Philippe Paparel

Cancer de la prostate

Mutations “ciblables” dans les cancers de la prostate métastatiques Fruit de la collaboration entre de grandes institutions américaines et européennes, un groupe de chercheurs international (1) a analysé, par séquençage systémique de l’exome entier et du transcriptome, les échantillons de 150 patients atteints d’un cancer de la prostate résistant à la castration métastatique (CPRCm). Près de 90 % des hommes testés présentaient au moins 1 mutation permettant de prédire une réponse ou une résistance à des thérapies connues. Des mutations au niveau du récepteur des androgènes (RA) ont été notées chez près du tiers des patients (63 %). Les autres anomalies génomiques retrouvées le plus fréquemment concernaient les gènes de fusion ETS, TP53 et PTEN (40 à 60 % des cas) avec, par rapport aux cancers de la prostate primaires, un enrichissement des altérations du RA et de TP53. De nouvelles altérations ont été identifiées : PI3K3CA/B, R-spondin , BRAF/RAF1, APC, β-caténine, ZBTB16/PLZF. Mais la découverte sans doute la plus importante est le fait, encore une fois par rapport aux tumeurs primaires, que de nombreux patients (23 %) présentaient des mutations des gènes de la réparation de l’ADN, comme BRCA2, BRCA1 et ATM, ouvrant des perspectives thérapeutiques particulières. Ces patients pourraient répondre à des inhibiteurs de PARP, comme l’olaparib (2) .

Urinary Prostate Cancer 3 Test: Toward the Age of Reason?

The prostate cancer 3 (PCA3) gene was discovered in 1999, on the basis of differential expression between cancer and noncancerous prostate tissue. Including the first study published in 2003, 11 clinical studies have evaluated its utility for the diagnosis of prostate cancer by measuring the number of PCA3 RNA copies in urine enriched with prostate cells. Although the sensitivity of the PCA3 test was less than that of serum prostate-specific antigen (PSA), its specificity appeared to be much better, particularly in patients with a previous negative biopsy. Recent studies also have suggested that this test could be used to predict cancer prognosis.

Recommandations en Onco-Urologie 2010 : Cancer du rein

Il s’agit d’une maladie a transmission autosomique dominante, a forte penetrance (95 % a 60 ans), pour laquelle un seul gene est en cause : le gene VHL situe sur le bras court du chromosome 3 (3p25-p26) (Tableau 1) [1]. La mutation causale du gene VHL est identifiable chez presque tous les patients atteints de cette affection. Il s’agit le plus souvent de mutations ponctuelles (75 % des cas) portant sur la sequence codante, mais des microdeletions, des micro-insertions, des deletions etendues ou une hypermethylation le plus souvent du promoteur ont egalement ete observees. Plus de 150 mutations differentes ont ete repertoriees sur l’ensemble des 3 exons [3-4]. Une consultation d’oncogenetique et un typage genetique du ou des sujets atteints puis des membres de la famille permet la mise en evidence de mutations du gene VHL et l’identification des sujets predisposes a cette maladie (Niveau de preuve 1). Il est recommande de depister les enfants a partir de 5 ans. Une imagerie abdominale annuelle est souhaitable car il existe un risque de 2,7 % de decouverte par an de nouvelle lesion renale (Niveau de preuve 4) [5-6].

What is the optimum dose of type A botulinum toxin for treating neurogenic bladder overactivity

To assess the effects of two doses of botulinum toxin A (Dysport®, Ipsen‐Biotech, France; 500 and 1000 Speywood units, SU) injected into the bladder for treating incontinence due to a neurogenic overactive bladder.

The epidemiology of trauma of the genitourinary system after traffic accidents: analysis of a register of over 43,000 victims

To analyse the frequency and type of injury to the genitourinary system, by user category, after traffic accidents.

Synergistic inhibitory effect of high-intensity focused ultrasound combined with chemotherapy on Dunning adenocarcinoma

To evaluate the therapeutic effect of high‐intensity focused ultrasound (HIFU) combined with chemotherapy (paclitaxel + estramustine) on AT2 Dunning adenocarcinoma, as no satisfactory treatment for localized prostate cancer is available for patients with a poor prognosis, e.g. stage T3, a high Gleason score, or a prostate‐specific antigen level of >15u2003ng/mL.

Transvaginal cervicoisthmic cerclage as an alternative to the transabdominal technique.

OBJECTIVESnTo analyse the foetal outcome after transvaginal cervicoisthmic cerclage, to determine whether it is a valid alternative to the reference transabdominal technique.nnnSTUDY DESIGNnDescription of the vaginal operative technique, retrospective review of 20 cervicoisthmic cerclage patients from 1990 to 2000.nnnRESULTSnIn the curative group of women with a history of late pregnancy losses or premature deliveries and usually previous failed classical cervical cerclage, the foetal survival rate improved from 18% before cerclage to 79% after cerclage. No operative complications were reported. In the prophylactic group, typically characterised by the absence of the cervix as a consequence of surgery for invasive cervical cancers, the foetal survival rate was 83% after cerclage.nnnCONCLUSIONSnThe transvaginal cervicoisthmic cerclage allows a high foetal survival rate without complications in highly selected patients with poor obstetrical history. Because of its simplicity, this technique should replace the transabdominal route for surgeons experienced in vaginal surgery.

Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

PCA3 and PCA3-Based Nomograms Improve Diagnostic Accuracy in Patients Undergoing First Prostate Biopsy

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.

[CCAFU Recommendations 2013: Penile cancer].

INTRODUCTIONnMalignant tumours of the penis are rare tumours. The objective of this article is to propose guidelines for the management of these tumours.nnnMATERIAL AND METHODSnA review of the literature was performed by selecting articles on penile cancer published in PUBMED.nnnRESULTSnThe most common histological type is squamous cell carcinoma. Clinical examination of the penis is usually sufficient to assess local extension of the primary tumour, but it can be completed by MRI to assess deeper extension. Inguinal lymph nodes must be systematically palpated on both sides to assess regional extension. In the presence of palpable lymph nodes, aspiration cytology is recommended in combination with abdomen and pelvis computed tomography and (18)F-FDG PET-CT. Sentinel lymph node biopsy is recommended in the case of penile cancer at high risk of lymph node extension with no palpable lymph nodes. Treatment of the primary tumour is usually surgical. It must be as conservative as possible while ensuring negative surgical margins. Brachytherapy or local treatment (laser, cytotoxic cream, etc.) can be proposed in some cases. Bilateral lymph node chains must be systematically treated at the time of diagnosis of the disease. Inguinal lymphadenectomy alone has a curative role in patients with metastatic invasion of a single lymph node (stage pN1). In the case of more extensive lymph node involvement, multimodal management combining chemotherapy, surgery and possibly radiotherapy, must be considered.nnnCONCLUSIONnThe treatment of penile cancer is usually surgical possibly in combination with chemotherapy in the presence of lymph node extension. The main prognostic factor is lymph node involvement, requiring appropriate management right from the time of diagnosis.