Laurent Kohnen

Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue.

Aims/hypothesisObesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its visceral component is more frequently associated with metabolic dysfunction than its subcutaneous component. The development of metabolic disorders is partly mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which increases the secretion of inflammatory cytokines via activation of caspase-1. We compared the immunological profile and NLRP3 activity in adipose tissue between MUO and MHO individuals.MethodsMHO and MUO phenotypes were defined, respectively, as the absence and the presence of the metabolic syndrome. Cellular composition and intrinsic inflammasome activity were investigated by flow cytometry, quantitative RT-PCR and tissue culture studies in subcutaneous and visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals.ResultsWe found significant differences between the three study groups, including an increased secretion of IL-1β, increased expression of IL1B and NLRP3, increased number of adipose tissue macrophages and decreased number of regulatory T cells in the visceral adipose tissue of MUO patients compared with MHO and lean participants. In macrophages derived from visceral adipose tissue, both caspase-1 activity and IL-1β levels were higher in MUO patients than in MHO patients. Furthermore, caspase-1 activity was higher in CD11c+CD206+ adipose tissue macrophages than in CD11c−CD206+ cells.Conclusions/interpretationThe MUO phenotype seems to be associated with an increased activation of the NLPR3 inflammasome in macrophages infiltrating visceral adipose tissue, and a less favourable inflammatory profile compared with the MHO phenotype.

Contribution of Donors After Cardiac Death to the Deceased Donor Pool: 2002 to 2009 University of Liege Experience

OBJECTIVE In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.

Prevalence, characteristics and risk factors of chronic post surgical pain after laparoscopic colorectal surgery: retrospective analysis

BACKGROUND The prevalence of chronic postsurgical pain (CPSP) is a critical medical problem with economic implications. Its prevalence after gastrointestinal surgery is not well documented, particularly when a laparoscopic approach is used. OBJECTIVE The aim of the study was to determine the prevalence, the characteristics and the risk factors for CPSP after laparoscopic colorectal surgery. DESIGN A retrospective analysis using a postal questionnaire. SETTING The study was conducted at a university teaching hospital. PATIENTS Patients who underwent laparoscopic colorectal surgery from April 2008 until December 2011 (n = 260). No epidural analgesia was used. MAIN OUTCOME MEASURES Postoperative pain intensity, incidence and characteristics of CPSP, and impact on quality of life and sleep. RESULTS Of 199 responses, 33 patients (17%) reported chronic pain at a median [interquartile range, IQR] of 38 [27 to 55] months after laparoscopic surgery with a median intensity of 4 [3 to 5]. CPSP had a negative impact on the quality of life in 84% of patients and on sleep in 43%. CPSP required regular analgesic(s) intake in 54% patients. Using a backward stepwise multivariate logistic regression model, the following variables were determined as independent risk factors for CPSP: redo surgery for anastomotic leakage (P = 0.01), inflammatory bowel disease (IBD) as the indication for surgery (P = 0.01) and preoperative pain (P = 0.05). CONCLUSION The incidence of CPSP after laparoscopic colorectal surgery (17%) is similar to those reported in the literature after laparotomy. Risk factors are redo surgery for postoperative peritonitis, IBD and preoperative pain. TRIAL REGISTRATION EudraCT 2012-005712-25.

Natural orifice transluminal endoscopic surgery (NOTES): when a step forward may be a step too soon or too far.

To the editor, In the 1980s and 1990s, the advent of laparoscopy revolutionized abdominal surgery. Despite the absence of a randomized, controlled, large-scale evaluation, laparoscopic cholecystectomy has become the gold standard for the management of symptomatic cholelithiasis. Laparoscopy has allowed cholecystectomy to be performed with very low rates of complications and mortality, a very short hospital stay (\12–24 h), and less postoperative pain. Moreover, the cosmetic results for laparoscopic cholecystectomy performed using a 10-mm trocar in the ombilicus and two other 2or 5-mm abdominal trocars are excellent. Recently, natural orifice transluminal endoscopic surgery (NOTES) was proposed as a new surgical technique, with the aim of performing abdominal surgical procedures through natural orifices such as the mouth, the vagina, or the rectum to avoid visible incisions, allowing for perfect cosmetic results. The NOTES approach has been sponsored largely by the surgical industry looking for a new potential market. Moreover, we, the surgical community, were the victims of our own pride, with many surgeons trying to be the ‘‘first to use NOTES’’ and to report it. In the past 5 years, experimental and clinical NOTES procedures have become a hot topic at nearly all abdominal surgical meetings, with very few cautionary tales. In the August 2009 issue of Surgical Endoscopy, Bachman et al. [1] compared two methods of colonic decontamination in their experimental study using a swine model. Both of their study groups showed a very significant decrease in live colonic bacteria, but NOTES performed in these animals resulted in peritoneal bacterial contamination. Someone may eventually publish a method for efficient decontamination of the colon after sterile NOTES procedures through the colon. But anyone who has experienced bowel preparation for colonoscopy (and I did) may testify that this is not great fun. To me, a total colonic decontamination to allow transcolonic cholecystectomy seems thoughtless. Moreover, inducing an iatrogenic perforation of the colon for a rather simple and safe abdominal procedure such as cholecystectomy will certainly induce postoperative colonic fistulas, a new complication that will be dramatic even if rare. The same problem of postoperative fistulas may be argued for transgastric NOTES. Another article in the August issue of Surgical Endoscopy reports that Peterson et al. [2] asked women whether they would undergo transvaginal NOTES cholecystectomy on the basis of better cosmesis and a lower rate of postoperative incisional hernia. Of course they were! However, nowhere in the article were the potential hazards of this new procedure mentioned, nor the possibility of severe complications including bladder or rectal perforation, Douglas abscess, or postoperative vaginal bleeding. These potential risks were not mentioned in the case of transvaginal hybrid NOTES reported in the same issue by Horgan et al. [3], who stated that the patient signed an informed consent. What is a truly informed consent for a surgical procedure that we, the surgeons, do not even know is safe? In addition, the procedure described by Horgan et al. [3] illustrates the recent NOTES trends. First the access was transvaginal, as in most reported cases to date due to the unsolved problems of transluminal access. Does another solution exist that may fit the male population? Moreover, they used a 5-mm transabdominal trocar, resulting in a O. Detry (&) B. Nsadi L. Kohnen Department of Abdominal Surgery and Transplantation, University of Liege, Sart Tilman B35, 4000 Liege, Belgium e-mail: oli.detry@chu.ulg.ac.be

Liver Transplantation Is Feasible in Super-Obese Patients: A Case Report

Short- and long-term results of liver transplantation in morbidly obese patients may be impaired compared with the general transplant population. As a consequence, severe obesity has been considered to be a relative contraindication to liver transplantation in many centers. Surgically, liver transplantation in severe obesity may be challenging. Moreover, obesity may lead to an increased rate of early and late medical complications. Herein we have reported successful liver transplantation in a super-obese patient (body mass index, 55.1 kg/m(2)) who had developed terminal acute-on-chronic liver disease. In the first 6 months of follow-up, the patient underwent a severe diet that led to a significant weight loss reduction to a body mass index of 39 kg/m(2). This report of successful liver transplantation in a super-obese patient suggests that severe obesity should not be considered to be an absolute contraindication to liver transplantation.

P2149 Différences d’activité de l’inflammasome NLRP3 entre sujets obèses avec et sans anomalies métaboliques

Objectif L’interleukine-1 beta (IL-1β), cytokine pro-inflammatoire, est impliquee dans la pathogenie de l’insulinoresistance associee a l’obesite via l’activation de l’inflammasome NLRP3. L’obesite est une maladie heterogene ; certains patients sont obeses mais « metaboliquement sains » (MHO pour Metabolically Healthy Obese), tandis que d’autres (MUO pour Metabolically Unhealthy Obese) developpent des anomalies metaboliques liees a l’insulinoresistance. Le tissu adipeux visceral, present en quantite plus abondante chez les sujets MUO, pourrait jouer a ce niveau un role pathogenique important. Le but de cette etude est de determiner si les anomalies metaboliques observees chez les sujets MUO peuvent s’expliquer par des differences d’activation de l’inflammasome et de composition cellulaire dans leur tissu adipeux visceral. Materiels et methodes Des biopsies de tissu adipeux visceral et sous-cutane ont ete realisees chez 23 sujets MUO (avec criteres de syndrome metabolique et une glycemie a jeun pathologique), 21 sujets MHO (definis par l’absence de syndrome metabolique) apparies pour l’âge et l’indice de masse corporel, ainsi que chez 9 sujets controles de poids normal. Resultats Compares aux sujets controles et MHO, le tissu adipeux visceral des sujets MUO est caracterise par une expression accrue des genes de l’IL-1β et de NLRP3, une secretion plus elevee d’IL-1β, une infiltration de macrophages pro-inflammatoires (avec une activite de caspase-1 et production d’IL-1β accrues) et un moindre pourcentage de lymphocytes T regulateurs, et ce de facon statistiquement significative. Des differences similaires ont egalement ete trouvees entre le tissu adipeux visceral et le tissu adipeux sous-cutane des sujets MUO. Conclusion La presence d’anomalies metaboliques chez les sujets MUO est associee a une activation de l’inflammasome NLRP3 dans les macrophages infiltrant leur tissu adipeux visceral. La graisse viscerale des sujets MHO est caracterisee par un profil inflammatoire plus favorable.