Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

Cytotoxic chemotherapy is an effective treatment for invasive breast cancer. However, experimental studies in mice also suggest that chemotherapy has pro-metastatic effects. Primary tumours release extracellular vesicles (EVs), including exosomes, that can facilitate the seeding and growth of metastatic cancer cells in distant organs, but the effects of chemotherapy on tumour-derived EVs remain unclear. Here we show that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity. Chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca2+-dependent protein that promotes NF-κB-dependent endothelial cell activation, Ccl2 induction and Ly6C+CCR2+ monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis. Genetic inactivation of Anxa6 in cancer cells or Ccr2 in host cells blunts the prometastatic effects of chemotherapy-elicited EVs. ANXA6 is detected, and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy

Place des ultrasons focalisés de haute intensité dans le traitement des cancers localisés de prostate (échecs de radiothérapie exclus) (à propos de 145 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mid-term results demonstrate salvage high-intensity focused ultrasound (HIFU) as an effective and acceptably morbid salvage treatment option for locally radiorecurrent prostate cancer.

BACKGROUND: Local occurrence of prostate cancer (PCa) after external beam radiation (EBRT) may benefit from definitive local therapy. OBJECTIVE: To evaluate the safety and efficacy of salvage high-intensity focal ultrasound (HIFU) in local PCa recurrence after EBRT and to determine prognostic factors for optimal patient selection. DESIGN, SETTING, AND PARTICIPANTS: Between 1995 and 2006, patients with a local PCa recurrence after EBRT were retrospectively included. INTERVENTION: All patients received salvage HIFU with the Ablatherm device. MEASUREMENTS: Prognostic factors (pre-EBRT risk group, androgen-deprivation [AD] use, pre-HIFU prostate-specific antigen [PSA], Gleason score and positive biopsy percentage) were studied in univariate and multivariate analyses. Progression was defined as positive biopsy and/or last PSA > nadir + 2 ng/ml and/or adjuvant therapy introduction. All complications were recorded. RESULTS AND LIMITATIONS: Some 194 HIFU sessions for 167 patients were performed. Local cancer control was achieved with negative biopsy results in 122 (73%) patients. The median PSA nadir was 0.19 ng/ml. The mean follow-up period was 18.1 mo (range: 3-121 mo). Seventy-four patients required no hormone therapy. The actuarial 5-yr overall survival rate was 84%. The actuarial 3-yr progression-free survival rate was significantly lower in three circumstances: (1) worsening of the pre-EBRT stage with 53%, 42%, and 25% for low-, intermediate-, and high-risk patients, respectively, (2) increase in the pre-HIFU PSA, and (3) use of AD during PCa management. In multivariate analyses, the risk ratio for intermediate- and high-risk patients were 1.32 and 1.96, respectively. The risk ratio was 2.8 if patients had received AD. No rectal complications were observed. Urinary incontinence accounted for 49.5% of the urinary sphincter implantations required in 11% of patients. This is a retrospective study in which the role of the PSA doubling time and the time until recurrence was not evaluated. CONCLUSIONS: Salvage HIFU is a curative treatment option for local relapse after EBRT with acceptable morbidity. Careful patient selection is imperative depending upon the aforementioned prognostic factors

Incontinence urinaire à la toux au cours des pneumopathies interstitielles diffuses

National audienceIntroduction Urinary stress incontinence affects 10% to 30% of the female population and may have a major impact on psychosocial health. In interstitial lung disease, chronic cough may lead to development of urinary incontinence, but the prevalence and impact of this symptom are unknown. Objectives To determine the rate and impact of urinary stress incontinence among women with chronic cough due to interstitial lung disease. Methods 28 female patients with chronic cough secondary to interstitial lung disease and 15 controls were evaluated by questionnaires to determine the prevalence of cough-related urinary incontinence, its severity, and its impact on quality of life. Results Cough-related urinary incontinence was present in 14/28 patients with interstitial lung disease and chronic cough (50%), but in only 1/15 controls (7%, p=0.005). On a 5-points quality of life scale, the median impact of urinary incontinence was 3 (minimum = 1, maximal = 5), and the median impact of chronic cough was 3.5. The majority of patients (64%) believed that incontinence was a natural phenomenon due to ageing, all were ashamed by this symptom and 79% were unable to mention it to their caring physician. Only one physician had previously addressed this issue. Conclusion Cough-related urinary incontinence is common in patients with interstitial lung disease and is largely overlooked. It may significantly alter quality of life. A systematic questioning by the physician would allow to promptly refer these patients for appropriate therapeutic interventions, such as perineal training.Introduction L’incontinence urinaire d’effort, dont la prévalence est estimée à 10-30 % dans la population féminine, peut avoir un retentissement psychosocial majeur. Dans les pneumopathies interstitielles diffuses (PID), la toux chronique peut favoriser l’apparition d’une incontinence urinaire, mais la prévalence et les conséquences de ce symptôme ne sont pas connues. Objectif Déterminer la fréquence et l’impact de l’incontinence urinaire chez les femmes présentant une toux chronique au cours d’une PID. Méthodes Vingt-huit patientes présentant une toux chronique associée à une PID et 15 patientes contrôles ont été interrogées à l’aide de questionnaires pour évaluer l’existence d’une incontinence urinaire d’effort, sa sévérité (questionnaire K. Bo Index), et son retentissement sur la qualité de vie (questionnaire Ditrovie). Résultats Une incontinence urinaire à la toux était présente chez 14/28 patientes ayant une PID avec toux chronique (50 %) mais chez seulement 1/15 patientes contrôles (7 %, p = 0,005). Sur une échelle de qualité de vie à 5 points, l’impact médian de l’incontinence urinaire était de 3 (aucun = 1, maximal = 5) et l’impact médian de la toux était de 3,5. La majorité des patientes (64 %) pensaient que l’incontinence était un phénomène naturel accompagnant le vieillissement, toutes éprouvaient un sentiment de honte vis-à-vis de leur incontinence et 79 % n’osaient pas en parler à leur médecin. Seul un médecin avait abordé ce problème auparavant. Conclusion L’incontinence urinaire à la toux est fréquente au cours des PID et largement méconnue. Elle peut entraîner une altération importante de la qualité de vie. Sa recherche systématique à l’interrogatoire permettrait d’orienter rapidement les patientes vers un traitement approprié, telle que la rééducation périnéale

Control of prostate cancer by transrectal HIFU in 227 patients.

International audiencePURPOSE: To evaluate the results of high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer with reference to disease-related prognostic factors. MATERIALS AND METHODS: Patients with T1-2 localized prostate cancers, prostate specific antigen (PSA

Avancées et synthèse des derniers congrès : ASCO-GU, EAU, AUA, ASCO concernant la prise en charge médicale du cancer du rein localement avancé ou métastatique. [Progress and summary of recent congress: ASCO-GU, EAU, AUA, ASCO about the medical management of locally advanced or metastatic kidney cancer]

International audienceDuring the recent congress of urology and oncology key topics discussed were the evolution of survival data in metastatic kidney cancer which median is now around 40 months, persistent questions about the role of nephrectomy, including access to the systemic treatment of nephrectomized patients and tumor resectability induced by systemic therapies, the emergence of new prognostic models which are adapted to new therapeutic standards, and the emergence of promising new drugs including pazopanib. This article describes these advances

Kystes atypiques et tumeurs kystiques du rein : considérations anatomopathologiques, radiologiques et chirurgicales. Conclusions du forum AFU 2007. [Atypical cysts and cystic tumours of the kidney: Histological, radiological and surgical considerations. Conclusions of the AFU 2007 forum.]

International audienceMalignant tumours may have a cystic appearance. They are dominated by multilocular cystic renal cell carcinoma, usually low-grade, which rarely metastasize. The Bosniak classification distinguishes non suspicious lesions (type I and II) from suspicious lesions (type III and IV) requiring resection and lesions requiring follow-up (type IIF). The main feature suggestive of malignancy is the enhancement of the septa and the walls of the cyst. Renal cysts classified as IIF require surveillance by contrast-enhanced imaging (CT, MRI or ultrasound). The treatment of cystic tumours is based on surgery. Partial nephrectomy is recommended in this type of tumour regardless of the size. Laparoscopy is a validated technique in experienced hands. Aspiration is not very effective for the treatment of benign cysts, but may be useful for diagnosis. Surgical resection of the roof of the cyst is the most effective technique