Susceptibility to Mycobacterium ulcerans Disease (Buruli ulcer) Is Associated with IFNG and iNOS Gene Polymorphisms

Buruli ulcer (BU) is a chronic necrotizing disease of the skin and subcutaneous fat tissue. The causative agent, Mycobacterium ulcerans, produces mycolactone, a macrolide toxin, which causes apoptosis of mammalian cells. Only a small proportion of individuals exposed to M. ulcerans develop clinical disease, as surrounding macrophages may control the infection by bacterial killing at an early stage, while mycolactone concentration is still low. Otherwise, bacterial multiplication leads to in higher concentrations of mycolactone, with formation of necrotizing lesions that are no more accessible to immune cells. By typing a cohort of 96 Ghanaian BU patients and 384 endemic controls without BU, we show an association between BU and single nucleotide polymorphisms (SNPs) in iNOS (rs9282799) and IFNG (rs2069705). Both polymorphisms influence promoter activity in vitro. A previously reported SNP in SLC11A1 (NRAMP, rs17235409) tended to be associated with BU. Altogether, these data reflect the importance of IFNG signaling in early defense against M. ulcerans infection

Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study

International audienceBACKGROUND: Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups.METHODS: Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables.RESULTS: Distribution of the 729 women with EC according to BMI was BMI < 30 (n = 442; 60.6 %), 30 ≤ BMI < 35 (n = 146; 20 %) and BMI ≥ 35 (n = 141; 19.4 %). Nodal staging was less likely to be performed in women with a BMI ≥ 35 (72 %) than for those with a BMI < 30 (90 %) (p < 0.0001). With a median follow-up of 27 months (interquartile range 13-52), the 3-year RFS was 84.5 %. BMI had no impact on RFS in obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group.CONCLUSION: Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women

Trachélectomie: comment faire en pratique ? Revue de la littérature par le groupe FRANCOGYN

International audienceBecause of the peak incidence of cervical cancer between the ages of 35 and 44 and the increasing age of first pregnancy, the issue of fertility preservation in cases of early-stage cervical cancer in women in this reproductive age category arises. Early-stage cervical cancer patients have a good prognosis and are surgically treated in cases of mildly aggressive human papillomavirus-related histological type (squamous cell carcinoma, adenocarcinoma), FIGO stage IA to IB1 (i.e., &lt;2 cm), with shallow stromal invasion (&lt;10 mm) and without the presence of lymph-vascular space invasion or lymph node or regional involvement. Under these conditions, conservative treatment by trachelectomy, which has recurrence-free and overall survival rates equivalent to that of hysterectomy, may be considered. After a complete pre-therapeutic assessment, including pelvic lymphadenectomy, to eliminate all contraindications to conservative treatment, a simple or enlarged trachelectomy can be chosen. According to some authors, the route of entry (vaginal, simple or robot-assisted laparoscopy, laparotomy) has no significant effect on survival or fertility, although the literature on the subject is limited. Trachelectomy offers good results in terms of fertility, with an estimated pregnancy rate of between 23% and 55% and a live birth rate of 70%. The significant reduction of the cervix associated with the procedure increases the risk of prematurity. However, this can be prevented by the use of a permanent cerclage. Close follow-up of these patients is essential for a minimum period of 5 years in order to detect any recurrence or postoperative complications

Honing the classification of high-risk endometrial cancer with inclusion of lymphovascular space invasion

International audienceObjectives: The purpose of this study was to analyse the clinical impact of LVSI status in a large French multicentre cohort of women with high-risk ECs according to the ESMO classification.Methods Data of 258 women with high-risk EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from prospective multicentre database. The end points were the recurrence and the lymph node metastasis (LNM) rates. Recurrence free survival (RFS) and overall survival (OS) were analyzed.Results: The recurrence and LNM rates in the whole population were 32.9% and 34.5%, respectively. The median follow-up and initial recurrence times were 27 (range: 1–151) and 23.5 (range: 1–151) months, respectively. The respective 3-year RFS rates according to the LNM and LVSI status were, 78.3% (95% CI, 70.1–87.3), 53.7% (95% CI, 40.8–70.6), 65.5% (95% CI, 46.1–93.2), 43.5% (95% CI, 30.3–62.3) for women with no LN metastasis/no LVSI; no LN metastasis/LVSI present; LN metastasis/no LVSI; LN metastasis/LVSI present, respectively (p = 0.0005).Conclusions: LVSI status remains a strong prognostic factor in high-risk ECs associated with a higher recurrence rate and lower RFS and OS whatever the histological type and lymph node status. It could thus be considered in future trials to guide decision-making about adjuvant therapy in high-risk ECs

Management and Survival of Elderly and Very Elderly Patients with Endometrial Cancer: An Age-Stratified Study of 1228 Women from the FRANCOGYN Group

International audienceBackground - Little data exist about the clinical management and survival of elderly patients with endometrial cancer. This study aimed to evaluate the management of elderly and very elderly patients with endometrial cancer as well as the overall survival (OS) rate, disease-free survival (DFS) rate, and cancer-specific survival (CSS) rate in a multicenter cohort. Methods - Data from 1228 patients with endometrial cancer who received primary treatment between January 2001 and December 2012 were collected from a multicenter database. Clinical management, DFS, CSS, and OS were analyzed. Results - Based on the international endometrial cancer risk classification, 36% (212/582) of women age 65 years or younger, 42% (220/526) of women ages 65-80 years, and 48% (58/120) of women older than 80 years showed high-risk endometrial cancer (p < 0.001). Pelvic lymphadenectomy was performed for 85% (230/271) of the women age 65 years or younger and 46% (33/71) of the women older than 80 years (p < 0.001). Radiotherapy was performed for 27% (33/120) of the very elderly and 40% (233/582) of the young patients (p = 0.009). The 3-year CSS rates were 95% (95% confidence interval [CI], 93-97%) for the women age 65 years or younger, 90% (95% CI, 87-94%) for the women ages 65-80 years, and 82% (95% CI, 73-93%) for the women older than 80 years (p < 0.001). Conclusions - The elderly and very elderly patients with endometrial cancer showed poorer prognosis than young patients. The significant lower CSS rate for the elderly patients could have be due to both the higher rate of high-risk endometrial cancer and undertreatment. Specific guidelines for the management of elderly and very elderly patients with endometrial cancer are needed to improve their prognosis

Comparison of pelvic and para-aortic lymphadenectomy versus para-aortic lymphadenectomy alone for locally advanced FIGO stage IB2 to IIB cervical cancer using a propensity score matching analysis: Results from the FRANCOGYN study group

International audienceINTRODUCTION:Pre-treatment evaluation of nodal status is crucial in women presenting with locally advanced cervical cancer (LACC). However, the prognostic impact of surgical staging remains to be proved, as published results comparing surgical versus radiological staging are contradictory. The aim of this study was to compare the prognosis of women with FIGO stage IB2-IIB CC who underwent surgical nodal staging including either exclusive para-aortic lymphadenectomy (PAL) or comprehensive pelvic + para-aortic lymphadenectomy (P-PAL).MATERIALS AND METHODS:Data of 314 women with FIGO stage IB2 to IIB CC treated between January 2000 and January 2015 were retrospectively abstracted from nine French institutions. The prognosis and outcomes were compared by Propensity score (PS) matching (PSM) analysis.RESULTS:The median follow-up was 33 months (2-114). When comparing women who underwent PAL vs P-PAL, the recurrence rates were 26% (37/144) and 28% (41/144), respectively (p = 0.595). The respective 3-year recurrence free survival (RFS) for P-PAL and PAL were 72.9% (95% CI, 65.7-81.0) and 70.7% (95% CI, 62.4-80.2), (p = 0.394). The respective 3-year overall survival (OS) rates for P-PAL and PAL were 86.8% (95% CI, 81.1-92.9) and 78.6% (95% CI, 70.4-87.7) (p = 0.592). In the sub-group of women with lymph node metastases, RFS was improved for women who underwent P-PAL compared to those with exclusive PAL (p = 0.027), with no difference in OS (p = 0.187).CONCLUSIONS:Comprehensive P-PAL does not seem to be of significant therapeutic benefit compared to exclusive PAL

A Proposal for a Classification for Recurrent Endometrial Cancer: Analysis of a French Multicenter Database From the FRANCOGYN Study Group

International audienceObjective: Endometrial cancer (EC) recurrences are relatively commonwith no standardized way of describing them.We propose a new classification for them called locoregional, nodal,metastasis, carcinomatosis recurrences (rLMNC).Patients and Methods: The data of 1230 women with EC who were initially treated by primary surgery were included in this French multicenter retrospective study. Recurrences were classified based on dissemination pathways: (1) locoregional recurrence (rL); (2) nodal recurrence (rN) for lymphatic pathway; (3) distant organ recurrence (rM) for hematogenous pathway; and (4) carcinomatosis recurrence (rC) for peritoneal pathway. These pathways were further divided into subgroups. We compared recurrence free survival and overall survival (OS) between the 4 groups (rL/rN/rM/rC).Results: The median follow-up was 35.6 months (range, 1.70Y167.60). One hundred ninety-eight women (18.2%) experienced a recurrence: 150 (75.8%) experienced a singlepathway recurrence and 48 (24.2%) a multiple-pathway recurrence. The 5-year OSwas 34.1% (95% confidence interval [CI], 27.02%Y43.1%), and the median time to first recurrence was 18.9 months (range, 0Y152 months). The median survival after recurrence was 14.8 months (95% CI, 11.7Y18.8). Amongwomenwith single pathway of recurrence, a difference in 5-year OS(PG 0.001) and survival after recurrence (P G 0.01)was found between the 4rLNMCgroups.The carcinomatosis group had the worst prognosis compared with other single recurrence pathways.Women with multiple recurrences had poorer 5-yearOS (P G 0.001) and survival after recurrence (P G 0.01) than those with single metastasis recurrence, other than women with peritoneal carcinomatosis.Conclusions: This easy-to-use and intuitive classification may be helpful to define EC recurrence risk groups and develop guidelines for the management of recurrence. Its prognosis value could also be a tool to select homogenous populations for further trials

Patterns of care and the survival of elderly patients with high-risk endometrial cancer: A case-control study from the FRANCOGYN group

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