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 ▲]Detailed reference viewed: 80 (2 ULg)
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: 40 (5 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: 32 (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: 27 (5 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: 34 (6 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: 30 (6 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: 46 (10 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: 40 (14 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: 57 (5 ULg)
Prognostic value of FDG PET/CT in patients with hepatocellular carcinoma treated with liver transplantation.
; DETRY, Olivier ; BLETARD, Noëlla et al
in European Journal of Nuclear Medicine and Molecular Imaging (2013), 2013(SUPPL), 287Detailed reference viewed: 9 (2 ULg)
Organized Proteomic Heterogeneity in Colorectal Cancer Liver Metastases and Implications for Therapies
Turtoi, Andrei ; ; et al
in Hepatology (Baltimore, Md.) (2013)
Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems ... [more ▼]
Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis dis- played increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demon- strate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of target- able antigens. [less ▲]Detailed reference viewed: 50 (14 ULg)
Feasibility and accessibility to the laparoscopic procedures in University Hospital of Kinshasa
; ; et al
in Surgical Endoscopy (2013), 27Detailed reference viewed: 25 (5 ULg)
Laparoscopic liver resection: a single center experience
SZECEL, Delphine ; DE ROOVER, Arnaud ; DELWAIDE, Jean et al
in Surgical Endoscopy (2013), 27Detailed reference viewed: 41 (6 ULg)
Intraperitoneal Adhesions After Open or Laparoscopic Abdominal Procedure: An Experimental Study in the Rat.
; Drion, Pierre ; Honoré, Pierre et al
in Surgical Endoscopy (2013), 27Detailed reference viewed: 27 (0 ULg)
La transplantation d'organes au CHU de Liège - Rapport d'activité 2012
DETRY, Olivier ; MEURISSE, Michel
Report (2013)Detailed reference viewed: 31 (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: 58 (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: 28 (6 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: 30 (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: 97 (10 ULg)