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s Introduction During the COVID-19 pandemic, teleconsultation was implemented in clinical practice to limit patient exposure to COVID-19 while monitoring their treatment and follow-up. We sought to examine the satisfaction of patients with breast cancer (BC) who underwent teleconsultations during this period. Methods Eighteen centres in France and Italy invited patients with BC who had at least one teleconsultation during the first wave of the COVID-19 pandemic to participate in a web-based survey that evaluated their satisfaction (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) with teleconsultation. Results Among the 1299 participants eligible for this analysis, 53% of participants were undergoing standard post-treatment follow-up while 22 and 17% were currently receiving active anticancer therapy for metastatic and localised cancers, respectively. The mean satisfaction scores were 77.4 and 73.3 for the EORTC OUT-PATSAT 35 and TSQ scores, respectively. In all, 52.6% of participants had low/no anxiety. Multivariable analysis showed that the EORTC OUT-PATSAT 35 score correlated to age, anxiety score and teleconsultation modality. The TSQ score correlated to disease status and anxiety score. Conclusion Patients with BC were satisfied with oncology teleconsultations during the COVID-19 pandemic. Teleconsultation may be an acceptable alternative follow-up modality in specific circumstances.

Introduction Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated. Materials and methods In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point. Results A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm). Conclusion SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.

Background Mesenchymal stem cells (MSCs) exhibit active abilities to suppress or modulate deleterious immune responses by various molecular mechanisms. These cells are the subject of major translational efforts as cellular therapies for immune-related diseases and transplantations. Plenty of preclinical studies and clinical trials employing MSCs have shown promising safety and efficacy outcomes and also shed light on the modifications in the frequency and function of regulatory T cells (T regs). Nevertheless, the mechanisms underlying these observations are not well known. Direct cell contact, soluble factor production, and turning antigen-presenting cells into tolerogenic phenotypes, have been proposed to be among possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion and activity. We and others demonstrated that adult bone marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ helper and CD8+ cytotoxic T cells but also indirectly through the induction of T regs. In parallel, we demonstrated that fetal liver (FL)-MSCs demonstrates much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs. Methods MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation, and their proliferation potential. Using different in vitro combinations, we performed co-cultures of FL- or BM-MSCs and murine CD3+CD25−T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results We demonstrated that although both types of MSC display similar cell surface phenotypic profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs. Conclusions These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02176-1.

Purpose The temporal lobe plays an important role in the perception of odors. Another important anatomical structure involved in the perception of smell is the olfactory bulb. The relationship between olfactory bulb volume (OBV) and olfactory function is unclear, however. In our study, we aimed to evaluate the relationship between OBV and olfactory function in patients with mesial temporal lobe epilepsy (MTLE). Method Forty-eight patients with MTLE who were managed in the Cerrahpasa Medical Faculty Neurology Department’s epilepsy outpatient clinic were recruited for the study. Tests with Sniffin’ Sticks and Taste Strips were performed and OBV measured in all patients. Two control groups were recruited, one for the Sniffin' Sticks and Taste Strip tests and one for OBV measurement. Results In the smell tests; the threshold, discrimination and identification scores were significantly lower in the MTLE group than in the control group. The mean taste test scores did not differ significantly between the MTLE and control groups. In the MTLE group, the mean right OBV was 40.2 ± 12.54 and the left OBV was 39.3 ± 10.54, both of which were significantly lower those in the control group. The mean OBVs of patients with hyposmia were significantly smaller bilaterally than the OBVs of those with normosmia. There was no correlation between the gustatory scores and OBV. Conclusions Olfactory function was significantly impaired in patients with MTLE compared with healthy controls in all domains, namely threshold, discrimination, and identification. In addition, olfactory bulbus volume was smaller in patients with olfactory dysfunction.

Aim of the study Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF). In this study, we aimed to demonstrate the effect of surgery on the ALF phenomena thus contributing to potential explanation of the causal mechanism. Materials and methods We evaluated 51 patients with TLE related to hippocampal sclerosis who had amygdalohippocampectomy and had remained seizure-free after surgery. A control group consisted of 24 healthy individuals. All were given a verbal learning test assessing recall after 30 min, 1 week and 6 weeks. Results In our study, the Left-TLE (L-TLE) group showed a statistically significant reduction in the performance at all assessment intervals from 30 min to 1 week compared to the Right-TLE and control groups regarding verbal learning memory test (VLMT) as well as for logical memory. The forgetting rates in the VLMT from 30 min to 1 week were not statistically significantly different between all 3 groups. The logical memory test results equally showed no statistically significant difference in the forgetting rates for the 3 groups between 30 min and 1 week. Conclusions and clinical implications These results may support ongoing debates assuming the initial low performance in the memory of L-TLE patients to be directly related with left hippocampal-temporal tissue loss irrespective of epileptic activity. The discovery of the ALF phenomenon explains that standard memory tests are unable to detect memory loss in some patients who are experiencing a significant level of problems with forgetfulness in their daily lives.

In France, participation in the organized breast cancer screening program remains insufficient. A personalized approach adapted to the risk factors for breast cancer (RBC) should make screening more efficient. A RBC evaluation consultation would therefore make it possible to personalize this screening. Here we report our initial experience.This is a prospective study on women who were seen at the RBC evaluation consultation and analyzing: their profile, their risk assessed according to Tyrer Cuzick model (TC)±Mammorisk© (MMR), the existence of an indication of oncogenetic consultation (Eisinger and Manchester score), their satisfaction and the recommended monitoring.Among the women who had had a TCS and/or MMR evaluation of SCR (n=153), 76 (50%) had a high risk (n=67) or a very high risk (n=9). Almost half (47%) had a possible (15%) or certain (32%) indication to an oncogenetic consultation. Regarding this consultation, 98% of women were satisfied or very satisfied. In total, 60% of women had a change in screening methods.This RBC evaluation consultation satisfies women and for a majority of them, modifies their methods of breast cancer screening.

Alterations in the gut microbiome have been implicated in the pathogenesis of several immune-mediated inflammatory diseases such as psoriatic arthritis. This work aimed to characterize the gut microbial signature of patients with active psoriasis as compared with age-, body mass index- and comorbidity-matched non-psoriatic controls and to correlate them with differential expression of metabolic pathways. Fecal samples were processed and 16S rRNA was sequenced. PICRUSt was used to perform an analysis of metabolic pathways. Of the 46 participants, 52% (n = 24) suffered from psoriasis. There was a significant difference in β-diversity between the two groups. Psoriatic patients had a significant increase in the Firmicutes and Actinobacteria phyla as compared with matched controls. At the genus level, psoriatic patients had a unique bacterial composition. At the species level, the psoriatic patients showed significant increases in the relative proportions of (false discovery rate

Summary: Gestation is accompanied by alterations in the microbial repertoire; however, the mechanisms driving these changes are unknown. Here, we demonstrate a dramatic shift in the gut microbial composition of women and mice during late pregnancy, including an increase in the relative abundance of Bifidobacterium. Using in-vivo-transplanted pellets, we found that progesterone, the principal gestation hormone, affects the microbial community. The effect of progesterone on the richness of several bacteria species, including Bifidobacterium, was also demonstrated in vitro, indicating a direct effect. Altogether, our results delineate a model in which progesterone promotes Bifidobacterium growth during late pregnancy. : Nuriel-Ohayon et al. demonstrate a dramatic shift in the gut microbial composition of women and mice during late pregnancy, including an increase in the relative abundance of Bifidobacterium. Using in vitro and in vivo experiments, they show that supplementation of progesterone affects the microbial communities, including increasing the relative abundance of Bifidobacterium. Keywords: progesterone, Bifidobacterium, pregnancy, gut microbiota, 16S rRNA, microbiome

BACKGROUND Colonoscopy is considered a valid primary screening tool for colorectal cancer (CRC). The decreasing risk of CRC observed in patients undergoing colonoscopy is correlated with the adenoma detection rate (ADR). Due to the fact that screening programs usually start from the age of 50, very few data are available on the risk of adenoma between 40 and 49 years. However, the incidence of CRC is increasing in young populations and it is not uncommon in routine practice to detect adenomas or even advanced neoplasia during colonoscopy in patients under 50 years. AIM To compare the ADR and advanced neoplasia detection rate (ANDR) according to age in a large series of patients during routine colonoscopy. METHODS All consecutive patients who were scheduled for colonoscopy were included. Exclusion criteria were as follows: patients scheduled for partial colonoscopy or interventional colonoscopy (for stent insertion or stenosis dilation). Colonoscopies were performed in our unit by a team of 30 gastroenterologists in 2016. We determined the ADR and ANDR in each age group in the whole population and in the population with an average risk of CRC (excluding patients with personal or family history of advanced adenoma or cancer). RESULTS 6027 colonoscopies were performed in patients with a median age of 57 years (range, 15-96). The ADR and ANDR were 28.6% and 9.7%, respectively, in the whole population. When comparing patients aged 40-44 (n = 382) and 45-49 years (n = 515), a strong increase in all parameters from 45 years was observed, with the ADR rising from 9.7% in patients aged 40-44 to 21.2% between 45 and 49 (P < 0.001) and the ANDR increasing from 3.1% in patients aged 40-44 to 6.4% in those aged 45-49 years (P < 0.03). With regard to patients aged 50-54 (n = 849), a statistically significant increase in the ADR and ANDR was not observed between patients aged 45-49 and those aged 50-54 years. In the population with an average risk of CRC, the ADR and ANDR were still significantly higher in patients aged 45-49 compared with those aged 40-44 years. CONCLUSION This study shows a significant two-fold increase in the ADR and ANDR in patients aged 45 years and over.

Funder: Action Bladder Cancer UK, Funder: Rosetrees Trust; Id: http://dx.doi.org/10.13039/501100000833, Funder: Urology Care Foundation; Id: http://dx.doi.org/10.13039/100006280, OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.

Our aim was to present the surgical technique of robotic radical trachelectomy (RRT) for early-stage squamous cell cervical cancer in women with a desire to preserve fertility. A surgical case to illustrate the entire surgical technique of RRT and sentinel lymph node dissection. Institutional Review Board approval was not required for this video presentation. University hospital. A 30-year-old patient with one child and no medical history. Pap smear and cervical biopsy were in favor of high-grade squamous intraepithelial lesion, and a conization procedure allowed the diagnosis of a 15 mm squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] 1B1). An RRT was performed to preserve the fertility of this young patient, after bilateral sentinel lymph node dissection to ensure the absence of nodal metastasis. The trachelectomy specimen was negative at final pathology examination and the disease was confirmed as stage 1B1 (FIGO 2018). There were no surgical complications and no adjuvant treatment was indicated. Fertility-sparing surgery is acceptable for women of childbearing age who want to become pregnant. Minimally invasive surgery is safe, effective, and particularly adapted for women who wish to preserve their fertility without compromising oncological outcomes.1–2 This option may be safely proposed in expert centers for tumors smaller than 2 cm, with primary vaginal closure, and without use of a uterine manipulator.3 Complete information about oncological and obstetrical outcomes is mandatory and patients should agree to comply with a close follow-up protocol.

Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, >25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells.

Background Endothelial progenitor cells (EPCs) are non-differentiated endothelial cells (ECs) present in blood circulation that are involved in neo-vascularization and correction of damaged endothelial sites. Since EPCs from patients with vascular disorders are impaired and inefficient, allogenic sources from adult or cord blood are considered as good alternatives. However, due to the reaction of immune system against allogenic cells which usually lead to their elimination, we focused on the exact role of EPCs on immune cells, particularly, T cells which are the most important cells applied in immune rejection. TNFα is one of the main activators of EPCs that recognizes two distinct receptors. TNFR1 is expressed ubiquitously and its interaction with TNFα leads to differentiation and apoptosis, whereas, TNFR2 is expressed predominantly on ECs, immune cells and neural cells and is involved in cell survival and proliferation. Interestingly, it has been shown that different immunosuppressive cells express TNFR2 and this is directly related to their immunosuppressive efficiency. However, little is known about immunological profile and function of TNFR2 in EPCs. Methods Using different in-vitro combinations, we performed co-cultures of ECs and T cells to investigate the immunological effect of EPCs on T cells. We interrupted in the TNFα/TNFR2 axis either by blocking the receptor using TNFR2 antagonist or blocking the ligand using T cells derived from TNFα KO mice. Results We demonstrated that EPCs are able to suppress T cell proliferation and modulate them towards less pro-inflammatory and active phenotypes. Moreover, we showed that TNFα/TNFR2 immune-checkpoint pathway is critical in EPC immunomodulatory effect. Conclusions Our results reveal for the first time a mechanism that EPCs use to suppress immune cells, therefore, enabling them to form new immunosuppressive vessels. Furthermore, we have shown the importance of TNFα/TNFR2 axis in EPCs as an immune checkpoint pathway. We believe that targeting TNFR2 is especially crucial in cancer immune therapy since it controls two crucial aspects of tumor microenvironment: 1) Immunosuppression and 2) Angiogenesis. Video Abstract. (MP4 46355 kb)

Background Adjuvant chemotherapy induces weight gain, glucose intolerance, and hypertension in about a third of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers. Methods Patients were recruited before starting adjuvant therapy. Weight and height were measured before treatment and 4–6 weeks after treatment completion. Weight gain was defined as an increase of 3% or more in body weight. A stool sample was collected before treatment, and 16S rRNA gene sequencing was performed. Data regarding oncological therapy, menopausal status, and antibiotic use was prospectively collected. Patients were excluded if they were treated by antibiotics during the study. Fecal transplant experiments from patients were conducted using Swiss Webster germ-free mice. Results Thirty-three patients were recruited; of them, 9 gained 3.5–10.6% of baseline weight. The pretreatment microbiome of women who gained weight following treatment was significantly different in diversity and taxonomy from that of control women. Fecal microbiota transplantation from pretreatment samples of patients that gained weight induced metabolic changes in germ-free mice compared to mice transplanted with pretreatment fecal samples from the control women. Conclusion The microbiome composition is predictive of weight gain following adjuvant chemotherapy and induces adverse metabolic changes in germ-free mice, suggesting it contributes to adverse metabolic changes seen in patients. Confirmation of these results in a larger patient cohort is warranted.

Anti-NMDA receptor antibody (anti-NMDAr) encephalitis, although still a rare condition, is well known to neurologists as it is the leading cause of non-infectious acute encephalitis in young women. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Indeed, in 30–60% of cases in women of childbearing age, it is associated with the presence of an ovarian teratoma, whose removal is crucial in the resolution of symptomatology. Primary objective of our work was to present a review in a very schematic and practical way for gynecologists, about the data on anti-NMDAr encephalitis in terms of epidemiology, clinical symptomatology, treatment and prognosis. The second objective was to propose a decision tree for gynecologists to guide them, in collaboration with neurologists and anesthesiologists, after the diagnosis of NMDAr encephalitis associated with an ovarian mass. We conducted an exhaustive review of existing data using PubMed and The Cochrane Library. Then, we illustrated this topic by presenting two typical cases from our experience. Anti-NMDA antibody encephalitis association with an ovarian teratoma is common, especially in women of reproductive age. Complementary examinations in search of an ovarian teratoma must therefore be systematic to envisage a possible surgical excision that may improve patient prognosis. Anti-NMDA antibody encephalitis should not be ignored by gynecologists whose role in management is central.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

This prospective study investigated whether antibodies from SARS-CoV-2 immunization of nursing mothers transferred to infants as a potentially protective effect.

Prepulse modulation (PPM) is an electrophysiological method which enables to assess sensory processing in vivo. Reflex responses may be facilitated or inhibited (prepulse inhibition, PPI) after a weak stimulus. Theoretically, in animal studies, the generator of PPI involves pedunculopontine nucleus which is modulated by various structures, including amygdala. We aimed to investigate whether or not there was a role of limbic structures in the generation of PPM in humans. For this purpose, we studied PPM of the blink reflex (BR) in 10 patients with mesial temporal lobe epilepsy (MTLE group) and in nine patients who had previously undergone amygdala resection for medically resistant MTLE (surgery group). A control group including 19 healthy volunteers was formed. Blink reflex, BR-PPM and BR excitability recovery were recorded in all participants. Two components of BR, first early ipsilateral component (R1) and second late bilateral components (R2 and R2c) were identified. All BR parameters after single stimulation were normal in all groups. Compared to healthy subjects, R2-PPI was more pronounced in the surgery group whereas there was a R2-PPI deficit in the MTLE group. R2-PPI deficit in the MTLE group was more prominent on the lesion side. Ipsilesional R1 facilitation was more evident at ISI of 100 ms in both MTLE and surgery groups compared to healthy subjects. BR excitability recovery was not different between groups. MTLE in humans leads to a PPI deficit. Interestingly, removal of amygdala in humans with MTLE probably provides more efficient functioning of PPI network. Amygdala and hippocampus play roles in the human R2-PPI circuit. Modulation of R1 facilitation is unilateral whereas the modulation of R2-PPI is bilateral, though asymmetric.

To analyse the clinical, imaging and histopathological data of patients who were diagnosed to have Dysembrioplastic Neuroepithelial Tumour (DNET) and underwent surgery between 1995-2015.Age at seizure onset, age at surgery, gender, disease duration, seizure outcome of 44 patients were analysed together with Magnetic Resonance Imaging (MRI) of 21 patients. MRI types were classified as type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodularlike,heterogeneous), type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring).Histopathological classification revealed simple form in 19, complex in 14 and non-specific in 11 patients. Lobar distribution of the lesions was as follows: 21 Temporal (47.7%), 12 parietal (27.3%), 8 frontal (18.2%) and 3 occipital (6.8%). Type 1 MRI was observed in 10, type 2 was in 7, and type 3 in 4 patients on radiological evaluation. All cases with type 1 MRI corresponded to either simple or complex forms and all cases with type 3 MRI corresponded to nonspecific form. The histopathological distribution of cases with type 2 MRI was 4 as non-specific, 2 as simple, 1 as complex. There was no significant difference in the age of onset, age at operation and duration of epilepsy between the patients with different MRI subtypes. The majority of patients (N:36) had Engel I outcome (81,8%). In groups with Engel II and III outcome, duration of epilepsy was significantly higher (p:0,014) and simple form of DNET has significantly higher seizure freedom after surgery compared to complex and nonspecific forms of DNET (p:0,002).Patients with DNET constitute a group with favorable outcomes after epilepsy surgery especially with early referral to surgery. Longer duration of epilepsy was associated with worse seizure outcome for DNET patients. There was significant correlation between radiological and histopathological types of DNET especially in type 1 and 3.

International audience; As obesity prevalence increases worldwide, healthcare professionals are often faced with challenging cases associated with massive obesity. A 33-year-old woman (weight 342 kg, body mass index = 100 kg/m²) presented with respiratory failure, limb edema and ascites. Abdominal CT scan became feasible after initial weight loss and showed a large pelvic mass in contact with the left ovary. The surgical removal performed despite a high-risk profile led to the diagnosis of a giant mucinous borderline tumor whose growth was due to delayed care and responsible for multiple severe complications: sepsis, anemia, esophagitis, constipation, anorexia due to mechanical compression, undernutrition, sarcopenia and lower limb edema contributing to a severe disability. After 7 months under specialized care, her weight decreased to 180 kg, complications were treated and disability improved. This case, showing that, despite barriers, a multidisciplinary approach makes quality of care possible even in massively obese patients, is an educational example to reduce stigma. A 33-year-old woman with extreme obesity (weight 342 kg, body mass index = 100 kg/m²) was admitted to the emergency department with respiratory failure, limb edema and ascites. Her weight had increased over the last months with worsening of her general health status. As her corpulence limited physical examination and excluded standard imaging investigations, she was empirically treated with anticoagulants and antibiotics for a possible pulmonary embolism and pneumonia. She also received a loop diuretic and continuous positive airway pressure was initiated. After initial improvement of her respiratory status, she was transferred to a post-acute rehabilitation department. Ascites remained unchanged despite draining and diuretic treatment. After 5 months under medical supervision and following a controlled diet, she had lost a large amount of weight (−92 kg) but remained disabled, bedridden and needed assistance from 6 professionals for routine hygienic care. She was referred to our obesity clinic for specialized nutritional care and etiological investigation of ascites. Ascites aspiration revealed a liquid exudate without bacterial pathogens. There was no evidence for hepatitis, cardiac or renal failure. Abdominal and pelvic intra-vaginal ultrasound performed at the patient's bed did not show any effusion in the Douglas pouch or behind the liver. However, we observed a very large abdominal mass of a multicystic nature. Because of technical difficulties, the ultra-sonographer could not exclude or confirm an ovarian-related disease. Although she had experienced substantial weight loss, the patient's body shape still prevented performing standard imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI). A duodenal echo-endoscopy and a proctoscopy were performed and did Christine Poitou and Margot Denis contributed equally to this work.

Introduction Complete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery. Methods We conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria. Results One hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the “IDS” subgroup. In the “PDS” subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS. Conclusion Initial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved.

International audience; Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

International audience; Endothelial dysfunction (ED) is part of the first steps in the development of cardiovascular diseases (CVD). Growth Differentiation Factor 15 (GDF15) is a cytokine belonging to the Transforming Growth Factor β superfamily and its expression is increased both during ED and in CVD. Because high blood levels of GDF15 have been reported during ED, we hypothesized that GDF15 could be produced by endothelial cells in response to a vascular stress, possibly to attenuate endothelial function loss. Since senescence is mainly involved in both vascular stress and endothelial function loss, we used Endothelial Colony Forming Cells generated from adult blood (AB-ECFCs) as a model of endothelial cells to investigate GDF15 expression during cellular senescence. Then, we analyzed the potential role of GDF15 in AB-ECFC functions and senescence. When AB-ECFCs become senescent, they secrete increased levels of GDF15. We investigated GDF15 paracrine effects on non-senescent AB-ECFCs and showed that GDF15 enhanced proliferation, migration, NO production and activated several signaling pathways including AKT, ERK1/2 and SMAD2 without triggering any oxidative stress. Taken together, our results suggest that GDF15 production by senescent AB-ECFCs could act in a paracrine manner on non-senescent AB-ECFCs, and that this interaction could be beneficial to its model cells. Therefore, GDF15 could play a beneficial role in a dysfunctional vascular system as previously reported in patients with CVD, by limiting ED related to vascular stress occurring in these diseases.

Adenoma detection rate (ADR) is correlated with the risk of interval colorectal cancer and is considered as a quality benchmark for colonoscopy. Serrated polyp detection rate (SPDR) might be a more stringent indicator of quality in polyp detection. To evaluate in a 2-year monocentric observational study patient-dependent and endoscopist-dependent factors influencing ADR and SPDR in daily practice. We determined ADR and SPDR. We collected patient-dependent factors and endoscopist-dependent factors. Links between these data and detection rates were assessed by uni- and multivariate analysis. A total of 11682 colonoscopies were performed (female: 54.3%; male: 45.7%; median age 58) by 30 endoscopists (female: 9; male: 21). ADR and SPDR were 29.2% and 8%, respectively. In multivariate analysis, ADR was associated with patient-dependent factors: age (OR 1.044, CI 95% 1.040–1.048), male gender (OR 1.7, CI 95% 1.56–1.85), personal history of polyp/cancer (OR 1.53, CI 95% 1.3–1.9), and positive fecal immunochemical test (OR 2.47, CI 95% 2.0–3.1). In multivariate analysis, SPDR was associated with withdrawal time (OR 1.25, CI 95% 1.17–1.32), low volume activity (OR 1.3, CI 95% 1.1–1.52), and personal history of polyp/cancer (OR 1.61, CI 95% 1.15–2.25). In this large series of routine colonoscopies, we found that ADR was mainly driven by patient-dependent conditions, i.e., age, male gender, colonoscopy indication for positive FIT, and a personal history of polyp or cancer. In contrast, SPDR was mainly related to endoscopist-dependent factor, i.e., withdrawal time and low volume activity.

To evaluate the value of high-risk HPV (HR HPV) testing in screening and post-treatment follow-up of high-grade squamous intraepithelial cervical lesions (HSIL).A systematic review of the literature from 2000 to 2019 was conducted including the following keywords: "human papilloma virus", "HPV testing", "cervical squamous intraepithelial lesion", "cervical cancer".Numerous recent randomized studies and meta-analyzes have concordant results in favor of HR HPV superiority over cervical smear in the screening and post-treatment monitoring of HSIL. In screening, the sensitivity of the HR HPV tests is 63% to 98% whereas that of the cervical smear is only 38% to 65% for the detection of HSIL+ (HSIL and invasive cancers). A negative HR HPV test is associated with less than 5% risk of LIEHG+at 6 years. In addition, after removal of a LIEHG, HR HPV tests have a sensitivity90% and specificity80% to predict treatment failure. After surgicale exision, a negative HR HPV test is associated with a risk of failure2% (negative predictive value of 98%), and 12-25% if it is positive.HR HPV tests are effective, allowing early detection of LIEHG+ identification of low-risk women in case of negative test, and a prediction of the risk of failure after treatment.

WOS: 000405969500005, PubMed ID: 28808489, INTRODUCTION: Patient examinations performed in a limited time period may lead to impairment in patient and physician relationship, defective and erroneous diagnosis, inappropriate prescriptions, less common use of preventive medicine practices, poor patient satisfaction, and increased violent acts against health-care staff. OBJECTIVE: This study aimed to determine the appropriate minimal duration of patient examination in the pulmonary practice. METHODS: A total of 49 researchers from ten different study groups of the Turkish Thoracic Society participated in the study. The researchers were asked to examine patients in an almost ideal manner, without time constraint under available conditions. RESULTS: A total of 1680 patient examinations were reviewed. The mean duration of patient examination in ideal conditions was determined to be 20.4 +/- 9.6 min. Among all steps of patient examination, the longest time was spent for "taking medical history." The total time spent for patient examination was statistically significantly longer in the university hospitals than in the governmental hospitals and training and research hospitals (P < 0.001). Among different patient categories, the patients with a chronic disorder presenting for the first time and were referred from primary or secondary to tertiary care for further evaluation have required the longest time for patient examination. CONCLUSION: According to our study, the appropriate minimal duration for patient examination is 20 min. It has been observed that in university hospitals and in patients with chronic pulmonary diseases, this duration has been increased to above 25 min. The durations in clinical practice should be planned accordingly.

Glomerulopathy associated with lecithin-cholesterol-acyltransferase deficiency (LCAT) is a rare automosal recessive disease. Acquired LCAT deficiency due to inhibitory autoantibodies against LCAT are also described. This disease is induced by systemic deposits related to a lipid metabolism disorder and lead to multi-organ involvement including renal involvement. Lipid profile usually shows variable cholesterol levels but very low HDL levels. Here we describe the case of a 33-year-old man presenting a nephrotic syndrome associated with moderate renal insufficiency for which the pathological analysis allowed to guide towards the diagnosis of LCAT deficiency. Laboratory and genetic data confirmed this diagnosis. Familial history and lipid profile abnormalities are important in the identification of this disease.

Objective To describe a surgical technique for laparoscopic uterine fixation (LUF) to decrease uterine radiation therapy side effects in case of rectal or anal cancer. Design This video article uses a surgical case to demonstrate the detailed technique. Institutional Review Board approval was not required for this video presentation. Setting University hospital. Patient(s) A 26-year-old nulliparous female patient diagnosed with rectal adenocarcinoma and liver metastases. After the completion of right hepatectomy and neoadjuvant chemotherapy with the use of the FOLFOX regimen, pelvic radiation therapy was applied before tumor excision. Intervention(s) The patient underwent laparoscopic ovarian transposition. During the same intervention, we fixed the uterus with three late resorbable sutures into the fascia of the anterior abdominal wall as cranial as possible to remove the uterus away from the radiation field. Main outcome measure(s) Value and feasibility of LUF. Result(s) LUF was feasible and effective. Estimated isodoses demonstrated that this intervention may decrease uterine consequences of pelvic radiotherapy. The patient did not report any specific pain or complication in the postoperative period. Three months after the completion of pelvic concurrent chemoradiation therapy, the patient had normal menstrual periods. Hormonal blood tests were satisfactory. Ultrasound showed persistent ovarian function. Conclusion(s) Considering its simplicity of realization, LUF should be discussed for reproductive-age patients before undergoing pelvic radiotherapy for anal or rectal cancer. A close collaboration is required between surgeons and radiation oncologists to optimize the treatment and to decrease side-effects of radiotherapy. Intensity-modulated radiation therapy may contribute to enhance a multimodal fertility-sparing strategy in global management of young patients.

BACKGROUND/AIM We aimed to evaluate the impact of bevacizumab on the lymphocele rate in patients after complete cytoreductive surgery for advanced ovarian cancer. PATIENTS AND METHODS This retrospective study included patients with advanced ovarian cancer who had undergone complete cytoreductive surgery with pelvic and para-aortic lymphadenectomy at the Gustave Roussy Institute from 2005 to 2014. The introduction of bevacizumab was discussed in a multidisciplinary meeting. RESULTS During the study period, 247 patients were included; 24.6% of patients (61 patients) received adjuvant bevacizumab. The rate of symptomatic lymphocele was 34% (84 patients). In the lymphocele group, patients tended to receive adjuvant bevacizumab more often than did the control group (32% and 21%, respectively, p=0.05). In multivariate analysis, bevacizumab was not significantly associated with the risk of symptomatic lymphocele (hazard ratio(HR)=1.62, 95% confidence interval(CI)=0.87-3.01, p=0.12). CONCLUSION Adjuvant bevacizumab has no impact on the formation or duration of symptomatic lymphocele in patients after complete cytoreductive surgery for advanced ovarian cancer.

ObjectiveRobotic surgical techniques are known to be expensive, but they can decrease the cost of hospitalization and improve patients’ outcomes. The aim of this study was to compare the costs and clinical outcomes of conventional laparoscopy vs robotic-assisted laparoscopy in the gynecologic oncologic indications.MethodsBetween 2007 and 2010, 312 patients referred for gynecologic oncologic indications (endometrial and cervical cancer), including 226 who underwent conventional laparoscopy and 80 who underwent robot-assisted laparoscopy, were included in this prospective multicenter study. The direct costs, operating theater costs, and hospital costs were calculated for both surgical strategies using the microcosting method.ResultsBased on an average number of 165 surgical cases performed per year with the robot, the total extra cost of using the robot was €1456 per intervention. The robot-specific costs amounted to €2213 per intervention, and the cost of the robot-specific surgical supplies was €957 per intervention. The cost of the surgical supplies specifically required by conventional laparoscopy amounted to €1432, which is significantly higher than that of the robotic supplies (P < 0.001). Hospital costs were lower in the case of the robotic strategy (€2380 vs €2841, P < 0.001) because these patients spent less time in intensive care (0.38 vs 0.85 days). Operating theater costs were higher in the case of the robotic strategy (€1490 vs €1311, P = 0.0004) because the procedure takes longer to perform (4.98 hours vs 4.38 hours).ConclusionsThe main driver of additional costs is the fixed cost of the robot, which is not compensated by the lower hospital room costs. The robot would be more cost-effective if robotic interventions were performed on a larger number of patients per year or if the purchase price of the robot was reduced. A shorter learning curve would also no doubt decrease the operating theater costs, resulting in financial benefits to society.

ObjectivesOvarian immature teratoma may be associated with peritoneal spread that could, after adjuvant chemotherapy, develop into disease exclusively composed of mature implants (growing teratoma syndrome) and/or gliomatosis peritonei (GP), defined as the presence of pure mature glial tissue. However, very few specific series are devoted to the outcomes of pure GP. This was the aim of the present study.PatientsFrom 1997 to 2013, data concerning patients treated for stage II/III immature teratoma were reviewed. All slides were reviewed by an expert pathologist. Patients with ovarian cancer associated with peritoneal spread in the form of pure GP (initially if patients were treated without adjuvant treatment or after adjuvant chemotherapy if done) were analyzed.ResultsTen patients fulfilled the inclusion criteria. The median age of patients at diagnosis was 36 years (range, 14–41 years). Six patients had undergone a conservative treatment. Five patients had macroscopic residual disease at the end of surgery.The median duration of follow-up from the diagnosis of GP was 39 months (range, 6–114 months). Six patients had undergone secondary surgery. Among them, 5 had incompletely resected macroscopic GP. No patients had died of their disease. All patients were asymptomatic at the time of the last consultation (1 of them with abnormal radiologic imaging).ConclusionsGliomatosis peritonei is a particular entity of the condition described as growing teratoma syndrome because residual peritoneal disease can be asymptomatic totally stable over a long period which raises the question of a more conservative surgical approach in patients with massive peritoneal spread.

OBJECTIVE To describe trends and ethnic differences in incidence of gynecologic cancer in Israel. METHODS In the present retrospective epidemiologic study, age-standardized rates (ASRs) rates of gynecologic malignancies that occurred between January 1, 1993, and December 31, 2013, were extracted from the Israeli National Cancer Registry. The annual percent change (APC) was calculated separately for Jewish and Arab patients for ovarian, endometrial, and cervical cancers. RESULTS Among Jewish patients, the ASR of ovarian cancer decreased (APC -2.27%, 95% confidence interval [CI], -2.7 to -1.84; P

Objective We sought to simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. Methods A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures. Each sample was stored at −80°C as rapidly as possible until the enzyme assay. Results The temporal cortex in the epilepsy patients had a significantly higher enzyme level than did the temporal cortex of the control group (P = 0.03). Correlation analysis showed that as the enzyme level increases in the temporal cortex, it also increases in the hippocampal complex (r2 = 0.06, P = 0.00001). More important, enzyme tissue levels showed positive correlations with seizure frequency in both the temporal cortex and hippocampal complex in patients (r2 = 0.7, P = 0.00001 and r2 = 0.4, P = 0.003, respectively). The duration of epilepsy was also positively correlated with the hippocampal enzyme level (r2 = 0.06, P = 0.00001). Conclusions Soluble human epoxy hydrolase enzyme-2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuroinflammation in experimental epilepsy models in the current literature.

Background Surgical results regarding MRI-negative epilepsy were presented and related clinical and histopathological parameters were discussed. Methods Thirty-six MRI-negative epilepsy patients were retrospectively analyzed. Histopathological specimens were re-reviewed by 2 blind neuropathologists and re-classified based on the current classifications. Results The mean age at surgery and seizure onset was 24.5 years and 9.3 years, respectively. Eight patients were younger than 18 years. Mean duration of seizures was 15.3 years. All but 2 underwent invasive monitorization. Eighteen patients had hypometabolism on FDG-PET with temporal lobe involvement in majority (66.7%). Hypometabolism was found in all patients with hippocampal sclerosis (HS), which was present in 50% and 66.7% of focal cortical dysplasia (FCD) type I and II patients, respectively. The frontal lobe resection was the most frequent type of operation followed by resections in temporal, parietal and occipital lobes. In 7 patients, multilobar resection was performed. Histopathological diagnosis was FCD type I, II, III, HS, and gliosis in 14, 12, 2, 3 and 2 patients, respectively. The mean follow-up was 5.8 years. Seventeen patients were seizure free and favorable outcome (Engel's I and II) was found in 69.7%. FCD type I tend to have more favorable seizure outcome. Duration of epilepsy and hypometabolism on FDG-PET was significantly related to outcome, whereas involved lobe was not. Conclusions Our results suggest it is worth pursuing resective surgery in adults as well as in children with drug-resistant epilepsy with normal MRI.

Purpose The present study aimed to determine if the specific characteristics of fluorodeoxyglucose-positron emission tomography (FDG-PET) analyses of the FCD subgroups were compatible with the magnetic resonance imaging (MRI) and clinical findings of the patients in these subgroups. Methods This study included 71 patients who had a presurgical evaluation workup performed due to drug-resistant seizures, who underwent epilepsy surgery, and who were histopathologically diagnosed with FCD. Relationships involving MRI and FDG-PET findings and clinical data from pathological subgroups and patients were assessed. Results According to the International League Against Epilepsy (ILAE) classifications of FCD, 28 of the patients were type I and 43 were type II. FCD was visible on the MRI scans of 53 patients, and a majority of this group was classified as type II FCD (n=34). Of these 53 patients, FCD was located in the temporal area of 21 patients, the extratemporal area of 29 patients. Of the patients who exhibited FDG-PET hypometabolism (PET-positive), 23 were classified as temporal, 17 as frontal, 11 showed involvement of the posterior cortex. The age of seizure onset was younger in PET-positive patients (p=0.032), and histopathological analyses revealed that 23 patients had type I FCD and 30 patients had type II FCD. Conclusion PET scans reveal a lesion by showing hypometabolism in patients who have refractory epilepsy and an early age of onset with FCD. The lesions of MRI-negative/PET-positive FCD patients tend to be localized in the temporal lobe and that FCD may be localized in the frontal lobe of MRI-negative/PET-negative patients. However, the histopathological examinations of MRI-positive/PET-positive, MRI-negative/PET-positive, and MRI-negative/PET-negative patients did not exhibit a particular histopathological subtype.

To develop a risk scoring system (RSS) for predicting recurrence in women with borderline ovarian tumours (BOTs).Cohort study of women with BOTs.French multicentre tertiary care centres.A cohort of 360 women with BOTs who received primary surgical treatment between January 2000 and December 2013.Clinical and pathological factors affecting recurrence in women with BOTs.The development of a model for the prediction of recurrence in women with BOTs.Overall the recurrence rate was 20.0% (72/360). Recurrence was associated with five variables: age 45 years; preoperative serum tumour marker CA125 150 IU/mL; a serous histological subtype; International Federation of Gynecology and Obstetrics (FIGO) stage other than IA; and ovarian surgery other than bilateral salpingo-oophorectomy (BSO; i.e. cystectomy and unilateral salpingo-oophorectomy). These variables were included in the RSS and assigned scores ranging from 0 to 6. The discrimination of the RSS was 0.82 (95% confidence interval, 95% CI 0.79-0.85). A total score of 8 points corresponded to the optimal threshold of the RSS, with a rate of recurrence of 11.8% (35/297) and 58.7% (37/63) for women at low risk (8 points) and women at high risk (≥8 points), respectively. The diagnostic accuracy was 85.0%.This study shows that the risk of BOT recurrence can be accurately predicted so that women at high risk can benefit from adapted surgical treatment.Our RSS permitted women with BOTs at low risk to be distinguished from women with BOTs at high risk of recurrence.

Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). We have investigated CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3 allelic variants in a Turkish population of patients on phenytoin therapy. Patients on phenytoin therapy (n = 102) for the prevention of epileptic seizures were included. Polymorphic alleles were analyzed by restriction fragment length polymorphism method. Serum concentrations of phenytoin were measured by fluorescence polarization immune assay method. The most frequent genotype was detected for CYP2C9 wild-type alleles (78.43 %), whereas CYP2C19*2/*2 (5.88 %) was the least frequent genotype group. According to the classification made with both enzyme polymorphisms, CYP2C9*1/*1-CYP2C19*1/*1 (G1: 41.17 %) genotype group was the most frequent whereas CYP2C9*1/*2-CYP2C19*1/*3 (G7: 0.98 %) was the least frequent one. The highest mean phenytoin level (27.95 ± 1.85 µg/ml) was detected in the G8 genotype group (CYP2C9*1/*3-CYP2C19*2/*3) and the G1 genotype group showed the lowest mean phenytoin level (7.43 ± 0.73 µg/ml). The mean serum concentration of phenytoin of the polymorphic patients with epilepsy was higher than that for the wild-type alleles both in the monotherapy and polytherapy patients. These results show the importance of the genetic polymorphism analysis of the main metabolizing enzyme groups of phenytoin for the dose adjustment.

To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis.

Background The overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors. Methods A retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries. Results From 2000 to 2010, 254 patients fulfilled inclusion criteria [140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT)], and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive). The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease. Conclusions In the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a ‘high-risk’ group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.

Background Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20–40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined. Methods Retrospective study of serous BOT+invasive implants treated with adjuvant CT. Results 36 patients were referred with serous BOTs+invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N=4). The majority (72%) received a combination of platinum+taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients. Conclusion This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants.

Objective To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. Design Retrospective multicenter study. Setting Teams having reported recurrence after FSS for EOC. Patient(s) Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. Intervention(s) FSS (salpingo-oophorectomy for a majority of cases) for EOC. Main Outcomes Measure(s) Recurrences rates and characteristics of recurrent disease. Result(s) Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28–294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow-up period of 34 months (range: 3–231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). Conclusion(s) The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences.

The buttocks are a major component of sexual attraction, and they have their place in the concept of beauty in most cultures and ethnic groups. The infragluteal sulcus, an important part of the gluteal region, determines the attractiveness of the buttocks. For that reason, any small change in the infragluteal sulcus makes a major cosmetic difference in the morphology of the buttock. In recent years, some flaps such as the infragluteal flap, the transverse upper gracilis flap, and the transverse musculocutaneous gracilis flap have become popular because of reduced donor area morbidity and their availability for hiding incision scars. In these cases, there may be distortion of the gluteal morphology and infragluteal sulcus. In this study, the anatomic and histologic features of the tissues that form the infragluteal sulcus were analyzed for their contribution to successful reconstruction of the infragluteal sulcus. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Objectives To assess the efficacy and morbidity of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) for relapsed ovarian granulosa cell tumors (OGCT). Study design Between 2007 and 2009, patients with relapsed OGCT who had been treated with HIPEC after CRS in our institution were retrospectively analyzed. Results We identified 7 patients who had undergone CRS plus HIPEC. Macroscopically complete cytoreduction had been performed in all patients. The location of the recurrence was exclusively the pelvis in 2 cases and both the pelvis and abdomen in 5 cases. We had administered an intraperitoneal perfusion of oxaliplatin (460mg/m 2 ) or oxaliplatin (360mg/m 2 ) plus irinotecan (360mg/m 2 ) heated up to 41–43°C for 30min. No post-operative mortality nor any grade IV morbidity (according to the Clavien and Dindo classification) had occurred. One lymphocyst (grade III) had appeared which had twice required percutaneous drainage. Six patients had experienced extra-abdominal complications (all grade II). Median follow-up after CRS plus HIPEC was 32 months (range, 25–56). Among the 7 patients, 2 are disease free, 3 had relapsed with peritoneal carcinomatosis and 2 had relapsed with liver metastases. Conclusions HIPEC (using oxaliplatin or oxaliplatin plus irinotecan) should not be recommended to treat relapsed OGCT.

Here we report the outcomes of 26 patients who relapsed following conservative surgical treatment of stage I serous borderline ovarian tumours treated initially with fertility-sparing surgery. All recurrences were diagnosed by systematic ultrasonography during follow-up. Eleven patients relapsed at least twice after such management. Twenty-one pregnancies were observed in 13 patients. Eleven of these patients became pregnant after the treatment of their first recurrence. All patients had a borderline ovarian tumour and/or non-invasive peritoneal implants at the time of the first recurrence but two of them had invasive ovarian and peritoneal disease at the time of the second or third recurrence (one of them died of disease). Fertility-preserving surgery remains a valuable alternative (if technically feasible), in young patients with recurrent SBOT, in the form of a non-invasive ovarian lesion, who wish to start a pregnancy. However, it should be associated with meticulous follow-up because the risk of progression to carcinoma exists, albeit small.

Purpose The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy. Patients and Methods We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded. Results Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET–computed tomography [CT] results)—16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001). Conclusion To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.

Women having access to prenatal care late in pregnancy may still wish to benefit from maternal serum screening for Down syndrome. Therefore, we established reference values for alpha-feto protein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG), and assessed the diagnostic value of maternal serum marker screening at 18-35 weeks' gestation based upon a series of 4072 sera from unaffected pregnancies and 118 sera from pregnant women with fetuses affected by Down syndrome. Using a 1/250 risk cut-off, a detection rate of 72.9% (95% CI = 71.5-74.3%) was achieved with a false-positive rate of 7.51% (95% CI = 6.71-8.3%). This was not significantly different from the percentages observed in our 14-17 weeks routine screening (50 596 patients): 71.9% (95% CI = 71.5-72.3%) and 6.48% (95% CI = 6.28-6.68%), respectively. Detection and screen-positive rates were, respectively, 51.3% (95% CI = 35.6-67.0%) and 5.95% (95% CI = 5.12-6.68%) in women aunder 35 years of age, and 84.8% (95% CI = 76.9-92.7%) and 24% (95% CI = 20.7-27.3%) in women aged 35 years and over. In conclusion, maternal serum marker screening is feasible at 18 weeks' gestation and later, which may be of interest in selected cases.

Background: The purpose of this study was to prospectively evaluate the combined use of The Memorial Sloan Kettering Cancer Center nomogram and Tenon score to select, in patients with metastatic sentinel lymph node (SN), those at low risk of metastatic non-SN for whom additional axillary lymph node dissection (ALND) could be avoided. Methods: From January 2011 to July 2012, a prospective non-interventional nationwide study was conducted (NCT01509963). We sought to identify the false reassurance rate (FRR, a negative test result is false) in patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 (low risk): the proportion of patients with metastatic non-SN at additional ALND. Our hypothesis was that these patients would have a FRR⩽5%. Results: Data on 2822 patients with breast cancer from 53 institutions were prospectively recorded. At least one SN was metastatic (isolated tumour cells, micro- or macrometastases) in 696 patients (24.7%). Among patients with ALND and complete data to calculate combined risk (n=504), 67 and 437 patients had low and high combined risk, respectively. Patients at low risk had less ALND (47%) compared to patients at high risk (P

Introduction Low-grade gliomas are infrequent lesions requiring special emphasis because of their relatively long follow-up time, and therefore the need for patients' well-being. Surgery provides not only increased survival but also improved quality of life for these patients. The purpose of this study was to present surgical series of frontal low-grade gliomas that were operated in our clinic and to discuss their epileptic and functional outcomes. Methods A series of 40 patients with low-grade glioma (WHO Grade II) were retrospectively analysed for patient characteristics, tumour location, epileptic history, surgery type (awake craniotomy, general anaesthesia), extent of resection and complications. Results Tumour was localized to primary motor area in most of the cases (35%, n = 14), 25 patients were operated under general anaesthesia and 15 with awake craniotomy. New deficit rate in the early postoperative period was 32.5% (dysarthria in one patient and motor deficits in 12). Karnofsky scores were ≥90 in 92.5% of the patients at the late follow-up. 31 patients were Engel I (77.5%), 5 were Engel II (12.5%) and 4 were Engel IV (10%) postoperatively. Conclusion Frontal LGGs are eligible to resect vigorously without persistent functional deficits. Patients with immediate postoperative complications benefit from neuro-rehabilitation. However, pre-existing speech dysfunctions are hard to recover with surgery. Surgical resection ends with favourable epileptic outcomes whereas tumour location may influence the results.

Background Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients and methods Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. Results The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. Conclusion The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS No 2007-A00399-44.