G. Robert

The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers.

PURPOSE Metastasis remains the main cause of death in both bladder (BCa) and prostate (PCa) cancers. The results of chemotherapy did not show any significant improvement of the survival the past years. Cancer research has led to the identification of signaling pathways involved and molecular targets that could change the natural history. The epithelial-mesenchymal transition (EMT), critical during embryonic development, becomes potentially destructive in many epithelial tumors progression where it is inappropriately activated. The cell-cell and cell-extracellular matrix interactions are altered to release cancer cells, which are able to migrate toward metastatic sites. Hallmarks of EMT include the down-regulation of E-cadherin expression, which is the main component of the adherens junctions. The protein TWIST is a transcriptional repressor of E-cadherin, tumor progression, and metastasis, and could be used as a molecular target to restore the chemosensitivity in BCa and PCa. MATERIALS AND METHODS We selected the last 5-year basic research literature on EMT and TWIST but also clinical studies on BCa and PCa in which TWIST is overexpressed and could be considered as an efficient prognostic marker and molecular target. RESULTS TWIST is considered as a potential oncogene promoting the proliferation and inhibiting the apoptosis. TWIST promotes the synthesis of the pro-angiogenic factor, vascular endothelial growth factor (VEGF) involved in tumor progression and metastasis. Apoptosis and angiogenesis are two essential cancer progression steps in many epithelial tumors, including BCa and PCa. CONCLUSIONS With the targeted therapy, oncology has entered into a new era, which is going to be critical in cancer treatment in combination with traditional anticancer drugs.

Multicentre prospective evaluation of the learning curve of holmium laser enucleation of the prostate (HoLEP)

To describe the step‐by‐step learning curve of the holmium laser enucleation of the prostate (HoLEP) surgical technique.

RecommandationBilan initial, suivi et traitement des troubles mictionnels en rapport avec hyperplasie bénigne de prostate : recommandations du CTMH de l’AFUInitial assessment, follow-up and treatment of lower urinary tract symptoms related to benign prostatic hyperplasia: Guidelines of the LUTS committee of the French Urological Association

AIM To elaborate guidelines for the diagnosis, the follow-up, and the treatment of benign prostatic hyperplasia (BPH). METHOD A systematic review of the literature was conducted to select more relevant publications. The level of evidence was evaluated. Graded recommendations were written by a working group, and then reviewed by a reviewer group according to the formalized consensus technique. RESULTS Terminology of the International Continence Society was used. Initial assessment has several aims: making sure that lower urinary tract symptoms (LUTS) are related to BPH, assessing bother related to LUTS and checking for a possible complicated bladder outlet obstruction (BOO). Initial assessment should include: medical history, LUTS assessment using a symptomatic score, physical examination including digital rectal examination, urinalysis, flow rate recording, and residual urine volume. Frequency volume chart is recommended when storage symptoms are predominant. Serum PSA should be done when the diagnosis of prostate cancer can modify the management. When a surgical treatment is discussed, serum PSA, serum creatinine and ultrasonography of the urinary tract are recommended. BPH patients should be informed of the benign and possibly progressive patterns of the disease. When LUTS cause no bother, annual follow-up should be planned. Medical treatment includes some phytotherapy agents, alpha-blockers and 5-alpha reductase inhibitors. The last two can be associated. The association of antimuscarinics and alpha-blockers can be offered to patients with residual storage symptoms when already under alpha-blockers therapy, after checking for the absence of severe BOO (residual volume more than 200mL or max urinary flow less than 10mL/s). Phosphodiesterase-5 inhibitors could be used in patients complaining for both LUTS and erectile dysfunction. In case of complication, or when medical treatment is inefficient or not tolerated, then a surgical treatment should be discussed. Treatment decision should be done according to type of LUTS and related bother, prostate anatomy, level of obstruction and its consequences on urinary tract, patient co-morbidities, experience of practitioner, and choice of patient. Surgical treatments with the higher level of evidence of efficacy include monopolar or bipolar transurethral resection of the prostate, open prostatectomy, transurethral incision of the prostate, photoselective vaporization of the prostate, and Holmium laser enuclation of the prostate. CONCLUSION Here are the first guidelines of the French Urological Association for the initial assessment, the follow-up and the treatment of urinary disorders related to BPH.

Transforming growth factor β‐receptor II protein expression in benign prostatic hyperplasia is associated with prostate volume and inflammation

What’s known on the subject? and What does the study add?

Bilan initial et suivi de l’hyperplasie bénigne de prostate : revue de littérature du CTMH de l’AFU

PURPOSE To perform an update on the initial evaluation and follow-up of benign prostatic hyperplasia (BPH). METHOD A systematic review of recent literature was performed. Level of evidence of publications was evaluated. RESULTS AND CONCLUSIONS Objectives of the initial evaluation are to assess the link between low urinary tract symptoms (LUTS) and BPH, to evaluate the bother associated to LUTS, assess a complicated bladder outlet obstruction (BOO), diagnose an adenocarcinoma of the prostate if it modifies the therapeutic strategy, and establish an evolutive profile of the disease. Clinical assessment with digital rectal examination, evaluation of symptoms by a dedicated questionnaire and urine analysis are the first steps of BPH evaluation. Bladder diary is useful to objective storage symptoms. Uroflowmetry and post-void residual volume assessment are useful if BOO is suspected. Measure of serum creatinine and ultrasound exam of the urinary tract are second line explorations. Urine cytology, neurological evaluation, urethrocystoscopy, urodynamics with pressure-flow studies are useful if the link between LUTS and BPH is unclear. PSA dosage is used for prostate cancer screening or as a prognostic marker of BPH evolution.

Traitement chirurgical de l’hyperplasie bénigne de la prostate par laser : revue de littérature du CTMH de l’AFU

PURPOSE To perform an update on the surgical treatment of benign prostatic hyperplasia (BPH) by laser. METHOD A systematic review of recent literature was performed. The level of evidence of each report was evaluated, and only recent publications of high level of evidence were included. RESULTS AND CONCLUSIONS Monopolar transurethral resection of the prostate (TURP) and open prostatectomy remain the gold standards. Alternative endoscopic options are laser photoselective vaporisation, holmium enucleation and thulium resection. These techniques seem to show functional results similar to those obtained after TURP and open prostatectomy, as well as an advantage in terms of bleeding.

Targeted therapies in non-muscle-invasive bladder cancer according to the signaling pathways.

With 300,000 annually new cases worldwide, urothelial-cell carcinoma of the bladder (UCCB) is the second most common urologic neoplasm after prostate carcinoma. Non-muscle-invasive bladder cancer (NMIBC), which is not immediately life-threatening, represents 70% to 80% of these initial cases. Despite optimal treatment (transurethral resection with intravesical chemo- or immunotherapy), 70% of these NMIBC will recur, and 10% to 20% will progress, highlighting the need for a new therapeutic approach. Indeed, the identification of patients at high risk of disease recurrence and progression would be beneficial in predicting which patients with NMIBC would benefit from strict follow-up and which would benefit from a more aggressive therapy. To date, conventional treatment remains disappointing in terms of oncologic results and morbidity. The growing understanding in tumor biology has enabled the signaling pathways involved in bladder tumorigenesis and progression to be identified, but few molecular targets have been available until now. The encouraging results seen in various human carcinomas suggests that these new agents should become part of the arsenal of drugs available in the treatment of NMIBC, alone or in combination with already known agents. In this article, we have tried to highlight the main molecular signaling pathways involved in NMIBC tumorigenesis and progression, and the potential targets useful for improving the treatment of NMIBC.

Prise en charge des patients sous traitement antithrombotique dans la résection transurétrale de prostate: étude multicentrique du CTMH de l'Afu

OBJECTIVE To determine how are managed patients with anticoagulation treatments who are operated by transuretral resection of the prostate (TURP), and to evaluate the morbidity associated to these treatments. MATERIALS AND METHODS This is a retrospective study on 226 patients operated consecutively in six french hospitals between January 2007 and August 2008 by TURP for symptomatic benign prostatic hypertrophy (BPH). RESULTS Eighty-three patients (37%) operated by TURP were under anticoagulation treatment before hospitalization. (23 cases under coumarin derivatives, 57 cases under platelet aggregation inhibitors, and three cases under low molecular weight heparin). Management of anticoagulation for the operative period was very heterogenic. Overall, patients under anticoagulation treatment had significantly longer hospitalization period (5.8 versus 4.9 days, p = 0.003) and were more frequently re-hospitalized for hematuria (14.5% versus 1.4%, p < 0.001). Considering early and late morbidity, no significant difference was observed between patients under coumarin derivatives and those under platelet aggregation inhibitors. CONCLUSIONS This study assessed the risk of anticoagulants in BPH surgery, and showed the necessity of establishing protocols and recommendations for the management of patients under anticoagulation treatment requiring BPH surgery.

Pathologies bénignes de l’ouraque chez l’adulte : origine embryologique, présentation clinique et traitements

Urachus pathologies are very rare but require to be known by urologists. Lack of appropriate treatment exposes the patients to the risks of symptoms recurrence, infectious complications or adenocarcinomatous degeneration. A partial or total defect of obliteration of the urachus channel after the fifth month of gestation can be at the origin of four benign pathologies. The ombilicovesical fistula (47.6%) is diagnosed at the native period. In the adult, the most frequent form is the cyst (30.7%) whereas the external (16.4%) and internal sinus (3.2%) are rarer. Diagnosis depends on the clinical examination and the association of sonography and TDM. The risk of complications must systematically result in proposing a surgical treatment for these benign pathologies. The umbilicus resection is not recommended, but the surgeon has to remove the urachus and its implantation base on the bladder. Laparoscopic surgery seems to be an interesting route for this intervention.

Article originalGuide de prise en charge en médecine générale des symptômes du bas appareil urinaire de l’homme liés à une hyperplasie bénigne de la prostateGuide dedicated to general practitioner for the management of lower urinary tract symptoms related to benign prostatic hyperplasia

OBJECTIVE To establish a guide dedicated to general practitioner for the diagnosis, the follow-up, and the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). METHOD Guidelines already published for urologists were modified to make them relevant for general practitioners. The role of specialists referral was defined. The whole content of the document was submitted to the formal consensus process in which urologists and general medicine teachers were involved. RESULTS Initial assessment has several aims: making sure that LUTS are related to BPH, assessing bother related to LUTS, and checking for a possible complication. Initial assessment should include: medical history, physical examination with digital rectal examination, and urinalysis. Some other explorations such as frequency volume chart, serum PSA or creatinine, and ultrasonography of the urinary tract were found optional, meaning they are necessary only in specific situations. Referring to urologist is justified when LUTS might not be related to BPH (particularly when urgencies are predominant), or when a severe bladder outlet obstruction is suspected (severe symptoms, palpable bladder, post-voiding residual volume>100ml), or when a complication is assessed. Follow-up without treatment is justified for patients with no bothersome symptoms related to not complicated BPH. Several drugs are available for the treatment of bothersome symptoms related to BPH. Alpha-blockers and plants extracts might be offered as monotherapy. Five alpha reductase inhibitors might be offered to patients with LUTS related to a significant prostate hypertrophy (>40 ml) ; they might be given for a minimum duration of one year, alone or in association with alpha-blocker. The association of antimuscarinic and alpha-blocker might be used in patients with persistent storage LUTS in spite of alpha-blocker treatment. Phosphodiesterase 5 inhibitors might be offered to patients with erectile dysfunction associated with LUTS related to BPH. In case of complicated BPH, or when medical treatment is not efficacious or not tolerated, a surgical option should be discussed. CONCLUSION The male lower urinary tract symptom committee of the French Urological Association and general practitioner present the first guide for the management of LUTS related to BPH dedicated to general practitioner. LEVEL OF EVIDENCE 5.