Is ultra-short cold ischemia the key to ischemic cholangiopathy avoidance in DCD-LT?
DETRY, Olivier ; DE ROOVER, Arnaud ; et al
in Acta Chirurgica Belgica (2013, May), Supplement 113(3), 6729Detailed reference viewed: 19 (5 ULg)
A modified surgical model of fulminant hepatic failure in the rat.
DETRY, Olivier ; ; CHERAMY-BIEN, Jean-Paul et al
in Journal of Surgical Research (2013), 181
BACKGROUND: There is a need for better animal models of fulminant liver failure (FHF). Eguchi et al described an interesting surgical model of FHF in the rat. This model includes 68% partial hepatectomy ... [more ▼]
BACKGROUND: There is a need for better animal models of fulminant liver failure (FHF). Eguchi et al described an interesting surgical model of FHF in the rat. This model includes 68% partial hepatectomy, ischemia of 24% of the liver mass, and 8% of remnant liver left intact. In the original description by Eguchi et al, rats were administered subcutaneous glucose. However, the authors found that normothermic FHF rats with subcutaneous glucose died from deep hypoglycemia. In this report, we describe a modification of that model, and show that administration of intravenous glucose allows better survival and development of intracranial hypertension. METHODS: We operated on FHF rats using the procedure described by Eguchi et al, kept them normothermic, and maintained normoglycemia by continuous intravenous glucose injection (glucose 10%, 1 mL/h). At 24 h, we monitored liver blood tests (n = 5), intracranial pressure (n = 5), clinical encephalopathy, and survival (n = 10), and compared them with sham and 68% hepatectomy rats. RESULTS: The FHF rats developed acute cytolysis, cholestasis, and liver failure, as demonstrated by the liver blood tests. They experienced progressive encephalopathy and intracranial hypertension leading to death. Mean survival was 45.9 h. Of 10 FHF rats from the survival evaluation cohort, one survived 7 d. Laparotomy showed necrosis of lateral liver lobes and enlargement of omental lobes with a normal hepatic aspect, suggesting liver recovery. CONCLUSIONS: This surgical rat model mimics the features of human FHF and seems interesting for further research into the pathophysiology and therapeutic management of the disease. [less ▲]Detailed reference viewed: 22 (5 ULg)
Superior Renal Function Sustained for 24 Months through Early Everolimus-Facilitated Reduction of Tacrolimus Versus Standard Tacrolimus in De Novo Liver Transplant Recipients: Results of a Randomized Trial.
; DETRY, Olivier ; et al
in American Journal of Transplantation (2013, April), 13(S5), 169450
mTOR inhibitors have the potential to reduce calcineurin inhibitor nephrotoxicity by minimizing or eliminating the need for their use. The 12 month (M) results of H2304 (NCT00622869) study demonstrated ... [more ▼]
mTOR inhibitors have the potential to reduce calcineurin inhibitor nephrotoxicity by minimizing or eliminating the need for their use. The 12 month (M) results of H2304 (NCT00622869) study demonstrated superior renal function with everolimus (EVR) plus reduced tacrolimus (rTAC) vs. standard TAC (TAC-C) in de novo liver transplant recipients (LTxR). Presented here are 24M renal function results. For this 24M, multicenter, open-label study 719 de novo LTxR were randomized (1:1:1) after a 30-day (±5 days) run-in period with TAC (±mycophenolate mofetil), to receive either EVR (C0 3-8 ng/mL) with rTAC (C0 3-5 ng/mL; EVR+rTAC, N=245) or EVR (C0 6-10 ng/mL) with TAC withdrawal (TAC-WD; N=231) at M4 or TAC-C (C0 6-10 ng/mL; TAC-C, N=243); all patients received corticosteroids. Enrollment in TAC-WD arm was stopped early due to higher rejection rates. Main endpoints at M24 included composite efcacy failure rate of treated biopsy proven acute rejection, graft loss or death, and evolution of renal function from randomization (RND) to M24 measured as eGFR by MDRD4. At M24, composite efcacy failure rate in EVR+rTAC arm was comparable to TAC-C (10.3% vs. 12.5%, p=0.452). Evolution of renal function from RND to M24 was superior for EVR+rTAC vs. TAC-C with an adjusted mean difference in eGFR change of 6.66 mL/min/1.73m2 (p=0.0018; ITT population). Signicantly higher eGFR with EVR+rTAC was achieved at M2 post-LTx and was maintained until M24. On-treatment data showed a decrease in mean eGFR from RND to M24 of 6.6 mL/min/1.73m2 with EVR+rTAC vs. 13 mL/min/1.73m2 with TAC-C and 2.5 mL/ min/1.73m2 gain with TAC-WD. Urinary protein:creatinine ratio (mg/g) at M24 was higher with EVR+rTAC vs. TAC-C (Mean±SD: 194±280 vs. 159±284, p=0.006). Early introduction of EVR at 1M post-LTx with rTAC showed superior renal function sustained for 24M compared to TAC-C, without compromising efcacy in de novo LTxR. [less ▲]
Retrospective analysis of Belgian experience with intestinal transplantation
; DE ROOVER, Arnaud ; DETRY, Olivier et al
Conference (2013, March 21)
Aim: The only alternative to Total Parenteral Nutrition (TPN) for complicated intestinal failure is Intesti- nal Transplantation (ITx) which is perceived as a high-risk procedure with inferior results ... [more ▼]
Aim: The only alternative to Total Parenteral Nutrition (TPN) for complicated intestinal failure is Intesti- nal Transplantation (ITx) which is perceived as a high-risk procedure with inferior results compared to other organ Tx. Therefore ITx has been rarely applied in Belgium. In a multicenter retrospective review, we analyzed the overall Belgian experience with ITx. Methods: The Belgium Liver Intestine Committee organized a survey among all Belgian Tx centers, based on the patient-specific data form of the international ITx registry. Overall activity and indications were reviewed. Patient/graft survival was calculated (Kaplan-Meier). Nutritional (TPN) independence and Quality of Life (QoL) (Karnofsky score) were analyzed. Results: 21 ITx were performed in 20 patients (03/99-11/12), distributed among 5 centers: KUL (12), ULg (5), UZG (2), UCL (1), UZA (1). Median age was 38y(8mo-56y). Male/female ratio was 10/10. 5 were pediatrics (<18y) and 15 adults. Indications were anatomical or functional short bowel syndrome: intestinal ischemia(5), volvulus(5), Crohn(2), chronic intestinal pseudo-obstruction(2), splanchnic thrombosis(2), Churg-Strauss(1), necrotizing enterocolitis(1), microvillus inclusion(1), intestinal atresia(1) and chronic rejection of a first ITx(1). Most patients also suffered from TPN-associated com- plications (infection/shortage of venous access or liver failure). An isolated small bowel was trans- planted in 9 patients (plus kidney Tx in 2; plus pancreas Tx in 1); 10 received a combined liver and ITx; 2 received a multivisceral Tx. At time of Tx, 11 patients were hospitalized and 10 at home. 20 grafts were procured from deceased donors; one segmental intestinal graft was procured from a living donor. ABO blood group was identical in 63%, compatible in 37%. Median cold ischemia time was 5h30 ́(3h17 ́-9h31 ́). All patients received tacrolimus-based immunosuppression. Basiliximab (anti-IL2 receptor antibody) induction was administered in 16 patients. In 11 patients donor specific blood was transfused as part of an immunomodulatory protocol. 5-year patient and graft survival is 59% and 55.6%, respectively. 8 patients died: 6 to sepsis, 1 to intracerebral hemorrhage; 1 sudden death re- mained unexplained. 1 patient developed postTx lymphoma. 2 chronic rejections occured for which one reTx was performed. Of 12 survivors (median follow-up 1870 days), 11 are nutritionally independent (TPN-free) and 10 have a Karnofsky score >90%. Conclusions: ITx has come of age in Belgium. During the last 13 years, 21 ITx were performed in 5 centers. A 5-year patient/graft survival of 59%/55.6% is achieved, which is similar to results reported by the International ITx registry. In Belgium, awareness should grow that ITx represents a life-saving (and QoL improving) treatment in selected patients with reduced life expectancy due to significant complica- tions from TPN and intestinal failure. [less ▲]Detailed reference viewed: 6 (4 ULg)
Belgian multicentre experience with intestinal transplantation
; DE ROOVER, Arnaud ; DETRY, Olivier et al
in Acta Gastro-Enterologica Belgica (2013, March), 76(1), 07Detailed reference viewed: 16 (3 ULg)
What is the potential increase in the heart graft pool by cardiac donation after circulatory death?
; HANS, Marie-France ; NELLESSEN, Eric et al
Conference (2013, February 09)Detailed reference viewed: 9 (2 ULg)
Is ultra-short cold ischemia the key to IBDL avoidance in DCD-LT?
DETRY, Olivier ; DE ROOVER, Arnaud ; et al
Poster (2013, February 08)Detailed reference viewed: 18 (3 ULg)
Delayed graft function (DGF) does not harm the results of controlled donation-after-cardiovascular death (DCD) in kidney transplantation.
; WEEKERS, Laurent ; BONVOISIN, Catherine et al
Poster (2013, February 08)Detailed reference viewed: 13 (3 ULg)
Do Maastricht category III donation after cardiovascular death (DCD) donors experience end-of-life shortening?
LEDOUX, Didier ; DELBOUILLE, Marie-Hélène ; DE ROOVER, Arnaud et al
Poster (2013, February 08)Detailed reference viewed: 9 (2 ULg)
Renal function following transplantation with kidneys from donation after brain death (DBD) or cardiac death (DCD)
WEEKERS, Laurent ; ; GROSCH, Stéphanie et al
Poster (2013, February 08)Detailed reference viewed: 29 (12 ULg)
What is the potential increase in the heart graft pool by cardiac donation after circulatory death?
; DETRY, Olivier ; HANS, Marie-France et al
in Transplant International (2013), 26(1), 61-66
Heart transplantation remains the only definite treatment option for end-stage heart diseases. The use of hearts procured after donation after circulatory death (DCD) could help decrease the heart graft ... [more ▼]
Heart transplantation remains the only definite treatment option for end-stage heart diseases. The use of hearts procured after donation after circulatory death (DCD) could help decrease the heart graft shortage. The aim of this study was to evaluate the potential increase in heart graft pool by developing DCD heart transplantation. We retrospectively reviewed our local donor database from 2006 to 2011, and screened the complete controlled DCD donor population for potential heart donors, using the same criteria as for donation after brain death (DBD) heart transplantation. Acceptable donation warm ischemic time (DWIT) was limited to 30 min. During this period 177 DBD and 70 DCD were performed. From the 177 DBD, a total of 70 (39.5%) hearts were procured and transplanted. Of the 70 DCD, eight (11%) donors fulfilled the criteria for heart procurement with a DWIT of under 30 min. Within the same period, 82 patients were newly listed for heart transplantation, of which 53 were transplanted, 20 died or were unlisted, and 9 were waiting. It could be estimated that 11% of the DCD might be heart donors, representing a 15% increase in heart transplant activity, as well as potential reduction in the deaths on the waiting list by 40%. [less ▲]Detailed reference viewed: 29 (5 ULg)
Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: A proof-of-concept study using discarded human livers.
; ; et al
in Liver Transplantation (2012), 18(12), 1495-507
The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk ... [more ▼]
The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk livers is the development of objective criteria for assessing their condition before transplantation. Compared to simple cold storage, hypothermic machine perfusion (HMP) provides a unique window for evaluating liver grafts between procurement and transplantation. In this proof-of-concept study, we tested basic parameters during HMP that may reflect the condition of human liver grafts, and we assessed their morphology after prolonged HMP. Seventeen discarded human livers were machine-perfused. Eleven livers were nontransplantable (major absolute contraindications and severe macrovesicular steatosis in the majority of the cases). Six livers were found in retrospect to be transplantable but could not be allocated and served as controls. Metabolic parameters (pH, lactate, partial pressure of oxygen, and partial pressure of carbon dioxide), enzyme release in the perfusate [aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)], and arterial/portal resistances were monitored during HMP. Nontransplantable livers released more AST and LDH than transplantable livers. In contrast, arterial/portal vascular resistances and metabolic profiles did not differ between the 2 groups. Morphologically, transplantable livers remained well preserved after 24 hours of HMP. In conclusion, HMP preserves the morphology of human livers for prolonged periods. A biochemical analysis of the perfusate provides information reflecting the extent of the injury endured. Liver Transpl, 2012. (c) 2012 AASLD. [less ▲]Detailed reference viewed: 8 (0 ULg)
What is the potential increase of the heart graft pool by cardiac donation after circulatory death?
; NELLESSEN, Eric ; HANS, Marie-France et al
in Transplantation (2012, November), 94
Background: Heart transplantation remains to date the only definite treatment option for end-stage heart diseases. Currently only heart procured from brain death (DBD) donors are used. Combined with an ... [more ▼]
Background: Heart transplantation remains to date the only definite treatment option for end-stage heart diseases. Currently only heart procured from brain death (DBD) donors are used. Combined with an increasing demand, the constant heart graft shortage leads to an increase of deaths on cardiac transplantation waiting lists. The use of hearts procured after donation after circulatory death (DCD) could help to partly decrease the heart graft shortage. The aim of this study was to evaluate the potential increase of heart graft pool by development of DCD heart transplantation. Methods: The authors retrospectively reviewed their local donor database for the period 2006-2011, and screened the complete controlled DCD donor population for potential heart donors, using the same criteria as for DBD heart transplantation. The acceptable warm ischemic time (WIT) was limited to 30min from life support withdrawal to aortic cannulation. Results: During the analyzed timespan, 177 DBD and 70 DCD were effectively performed. From the 177 DBD, a total of 70 (39.5%) hearts were procured and transplanted locally or in another center. Out of the 70 DCD, 8 (11%) donors fulfilled the criteria for heart graft procurement and had a WIT of less than 30 minutes. During the same period, 82 patients were newly listed for heart transplantation, of which 53 were transplanted, 20 died or were unlisted, and 9 were still awaiting transplantation. Conclusions: Based on our database and a WIT of less than 30min, it could be estimated that 11% of the DCD might be heart graft donors, representing a 11% increase in heart graft procurement, as well as potential reduction of the deaths on the waiting list by 40%. [less ▲]Detailed reference viewed: 11 (3 ULg)
Effects of Large-Pore Hemofiltration in a Swine Model of Fulminant Hepatic Failure.
DETRY, Olivier ; JANSSEN, Nathalie ; CHERAMY-BIEN, Jean-Paul et al
in Artificial Organs (2012), 36(11), 981-987
Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation ... [more ▼]
Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation might be in part responsible for an increase in cerebral blood flow (CBF) and brain water content. In this study, the authors used a validated ischemic FHF swine model to evaluate the effects of 80 kDa large-pore membrane hemofiltration (LPHF) on intracranial pressure (ICP) and CBF, in relation with the clearance of proinflammatory cytokines and blood liver tests, as primary end points. Fifteen pigs were randomized into one of three groups: SHAM, FHF, and FHF + LPHF. All experiments lasted 6 h. In the FHF groups, liver failure was induced by liver ischemia. After 2 h, the FHF + LPHF group underwent 4 h of a zero-balance continuous veno-venous hemofiltration using a 0.7-m(2) , large-pore (78 A) membrane with a cutoff of 80 kDa. ICP, CBF, mean arterial pressure, central venous pressure, and heart rate were continuously monitored and recorded. Arterial aspartate aminotransferase, total bilirubin, creatinine, international normalized ratio, glucose, lactate and serum cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha were measured at T0, T120, and T360. Over the 6 h following liver ischemia, the FHF group developed a significant increase in ICP. This ICP rise was not observed in the SHAM group and was attenuated in the FHF + LDHF group. However, the ICP levels were not different at T360 in the FHF + LDHF group compared to the FHF group. No significant effect of LPHF on liver tests or levels of proinflammatory cytokines could be demonstrated. In this model, 80 kDa LPHF was not efficient to control FHF intracranial hypertension and to decrease serum cytokine levels. [less ▲]Detailed reference viewed: 20 (2 ULg)
Infusion of third party mesenchymal stem cells (MSC) after kidney and liver transplantation: a phase I-II, open-label, clinical study
DETRY, Olivier ; DELBOUILLE, Marie-Hélène ; LECHANTEUR, Chantal et al
Conference (2012, October 19)
MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]
MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]Detailed reference viewed: 43 (2 ULg)
Strategies to decrease bleeding and biliary fistula
Conference (2012, September 21)Detailed reference viewed: 3 (1 ULg)
Donation after cardio-circulatory death liver transplantation.
; DE ROOVER, Arnaud ; KABA, Abdourahmane et al
in World Journal of Gastroenterology (2012), 18(33), 4491-506
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 ... [more ▼]
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. [less ▲]Detailed reference viewed: 17 (5 ULg)
Intraperitoneal Adhesions After Open or Laparoscopic Abdominal Procedure: An Experimental Study in the Rat.
; Drion, Pierre ; CHERAMY-BIEN, Jean-Paul et al
in Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. (2012), 22(7), 651-657
Abstract Background: Adhesion formation is common after abdominal surgery. The incidence and severity of adhesion formation following open or laparoscopic surgery remain controversial. The role of CO(2 ... [more ▼]
Abstract Background: Adhesion formation is common after abdominal surgery. The incidence and severity of adhesion formation following open or laparoscopic surgery remain controversial. The role of CO(2) pneumoperitoneum is also widely discussed. This study aimed to compare adhesion formation following peritoneal injury by electrocoagulation performed through open or laparoscopic procedures in a rat model. Materials and Methods: Sixty male rats were randomized to undergo a 1.5-cm peritoneal injury with unipolar cautery under general anesthesia: open surgery (Group A, n=20), laparoscopic surgery with CO(2) pneumoperitoneum (Group B, n=20), and laparoscopic surgery with air pneumoperitoneum (Group C, n=20). Duration of the procedures was fixed at 90 minutes in all groups, and pneumoperitoneum pressure was kept at 10 mm Hg. Ten days later, the animals underwent a secondary laparotomy to score peritoneal adhesions using qualitative and quantitative parameters. Results: Forty-five rats developed at least one adhesion: 95% in Group A, 83% in Group B, and 55% in Group C (P<.01; Group C versus Group A, P<.01). According to number, thickness, tenacity, vascularization, extent, type, and grading according to the Zuhkle classification, no significant difference was observed between Groups A and B. The distribution of adhesions after open surgery was significantly different than after laparoscopic surgery (P<.001). It is interesting that Group C rats developed significantly fewer adhesions at the traumatized site, and their adhesions had less severe qualitative scores compared with those after open surgery (P<.01). Conclusions: In this animal model, CO(2) laparoscopic surgery did not decrease the formation of postoperative adhesion, compared with open surgery. The difference with the animals operated on with air pneumoperitoneum emphasizes the role of CO(2) in peritoneal injury leading to adhesion formation. [less ▲]Detailed reference viewed: 17 (2 ULg)