Azaïs H., Frochot C., Grabarz A., Khodja Bach S., Colombeau L., Delhem N., Mordon S., Collinet P.   Specific folic-acid targeted photosensitizer. The first step toward intraperitoneal photodynamic therapy for epithelial ovarian cancer.  Gynecol. Obstet. Fertil. Senol..  2017 ;45 :190-196

OBJECTIVE: Epithelial ovarian cancer (EOC) management remains association of debulking surgery in combination with platinum-based chemotherapy. Sixty percent of women with EOC considered in remission will develop recurrent disease. An option to improve the completion of cytoreductive surgery may be the use of photodynamic therapy to induce necrosis of peritoneal metastases. A limit of this technique was the toxicity induced by the lack of specificity of old-generation photosensitizer (PS) for tumor tissue if the light could not be specifically applied. To solve this problem, a solution is the design of selective PS. Folate receptor is a promising target for EOC targeted therapy. We present preclinical results concerning properties of a folic-acid targeted photosensitizer. METHOD: Preclinical studies have been performed in vitro on murine and human cell lines of EOC and in vivo with a preclinical model of peritoneal carcinomatosis (Fisher F344 rat/NuTu-19 cell line). They aimed to precise the ability of PS to target specifically tumor tissue, to emit specific fluorescence, and to obtain cell death. RESULTS: Tissue quantification of the PS showed specific incorporation of the folate-targeted PS within tumor tissue. Specificity for ovarian cancer metastases is better than previously reported with others photosensitizers (tumor-to-normal tissue ratio 9.6). We could detect specific fluorescence in vitro and in vivo on peritoneal metastases. Folic-acid targeted PDT allows to obtain human EOC cells death. CONCLUSION: Specific PS may allow the development of efficient and safe intraperitoneal PDT procedure, which could play a role in the prevention of EOC peritoneal recurrences.

Vidmar R., Marcq G., Flamand V., Fantoni J. C., Hénon F., Villers A., Ouzzane A.   Salvage radical prostatectomy for recurrent prostate cancer. Morbidity, oncological and functional results.  Prog. Urol..  2017 ;27 :458-466

INTRODUCTION: Salvage radical prostatectomy (sRP) for radiorecurrent prostate cancer (PCa) is a challenging procedure. To report our experience with sRP for selected patients with local recurrence after primary treatment for localised PCa. METHODS: From 2005 to 2015, 24 patients underwent sRP for recurrent PCa in our center and were included in this retrospective study. Local recurrence was suspected by PSA increase>nadir+2ng/mL and was confirmed by biopsy. Perioperative complications according to Clavien-Dindo classification, oncological and functional results were analysed. RESULTS: Overall, 24 patients with a median age of 59 years (IQR: 55-60) were included. Median follow-up was 25 months (IQR: 9-26). Procedures were performed with open-retropubic approach in 50 % and robot-assisted laparoscopic approach in 50 %. Overall, 5 (21 %) and 2 (8 %) patients experienced grade/=IIIb postoperative complication, respectively. Surgical margins were positive in 46 % of cases. Three out of 4 patients with postoperatively detectable PSA (>0.2ng/mL) had positive surgical margins. Seven patients experienced biochemical recurrence in a median delay of 19 months (9-62). Seventy-one percent (5) of these patients experienced clinical recurrence in a median delay of 24 months (10-113). Severe urinary incontinence (>/=3 pads/day) and erectile dysfunction were reported in 25 % and 63 %, respectively. CONCLUSION: sRP for patients is a feasible procedure with encouraging local control rate and acceptable morbidity. This technique should be discussed as a treatment option for locally recurrent PCa in well-selected patients. LEVEL OF EVIDENCE: 4.

Reyns N., Leroy H. A., Delmaire C., Derre B., Le-Rhun E., Lejeune J. P.   Intraoperative MRI for the management of brain lesions adjacent to eloquent areas.  Neurochirurgie.  2017 ;63 :181-188

BACKGROUND: The aim of our study was to report the usefulness of intraoperative MRI guidance in the resection of brain lesions adjacent to eloquent areas. PATIENTS AND METHODS: A single center prospective series of gliomas amenable to optimized resection with intraoperative MRI between September 2014 and December 2015. RESULTS: The study included 56 patients. The median duration of the first intraoperative MRI was 38min, interquartile range (IQR 30-46). Fourteen patients (40%) underwent a second intraoperative MRI, which had a median duration of 26min (IQR, 18-30). The median total operative time was 265min (IQR, 242-337). After the first intraoperative MRI, the median residual glioma volume of the 35 gliomas adjacent to eloquent areas was 7.04cm(3) (IQR, 2.22-13.8), which did not significantly differ from the other gliomas (P=0.07). After the second intraoperative MRI, the median residual glioma volume was 3.86cm(3) (IQR, 0.82-6.99), which did not significantly differ from the other patients (P=0.700). On the postoperative MRI, the median extent of the glioma resections adjacent to eloquent areas was 99.78% (IQR, 88.9-100), which was not significantly different from the rest of the population (P=0.290). At 6 months after surgery, the median Karnofsky Performance Score was 90, and 2.8% of the patients presented a permanent new neurological deficit. CONCLUSION: Our results suggest that intraoperative MRI is an effective and safe technique to improve the extent of brain lesion resections close to eloquent areas.

Le Guern A., Touzet-Huffman L., Greliak A., Mortier L.   Decisions to limit or withdraw treatment in young adults with melanoma.  J. Eur. Acad. Dermatol. Venereol..  2017 ;31 :E521-E522
Bruinsma S. M., Roobol M. J., Carroll P. R., Klotz L., Pickles T., Moore C. M., Gnanapragasam V. J., Villers A., Rannikko A., Valdagni R., Frydenberg M., Kakehi Y., Filson C. P., Bangma C. H.   Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure.  Nat. Rev. Urol..  2017 ;14 :312-+

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if >/=70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.

Mesdag V., Regis C., Tresch E., Chauvet M. P., Boulanger L., Collinet P., Giard S.   Nipple sparing mastectomy for breast cancer is associated with high patient satisfaction and safe oncological outcomes.  J. Gynecol. Obstet. Hum. Reprod..  2017 ;46 :637-642

BACKGROUND: The preservation of the nipple areolar complex (NAC) for cancer treatment is still a matter of debate because of suspected increase of local recurrence and surgery-specific complications. The aim of the study was to investigate both the relapse risk associated with nipple sparing mastectomy (NSM) for breast cancer and women's satisfaction with preservation of the NAC. METHODS: We included retrospectively all patients who had skin-sparing mastectomy (SSM) or NSM from 2007 to 2012 for breast cancer or ductal carcinoma in situ (DCIS). We compared NSM and SSM group for oncological and surgical outcomes. Patients' satisfaction and quality of life has been evaluated by a specifically designed questionnaire. RESULTS: We included 63NSM (41.5%) and 89SM (58.5%). Eighty-nine (58.6%) patients had DCIS, and the other had small invasive disease. Median follow-up was 42 (IQR: 18-58) months. Local recurrence rate was 1.7% (n=1) in the NSM group and 0% in the SSM group without recurrence in the preserved nipple. After NSM, one patient had complete NAC necrosis, and three patients suffered partial necrosis. Satisfaction with the NAC was higher in the NSM group compared to the SSM group with delayed reconstruction of the nipple (75% vs. 59%, P=0.14). Patients with NSM required less psychological support before (P=0.028) and immediately after surgery (P=0.14) than patients in the SSM group. CONCLUSION: NSM can successfully and safely be performed for pre-invasive and small invasive breast cancer. Besides esthetic aspects, preserving the nipple may ease the acceptance of these radical form of surgery.

Rischmann P., Gelet A., Riche B., Villers A., Pasticier G., Bondil P., Jung J. L., Bugel H., Petit J., Toledano H., Mallick S., Rouvière O., Rabilloud M., Tonoli-Catez H., Crouzet S.   Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients.  Eur. Urol..  2017 ;71 :267-273

BACKGROUND: Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. OBJECTIVE: To evaluate the ability of high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The French Urological Association initiated a prospective IDEAL multi-institutional study (2009-2015), to evaluate HIFU-hemiablation as a primary treatment. INTERVENTION: Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score >/= 7 or cancer core length>3mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 >/= 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. RESULTS AND LIMITATIONS: One hundred and eleven patients were treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. CONCLUSIONS: At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. PATIENT SUMMARY: This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.

Campello C., Parker F., Slimani S., Le Floch A., Herbrecht A., Aghakhani N., Lacroix C., Loiseau H., Lejeune J. P., Perrin G., Honnorat J., Dufour H., Chinot O., Figarella D., Bauchet L., Duffau H., Lonjon M., Labauge P., Messerer M., Daures J. P., Fabbro P., Ducot B.   Adult intramedullary gliomas.  Neurochirurgie.  2017 ;63 :381-390

OBJECTIVES: Intramedullary gliomas are rare tumors accounting for less than 4% of all primary central nervous system tumors. The aims of this retrospective multicenter study were to assess their natural outcome as well as management. METHODS AND MATERIALS: We studied 332 patients from 1984 to 2011. Histopathological examination revealed 72% ependymomas (94% were low grade tumors), 24% astrocytomas (29% were high grade tumors), 2.4% mixed gliomas and 1.7% oligodendrogliomas. RESULTS: The mean age at diagnosis was 42.4 years for ependymomas, with male predominance, versus 39.6 years for astrocytomas. Pain was the most common initial presentation. In 20% of cases, astrocytomas were biopsied alone, but more than 80% of ependymomas had surgical resection. Radiotherapy and chemotherapy were reserved for malignant tumors, especially if they were ependymomas. The 5-year survival rate was 76.8% for astrocytomas and 94.5% for ependymomas. Histology, functional status prior to surgery, and tumor grade are among the prognostic factors. CONCLUSION: Our study showed that surgical treatment of gliomas is well codified, at least for ependymomas, but adjuvant treatment continues to play a marginal role in the management even in astrocytomas, which are infiltrative tumors.

Marien A., Abreu A. D. C., Gill I., Villers A., Ukimura O.   Interest using 3D ultrasound and MR1 fusion biopsy for prostate cancer detection.  Prog. Urol..  2017 ;27 :521-528

INTRODUCTION: The strategic therapy for prostate cancer depends on histo-pronostics data, which could be upgraded by obtaining targeted biopsies (TB) with MRI (magnetic resonance imagery) fusion 3D ultrasound. OBJECTIVES: To compare diagnostic yield of image fusion guided prostate biopsy using image fusion of multi-parametric MRI (mpMRI) with 3D-TRUS. MATERIALS AND METHODS: Between January 2010 and April 2013, 179 consecutive patients underwent outpatient TRUS biopsy using the real-time 3D TRUS tracking system (Urostation). These patients underwent MRI-TRUS fusion targeted biopsies (TB) with 3D volume data of the MRI elastically fused with 3D TRUS at the time of biopsy. RESULTS: A hundred and seventy-three patients had TBs with fusion. Mean biopsy core per patient were 11.1 (6-14) for SB and 2.4 (1-6) for TB. SBs were positive in 11% compared to 56% for TB (P<0.001). TB outperformed systematic biopsy(SB) in overall any cancer detection rate, detection of clinically significant cancer (58% vs. 36%), cancer core length (6.8mm vs. 2.8mm), and cancer rate per core (P<0.001). In multivariable logistic regression, with TB we have more chance to find a clinically significant cancer (OR:3.72 [2-6.95]). When both TRUS and MRI are positive, there is 2.73 more chance to find a clinically significant cancer. CONCLUSION: MR/TRUS elastic fusion-guided biopsies outperform systematic random biopsies in diagnosing clinically significant cancer. Ability of interpretation of real-time TRUS is essential to perform the higher level of MR/US fusion and should be use for active surveillance. LEVEL OF PROOF: 4.

Ouzzane A., Betrouni N., Valerio M., Rastinehad A., Colin P., Ploussard G.   Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.  Future Oncol..  2017 ;13 :727-741

Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.