Robotic assisted laparoscopy for deep infiltrating endometriosis.

Deep infiltrative endometriosis is a condition affecting up to 15 % of women of childbearing age, defined by extra uterine location of endometrial like tissues. The symptoms of endometriosis range from severe dysmenorrhea to infertility, chronic pelvic pain, bowel dysfunction and urinary tract involvement to name the most common. Endometriosis has an impact on the quality of life of patients, with personal and social consequences. Although medical treatment is indicated in the first instance, surgery may be necessary. Standard laparoscopy has become the gold standard for this surgery. However, surgery for deep infiltrative endometriosis is known to be highly complex, and the significant development of robotic assistance in recent years has had an impact on the evolution of surgical practice. This comprehensive review of the literature provides an overview of the contributions of robotic surgery in the field of endometriosis and gives an insight into the next steps in its development.

Robot-assisted laparoscopy for deep infiltrating endometriosis: a retrospective French multicentric study (2008-2019) using the Society of European Robotic Gynecological Surgery endometriosis database.

OBJECTIVE: This study aimed at assessing perioperative results of robot-assisted laparoscopy (RAL) in the context of deep infiltrating endometriosis (DIE). METHODS: This retrospective French multicentric study included all patients with DIE who underwent surgical treatment managed by RAL (Da Vinci® System). From November 2008 to June 2019, patients were included in a single European database, in Robotic Assisted Laparoscopic Gynecologic Surgery, with Society of European Robotic Gynecological Surgery collaboration. Patients had different DIE sites as follows: gynecological, urological, or digestive, or combinations of these. Surgical procedures and perioperative complications were evaluated. To assess complications, patients were divided into the following four groups according to surgical procedure and DIE site: gynecological only; gynecological and urological; gynecological and digestive; and gynecological, urological, and digestive. RESULTS: A total of 460 patients treated at one of eight health-care facilities from November 2008 to June 2019 were included. Median operative time was 245 min (IQR 186-320), surgeon console time was 138 ± 75 min and estimated blood loss was 70.0 mL ± 107 mL. Among this patient sample, 42.1% had a multidisciplinary surgical approach with a digestive or urology surgeon in addition to gynecology surgeon (25.5% and 16.6% of cases, respectively). Among those with intraoperative complications (n = 25, 5.4%) were primarily conversion to laparotomy (n = 6, 2.0%), transfusion (n = 2, 0.6%), and organ wounds (n = 8, 1.7%). Overall, 5.6% had severe postoperative complications (Clavien-Dindo classification ≥ Grade 3). CONCLUSION: This is among the largest published series addressing RAL for DIE. Interest in this procedure appears promising, with no observed increases in blood loss or in peri- or post-operative complications. DIE laparoscopic surgery can require complex surgical procedures performed by multidisciplinary surgical teams. Thus, it may be one of the best candidates for RAL within gynecology surgery.

Lomboaortic Lymphadenectomy in Gynecological Oncology: Laparotomy, Laparoscopy or Robot-Assisted Laparoscopy?

BACKGROUND: The outcomes of paraaortic lymphadenectomy were compared for the treatment of gynecological malignancies to identify the most appropriate surgical approach. METHODS: Our retrospective, multicentric study included 1304 patients who underwent paraaortic lymphadenectomy for gynecological malignancies. The patients were categorized into the following five groups based on treatment type: transperitoneal laparoscopy (group A, n = 198), extraperitoneal laparoscopy (group B, n = 681), robot-assisted transperitoneal laparoscopy (group C, n = 135), robot-assisted extraperitoneal laparoscopy (group D, n = 44), and laparotomy (group E, n = 246). RESULTS: The prevalence of cancer types differed according to the surgical approach: there were more ovarian cancers in group E and more cervical cancers in groups B and D (p < 0.001). Estimated blood loss was higher in group E (844.2 mL) than in groups treated with minimally invasive interventions (115.8-141.5 mL, p < 0.005). For infrarenal dissection, fewer nodes were removed in group C compared with the other approaches (16 vs. 21 nodes, respectively, p < 0.05). The average operative time ranged from 169 min for group A to 247 min for group E (p < 0.001). Length of hospital stay was 14 days for group E versus 3.5 days for minimally invasive procedures (p < 0.05). The early postoperative grade 3 and superior Dindo-Clavien complications occurred in 9-10% of the patients in groups B-D, 15% of the patients in group E, and only 3% and 4% for groups A and C, respectively. The most common complication was lymphocele. CONCLUSIONS: Laparotomy increases preoperative and postoperative morbidity. The robot-assisted transperitoneal approach demonstrated a poorer lymph node yield than laparotomy and extraperitoneal approaches.

The amidated PACAP1-23 fragment is a potent reduced-size neuroprotective agent.

BACKGROUND: Neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by neuronal death involving, among other events, mitochondrial dysfunction and excitotoxicity. Along these lines, several attempts have been made to slow this pathology but none have been yet discovered. Based on its capacity to cross the blood-brain barrier and provide neuronal protection in vitro and in vivo, the pituitary adenylate cyclase-activating polypeptide (PACAP) represents a promising lead molecule. Pharmacological studies showed that PACAP interacts with three different G protein-coupled receptors, i.e. PAC1, VPAC1 and VPAC2. However, only PAC1 is associated with neuronal anti-apoptotic actions, whilst VPAC activation might cause adverse effects. In the context of the development of PAC1-selective agonists, PACAP(1-23) (PACAP23) appears as the shortest known PACAP bioactive fragment. METHODS: Hence, the capacity of this peptide to bind PACAP receptors and protect neuroblastoma cells was evaluated under conditions of mitochondrial dysfunction and glutamate excitotoxicity. In addition, its ability to activate downstream signaling events involving G proteins (Gαs and Gαq), EPAC, and calcium was also assessed. RESULTS: Compared to the endogenous peptide, PACAP23 showed a reduced affinity towards PAC1, although this fragment exerted potent neuroprotection. However, surprisingly, some disparities were observed for PACAP23 signaling compared to full length PACAP, suggesting that downstream signaling related to neuroprotection is distinctly regulated following subtle differences in their PAC1 interactions. CONCLUSIONS: Altogether, this study demonstrates the potent neuroprotective action of amidated PACAP23. GENERAL SIGNIFICANCE: PACAP23 represents an attractive template for development of shorter PACAP-derived neuroprotective molecules.

The definition of Endometriosis Expert Centres.

Endometriosis is a common condition that causes pain and infertility. It can lead to absenteeism and also to multiple surgeries with a consequent risk of impaired fertility, and constitutes a major public health cost. Despite the existence of numerous national and international guidelines, the management of endometriosis remains suboptimal. To address this issue, the French College of Gynaecologists and Obstetricians (CNGOF) and the Society of Gynaecological and Pelvic Surgery (SCGP) convened a committee of experts tasked with defining the criteria for establishing a system of care networks, headed by Expert Centres, covering all of mainland France and its overseas territories. This document sets out the criteria for the designation of Expert Centres. It will serve as a guide for the authorities concerned, to ensure that the means are provided to adequately manage patients with endometriosis.

[Definition of endometriosis expert centres]. / Définition des centres experts en endométriose.

OBJECTIVES: The Collège national des gynécologues obstétriciens français (CNGOF), in agreement with the Société de chirurgie gynécologique et pelvienne (SCGP), has set up a commission in 2017 to define endometriosis expert centres, with the aim of optimizing endometriosis care in France. METHODS: The committee included members from university and general hospitals as well as private facilities, representing medical, surgical and radiological aspects of endometriosis care. Opinion of endometriosis patients' associations was obtained prior to writing this work. The final text was presented and unanimously validated by the members of the CNGOF Board of Directors at its meeting of October 13, 2017. RESULTS: Based on analysis of current management of endometriosis and the last ten years opportunities in France, the committee has been able to define the contours of endometriosis expert centres. The objectives, production specifications, mode of operation, missions and funding for these centres were described. The following missions have been specifically defined: territorial organization, global and referral care, communication and teaching as well as research and evaluation. CONCLUSION: Because of its daily impact for women and its economic burden in France, endometriosis justifies launching of expert centres throughout the country with formal accreditation by health authorities, ideally as part of the National Health Plan.

[Treatment of vulvar intra-epithelial neoplasias with Imiquimod]. / Traitement des néoplasies vulvaires intra-épithéliales par imiquimod.

The incidence of vulvar intra-epithelial neoplasia (VIN) is increasing in the developed countries especially in young women. There is little consensus regarding the optimal management. Surgery used to be the gold standard. Alternatives to surgery are now needed for the treatment of VIN. Many studies investigated the effectiveness of Imiquimod 5% cream in this pathology. We present a literature review of the results published on the subject.

[Robotic assisted laparoscopy: comparison of segmentary colorectal resection and shaving for colorectal endometriosis]. / Laparoscopie robot-assistée pour endométriose colorectale: morbidité de la résection digestive et du shaving.

OBJECTIVES: To compare perioperative complications of two surgical methods for digestive endometriosis management: "shaving" and colorectal resection in robotic-assisted laparoscopy. METHODS: Twenty-eight women underwent robotic-assisted laparoscopy for digestive endometriosis, confirmed histologically. Six women had a digestive resection and twenty-one women had a shaving procedure. Short-term and long-term results and complications were compared between the two groups. RESULTS: Operative time was significantly shorter (P=0.0002) and estimated blood loss was significantly lower (200 ml vs 560 ml, P=0.04) in the shaving procedure group in comparison with the resection group. We observed one conversion to laparotomy in the resection group and one case of bladder injury in the shaving group. Length of hospital stay was longer (P=0.0001) in the resection group than in the shaving group. At the two-month re-evaluation, there was no significant difference between the two groups for the number of women in full remission for pelvic pain, urinary or gastrointestinal symptoms or dyspareunia. Two women of the resection group reported functional gastrointestinal signs that persisted 24 months after the intervention. CONCLUSION: Both immediate and delayed operative morbidity are more frequent in case of resection. Surgery for deep infiltrating endometriosis, even if operated with robotic assisted laparoscopy, is associated with significant morbidity.

[Quilting suture after mastectomy in prevention of postoperative seroma: a prospective observational study]. / Intérêt du capitonnage de la loge de mastectomie dans la prévention des séromes post-opératoires : étude prospective.

OBJECTIVES: The occurrence of a postoperative seroma is the main complication of mastectomy. In 2011, Ouldamer et al. adapted a quilting technique used in reconstructive surgery in mastectomy closure. The aim of this study is to evaluate the impact of quilting in the prevention of postoperative seroma. PATIENTS AND METHODS: This is an observational prospective study to the Centre Hospital-University of Tours. Hundred and forty-four patients who underwent a mastectomy between January 1st, 2011 and October 1st, 2012 were included. Patients were divided into 2 groups, one with a classic wound closure with drainage and the second with quilting suture of skin flaps to the underlying musculature after mastectomy without drainage. RESULTS: Quilting suture significantly reduces the postoperative seroma appearance (OR=0.15; CI95% [0.06-0.39]; P<0.001). Operative time is increased by 20minutes in the quilted group (P<0.001). Postoperative pain is not changed by quilting. The duration of hospitalization is significantly shorter (5.09±1.46 days versus 6.49±2.77 days; P<0.001). Quality of the healing and appearance of the scar, rated by patients, are identical in both groups. CONCLUSION: Quilting is an effective method not only for prevention of seroma, but also for reducing of hospitalization duration, without increasing of postoperative pain and complications.

[Robotic-assisted laparoscopy for deep infiltrating endometriosis: the Register of the Society of European Robotic Gynaecological Surgery]. / Place de la robotique dans l'endométriose pelvienne profonde : à propos du registre de la SERGS.

OBJECTIVES: To assess the interest of robotic-assisted laparoscopy in the context of deep infiltrating endometriosis and to investigate perioperative results. PATIENTS AND METHODS: From November 2008 to April 2012, 164 women with stage IV endometriosis who underwent robotic-assisted laparoscopy (DA VINCI Intuitive Surgical System(®)) were included by eight international participating clinical centers. Patients were divided in 4 groups according to the localization of the nodule(s): rectum (n=88), bladder (n=23), ureter and uterosacral ligaments (n=115) et hysterectomy (n=28). We evaluated the procedures performed, the duration of intervention, the complications, the recurrence and the impact on fertility. RESULTS: In the rectum group, there was a laparotomy conversion, 2 sutured rectal injuries and a red cells blood transfusion. In the bladder group, there was a vesicovaginal hematoma and a prolongated intermittent self-catheterization. In the ureter and uterosacral ligaments group, there was 2 ureteral fistulas and there was no complication in the hysterectomy group. DISCUSSION AND CONCLUSION: This study is the largest series published in the literature on robotic-assisted laparoscopy for deep infiltrating endometriosis. The interest of robotic-assisted laparoscopy in deep infiltrating endometriosis seems to be promising while no increase in surgical time, blood loss, and intra- and postoperative complications were observed.

[Bartholin's gland carcinoma]. / Cancer de la glande de Bartholin.

Bartholin gland carcinoma is a rare tumor. Treatment is not consensual due to the absence of prospective and randomized controlled trials. Bartholin gland carcinoma is actually treated similarly to primary median squamous cell carcinoma of the vulva. Here we report two cases of 42- and 67-year-old females who developed respectively an adenoid cystic carcinoma, and a squamous carcinoma of Bartholin gland.

Overall care cost comparison between robotic and laparoscopic surgery for endometrial and cervical cancer.

OBJECTIVE: The aim of our medico-economic study was to compare robotic surgery cost with conventional laparoscopic cost in endometrial and cervical cancer. STUDY DESIGN: Our study included laparoscopic and robot-assisted procedures (radical hysterectomies and lymphadenectomies) for endometrial or cervical cancer ever since first using the Da Vinci® in 2008 within a hospital setting. In the hospital perspective, direct costs were determined by examining the overall medical pathway for each type of intervention. Actual costs were calculated for 27 conventional laparoscopic procedures and for 30 robot-assisted procedures including initial cost of the robot and its maintenance. We estimated the complete medical "overall care" costs by adding the costs of consultations, surgery and post-operative hospital stay to the costs of any eventual emergency consultation and/or hospitalisation within the two months that followed surgery. A sensitivity analysis was performed to evaluate the effects of variable modulations. RESULTS: For endometrial cancer, surgical procedure cost for robotic-assisted surgery was €7402 compared to €2733 for conventional laparoscopic surgery. When considering overall medical care, the patient treatment average cost was €6666 for the laparoscopic group (with an average length of stay of 5.27 days) as compared to €10,816 for robotic group (with an average hospital stay of 4.60 days), p=0.39. For cervical cancer, average surgical cost with robotic-assisted surgery was €8501 compared to conventional laparoscopic surgery at €3239. For cervical cancer, overall care average cost was €7803 for the laparoscopic group (with an average length of stay of 5.83 days) as compared to €12,211 for the robotic group (with an average hospital stay of 4.70 days) p=0.07. Sensitivity analysis results confirmed the cost overrun with the use of robotic assisted surgery. CONCLUSIONS: Conventional laparoscopy was less expensive in our institution than robotic-assisted surgery for the surgery of endometrial (1:2.7) and cervical (1:2.6) cancers. When considering overall medical care, the use of robotic-assisted surgery was found to be 1.6 times more expensive than conventional surgery.

Assessment of supplement use (including vitamin D) in Inuvialuit adults in the Northwest Territories, Canada.

BACKGROUND: Inuvialuit of Arctic Canada are at high risk for inadequate vitamin D status as a result of rapid dietary transitions and a lack of solar ultraviolet B exposure. This may have implications for the development of adverse skeletal diseases, cardiovascular diseases and cancers. Data are limited regarding supplement use in Arctic Aboriginal populations. The present study aimed to describe the type and extent of supplement use, emphasising vitamin D, and to identify differences between supplement users and non-users. METHODS: Supplement information was collected from a population-specific quantitative food frequency questionnaire in three communities in the Northwest Territories, Canada, as part of a cross-sectional study. Data were analysed for frequency of supplementation and types of supplements. Users and non-users were compared in terms of age, sex, body mass index, education, marital status, income support, employment and chronic disease diagnosis using nonparametric tests and the chi-squared test. RESULTS: Response rates ranged from 65% to 85%. Included in the analysis were 192 Inuvialuit (45 males, 147 females) with a mean (SD) age of 43.6 (13.9) years. Twenty-three percent reported using a supplement, with multivitamins being the most common. Three percent indicated taking a vitamin D-containing supplement. No significant differences between supplement users and non-users were found. CONCLUSIONS: Despite limited sun exposure for many months of the year, a small proportion of Inuvialuit adults were using supplements, and specifically vitamin D-containing supplements. Future population-based intervention strategies should promote consumption of vitamin D rich foods and encourage the use of vitamin D supplements if diet alone is unable to meet recommendations.

Functional selectivity in GPCR signaling: understanding the full spectrum of receptor conformations.

The great versatility of G protein-coupled receptors (GPCRs), in terms of both their ability to bind different types of ligands and initiate a large number of distinct cellular signaling events, remains incompletely understood. In recent years, the classical view of the nature and consequences of ligand binding to GPCRs has dramatically changed. The notion of functional selectivity, achieved through both biased ligands and allosteric modulators, has brought substantial new insight into our comprehension of the pluridimensionality of signaling achieved by GPCRs. Moreover, receptor heterodimerization adds another important dimension to the diversity of cellular responses controlled by GPCRs. Here, we review these considerations and discuss how they will impact the design of improved therapeutics.

Ovariectomy and genes encoding core circadian regulatory proteins in murine bone.

SUMMARY: This study investigated the influence of ovarian hormone deficiency on core circadian regulatory protein (CCRP) in the context of bone loss. Our data suggest that ovarian hormone deficiency disrupts diurnal rhythmicity and CCRP expression in bone. Further studies should determine if chronobiology provides a novel therapeutic target for osteoporosis intervention. INTRODUCTION: CCRP synchronize metabolic activities and display an oscillatory expression profile in murine bone. In vitro studies using bone marrow mesenchymal stromal/stem cells have demonstrated that the CCRP is present and can be regulated within osteoblast progenitors. In vivo studies have shown that the CCRP regulates bone mass via leptin/neuroendocrine pathways. The current study used an ovariectomized murine model to test the hypothesis that ovarian hormone deficiency is associated with either an attenuation and/or temporal phase shift of the CCRP oscillatory expression in bone and that these changes are correlated with the onset of osteoporosis. METHODS: Sham-operated controls and ovariectomized female C57BL/6 mice were euthanized at 4-h intervals 2 weeks post-operatively. RESULTS: Ovariectomy attenuated the oscillatory expression of CCRP mRNAs in the femur and vertebra relative to the controls and reduced the wheel-running activity profile. CONCLUSION: Ovarian hormone deficiency modulates the expression profile of the CCRP with potential impact on bone marrow mesenchymal stem cell lineage commitment.

Chimio-embolisation trans-artérielle des carcinomes hépatocellulaires par billes chargées à la doxorubicine. Transarterial chemoembolization of hepatocellular carcinoma with doxorubicin eluting beads.

OBJECTIVES: The goal of our study was to describe the chemoembolization technique of transarterial catheterization using microspheres loaded with doxorubicin and to evaluate its tolerance and short-term efficacy on a small number of patients. MATERIALS AND METHODS: Our retrospective study was conducted over 8 months (December 2007-July 2008). It was done at the Brest University Medical Centre (France), in the radiology and hepato-gastroenterology departments of the Hôpital de la Cavale Blanche. We performed a transarterial chemoembolization using microspheres loaded with doxorubicin to 9 patients who had hepatocellular carcinoma in relation to alcoholic cirrhosis. RESULTS: Eight of 9 patients have benefited from a complete procedure (88.9% technical success) and in 100% of these cases, there were no clinical complications or biologic modifications immediately after embolization. After 4 weeks, there were seven cases of regression of more than 30% of the size of the tumor nodules, six cases of total tumor necrosis, and two cases of contrast uptake inside the nodules (partial tumor necrosis). In three cases (37.5%), there was an emergence of new tumor nodules. CONCLUSION: Chemoembolization accomplished by transarterial catheterization using microspheres loaded with doxoribicin is a probable technique for the future of palliative treatment of hepatocellular carcinomas. The technique is simple to perform and seems to be well tolerated by patients in terms of clinical and biological aspects.

[Obstructive hypertrophic cardiomyopathy and caesarean section under combined spinal and epidural anaesthesia with prophylactic vascular ligation: regarding a case]. / Cardiomyopathie hypertrophique obstructive et césarienne sous rachianesthésie-péridurale séquentielle avec ligature vasculaire préventive : à propos d'un cas.

We report the case of a caesarean section under combined spinal and epidural anaesthesia in a pregnant 32-year-old woman with an hypertrophic obstructive cardiomyopathy. In these patients, variations of the ventricular load conditions may induce a cardiac inefficacy. In this context, the post-partum haemorrhage is a feared complication, prevent in part by oxytocine intravenously. However, its injection can be associated with haemodynamic instability, even at a low dose, and it does not spread post-partum haemorrhage. The arterial ligation according to the technique of Tsirulnikov is an alternative that we reported. This technique is followed by a good obstetrical prognosis.

Delta sleep-inducing peptide and glucocorticoid-induced leucine zipper: potential links between circadian mechanisms and obesity?

As the obesity pandemic has accelerated, investigators have begun to explore alternative mechanisms linking circadian biology and sleep to adipose tissue metabolism and obesity. This manuscript reviews recent findings in murine and human models demonstrating the oscillatory expression of the mRNAs encoding the core circadian regulatory proteins in adipose tissue. Comparative transcriptomic analyses of circadian oscillating genes have been used to identify the 'delta sleep-inducing peptide immunoreactor', also known as 'glucocorticoid-induced leucine zipper (GILZ)', as a potential link in this chain. The GILZ gene has been found to differentially regulate stromal stem cell adipogenic and osteogenic differentiation in a reciprocal manner. In adipose and other metabolically active tissues, the circadian oscillation of GILZ expression is subject to entrainment by external stimuli. Together, these observations suggest that GILZ is an attractive candidate for future studies evaluating the role of circadian mechanisms in adipose tissue physiology and pathology.

Expression profile of mRNAs encoding core circadian regulatory proteins in human subcutaneous adipose tissue: correlation with age and body mass index.

OBJECTIVE: Circadian mechanisms underlie the physiology of mammals as an adaptation to the earth's rotation on its axis. Highly conserved core circadian regulatory proteins (CCRPs) maintain an oscillatory expression profile in the central and peripheral tissues. The CCRP include both a positive and negative arm, as well as downstream transcriptional regulators. Recent studies in murine models have determined that the mRNAs encoding the CCRP are present in multiple adipose tissue depots and exhibit a robust oscillatory expression profile. This study set out to examine the expression of CCRP mRNAs in human subcutaneous adipose tissues. DESIGN: Retrospective analysis of total RNA isolated from subcutaneous adipose tissue. SUBJECTS: A total of 150 healthy female and male lean (body mass index (BMI) <25), overweight (BMI between 25 and 29.99) or obese (BMI >30) subjects of varied ethnic backgrounds undergoing elective liposuction or surgical procedures. RESULTS: The expression of the CCRP mRNAs displayed a significant correlation between each other and mRNAs representative of adipogenic biomarkers. Hierarchical cluster analyses of mRNAs isolated from the cohort of female Caucasian subjects (n=116) identified three major clusters based on expression of downstream CCRP mRNAs. The mRNAs encoding D site of albumin promoter-binding protein (DBP), E4 promoter-binding protein 4 (E4BP4), PPARgamma coactivator-1beta (PGC-1beta) and Rev-erbalpha were negatively correlated with BMI in a lean cluster (n=66), positively correlated with BMI in a younger overweight/obese cluster (n=19), and not significantly correlated with BMI in an older, overweight/obese cluster (n=31). CONCLUSIONS: These data confirm and extend findings that link the CCRP and circadian mechanisms to the risk of obesity.

[How to confirm acute fatty liver of pregnancy in case of emergency]. / Comment confirmer le diagnostic de stéatose hépatique aiguë gravidique en urgence?

Acute fatty liver of pregnancy (AFLP) is a rare disease of which prognosis could be adverse if diagnosis is delayed. Certain diagnosis is sometimes made complex because of undercurrent symptoms with pre-eclampsia or hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome. Several reports announce an increase of incidence and illustrate cases confirmed by non-invasive methods. They permit early diagnosis and improve morbidity and mortality. Reviewing seven of the most important series of AFLP, we demonstrate how to use ultrasonography or computed tomography scan to confirm AFLP. However, liver biopsy should be realised after delivery in case of uncertain diagnosis.