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Background: To assess skill enhancement and maintenance by virtual-reality simulation of laparoscopic salpingectomy in gynecologic surgery fellows. Skill acquisition by virtual-reality surgical simulation is an active field of research and technological development. Salpingectomy is one of the first gynecologic surgery techniques taught to fellows that requires accompanied learning., Methods: A single-center prospective study was performed in the University of Lyon, France, including 26 junior fellows (≤ 3 semesters' internship) performing laparoscopic salpingectomy exercises on a LapSim® virtual reality simulator. Salpingectomy was performed and timed on 3 trials in session 1 and 3 trials in session 2, at a 3-month interval. Analysis was based on students' subjective assessments and a senior surgeon's objective assessment of skill. Progress between the 2 sessions was assessed on McNemar test and Wilcoxon test for matched series., Results: 26 junior specialist trainees performed all trials. Most performed anterograde salpingectomy, both in session 1 (69 %) and session 2 (86 %). Mean procedure time was significantly shorter in session 2: 6.10min versus 7.82min (p=0.0003). There was a significant decrease in blood loss between the first trial in session 1 and the last trial in session 2: 167ml versus 70.3ml (p=0.02). Subjective assessment showed a significant decrease in anxiety and significant increase in perceived efficacy, eye-hand coordination and ergonomics. Efficacy, performance quality and speed of execution as assessed by the senior surgeon all improved significantly from trial to trial, while hesitation significantly decreased., Conclusions: The study showed that junior trainees improved their surgical skills on a short laparoscopic exercise using a virtual reality simulator. Virtual reality simulation is useful in the early learning curve, accelerating the acquisition of reflexes. Maintaining skill requires simulation sessions at shorter intervals., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: In the light of recent progress in pelvic organ prolapse surgery, the modalities of hospital admission need reconsidering. This work aims to assess success rate of outpatient (ambulatory) vaginal mesh surgery for genital prolapse., Methods: A prospective observational study was conducted between January 2015 and July 2017, including all patients presenting with POP-Q stage ≥3 anterior and/or apical prolapse., Results: Sixty-nine of the 89 eligible patients were treated on an ambulatory basis (group A); 20 required overnight admission (group B): i.e., ambulatory success rate, 77.5%. Mean operative time was 44.9±2.5 min in group A and 62±6.5 min in group B. Reasons for ineligibility for ambulatory management comprised organizational issues at home (10.5%) and excessive home-to-hospital distance (5.7%). The postoperative urinary retention rate was 4.5%. Rates for successful cystocele correction (POP-Q <2) at 2 months were similar in the two groups: 94.2% in group A and 94.4% in group B (P=ns). Mean satisfaction score was 8.6±0.3/10., Conclusions: Outpatient anterior vaginal mesh surgery for prolapse is safe and effective. The current medical-economic context favors ambulatory management. Patient selection, prior information and continuity of care seem primordial.

Malnutrition is a common comorbidity in patients with cirrhosis. Its prognostic value is indisputable as it greatly affects the evolution of liver diseases. It has a major impact on both morbi-mortality before and after liver transplantation. Being now integrated in the definition of malnutrition and recognized as a new entity in the international classification of diseases, physicians have taken great interest in sarcopenia. Its negative consequences on the fate of patients with cirrhosis are well-demonstrated. The concept of frailty has recently been enlarged to chronic liver diseases as symptoms of impaired global physical functioning. In this article, we will discuss the definitions of malnutrition and emphasize its links with sarcopenia and frailty. We will show the relevance of frailty and sarcopenia in the course of liver diseases. The emerging role of muscle depletion on the cardiorespiratory system will also be highlighted. The importance of body composition will be demonstrated and the main tools reviewed. Finally, we adapted the definition of malnutrition to patients with cirrhosis based on the assessment of sarcopenia together with reduced food intakes., Competing Interests: The author declares no conflict of interest.

Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). Severe alcohol relapse can rapidly lead to recurrent alcohol-related cirrhosis (RAC) for the graft. The aim of this study was to describe the natural history of RAC and the overall survival after LT and after an RAC diagnosis. From 1992 to 2012, 812 patients underwent primary LT for ALD in 5 French transplant centers. All patients with severe alcohol relapse and an RAC diagnosis on the graft were included. The diagnosis of cirrhosis was based on the analysis of liver biopsy or on the association of clinical, biological, radiological, and/or endoscopic features of cirrhosis. RAC was diagnosed in 57/162 patients (35.2%) with severe alcohol relapse, and 31 (54.4%) of those patients had at least 1 episode of liver decompensation. The main types of decompensation were ascites (70.9%), jaundice (58.0%), and hepatic encephalopathy (9.6%). The cumulative probability of decompensation was 23.8% at 5 years, 50.1% at 10 years, and 69.9% at 15 years after LT. During the follow-up, 36 (63.2%) patients died, the main cause of death being liver failure (61.1%). After diagnosis of cirrhosis, the survival rate was 66.3% at 1 year, 37.8% at 5 years, and 20.6% at 10 years. In conclusion, RAC is associated with a high risk of liver decompensation and a poor prognosis. Prevention of severe alcohol relapse after LT is a major goal to improve patient survival., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Objective: Postpartum urinary retention (PUR) is an uncommon complication of vaginal delivery, defined as a failure to void spontaneously in the six hours following vaginal birth. The objective of this study was to identify risk factors for PUR in order to provide prompt management., Study Design: A retrospective, comparative, case-control study, including two groups of 96 patients who delivered vaginally, was conducted at the Women and Children's University Hospital in Lyon, France. Patients were selected based on data extraction from the medical records of the obstetrics and gynecology department. The first group included patients with postpartum urinary retention and the second group, without PUR, was selected randomly, respecting 1:1 matching criteria, paired according to the year of delivery and patient's age at delivery., Results: Logistic regression analysis found that instrumental delivery (OR 13.42, 95%CI [3.34;53.86], p = 0.0002), absence of spontaneous voiding before leaving the delivery room (OR 6.14, 95%CI [2.56;14.73], p < 0.0001), no intact perineum (OR 3.29, 95%CI [1.10;9.90], p = 0.03) and vulvar edema or perineal hematoma (OR 8.05, 95%CI [1.59;40.67], p = 0.01) were independent risk factors associated with PUR., Conclusion: The present study identified risk factors for PUR that should be taken into consideration as soon as delivery is over in order to implement appropriate management. Future studies are needed to assess the contribution of early systematic bladder scanning in patients with risk factors for early diagnosis of PUR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To assess changes in quality of life after laparoscopic removal of Essure ® sterilization devices (Bayer AG, Leverkusen, Germany)., Study Design: In this prospective observational study in an academic research hospital, 80 women with new or worsening symptoms since placement of Essure ® sterilization devices undergoing subsequent surgical removal were included. Laparoscopic removal of Essure ® devices and salpingectomy with or without cornual excision were performed. Concomitant uterine procedures could be associated where indicated for gynaecological complaints. Comparison using the T student test for coupled series was done in this before-and-after study., Results: Health related quality of life (HRQL) was the primary outcome measured by the Short Form 12 (SF-12) questionnaire and a global 10 cm visual analogue scale (VAS). Secondary outcomes included assessment of pain, using continuous (VAS) and ordinal scales (Modified McGill Pain Questionnaire), menstrual bleeding (pictorial blood loss assessment chart (PBAC) score) and surgical feasibility and safety. There was a significant improvement in quality of life in both mental and physical health aspects of the SF-12 (34.02 (+/-1.19) vs. 49.61 (+/-1.42, P < .0001) and 36.55 (+/-0.99) vs. 43.32 (+/-1.18, P < .0001 respectively) as well as global VAS assessment (+2.91 (SD +/-0.27)) at the end of the first post-operative month. These improvements were maintained at three and six months. Mean pain decreased at one month following surgery compared to baseline (VAS 3.6 (+/-0.36) to 1.4 (+/-0.25), P < .0001 and McGill pain score 18.70 (+/-1.88) to 4.73 (+/-0.90), P < .0001). Improvements of a similar magnitude were observed when analysis was restricted to the 47 women without concomitant uterine surgery. No significant changes in bleeding were seen following of Essure ® device removal. Planned procedures were all successfully completed., Conclusion: Laparoscopic removal of Essure® devices in symptomatic women is technically successful and associated with short and medium-term improvement in quality of life as well as reduction in pelvic pain.

Objective: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) recurrent disease and the impact of colposcopic guidance at the time of LLETZ on that risk., Materials and Methods: From December 2013 to July 2014, 204 patients who had undergone LLETZ for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. The use of colposcopy during each procedure was systematically documented. The dimensions and volume of LLETZ specimens were measured at the time of the procedure before formaldehyde fixation. All participants were invited for a follow-up. The primary endpoint was the diagnosis of post-LLETZ recurrent disease defined as the histologic diagnosis of a high-grade cervical intraepithelial lesion., Results: The median duration of post-LLETZ follow-up was 25.8 months. Recurrent disease was diagnosed in 8 (3.6%) patients. Older than 38 years (adjusted hazard ratio [aHR] = 11.9, 95% CI = 1.6-86.0), history of excisional therapy (aHR = 21.6, 95% CI = 3.5-135.3), and the absence of colposcopy for the guidance of LLETZ (aHR = 6.4, 95% CI = 1.1-37.7) were found to significantly increase the risk of post-LLETZ recurrent disease. The dimensions and volume of the specimen were not found to have any impact. Only positive endocervical margins were identified to significantly increase the risk of post-LLETZ recurrent disease (aHR = 14.4, 95% CI = 2.0-101.1)., Conclusions: Risk factors of post-LLETZ recurrent disease are older than 38 years, history of excisional therapy, positive endocervical margins, and lack of colposcopic guidance at the time of LLETZ.

Menstrual toxic shock syndrome (mTSS) is a severe disease that occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock toxin 1 and who use tampons. The aim of the present study was to determine the impact of the composition of vaginal microbial communities on tampon colonisation by S. aureus during menses. We analysed the microbiota in menstrual fluids extracted from tampons from 108 healthy women and 7 mTSS cases. Using culture, S. aureus was detected in menstrual fluids of 40% of healthy volunteers and 100% of mTSS patients. Between class analysis of culturomic and 16S rRNA gene metabarcoding data indicated that the composition of the tampons' microbiota differs according to the presence or absence of S. aureus and identify discriminating genera. However, the bacterial communities of tampon fluid positive for S. aureus did not cluster together. No difference in tampon microbiome richness, diversity, and ecological distance was observed between tampon vaginal fluids with or without S. aureus, and between healthy donors carrying S. aureus and mTSS patients. Our results show that the vagina is a major niche of. S. aureus in tampon users and the composition of the tampon microbiota control its virulence though more complex interactions than simple inhibition by lactic acid-producing bacterial species.

Background: There is a lack of consensus regarding the treatment of inflammatory bowel disease (IBD) after liver transplantation (LT) forprimary sclerosing cholangitis (PSC)., Aim: To investigate the safety and effectiveness of anti-TNF therapy in patients with IBD after a LT for PSC., Methods: We reviewed the medical files of all of the IBD patients who underwent a LT for PSC and who were treated with anti-TNF therapy at 23 French liver transplantation centers between 1989 and 2012., Results: Eighteen patients (12 with ulcerative colitis and 6 who had Crohn's disease) were recruited at 9 LT centers. All of these patients received infliximab or adalimumab following their LT, and the median duration of their anti-TNF treatment was 10.4 months. The most frequent concomitant immunosuppressive treatment comprised a combination of tacrolimus and corticosteroids. Following anti-TNF therapy induction, a clinical response was seen in 16/18 patients (89%) and clinical remission in 10 (56%). At the end of the anti-TNF treatment or at the last follow-up examination (the median follow-up was 20.9 months), a clinical response was achieved in 12 patients (67%) and clinical remission in 7 (39%). A significant endoscopic improvement was observed in 9 out of 14 patients and a complete mucosal healing in 3 out of 14 patients (21%). Six patients experienced a severe infection. These were due to cholangitis, cytomegalovirus (CMV) infection, Clostridium difficile, cryptosporidiosis, or Enterococcus faecalis. Three patients developed colorectal cancer after LT, and two patients died during the follow-up period., Conclusions: Anti-TNF therapy proved to be effective for treating IBD after LT for PSC. However, as 17% of the patients developed colorectal cancer during the follow-up, colonoscopic annual surveillance is recommended after LT, as specified in the current guidelines., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study is to assess the prevalence of tubal histopathological abnormalities (serous tubal intraepithelial carcinoma STIC and p53 signatures) and the prevalence of perioperative and postoperative complications related to opportunistic laparoscopic salpingectomy in a low risk population., Materials and Methods: In this observational prospective cohort, prophylactic bilateral salpingectomy during benign laparoscopic hysterectomy was systematically performed in 100 consecutive women. Peri- and postoperative complications were registered. Duration of salpingectomy and post-salpingectomy blood loss were also measured. Histopathological and immunohistochemical analysis with anti-p53 antibody were performed on the whole fallopian tubes according to a specific and validated protocol., Results: Laparoscopic salpingectomy was always possible without any peri- or postoperative complication attributable to the salpingectomy itself. The mean duration was 428 seconds (354 - 596) and the blood loss was 9 cm 3 (2 - 15). Using histopathological and immunohistochemical assessment with anti-p53 antibody on 199 fallopian tubes (99 bilateral salpingectomies and one unilateral salpingectomy because of previous salpingectomy for ectopic pregnancy), there was a prevalence of 5.52% (11/199) of p53 signatures. No STIC were observed and no associated cancer., Conclusions: Laparoscopic salpingectomy is both feasible and innocuous during benign hysterectomy. Meticulous histopathologic examination of the tubes may reveal specific abnormalities.

Essentials The role of increased factor VIII in cirrhosis-induced hypercoagulability has never been demonstrated. Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin. Factor VIII elevation plays a significant role in cirrhosis-induced plasma hypercoagulability. Only protein C and factor VIII normalization led to thrombin generation similar to controls., Summary: Background In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed. Objectives We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM. Methods Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child-Turcotte-Pugh [CTP]-A, n = 61; CTP-B, n = 19; and CTP-C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were normalized by adding an inhibitory anti-FVIII antibody and exogenous PC, respectively. Results The endogenous thrombin potential (ETP) in the presence of TM was higher in patients than in controls. After FVIII normalization, the ETP (median) decreased from 929 nm min to 621 nm min (CTP-A), 1122 nm min to 1082 nm min (CTP-B), and 1221 nm min to 1143 nm min (CTP-C); after PC normalization, it decreased from 776 nm min to 566 nm min (CTP-A), 1120 nm min to 790 nm min (CTP-B), and 995 nm min to 790 nm min (CTP-C). The ETP was reduced by 17% and 30%, respectively, but normal TG was not restored. When both FVIII and PC levels were normalized, the ETP decreased from 929 nm min to 340 nm min (CTP-A), 1122 nm min to 506 nm min (CTP-B), and 1226 nm min to 586 nm min (CTP-C), becoming similar to control levels. Conclusion Cirrhosis-induced plasma hypercoagulability, as demonstrated in these experimental conditions, can be partly explained by opposite changes in two factors: PC level (decrease) and FVIII level (increase)., (© 2018 International Society on Thrombosis and Haemostasis.)

The electrochemical management of the proton concentration in miniaturized dimensions opens the way to control and parallelize multistep chemical reactions, but still it faces many challenges linked to the efficient proton generation and control of their diffusion. Here we present a device operated electrochemically that demonstrates the control of the pH in a cell of ∼140 nL. The device comprises a microfluidic reactor integrated with a pneumatic mechanism that allows the exchange of reagents and the isolation of protons to decrease the effect of their diffusion. We monitored the pH with a fluorescence marker and calculated the final value from the redox currents. We demonstrate a large pH amplitude control from neutral pH values beyond the fluorescence marker range at pH 5. On the basis of the calculations from the Faradaic currents, the minimum pH reached should undergo pH ∼ 0.9. The pH contrast between neutral and acid pH cells can be maintained during periods longer than 15 min with an appropriate design of a diffusion barrier.

Introduction and Hypothesis: The objective was to evaluate the surgical feasibility of opportunistic salpingectomy or salpingo-oophorectomy during benign vaginal hysterectomy (HV) and the prevalence of occult tubal lesions., Methods: In this prospective study from 1 September 2013 to 1 November 2015, the prevalence of bilateral salpingectomy with or without ovariectomy and the prevalence of histopathological and immunohistochemical tubal abnormalities were assessed., Results: A total 115 patients were included. Bilateral salpingectomy was performed in 85 patients (73.92%; group A) and was technically impossible in 30 patients (26.08%; group B). Older patients (62.9 vs 57.5 years, p = 0.009), menopausal status (83.33% vs 62.35%, p = 0.03) and elevated BMI (27.58 vs 25.05 p = 0.03) were statistically associated with failure of salpingectomy. There was only one case of postoperative hemorrhage in group A. There was no difference with regard to intra- or postoperative complications, blood loss, and operating time between the two groups. Among the 67 fallopian tubes analyzed with a validated histopathological protocol, there were 8 (11.94%) immunohistochemical abnormalities with a "p53 signature.", Conclusions: With the recent demonstration of a tubal origin of most ovarian cancer, opportunistic salpingectomy could be a theoretically relevant prevention strategy. Bilateral salpingectomy could be performed during benign vaginal hysterectomy by experienced surgeons. The advantages and disadvantages of exclusive salpingectomy during pelvic floor surgery should be discussed with the patients.

Objective: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy., Materials and Methods: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis., Results: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colposcopy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027)., Conclusions: Although the risk of post-LLETZ inadequate colposcopy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins.

Background: The outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay., Aim: To perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay., Methods: The files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease., Results: Between 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests., Conclusions: In patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies., (© 2017 John Wiley & Sons Ltd.)

The reversibility of redox processes is an important function for sensing and molecular electronic devices such as pH reporters or molecular switches. Here we report the electrochemical behaviour and redox reversibility of para-aminothiolphenol (PATP) after different polymerisation methods. We used electrochemical and photo-polymerisation in neutral buffers and plasma polymerisation in air to induce reversible redox states. The chemical stoichiometry and surface coverage of PATP in the polymerized layers were characterized by X-ray photoelectron spectroscopy (XPS), while cyclic voltammetry (CV) was used to measure the charge transfer, double layer capacitance and electrochemical rate of the layers during successive potential cycles. Our results show that the surface coverage of the redox active species is higher on electro-polymerised samples, however, after consecutive cycles all the methods converge to the same charge transfer, while the plasma polymerised samples achieve higher efficiency per molecule and UV polymerised samples have a higher electron transfer rate.

Background: The prediction of persistent common bile duct stones (CBDS) in patients during choledocholithiasis crisis is challenging. We developed a model based on the course over time of commonly used biochemical parameters to reduce the rate of unnecessary endoscopic cholangiopancreatography (ERCP) and the risk of perioperative discovery of CBDS., Methods: Medical charts of patients who presented between 2010 and 2015 for symptomatic gallstone disease with suspected choledocholithiasis were reviewed and compared according to the presence/absence of CBDS on preoperative ERCP or during cholecystectomy., Results: 210 patients were included. Unnecessary ERCP and the discovery rate of CBDS were 9.0 and 22.4%, respectively. Multivariate analysis demonstrated age ≥80 years, neutrophils ≥12000/µL and gamma-glutamyl transpeptidase (GGT) ≥300 units/L at admission, alkaline phosphatase ≥180 units/L at days 3-5 post admission, and a decrease in C-reactive protein ≤10%, aspartate aminotransferase ≤35%, GGT ≤25%, and total bilirubin ≤15% between day 0 and days 3-5 to be predictive of CBDS. The area under the receiver-operator characteristic curve was 0.881. When used to select patients for preoperative ERCP, diagnostic accuracy was 94.8% when three predictors were present. Negative and positive predictive values were 100% in the absence of predictors and when five predictors were present, respectively. Unnecessary ERCP and CBDS discovery rates both decreased to 2.6%., Conclusions: Commonly used biochemical parameters correctly predict CBDS when they are analysed in a dynamic setting rather than at discrete time points. The proposed model constitutes a reliable tool to decrease unnecessary ERCP and perioperative discovery rates of CBDS.

There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD . To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis ( n = 9), normal liver ( n = 6) and NAFLD ( n = 13). Metabolomics was performed using 1H-NMR Spectroscopy on tissue extracts and combined to multivariate statistical analysis. In HCC compared to NTT, statistical models showed high levels of lactate and phosphocholine, and low level of glucose. Shared and Unique Structures (SUS) plots were performed to remove the impact of underlying disease on the metabolic profile of HCC. HCC-cirrhosis was characterized by high levels of β-hydroxybutyrate, tyrosine, phenylalanine and histidine whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. In addition, the overexpression glutamine/glutamate on HCC-NAFLD was confirmed by both Glutamine Synthetase (GS) immuno-staining and NMR-spectroscopy glutamine quantification. This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processes., Competing Interests: The authors declare no conflict of interest.

Introduction: To investigate the technical feasibility of optical biopsy (probe-based confocal laser endomicroscopy [pCLE]) during laparoscopy and by the vaginal route in the exploration of pelvic gynecological cancers., Methods: Prospective study including 31 patients undergoing laparoscopic hysterectomy (benign or malignant indication). Confocal microlaparoscopy (analysis of tubes, ovaries, and depending on the type de cancer, pelvic adenopathies) and optical biopsy of the endometrium were first carried out by the vaginal route under general anesthesia. The surgical procedure was then carried out., Results: Thirty-one consecutive patients were included (16 for benign hysterectomy, 12 for endometrial cancer and 3 for ovarian carcinoma). pCLE offered dynamic pictures that were correlated with the histopathological images., Discussion and Conclusion: pCLE provides high resolution imaging of cancerous and benign tissues in real-time similar to histopathological results. Both feasibility and safety were confirmed., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To compare ovarian function before and after laparoscopic hysterectomy with bilateral salpingectomy for benign lesions with two different systems of haemostasis., Methods: In this prospective randomized study comparing two types of energy used for coagulation in bilateral salpingectomy (group A: bipolar electric energy, versus group B: ultrasonic advanced energy [Harmonic ® ]), forty consecutive non-menopausal patients undergoing laparoscopic hysterectomy for benign lesions were included. Values of anti-Müllerian hormone (AMH), LH and FSH, antral follicle count (AFC) and ovarian vascularization on bilateral Doppler ultrasound, quality of life (questionnaire) were assessed preoperatively and at 1 and 3 months postoperatively., Results: Preliminary analysis showed shorter salpingectomy operating time (P<0.0001) and less bleeding (P<0.005) in group B. In group A, there was no statistical difference except a decrease in AFC at 1 and 3 months on the right ovary (P=0.04). In group B, AMH levels were significantly lower postoperatively at 3 months and LH levels were increased at 3 months (respectively P=0.02 et P=0.04). There was no statistical difference in the ultrasonographic data. Quality of life did not significantly differ in both groups., Conclusion: Preliminary findings showed reduced AMH levels at 3months postoperatively in ultrasonic energy group whereas there was no significative menopausal symptoms. It seems important to continue this study in order to know the real effects of both energy systems on the ovarian function., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: Recently it has been postulated that most ovarian cancers have a tubal origin. The identification of preinvasive tubal lesions would be of great interest in the early diagnosis of ovarian cancer. Optical biopsy has been developed and validated in the detection of precancerous lesions (such as Barrett's oesophagus). The first objective of this study was to assess the feasibility of optical biopsy in the study of fallopian tubes during laparoscopy. The second objective was to describe the images in benign premalignant and malignant tubes with a histopathological and immunohistochemical (p53 and Ki67 expressions) correlation., Study Design: In this prospective study, 40 patients undergoing laparoscopic salpingectomy for benign conditions (benign hysterectomy), prophylactic conditions (BRCA mutation) or in case of pelvic cancers were included after obtaining informed and signed consent prior to surgery. The optical biopsy was performed on the fimbria of each tube in and ex vivo. A correlation was made with the histopathological and immunohistochemical analysis., Results: The feasibility of optical biopsy was always confirmed during laparoscopy. The optical biopsy iconography revealed different images in benign tubal epithelium (well-defined black and grey structure), in adenomatoid tumour (tortuous architectural organization), in STIC precancerous lesion (enlarged, irregular and pleomorphic cells, dilated and distorted vessels) and in tubal metastasis of high grade serous ovarian cancer (dark neoplastic cells irregular in size and shape) CONCLUSIONS: Optical biopsy may be the first emerging mini-invasive technology that could detect tubal lesions and may be considered as a promising tool in the early detection of ovarian cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess postoperative complications, improvement of pain symptoms and residual urinary functional symptoms after surgery for deep infiltrative endometriosis affecting ureter or bladder., Methods: Retrospective study of complications (Clavien-Dindo classification), pain (visual analog scale [VAS]) and urinary functional symptoms (Urinary Symptom Profile questionnaire [USP]) of patients surgically treated between 2007 and 2015 in University Hospitals of Lyon., Results: Among 31 patients with endometriosis involving the bladder, 83.9% had a partial cystectomy and 16.1% an extra-mucosal resection. Among patients (n=20) with ureteral involvement, 85% had ureterectomy with ureterocystoneostomy and 15% had only ureterolysis. Grade III postoperative complications occurred in 6% and 0% of patients with bladder or ureteral surgery, respectively and no grade IV or V complications were reported. Mean bladder VAS dropped from 5.3±4.2 to 0.3±0.9 after a follow-up of 42 months (P<0.0001). In patients with ureteral involvement, mean flank VAS dropped from 3.6 to 0.9 after a follow-up of 33 months (P<0.0005). Mean postoperative USP score for dysuria and detrusor overactivity were 1.35/9 and 2.48/21 in case of bladder involvement, and 1.10/9 and 2.15/21 in case of ureteral involvement., Conclusion: Multidisciplinary surgical management of deep infiltrative endometriosis affecting urinary tract was associated to a low risk of severe postoperative complications and to a long-term significant improvement of pain symptoms without significant residual functional urinary symptoms., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: The aim of the study was to determine which mathematical formula of specimen dimensions is the most accurate method of determining volume of the excised specimen at loop excision of the transformation zone., Materials and Methods: A multicenter prospective observational study was conducted. A total of 258 patients who had a loop excision of the transformation zone performed as treatment of cervical intraepithelial neoplasia 2-3 were included. The dimensions and the volume of the specimen were measured at the time of the procedure, before formaldehyde fixation. The volume was measured by immersing the specimen in a graduated cylinder using Archimedes fluid displacement technique. The measured volume was compared with the calculated volume using different volume formulas, that is, a cone, a cylinder, a parallelepiped, and a hemiellipsoid. The main outcome measure was the relationship between calculated volume (using the dimensions of thickness, length, and circumference) and the measured volume of the specimen., Results: The mean (SD) thickness, length, and circumference of specimens were 8.8 mm (3.8), 12.7 mm (5.9), and 45.7 mm (16.8), respectively. The mean (SD) measured volume was 2.53 (1.49) mL. Using the formula for the volume of a cone, a cylinder, a parallelepiped and a hemiellipsoid, estimated volumes were 1.03 mL (1.22), 3.10 mL (3.65), 6.20 mL (7.31), and 2.07 mL (2.44), respectively. The highest intraclass correlation coefficient between measured and calculated volume was observed when using the formula for the volume of a hemiellipsoid specimen (0.47, 95% CI = 0.36-0.56)., Conclusions: The hemiellipsoid formula is the most accurate determinant of the excised volume. Other formulas do not allow for an accurate estimation of the excised volume.

Background and Aims: Cirrhosis significantly changes all hemostasis steps. Recent studies suggest that cirrhosis is associated with a coagulopathy leading to a hypercoagulable state. The underlying mechanisms are not fully understood, but protein C deficiency is probably a major determinant of this phenotype. The aim of this study was to compare the results of thrombin generation assays performed with addition of thrombomodulin or activated protein C to assess the effect of by-passing the protein C activation step in cirrhotic patients and healthy controls., Methods: Fifty-eight patients with cirrhosis and 26 healthy controls were prospectively included in this study. Thrombin generation was determined in platelet-poor plasma using 5 pM of tissue factor and 4 nM of phospholipids, without and with external addition of 1 nM thrombomodulin or 4 nM activated protein C. All results were normalized with the values of a pool of normal plasma samples to limit inter-plate variability., Results: When thrombin generation assays were performed in the presence of thrombomodulin, endogenous thrombin potential (ETP) and ETP with/ETP without TM ratio were significantly higher in cirrhotic patients than in healthy controls (P < 0.0001). Moreover, these values progressively increased with cirrhosis severity. When thrombin generation assays were performed with activated protein C, all thrombin generation parameters were comparable between healthy controls and cirrhotic patients, despite an acquired protein S deficiency., Conclusion: In the presence of activated protein C, no hypercoagulability was observed, adding to the current evidence that acquired protein C deficiency plays a key role in the coagulation imbalance., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Several direct-acting antiviral agents (DAAs) have marketing authorization in Europe and in the USA and have changed the landscape of hepatitis C treatment: each DAA has its own metabolism and drug-drug interactions (DDIs), and managing them is a challenge. To compile the pharmacokinetics and DDI data of the new DAA and to provide a guide for management of DDI. An indexed MEDLINE search was conducted using the keywords: DAA, hepatitis C, simeprevir, daclatasvir, ledipasvir, sofosbuvir, 3D regimen (paritaprevir/ritonavir, ombitasvir, dasabuvir), DDI and pharmacokinetics. Data were also collected from hepatology, and infectious disease and clinical pharmacology conferences abstracts. Food can play a role in the absorption of DAAs. Most of the interactions are linked to metabolism (cytochrome P450-3 A4 [CYP3A4]) or hepatic and/or intestinal transporters (organic anion-transporting polypeptide and P-glycoprotein [P-gp]). To a lesser extent other pathways can be involved such as breast cancer resistance protein transporter or UDP-glucuronosyltransferase metabolism. DDI are more likely to occur with 3D regimen, daclatasvir, simeprevir and ledipasvir, as they are all both substrates and inhibitors of P-gp and/or CYP3A4, than with sofosbuvir. They can increase concentrations of coadministered drugs and their concentrations may be influenced by P-gp or CYP3A4 inducers or inhibitors. Overdosage or low dosage can be encountered with potent inducers or inhibitors of CYP3A4 or drugs with a narrow therapeutic range. The key to interpret DDI data is a good understanding of the pharmacokinetic profiles of the drugs involved. Their ability to inhibit CYP450-3A4 and transporters (hepatic and/or intestinal) can have significant clinical consequences., (© 2016 The British Pharmacological Society.)

Objective: We sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort., Study Design: For this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure., Results: Between February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%., Conclusion: In this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We describe here a case of high-grade vaginal squamous lesion in a 54-year-old woman with a papillomaviruses (HPV) genital infection that developed from a cervical low-grade squamous intraepithelial lesion (SIL) to a high-grade SIL (H-SIL) on cytological examination. A colposcopy exam led to the detection of suspect vaginal lesions with granulomatous infiltrations, which were classified as a Vaginal Intra-Epithelial Neoplasia grade 2 after pathologists' analyses. After a laser vaginal surgery and a loop excision of the transformation zone, the analyses of the anatomical pieces using a near-complete HPV screening panel revealed an HPV-4 infection that was not detected before in cervical smears. This HPV-infection is associated with a high human herpesvirus type 6A (HHV-6A) viral load in the same anatomical piece. The presence of an inherited chromosomally integrated HHV-6A (iciHHV-6A) was proved in this patient by real-time polymerase chain reaction on hair follicles and nail. This case suggests reconsidering both the benign nature of low-grade lesions in the female genital tract and the well-known "good" prognosis of low-risk HPV infection, especially when iciHHV-6A is diagnosed. This clinical course insists on the benefits of the multiplex panel use or global sequencing in order to optimize biological testing sensitivity, and so enhance clinical management of infection-induced neoplasia., (© 2017 S. Karger AG, Basel.)

Introduction and Hypothesis: To compare apical correction in stage ≥3 cystocele between two mesh kits., Methods: This was a retrospective, nonrandomized study that compared two groups matched on anterior/apical POP-Q stage: 84 received Elevate Ant™ single-incision mesh (Elevate Ant group) and 42 Perigee™ transvaginal mesh (Perigee group). Follow-up at 1 and 2 years comprised objective (POP-Q) and subjective (PFDI-20, PFIQ-7, PISQ-12) assessments. The primary endpoint was objective success: 2-year apical POP-Q stage ≤1. Secondary endpoints were anterior POP-Q stage, subjective results and complications., Results: Groups were comparable in terms of age (66.6 and 64.7 years, respectively; p = 0.19), BMI (both 25.4 kg/m 2 ; p = 0.93), and history of hysterectomy (7.2 % and 14.3 %; p = 0.21) or prolapse surgery (12 % and 14.3 %; p = 0.72). Operative time was shorter in the Elevate Ant group (54.1 vs. 62.5 min; p = 0.048), and the 2-year objective apical success rate was higher (92.9 % vs. 66.7 %; p < 0.0001), with better point C correction (-5 vs. -3.8; p = 0.006). Function improved in both groups, with significantly better PFIQ-7 (p = 0.03) and PFDI-20 (p = 0.02) scores in the Elevate Ant group at 2 years. Vaginal exposure was not seen in the Elevate Ant group but occurred in two patients in the Perigee group (p = 0.33). Factors associated with success were age >65 years (OR 7.16, 95 % CI 1.83 - 27.97) and treatment with Elevate Ant mesh (OR 10.16, 95 % CI 2.78 - 37.14). Postoperative stress urinary incontinence rate was greater with the Elevate Ant group (29.8 % and 16.7 %; p = 0.11)., Conclusions: The use of the Elevate Ant mesh was associated with significantly better apical correction at 2 years. Function improved in both groups, but with a significantly better PFDI-20 score in the Elevate Ant group at 1 and 2 years. The postoperative stress urinary incontinence rate, however, tended to be greater in the Elevate Ant group. The results need confirming with longer follow-up of these cohorts and in randomized studies.