuria were the main symptoms. At presentation 2 T1N0M0, 1 T2N0M0, 1 T3N0M0, 1 T3N+M0 and 2 T4N+M+ tumors were seen. All patients underwent a radical nephrectomy. The two patients who had TNM stage I disease survived without evidence of disease at 5 years and 11 years respectively. Patients with a T4N+M+ tumor experienced rapid progression and died respectively at 3 and 5 months after nephretomy. The 3 other patients with T3N+M0, T3N0M0 and T2N0M0 disease; respectively; progressed rapidly and were lost to follow-up after one year. CONCLUSION: CDC is an aggressive variety of kidney neoplasm that is often associated with nodal and visceral metastases at presentation.It is associated with poor prognosis. For the majority of patients surgical treatment will not result in a cure. Early detection may be the best method for prolonging patient survival.

[Intradiverticular tumors of the bladder: diagnostic and therapeutic problems: report of 32 cases]. / Les carcinomes urotheliaux intra-diverticulaires de la vessie. Problèmes diagnostiques et thérapeutiques : A propos de 32 cas.

BACKGROUND: The transitional cell carcinoma within the bladder diverticular is a rare and poorly known entity. AIM: To evaluate diagnostic and therapeutic approaches of transitional cell carcinoma within the bladder diverticular. METHODS: Thirty men and two women (median: 70 years; 44- 83 years) were included. The main reason for consultation was hematuria. The intra-diverticular tumor was suspected by radiological assessment in 9 patients only. All these patients underwent an endoscopic resection of the tumor. RESULTS: The histological study concluded to a pta stage in 16 patients, pt1 stage in 8 patients and invasive tumors in 8 patients. A complementary endovesical BCG-therapy was performed in patients with superficial tumors and a radical cystectomy in patients with invasive tumors. With an average follow-up of 27 months, seven recurrences were found in the group of superficial tumors, including 3 cases of progression to invasive stage. CONCLUSION: Bladder intra-diverticular tumors are rare and more common in elderly. In a bladder diverticulum, there are superficial tumors (pta, pt1) which are the most frequent and invasive tumors. Radical cystectomy is the gold standard for invasive tumors.Endoscopic resection combined with endo-vesical immunotherapy should be reserved for superficial tumors.

[Renal colic in pregnancy and lactation: diagnostic and therapeutic approaches]. / La colique néphrétique chez la femme enceinte ou allaitante: problèmes diagnostiques et thérapeutiques.

BACKGROUND: Renal colics due to urinary stones are also common in women of childbearing age whether pregnant or not. AIM: Through a review of literature, we evaluated diagnostic and therapeutic approaches in renal colic in pregnancy and lactation. METHODS: Review of literature. RESULTS: The clinical diagnosis is sometimes difficult requiring additional medical imaging based on ultrasound. Other radiological investigations using X-rays are formally forbidden. The prescription of analgesic treatment during pregnancy and lactation must take into account mainly the teratogenic risk in addition to maternal risk by altering drug pharmacokinetics during pregnancy. CONCLUSION: During pregnancy, NSAIDs are prohibited because of their teratogenicity effect. Salicylates and opiates should be used with care, especially in cases of threat of confinement. Paracetamol remains the treatment of choice. Salicylates and corticosteroids should be used with caution during lactation.

[Sclerotherapy of idiopatic hydrocele with polidocanol: a study about 190 cases]. / La sclérothérapie au polidocanol dans le traitement des hydrocèles vaginales idiopathiques : Etude à propos de 190 cas.

AIM: To evaluate the efficacy and side-effects of Polidocanol used as sclerosing agent for testicular hydrocele. METHODS: One hundred and ninety men, with a median age of 55,9 years (40-89), treated for idiopatic hydrocele were assessed. After puncture and aspiration, the empty sac was instilled with 3% Polidocanol. We recorded recurrence, complications and associated pain on a visual analogue scale. RESULTS: With a median follow-up of 19 months, The cure rate of hydroceles after one sclerotherapy session was 62,1%, and the overall cure rate using the procedure was 82,6%. Re-instillation was done for recurrences in 41% of patients. Polidocanol therapy was almost pain-free. A low rate of complications was observed. CONCLUSION: Polidocanol is a useful sclerosing agent for treating testicular hydrocele. Due to its ease of administration, low frequency of complications, high rate of effectiveness, and excellent tolerability; we recommend sclerotherapy with polidocanol as the primary treatment for hydroceles.