C. Bastide

Recommandations en onco-urologie 2013 du CCAFU : Cancer de la prostate

OBJECTIVES The purpose of the guidelines national committee CCAFU was to propose updated french guidelines for localized and metastatic prostate cancer (PCa). METHODS A Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of PCa, to evaluate different references with levels of evidence. RESULTS Epidemiology, classification, staging systems, diagnostic evaluation are reported. Disease management options are detailed. Recommandations are reported according to the different clinical situations. Active surveillance is a major option in low risk PCa. Radical prostatectomy remains a standard of care of localized PCa. The three-dimensional conformal radiotherapy is the technical standard. A dose of > 74Gy is recommended. Moderate hypofractionation provides short-term biochemical control comparable to conventional fractionation. In case of intermediate risk PCa, radiotherapy can be combined with short-term androgen deprivation therapy (ADT). In case of high risk disease, long-term ADT remains the standard of care. ADT is the backbone therapy of metastatic disease. In men with metastases at first presentation, upfront chemotherapy combined with ADT should be considered as a new standard. In case of metastatic castration-resistant PCa (mCRPC), new hormonal treatments and chemotherapy provide a better control of tumor progression and increase survival. CONCLUSIONS These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.

Incidence, Risk Profile and Morphological Pattern of Lower Extremity Venous Thromboembolism After Urological Cancer Surgery

PURPOSE We examined the incidence of asymptomatic and symptomatic lower extremity venous thromboembolism in patients who underwent urological surgery for cancer, and identified preoperative and operative risk factors predictive of the thromboembolism. MATERIALS AND METHODS A cohort of 583 consecutive patients undergoing urological cancer surgery was prospectively assessed using complete lower limb ultrasound at postoperative day 7 from January 2005 to July 2009. In all patients heparin and mechanical thromboprophylaxis were prescribed until complete ambulation. Potential variables predictive of venous thrombosis were analyzed. RESULTS Complete data were available in 538 patients (463 male and 75 female), of whom 177 underwent nephrectomy, 86 radical cystectomy and 275 radical prostatectomy. A total of 40 deep venous thrombosis cases were found (7.4%), most of which were asymptomatic (92%) and limited to deep calf veins (80%). Of those asymptomatic deep venous thrombosis cases 86% were limited to deep calf veins. In all, 12 pulmonary embolisms were diagnosed, of which 4 were lethal. On multivariate analysis history of venous thromboembolism (OR 5.16, p = 0.02) and radical cystectomy (OR 3.47, p = 0.002) were independently associated with venous thromboembolism. CONCLUSIONS Lower extremity venous thromboembolism has a high rate of occurrence after urological surgery for cancer despite the recommended venous thromboembolism prophylaxis. Most cases are asymptomatic and limited to deep calf veins. Our results suggest that complete lower limb ultrasound should be performed early after radical cystectomy and in patients with a personal history of venous thromboembolism.

Positive surgical margins and their locations in specimens are adverse prognosis features after radical cystectomy in non-metastatic carcinoma invading bladder muscle: results from a nationwide case–control study

Positive surgical margin (PSM) frequency after radical cystectomy has been estimated to be 4–15%. Studies that have not distinguished between the different sites of PSM have failed to show that they are an independent prognostic factor for disease‐free survival. Only perivesical soft tissue PSMs have been associated with an increased risk of cancer recurrence and cancer‐specific death. This is the first comprehensive published analysis of PSMs occurring during radical cystectomy for pTx pN0 M0 bladder cancer according to their location, comparing their cancer‐specific survival (CSS) and other outcomes with those of a control group paired according to TNM status, age, sex and urinary diversion method. Local recurrence‐free survival rates were found to be lower in patients with both soft tissue and urethral PSMs. Moreover, soft‐tissue PSMs were associated with lower metastatic recurrence‐free and CSS rates.

Adrenomedullin Blockade Suppresses Growth of Human Hormone-Independent Prostate Tumor Xenograft in Mice

Purpose: To study the role of the adrenomedullin system [adrenomedullin and its receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent growth. Experimental Design: Androgen-dependent and -independent prostate cancer models were used to investigate the role and mechanisms of adrenomedullin in prostate cancer hormone-independent growth and tumor-associated angiogenesis and lymphangiogenesis. Results: Adrenomedullin and AMR were immunohistochemically localized in the carcinomatous epithelial compartment of prostate cancer specimens of high grade (Gleason score >7), suggesting a role of the adrenomedullin system in prostate cancer growth. We used the androgen-independent Du145 cells, for which we demonstrate that adrenomedullin stimulated cell proliferation in vitro through the cAMP/CRAF/MEK/ERK pathway. The proliferation of Du145 and PC3 cells is decreased by anti-adrenomedullin antibody (αAM), supporting the fact that adrenomedullin may function as a potent autocrine/paracrine growth factor for prostate cancer androgen-independent cells. In vivo, αAM therapy inhibits the growth of Du145 androgen-independent xenografts and interestingly of LNCaP androgen-dependent xenografts only in castrated animals, suggesting strongly that adrenomedullin might play an important role in tumor regrowth following androgen ablation. Histologic examination of αAM-treated tumors showed evidence of disruption of tumor vascularity, with depletion of vascular as well as lymphatic endothelial cells and pericytes, and increased lymphatic endothelial cell apoptosis. Importantly, αAM potently blocks tumor-associated lymphangiogenesis, but does not affect established vasculature and lymphatic vessels in normal adult mice. Conclusions: We conclude that expression of adrenomedullin upon androgen ablation in prostate cancer plays an important role in hormone-independent tumor growth and in neovascularization by supplying/amplifying signals essential for pathologic neoangiogenesis and lymphangiogenesis. Clin Cancer Res; 19(22); 6138–50. ©2013 AACR.

Intérêts des ponctions biopsies rénales percutanées dans la prise en charge des tumeurs solides du rein inférieures ou égales à 4 cm

OBJECTIVE To assess the value of diagnostic percutaneous kidney biopsy of solid renal tumours less or equal to 4 cm and its impact on management. MATERIALS AND METHOD From January 2001 to October 2006, all solid renal tumours less or equal to 4 cm were systematically assessed by CT-guided percutaneous biopsy: 66 tumours were biopsied in 65 patients (one bilateral tumour) and four patients had a second biopsy. A total of 70 biopsies were performed. RESULTS Among the biopsies, 18% (12/66) were not contributive. Four were repeated and provided a diagnosis in 50% of cases. Two patients with non contributive biopsies were lost to follow-up. Seven benign tumours (10.9%) and 54 malignant tumours were diagnosed. The kidney biopsy diagnosed 91% (52/57) of malignant tumours and 57% (4/7) of benign tumours. The concordance between biopsy results and pathology results was 90.7% for histological type of tumour and 64% for Fuhrman nuclear grade. Histological type and tumour grade had no impact on the type of surgery performed (51 patients operated, 29 kidney-preserving procedures, by necessity in seven cases). Four patients (6.3%) in whom a benign tumour was diagnosed on biopsy were simply followed, thereby avoiding surgery. CONCLUSION This series revealed 10.9% of benign tumours, only 57% of which were diagnosed by biopsy. Management was modified for only four patients (6.3%). Kidney biopsy remains an option in the pretreatment assessment of renal tumours less or equal to 4 cm, but cannot be proposed systematically.

TP53INP1 overexpression in prostate cancer correlates with poor prognostic factors and is predictive of biological cancer relapse.

Tumor protein 53‐induced nuclear protein 1 (TP53INP1) is a proapoptotic protein involved in cell stress response. Whereas there is an overexpression of TP53INP1 in numerous tissues submitted to stress agents, TP53INP1 is down‐expressed in stomach, pancreatic, and inflammation–mediated colic carcinomas. In medullary thyroid carcinomas, TP53INP1 overexpression correlates with poor prognosis. TP53INP1 expression has never been reported in Prostate Cancer (PC). Our aim was to investigate variations of TP53INP1 expression and their correlation to clinicopathological parameters in PC.

Primary malignant melanoma of the adrenal gland

Abstract  Primary malignant melanoma of the adrenal gland is an established entity. Fewer than 20 cases have been reported in the published literature. Because of the high frequency of adrenal gland metastases from malignant melanoma and pigmented pheochromocytoma, several rigid diagnostic criteria have been established for accepting an adrenal melanoma as primary. A new case is reported in this article. This observation is an opportunity update the literature on the diagnostic difficulties in this rare pathology.

Marges après prostatectomie totale : aspects techniques et valeur pronostique

The status of surgical margins after radical prostatectomy is a major prognostic factor. The role of several technical aspects of radical prostatectomy, such have surgical access, bladder neck preservation or neurovascular bundle sparing, in generating supplementary positive margins has been controversial for many years. Positive margins along with other poor prognostic factors are important elements in the decision to perform adjuvant therapy after radical prostatectomy. This review of the literature, based on a Medline search, was designed to update these various issues encountered by urologists in their everyday practice.

Cancer de la prostate à haut risque de progression. Article de revue du comité de cancérologie de l’association française d’urologie

INTRODUCTION Localized prostate tumors have various clinical, biological and histopathological characteristics that lead to different progression profiles. High-risk prostate cancer has been classically defined by clinical examination, PSA levels and histopathological data. High-risk prostate cancer has usually a worse outcome, but classic stratification predictive of outcome for prostate cancer is a matter of debate concerning its accuracy. METHODS A systematic review of the literature on high-risk prostate cancer over the 15 last years was carried out on Medline database. The literature selection was based on evidence and practical considerations. RESULTS A great deal of scientific work have been deployed to prove that high-risk prostate cancer should be approached by teamwork including radio-hormone therapy, systemic treatment with long term use of LH-RH and a radical prostatectomy with adequate lymph node dissection. Selection of patients is essential to define individualized therapeutic strategy and timing for every modality should come as a consensus of medical supported evidence. CONCLUSION Accurate patient selection and multimodal treatment offer the best therapeutic option in high-risk prostate cancer.

Les médicaments de la médecine sexuelle

AIM To describe drugs used in sexual medicine. METHOD Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). RESULTS 5PDIs and intracavernous injection of alprostadil are first- and second-line therapies of erectile dysfunction. Dapoxetine is the first specific and approved treatment of premature ejaculation. Androgene supplementation improves sexual desire among patient with hypogonadism as much as initial serum testosterone levels are low. Female sexual dysfunctions pharmacology is to date less developed, although candidate drugs reach phase III clinical studies. CONCLUSION Pharmacology is one but not the only therapeutic avenue in sexual medicine. Despite real breakthrough such as 5PDIs for erectile dysfunction, incomplete knowledge and understanding of physiology, pathophysiology and pharmacology of human sexual function reduces its development particularly for women.