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See detailMesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Fourth Meeting: Lessons Learned from First Clinical Trials.
Franquesa, Marcella; Hoogduijn, Martin J.; Reinders, Marlies E. et al

in Transplantation (2013), 96(3), 234-238

The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of ... [more ▼]

The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem cells as a therapeutic agent in solid organ transplantation and emphasizes the issues (proper timing, concomitant immunossupression, source and immunogenicity of mesenchymal stem cells, and oncogenicity) that have been addressed and will be followed up by the MiSOT Consortium in future studies. [less ▲]

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See detailMosquito net for abdominal wall repair: a comparison of their chemical, physical, morphological and mechanical properties to commercial meshes
Sevrin, Chantal ULg; Nsadi Fwene, Berthier; Arung, Willy et al

in Biomedica proceedings (2013, June 23)

Meshes are the actual standard in abdominal wall repair. Commercial medical meshes are however either unavailable or unaffordable too expensive for developing countries. Therefore in most resource-poor ... [more ▼]

Meshes are the actual standard in abdominal wall repair. Commercial medical meshes are however either unavailable or unaffordable too expensive for developing countries. Therefore in most resource-poor developing countries a traditional sutured repair is still commonplace although with significantly inferior results. Sterilized mosquito nets have been recently roposed by several authors to replace medical meshes in low-income countries . However in the perspective of their clinical use a better understanding of this mosquito net is obviously requested both in terms of material properties and of in vivo biocompatibility. [less ▲]

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See detailINFUSION OF THIRD-PARTY MESENCHYMAL STEM CELLS (MSC) AFTER KIDNEY AND LIVER TRANSPLANTATION: A PHASE I-II, OPEN-LABEL, CLINICAL STUDY (EudraCT 2011-001822-81 & NCT01429038)
DETRY, Olivier ULg; DELBOUILLE, Marie-Hélène ULg; LECHANTEUR, Chantal ULg et al

Poster (2013, May 30)

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 ▲]

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See detailThe prognostic value of preoperative FDG PET-CT in hepatocellular carcinoma treated by liver transplantation.
GOVAERTS, L.; DETRY, Olivier ULg; BLETARD, Noëlla ULg et al

in PROCEEDINGS OF THE XVIth SYMPOSIUM OF THE BELGIAN SOCIETY OF NUCLEAR MEDICINE (2013, May)

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See detailIs ultra-short cold ischemia the key to ischemic cholangiopathy avoidance in DCD-LT?
DETRY, Olivier ULg; DE ROOVER, Arnaud ULg; Cheham, S et al

in Acta Chirurgica Belgica (2013, May), Supplement 113(3), 6729

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See detailA modified surgical model of fulminant hepatic failure in the rat.
DETRY, Olivier ULg; Gaspar, Yves; CHERAMY-BIEN, Jean-Paul ULg 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 ▲]

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See detailChirurgie et cancer en 2013
DETRY, Olivier ULg

Scientific conference (2013, April 29)

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See detailSuperior 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.
De Simone, Pierre; DETRY, Olivier ULg; Kintmalm, G 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 ef􏰀cacy 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 ef􏰀cacy 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). Signi􏰀cantly 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 ef􏰀cacy in de novo LTxR. [less ▲]

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See detailRetrospective analysis of Belgian experience with intestinal transplantation
Ceulemans, L.J.; DE ROOVER, Arnaud ULg; DETRY, Olivier ULg 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 ▲]

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See detailBelgian multicentre experience with intestinal transplantation
Ceulemans, L; DE ROOVER, Arnaud ULg; DETRY, Olivier ULg et al

in Acta Gastro-Enterologica Belgica (2013, March), 76(1), 07

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See detailWhat is the potential increase in the heart graft pool by cardiac donation after circulatory death?
Noterdaeme, Timothée; HANS, Marie-France ULg; NELLESSEN, Eric ULg et al

Conference (2013, February 09)

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See detailIs ultra-short cold ischemia the key to IBDL avoidance in DCD-LT?
DETRY, Olivier ULg; DE ROOVER, Arnaud ULg; Ledinh, Hieu et al

Poster (2013, February 08)

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See detailWhat is the potential increase in the heart graft pool by cardiac donation after circulatory death?
NOTERDAEME, Timothée; DETRY, Olivier ULg; HANS, Marie-France ULg 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 ▲]

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See detailPrognostic value of FDG PET/CT in patients with hepatocellular carcinoma treated with liver transplantation.
GOVAERTS, L.; DETRY, Olivier ULg; BLETARD, Noëlla ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging (2013), 2013(SUPPL), 287

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See detailOrganized Proteomic Heterogeneity in Colorectal Cancer Liver Metastases and Implications for Therapies
Turtoi, Andrei ULg; Blomme, Arnaud; Debois, Delphine 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 ▲]

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See detailFeasibility and accessibility to the laparoscopic procedures in University Hospital of Kinshasa
Nsadi Fwene, Berthier; Veyi Tadulu, D.; Kazadi Mutshim, JM et al

in Surgical Endoscopy (2013), 27

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