Arnaud De Roover

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.

Liver transplantation from donation after cardiac death donors: initial Belgian experience 2003–2007

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From 2003 to 2007, 58 DCD‐LT were performed in Belgium. Mean procurement total warm ischemia time was 25 ± 2 min (mean ± SEM). Mean cold ischemia time was 451 ± 18 min. Mean follow‐up was 23 ± 2.2 months. Post‐transplant peak aspartate aminotransminases was 2241 ± 338 UI/l. Patient survivals at 1 month, 1 and 3 years, were 91.3%, 83.3% and 66.9% respectively. Graft survivals at 1 month, 1 and 3 years, were 84.4%, 72.4% and 48.8% respectively. Two patients (3.4%) developed primary nonfunction. Regarding the biliary complications, seven grafts (12%) were lost because of intrahepatic cholangiopathy, and 12 other patients (20.6%) developed bile duct stenoses requiring endoscopic and/or surgical management. The rate of symptomatic ischemic biliary lesions for grafts surviving more than 3 months was 38% (19/50). Although DCD organ donors may be a source of viable liver grafts, results were inferior to those obtained with donation after brain death LT in this series. Prognostic criteria have to be developed to improve results of DCD‐LT.

Report of two cases of gastric cancer after bariatric surgery: lymphoma of the bypassed stomach after Roux-en-Y gastric bypass and gastrointestinal stromal tumor (GIST) after vertical banded gastroplasty.

We report two new cases of gastric cancer diagnosed after a bariatric operation. The first case is a 66-year-old male who 3 years after gastric bypass suffered from a perforation of the fundus that was found to be secondary to a diffuse large B-cell lymphoma of the distal stomach. The second case is a 47-year-old woman who presented 12 years after a vertical banded gastroplasty with a gastric pouch outlet obstruction caused by a gastrointestinal stromal tumor (GIST). Based on the few reports of cancer in the literature, analysis of these cases suggests that the main risk of gastric cancer after bariatric surgery comes from the delayed diagnosis of malignancy.

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.

Risk of upper gastrointestinal cancer after bariatric operations

The authors discuss the potential influence of obesity surgery on the risk of cancer, focusing on the upper GI tract directly affected by operations. There is currently no substantiation for an increased risk of cancer after bariatric surgery, because there are only about 25 reports of subsequent cancer of the esophagus and the stomach. However, this review emphasizes the need to detect potential precancerous conditions before surgery. Candidates for postoperative endoscopic surveillance may include patients >15 years after gastric surgery, but also patients symptomatic for gastroesophageal reflux disease in whom a high incidence of Barretts metaplasia has been reported. The greatest concern is a delay in diagnosis from inadequate investigation due to mistaking serious upper GI symptoms as a consequence of the past operation.

Results of kidney transplantation from controlled donors after cardio‐circulatory death: a single center experience

The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio‐circulatory death (DCD). Primary end‐points were graft and patient survival, and post‐transplant complications. The influence of delayed graft function (DGF) on graft survival and DGF risk factors were analyzed as secondary end‐points. This is a retrospective mono‐center review of a consecutive series of 59 DCD‐KT performed between 2005 and 2010. Overall graft survival was 96.6%, 94.6%, and 90.7% at 3 months, 1 and 3 years, respectively. Main cause of graft loss was patient’s death with a functioning graft. No primary nonfunction grafts. Renal graft function was suboptimal at hospital discharge, but nearly normalized at 3 months. DGF was observed in 45.6% of all DCD‐KT. DGF significantly increased postoperative length of hospitalization, but had no deleterious impact on graft function or survival. Donor body mass index ≥30 was the only donor factor that was found to significantly increase the risk of DGF (P < 0.05). Despite a higher rate of DGF, controlled DCD‐KT offers a valuable contribution to the pool of deceased donor kidney grafts, with comparable mid‐term results to those procured after brain death.

Organ donation after physician-assisted death

In 2002, Belgium was the second country in the world, after the Netherlands, to legalize physician-assisted death and euthanasia in very restricted conditions [1]. Euthanasia has to be required by a conscious patient suffering from an irreversible affliction inducing physical and/or psychological suffering, with no hope for improvement or for rapid spontaneous death; request for euthanasia has to be written by the patient or by his (her) representative who has no interest in the patient death; patient’s general and psychiatric health status has to be confirmed by an external medical expert; request for euthanasia and the procedure itself have to be separated by at least 30 days. We report herein the case of a patient who requested that her organs be donated after physician-assisted death. These two separate processes were performed according to the Belgian legal requirements for euthanasia and organ procurement and guidelines for organ donation after cardiac death [2,3]. A 44-year-old woman was suffering from locked-in syndrome after brain stem vascular accident [4]. She was fully conscious and communicated only with eyelid movement. She spontaneously breathed through a tracheostomy and was fed through a gastrostomy. After 4 years of this assisted life, she asked for physician-assisted suicide according to the Belgian law. She was examined by a psychiatrist and a neuropsychologist who excluded depression and confirmed preserved cognitive function, and by an independent palliative care physician who confirmed dismal medical prognosis and the patient’s willingness to die. Euthanasia was granted and scheduled for a month later, as required by the Belgian law. The day before the euthanasia, the patient expressed her will of after-death organ donation. The ethical and legal possibility of combination of the two separate processes, physician-assisted suicide and after-death organ donation was then considered and agreed by the institutional ethical committee president. The intravenous euthanasia procedure was performed according to the regular protocol, in the presence of the patient’s husband, in a room adjacent to the operative room. The patient was in her regular hospital bed. No member of the transplant team was present during the euthanasia. When the patient’s death was declared by three independent physicians after 10 min of absence of cardiac activity, her cadaver was placed on the operative table. The liver and both kidneys were harvested and transplanted according to the regular Eurotransplant organ allocation rules for after-death organ donation [3]. Currently, more than 1 year later, all three recipients are enjoying a normal graft function. This case of two separate requests, first euthanasia and second, organ donation after death, demonstrates that organ harvesting after euthanasia may be considered and accepted from ethical, legal and practical viewpoints in countries where euthanasia is legally accepted. This possibility may increase the number of transplantable organs and may also provide some comfort to the donor and his (her) family, considering that the termination of the patient’s life may somehow help other human beings in need for organ transplantation.

Pylephlebitis of the portal vein complicating intragastric migration of an adjustable gastric band.

Pylephlebitis, or septic thrombophlebitis of the portal vein, is an infrequent but life-threatening complication of abdominal septic events. The authors report the occurrence of pylephlebitis and multiple liver abscesses induced by a neglected intra-gastric migration of an adjustable silicone gastric band. The patient was successfully treated by broad-spectrum antibiotics and total gastrectomy with Roux-en-Y esophago-jejunostomy. Postoperative recovery was marked by acute liver failure that was managed conservatively. The patient is alive and well at 1-year follow-up. This case emphasizes the interest in early removal of the band when intra-gastric migration is diagnosed.

Belgian multicenter experience with intestinal transplantation.

Intestinal transplantation (ITx) has evolved from an experimental procedure toward a clinical reality but remains a challenging procedure. The aim of this survey was to analyze the multicenter Belgian ITx experience. From 1999 to 2014, 24 ITx in 23 patients were performed in Belgium, divided over five centers. Median recipient age was 38 years (8 months–57 years); male/female ratio was 13/10; six were children; and 17 adults. Intestinal failure was related to intestinal ischemia (n = 5), volvulus (n = 5), splanchnic thrombosis (n = 4), Crohn (n = 2), pseudo‐obstruction (n = 2), microvillus inclusion (n = 2), Churg‐Strauss (n = 1), necrotizing enterocolitis (n = 1), intestinal atresia (n = 1), and chronic rejection (n = 1). Graft type was isolated ITx (n = 9), combined liver‐ITx (n = 11) and multivisceralTx (n = 4). One was a living donor‐related transplantation and five patients received simultaneously a kidney graft. Early acute rejection occurred in 8; late acute rejection in 4; and chronic rejection in 2. Two patients developed a post‐transplant lymphoproliferative disease. Nine patients have died. Among 14 survivors at last follow‐up, 11 have been transplanted for more than 1 year. None of the latter has developed renal failure, and all were nutritionally independent with a Karnofsky score > 90%. One‐/five‐year patient and graft survivals were 71.1%, 62.8%, 58.7% and 53.1%, respectively. Based on this experience, ITx has come of age in Belgium as a lifesaving and potentially quality of life restoring therapy.

Exocrine pancreas graft drainage in recipient duodenum through side‐to‐side duodeno‐duodenostomy

The interesting report by Hummel et al. in the Februaryissue of this Journal [1] confirmed our previouspublication indicating that, in pancreas transplantation,side-to-side duodeno-duodenal anastomosis is technicallyfeasible and allows easy access to the graft duodenalmucosa for repeated biopsies and rejection monitoring[2]. In our experience we prefer to anastomose the graftportal vein to the infrapancreatic superior mesenteric veinsimilarly to the technique described by Boggi et al. [3].With this procedure, the pancreas graft is positioned in apure retroperitoneal and physiologic location for bothendocrine and exocrine drainage, but it is uncertain ifthis fact has any influence on the functional results of thetransplantation.The main drawback of this technique is the potentialfor anastomotic leak that could be challenging to controlas the recipient duodenum cannot be resected. Directduodenal repair, plasty with a Roux-en-Y limb, orlaterolateral duodenojejunostomy may be surgical optionsto achieve recipient duodenal closure in case of anasto-motic leak [2].We considered using this technique in our last fivepancreas transplantations (three pancreas alone and twosimultaneous pancreas-kidney transplantations). In fourpatients, side-to-side duodeno-duodenal anastomosis wasperformed (three manually and one with a circularstapling device, according to the surgeon’s preference).Immunosuppression consisted of quadruple therapy,including induction with polyclonal antibodies andmaintenance with tacrolimus, mycophenolate mofetil andlow-dose steroids. These patients underwent regularprotocol duodenal biopsies, without any evidence of acuteor chronic rejection. Pancreas graft and patient survival is100% at follow-up. One patient required two re-laparoto-mies, for early non-infected peripancreatic hematoma andfor late (>6 months) mechanical intestinal occlusion. Nopatient experienced any complication linked to theduodenal anastomosis or to the vascular reconstruction.In the fifth patient recipient of simultaneous pancreas-kidney transplantation, pancreas graft duodenum wasfound to be badly preserved at reperfusion, and we thenchose to perform duodenal drainage through a Roux-en-Y jejunal limb. This patient developed anastomoticleakage requiring life-saving pancreas graft resection afterthree unsuccessful attempts of surgical correction.This small series of duodeno-duodenal drainage ofpancreas grafts, and the case described by Hummel,provide some evidence that this technique is feasible,appears to be safe in pancreas grafts with good duodenalpreservation, and provides easy access of the duodenalmucosa for rejection monitoring. All these pancreas graftsare functioning perfectly and did not develop any episodeof rejection. These promising results need to beconfirmed by larger series and controlled comparisonwith classical enteric drainage.Arnaud De Roover, Olivier Detry,Carla Coimbra, Jean-Paul Squifflet,Pierre Honore´ and Michel MeurisseDepartment of Abdominal Surgeryand Transplantation,University of Liege,Liege, BelgiumReferences1. Hummel R, Langer M, Wolters HH, Senninger N, Brock-mann JG. Exocrine drainage into the duodenum: a noveltechnique for pancreas transplantation. Transpl Int 2008;21: 178.2. De Roover A, Coimbra C, Detry O, et al. Pancreas graftdrainage in recipient duodenum: preliminary experience.Transplantation 2007; 84: 795.3. Boggi U, Vistoli F, Signori S, et al. A technique forretroperitoneal pancreas transplantation with portal-entericdrainage. Transplantation 2005; 79: 1137.