Kasivisvanathan V., Jichi F., Klotz L., Villers A., Taneja S. S., Punwani S., Freeman A., Emberton M., Moore C. M.   A multicentre randomised controlled trial assessing whether MRI-targeted biopsy is non-inferior to standard transrectal ultrasound guided biopsy for the diagnosis of clinically significant prostate cancer in men without prior biopsy: a study protocol.  BMJ Open.  2017 ;7 :e017863

INTRODUCTION: The classical pathway for the diagnosis of prostate cancer is transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the basis of a raised prostate-specific antigen (PSA). An alternative pathway is to perform multi-parametricMRI (MPMRI) to localise cancer and to use this information to influence the decision for, and conduct of, a subsequent biopsy, known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a similar or greater amount of clinically significant cancer as TRUS biopsy but has several advantages, including the potential to biopsy fewer men with fewer cores. METHODS: This is a pragmatic, international, multicentre, parallel group randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically significant cancer.Men in the MRI arm will undergo targeted biopsy of suspicious areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in the TRUS biopsy will undergo a standard 10-12-core TRUS biopsy. The main inclusion criteria are a serum PSA

Olariu R., Denoyelle J., Leclere F. M., Dzhonova D. V., Gajanayake T., Banz Y., Hayoz M., Constantinescu M., Rieben R., Vogelin E., Taddeo A.   Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation.  J. Surg. Res..  2017 ;218 :49-57

BACKGROUND: Immunosuppressive therapies derived from solid organ transplantation are effective in promoting survival of vascularized composite allotransplantation (VCA), but they cause serious side effects that are difficult to justify for this non-life-saving procedure. Unlike solid organ transplantation, hand and face transplants offer the possibility of site-specific immunosuppression for reducing systemic exposure while increasing intra-graft concentrations of the drug. Therefore, in this study, we tested whether a single intra-graft injection tacrolimus could promote VCA survival. METHODS: Brown Norway-to-Lewis hind limb transplantations were performed, and animals were left untreated (group I), treated with a daily injection of 1-mg/kg tacrolimus for 21 days (group 2) or injected with 7-mg tacrolimus directly into the transplanted limb on day 1 (group III). Graft rejection was monitored, and animals were sacrificed at grade 3 rejection or 200 days after transplantation. RESULTS: Intra-graft injection of tacrolimus significantly prolonged allograft survival as compared to untreated animals or animals treated with systemic tacrolimus. Half of the intra-graft-treated rats rejected their graft on average at day 70.5. Interestingly, the other half remained rejection-free for more than 200 days without signs of kidney or liver toxicity. In these animals, tacrolimus was detected in the VCA skin but not in the blood until day 200. Long-term survival was not linked to induction of donor-specific tolerance but to a higher level of lymphocyte chimerism. CONCLUSIONS: Intra-graft delivery of tacrolimus may promote VCA survival by increasing tissue drug availability and promoting the establishment of transient chimerism and thus long-term graft acceptance.

Leroy H. A., Vermandel M., Leroux B., Duhamel A., Lejeune J. P., Mordon S., Reyns N.   MRI assessment of treatment delivery for interstitial photodynamic therapy of high-grade glioma in a preclinical model.  Lasers Surg Med.  2017 ;50 :460-468

BACKGROUND: High-grade gliomas are primary brain tumors that have shown increasing incidence and unfavorable outcomes. Local control is crucial to the management of this pathology. Photodynamic therapy (PDT), based on the light-induced activation of a photosensitizer (PS), achieves local treatment by inducing selective lesions in tumor tissue. OBJECTIVES: Previous studies have reported the outcomes of PDT for glioblastoma via immunohistological data. Our study aimed to evaluate MRI findings, including diffusion, and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation. MATERIALS AND METHODS: Twenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers. RESULTS: Elevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (P = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm(3) versus 2.67 mm(3) , P < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (P < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (P = 0.01). CONCLUSION: Diffusion and perfusion MRI revealed histological lesions. Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT. Lasers Surg. Med. 50:460-468, 2018. (c) 2017 Wiley Periodicals, Inc.

Antoine J. M., Azria E., Barranger E., Belaisch-Allart J., Boutet G., Buisson O., Canis M., Chene G., Christin-Maitre S., Collinet P., Deval B., Gallot D., Homasson N., Kayem G., Leblanc E., Madelenat P., Marret H., Mathelin C., Mimoun S., Panel P., Pirot F., Quarello E., Salomon L., Sentilhes L., Sifer C., Simon E., Simon-Bouy B., Yazbeck C.   Roots and wings.  Gynecol. Obstet. Fertil. Senol..  2017 ;45 :1-2
Deshayes E., Roumiguie M., Thibault C., Beuzeboc P., Cachin F., Hennequin C., Huglo D., Rozet F., Kassab-Chahmi D., Rebillard X., Houede N.   Radium 223 dichloride for prostate cancer treatment.  Drug Des. Dev. Ther..  2017 ;11 :2643-2651

Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo((R))) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases. In this review, first we summarize the interplay between prostate tumor cells and bone microenvironment; then, we discuss radium-223 dichloride mechanism of action and present the results of the available clinical trials and future developments for this new drug.

Durand M., Jain M., Robinson B., Aronowitz E., El Douahy Y., Leung R., Scherr D. S., Ng A., Dominique D., Amiel J., Spincemaille P., Villers A., Ballon D. J.   Magnetic resonance microscopy may enable distinction between normal histomorphological features and prostate cancer in the resected prostate gland.  BJU Int..  2017 ;119 :414-423

OBJECTIVES: To determine imaging protocol parameters for characterization of prostate tissue at histological length scales. MATERIAL AND METHODS: Rapid acquisition with relaxation enhancement, spin echo and gradient echo fast low angle shot data were acquired using ex vivo 3-Tesla or 7-Tesla magnetic field strengths from fresh prostatectomy specimens (n = 15) obtained from either organ donor or patients with prostate cancer (PCa). To achieve the closest correspondence between histopathological components and magnetic resonance imaging (MRI) results, in terms of resolution and sectioning planes, multiple high-resolution imaging protocols (ranging from a few minutes to overnight) were tested. Ductograms were generated as part of image post-processing. Specimens were subsequently submitted for histopathological evaluation. RESULTS: A total of seven imaging protocols were tested. Ex vivo 7-Tesla MRI identified normal components of prostate glands, including ducts, blood vessels, concretions and stroma at a spatial resolution of 60 x 60 x 60 mum(3) to 107 x 107 x 500 mum(3) . Malignant glands and nests of tumour cells identified at 60 x 60 x 90 mum(3) were highly similar to low-magnification (x2) histopathology. Ductograms enhanced the differentiation between benign and malignant glands. The results of the present study were encouraging, and further work is warranted with a larger sample size. CONCLUSION: We showed that critical histopathological features of the prostate gland can be identified with high-resolution ex vivo MRI examination and this offers promise that MRI microscopy of PCa will ultimately be possible in vivo.

Ferracci F. X., Gilard V., Cebula H., Magne N., Lejeune J. P., Langlois O., Proust F.   Growth of giant intracranial aneurysms: An aneurysmal wall disorder?.  Neurochirurgie.  2017 ;63 :6-12

The enlargement of giant intracranial aneurysms (IA) can be observed in 30 % of cases resulting in a neurological deficit and epilepsy due to its mass effect. This growth process could be due to a morphological disorder of the IA wall. The authors report on 2 cases of giant IA growth responsible for intracranial hypertension. The treatment of these giant IA required a microsurgical excision combined with a series of cerebral revascularization procedures. The role of vasa vasorum on the inflammatory granuloma outside the vessel, which induced the enlargement, is discussed. These cases illustrate the abluminal vasculopathy as the main involvement of this unfavourable natural history.

Leroy A., Azaïs H., Giraudet G., Cosson M.   Quality of life and symptoms before and after surgical treatment of rectovaginal fistula.  Prog. Urol..  2017 ;27 :229-237

INTRODUCTION: Rectovaginal fistula requires a complex management because it has an important psychological impact associated with impaired quality of life of patients. Thus, the aim of our study was to evaluate the improvement of the quality of life of patients after surgical management. METHODS: This is a retrospective study. We included patients operated between 2009 and 2014 for the treatment of a rectovaginal fistula, whose data were available and who agreed to answer a questionnaire. We evaluated the satisfaction of short-term and long-term patients on the answer to the basic PFDI-20 and PFIQ-7 questionnaires. We then evaluated whether there was an improvement in symptoms and quality of life after surgery. RESULTS: Nine patients were included but only 4 patients completed the PFDI-20 and PFIQ-7 questionnaires. Fistula was secondary to either surgical intervention (44%, n=4) or complicated perineal tear (44%, n=4) or unknown cause (11%, n=1). After surgery, we found the short term a significant decrease in stool incontinence, as there was no stool incontinence (0/5) in the postoperative period, while preoperatively 55% (5/9) (P=0.03). Postoperatively, 33% (3/9) of the patients had genital discomfort and 44% (4/9) had gas incontinence compared to 0% preoperatively (P=0.2 and P=0.6). There appears to be an improvement in pelvic static disorders after surgical management. However, we found a slight improvement in nauseous leucorrhoea in the immediate postoperative period, as the prevalence decreased from 33% (3/9) preoperatively to 22% (2/9) postoperatively (P>0.9). In the long term, we observed an improvement in the sensation of perineal heaviness and gas incontinence because only 25% (1/4) of the 75% (3/4) preoperative patients still showed slight discomfort (P=0.5). The quality of life and the emotional state of the patients were no altered postoperatively. Indeed, preoperatively, 50% (2/4) of the patients reported anxiety compared to 0% (0/4) postoperatively (P=0.4). Similarly, 75% (3/4) complained of a decrease in their quality of life (social, sports, etc.) preoperatively compared with 0% (0/4) postoperatively (P>0.9). CONCLUSION: A simple surgical management of rectovaginal fistulas would allow a significant decrease in stool incontinence and improved quality of life and their emotional state, which confirms the beneficial effect of this therapeutic strategy. LEVEL OF EVIDENCE: 4.

Azaïs H., Estevez J. P., Foucher P., Kerbage Y., Mordon S., Collinet P.   Dealing with microscopic peritoneal metastases of epithelial ovarian cancer. A surgical challenge.  Surg. Oncol.-Oxf..  2017 ;26 :46-52

Understanding biology and progression mechanisms of peritoneal metastases of epithelial ovarian cancer (EOC) is a cornerstone in the knowledge and the comprehensive management of the disease. Despite clinical remission after the association of complete cytoreductive surgery and platinum-based chemotherapy, peritoneal recurrence still occurs in 60% of patients. Eligible studies, published from 1980 to June 2016, were retrieved through ClinicalTrials.gov, MEDLINE, Cochrane databases and bibliography searches. We reviewed all publications that deals with microscopic peritoneal metastases of EOC in French and English. To discuss expected benefits of intraperitoneal (IP) chemotherapy, fluorescence-guided surgery or IP photodynamic therapy, we reviewed most recent and relevant studies. The final reference list was generated on the basis of originality and relevance to the broad scope of this review. Published data concerning early-stage ovarian cancer suggest that occult peritoneal or epiploic metastases are present in 1.2%-15.1% of cases. In the frequent case of advanced-stage disease, residual microscopic lesions are ignored by conventional surgery. We are convinced that microscopic peritoneal metastases are a relevant surgical therapeutic target. This article discusses existing data on microscopic peritoneal metastases, the treatment indications, the diagnostic and therapeutic surgical approaches to be developed and their expected benefits. A local therapeutic strategy to target microscopic lesions is needed in addition to complete macroscopic cytoreductive surgery to decrease the rate of peritoneal recurrence. Intraperitoneal chemotherapy, and targeted photodynamic therapy could play a role in this new paradigm. The roles of these different options must be defined by future researches.

Zairi F., Aboukais R., L. E. Rhun E, Marinho P., Maurage C. A., Lejeune J. P.   Close follow-up after discontinuation of cyproterone acetate: a possible option to defer surgery in patients with voluminous intracranial meningioma.  J. Neurosurg. Sci..  2017 ;61 :98-101