References of "Honoré, Pierre"
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See detailRationale for the potential use of mesenchymal stromal cells in liver transplantation
Vandermeulen, M.; DE ROOVER, Arnaud ULg; BRIQUET, Alexandra ULg et al

in World Journal of Gastroenterology (in press)

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See detailDonor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme.
DETRY, Olivier ULg; DE ROOVER, Arnaud ULg; MEURISSE, Nicolas ULg et al

in The British journal of surgery (2014), 10(7), 784-792

BACKGROUND: Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in ... [more ▼]

BACKGROUND: Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. METHODS: All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. RESULTS: A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). CONCLUSION: Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized. [less ▲]

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See detailControlled DCD donation is part of the solution to liver graft shortage, regardless of donor age
DETRY, Olivier ULg; MEURISSE, Nicolas ULg; DELWAIDE, Jean ULg et al

in Acta Gastro-Enterologica Belgica (2014, March), 77(1), 16

Aim: Results of donation after circulatory death (DCD) liver transplantation (LT) are impaired by ischemic bile duct lesions caused by procurement warm ischemia. Donor age is a risk factor in deceased ... [more ▼]

Aim: Results of donation after circulatory death (DCD) liver transplantation (LT) are impaired by ischemic bile duct lesions caused by procurement warm ischemia. Donor age is a risk factor in deceased donor LT, and particularly in DCD-LT. At the authors institute, age is not an absolute exclusion criterion to discard DCD liver grafts, controlled DCD donors receive comfort therapy before withdrawal, and cold ischemia is minimized. The aim of the present study was to report on the results of the first 10 years of this experience, and particularly on graft survival and the rate of post-transplant biliary complications, according to DCD donor age. 
 Methods: The authors retrospectively studied a consecutive series of 70 DCD-LT performed from 2003 to 2012, with at least one year of follow-up. This series was divided according to donor’s age, including 32 liver grafts from donors <55years, 20 between 56 and 69 years, and 18 from older donors >69 years. The three groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 hours, and results at one and four years. Median follow-up was 43 months. 
 Results: Overall graft survival was 98.5%, 91.4% and 69.5% at 1 month, 1 year and 4 years, respectively, without graft loss secondary to ischemic bile duct lesions. Cancer was the primary cause of graft loss and patient death. No difference other than age was noted between the three groups in donor and recipient characteristics, and in procurement conditions. There was no primary non-function but one patient needed re-transplantation for artery thrombosis. Biliary complications occurred similarly in the three groups. Graft and patient survival rates were not different at one and four years between the three groups. During the study period, there was an increasing liver procurement and transplantation activity, and in 2012, 30% of performed LT were DCD-LT, allowing a mean LT waiting time of 66 days. 
 Conclusions: This study shows comparable results between controlled DCD-LT from younger and older donors. Donor age >50 years should not be a contraindication to DCD-LT if other donor risk factors (such as warm and cold ischemia time) are minimized. DCD-LT with short cold ischemia may provide a significant source of liver grafts, decreasing waiting time. [less ▲]

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See detailPrognostic value of FDG PET/CT in liver transplantation for hepatocarcinoma
DETRY, Olivier ULg; Govaerts, L; BLETARD, Noëlla ULg et al

in Acta Gastro-Enterologica Belgica (2014, March), 77(1), 08

AIM : FDG uptake has been shown to predict the outcome in large series of patients with hepatocarcinoma (HCC) in Asia, but few data are available regarding European populations. Our aim was to evaluate ... [more ▼]

AIM : FDG uptake has been shown to predict the outcome in large series of patients with hepatocarcinoma (HCC) in Asia, but few data are available regarding European populations. Our aim was to evaluate the prognostic value of pretreatment FDG PET-CT in patients treated by liver transplantation. Methods: We retrospectively analyzed the data of 27 patients (24 M and 3 W, mean age 58 ± 9 years). The mean follow-up was 26 ± 18 months (min 1 month, max 66 months). All patients had an FDG PET-CT before the transplantation. The FDG PET/CT was performed according to a standard clinical protocol: 4 MBqFDG/kg body weight, uptake 60 min., low-dose non-enhanced CT. We measured the SUVmax and SUVmean of the tumor and the normal liver. The tumor/liver activity ratios (RSUVmax and RSUVmean) were tested as prognostic factors and compared to the following conventional prognostic factors: MILAN, CLIP, OKUDA, TNM stage, alphafoetoprotein level, portal thrombosis, size of the largest nodule, tumor differentiation, microvascular invasion, underlying cirrhosis and liver function. Results : The DFS was 87.2% at 1y and 72.1% at 3y. The OS was 85.2% at 1y and 80.7% at 3y. According to an univariate Cox model, RSUVmax, RSUVmean and healthy liver were predictors of DFS and RSUVmax, RSUVmean, size of the largest nodule, CLIP, liver involvement>50%, and healthy liver predicted the OS. According to a multivariate Cox model, only RSUVmax predicted DFS and RSUVmax and liver involvement>50% predicted OS. An ROC analysis of the ratios showed that the 1.15 cut-off for RSUVmax was best for predicting both the DFS (Cox regression:HR 14.4, p=0.02) and OS (HR 5.6, p=0.049). The Kaplan-Meier curves and Logrank tests confirmed those results. Even though the MILAN criteria alone were not predictive, it is worth noting that none of the patients outside the MILAN criteria and with RSUVmax<1.15 relapsed. Conclusions: The RSUVmax is a strong prognostic factor for recurrence and death in patients with HCC treated by liver transplantation with a cut-off value of 1,15. further prospective studies should test whether the metabolic index should be systematically included in the preoperative assessment. [less ▲]

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See detailA More Than 20% Increase in Deceased-Donor Organ Procurement and Transplantation Activity After the Use of Donation After Circulatory Death.
Le Dinh, H.; MONARD, Josée ULg; DELBOUILLE, Marie-Hélène ULg et al

in Transplantation proceedings (2014), 46(1), 9-13

BACKGROUND: Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the ... [more ▼]

BACKGROUND: Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the transplant and donation after brain death (DBD) activities. MATERIAL AND METHODS: Deceased donor (DD) procurement and transplant data were prospectively collected in a local database for retrospective review. RESULTS: There was an increasing trend in the potential and actual DCD numbers over time. DCD accounted for 21.9% of the DD pool over 11 years, representing 23.7% and 24.2% of the DD kidney and liver pool, respectively. The DBD retrieval and transplant activity increased during the same time period. Mean conversion rate turning potential into effective DCD donors was 47.3%. Mean DCD donor age was 54.6 years (range, 3-83). Donors >/=60 years old made up 44.1% of the DCD pool. Among referred donors, reasons for nondonation were medical contraindications (33.7%) and family refusals (19%). Mean organ yield per DCD donor was 2.3 organs. Mean total procurement warm ischemia time was 19.5 minutes (range, 6-39). In 2012, 17 DCD and 37 DBD procurements were performed in the Liege region, which has slightly >1 million inhabitants. CONCLUSIONS: This DCD program implementation enlarged the DD pool and did not compromise the development of DBD programs. The potential DCD pool might be underused and seems to be a valuable organ donor source. [less ▲]

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See detailDONATION AFTER CIRCULATORY DEATH INCREASES THE CADAVERIC DONOR POOL
Le Dinh, H.; DE ROOVER, Arnaud ULg; SQUIFFLET, Jean-Paul ULg et al

in Transplant International (2013, December), 26(S2), 54-101

Background: There is a controversy on the possibility to increase the organ donor pool by donation-after-circulatory-death (DCD) and the possible decrease in donation-after-brain-death (DBD) by DCD ... [more ▼]

Background: There is a controversy on the possibility to increase the organ donor pool by donation-after-circulatory-death (DCD) and the possible decrease in donation-after-brain-death (DBD) by DCD programs. Our aim is to report the DCD experience at the University Hospital of Liege, Belgium, from 2002 through 2012, in a donor region of about 1 million inhabitants. Methods: The prospective organ donor and recipient databases were retrospectively reviewed. Results: 94 and 331 procurements were performed from controlled DCD and DBD donors in the time period, respectively. DCD donors contributed to 22.1% of the deceased donor (DD) organ procurement activity from Jan 2002 to Dec 2012, and up to one-third annually since 2009. DCD liver and kidneys contributed 23.7% and 24.2% of the DD liver and kidney transplantation activity, respectively. There was no decrease of the DBD procurement in the study period. In 2012, overall 54 DD were procured in the Liege region, reaching a high procurement activity.Conclusions: Controlled DCD donors are a valuable source of transplantable liver and kidney grafts, and in our experience do not adversely affect DBD organ procurement activity. [less ▲]

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See detailDONATION AFTER CIRCULATORY DEATH LIVER TRANSPLANTATION: IS DONOR AGE AN ISSUE?
DETRY, Olivier ULg; Ledinh, Heu; HONORE, Pierre ULg et al

in Transplant International (2013, December), 26(s2), 112-228

Background: Donation after circulatory death (DCD) donors > 55 years are usually not considered suitable for liver transplantation (LT). At our institute, age is not an absolute exclusion criterion to ... [more ▼]

Background: Donation after circulatory death (DCD) donors > 55 years are usually not considered suitable for liver transplantation (LT). At our institute, age is not an absolute exclusion criterion to refuse DCD liver grafts. We retrospectively compared the transplant outcome of patients receiving older DCD liver grafts to the younger ones. Methods: 70 DCD liver transplants have been performed from 2003 to 2012, which includes 32 liver grafts from younger donors <55y (group A), 20 between 56 and 69 years (group B), and 18 from older donors ≥70 years (group C). The three groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant week and results at one and three years. Results are expressed as median IQR. Results: No difference other than age in donor and recipient characteristics as well as procurement conditions was noted between both groups. Median donor age of the group A was 44 (38-45) years, in group B 62 (60-64) years and 73 (71-75) in group C. Median primary warm ischemia time (WIT) were 20 (17-22), 21 (19-25) and 19 (16-23) min, respectively (NS). Median cold ischemia time (CIT) was 236 (229-294), 245 (227-290) and 210 (195-277) min, respectively (NS). Peak AST (UI/ml) was 1162 (1072-3971), 1416 (1006-2752), and 1067 (902-4037), respectively (NS). There was no primary nonfunction and one patient needed retransplantation for artery thrombosis. Biliary complications occurred similarly in both groups, without graft loss secondary to ischemic cholangiopathy. Graft and patient survivals were not different at one and three years. Conclusion: This study shows comparable results between DCD liver transplants from younger and older donors. Therefore donor age >55 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as WIT, CIT) are minimized. [less ▲]

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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, Samir et al

in Transplant International (2013, December), 26(S2), 53-98

Introduction: Donation after circulatory death (DCD) donors have been proposed to partially overcome the organ donor shortage. DCD-LT remains controversial, with reported increased risk of ischemic ... [more ▼]

Introduction: Donation after circulatory death (DCD) donors have been proposed to partially overcome the organ donor shortage. DCD-LT remains controversial, with reported increased risk of ischemic cholangiopathy leading to graft loss. The authors retrospectively reviewed a single centre experience with DCD-LT in a 9-year period. Patients and Methods: 70 DCD-LT were performed from 2003 to November 2012. All DCD procedures were performed in operative rooms. Median donor age was 59 years. Most grafts were flushed with HTK solution. Allocation was centre-based. Median total DCD warm ischemia was 19.5 min. Mean follow-up was 36 months. No patient was lost to follow-up. Results: Median MELD score at LT was 15. Median cold ischemia was 235 min. Median peak AST was 1,162 U/L. Median peak bilirubin was 31.2 mg/dL. Patient and graft survivals were 92.8% and 91.3% at one year and 79% and 77.7% at 3 years, respectively. One graft was lost due to hepatic artery thrombosis. No PNF or graft loss due to ischemic cholangiopathy was observed in this series. Causes of death were malignancies in 8 cases. Discussion: In this series, DCD LT appears to provide results equal to classical LT. Short cold ischemia and recipient selection with low MELD score may be the keys to good results in DCD LT, in terms of graft survival and avoidance of ischemic cholangiopathy. [less ▲]

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See detailEffects of Parecoxib on The Prevention of Postoperative Peritoneal Adhesions in Rats.
Arung, Willy; Jehaes, Francois; Cheramy, Jean-Paul et al

in Journal of Investigative Surgery : The Official Journal of the Academy of Surgical Research (2013), 26(6), 340-346

ABSTRACT Background: No systemic preventive therapy has been successful in inhibiting the development of postoperative peritoneal adhesions (PPAs). Objective: The aim of this study was to evaluate the ... [more ▼]

ABSTRACT Background: No systemic preventive therapy has been successful in inhibiting the development of postoperative peritoneal adhesions (PPAs). Objective: The aim of this study was to evaluate the potential effects of 5 day administration of parecoxib, on PPA prevention and on suture or wound healing in rats. Methods: In a model of PPAs induced by peritoneal electrical burn, 30 rats were randomized into 3 groups according to parecoxib administration route (control; intraperitoneal (IP); intramuscular (IM)). Plasma and peritoneal levels of PAI-1 and tPA were measured at T0, after 90 min of surgery (T90), and on postoperative day 10 (D10). In a cecum resection model, 20 rats were randomized into two groups (control and IP parecoxib), and abdominal wound healing and suture leakage were assessed at D10. In both models, PPAs were evaluated quantitatively and qualitatively on D10. Results: Administration of parecoxib significantly decreased the quantity (p < .05) and the severity (p < .01) of PPAs in both models. In addition, parecoxib administration did not cause healing defects or infectious complications in the two models. In the peritoneal burn model, IP or IM parecoxib administration inhibited the increase of postoperative plasma and peritoneum PAI-1 levels, an increase that was observed in the control group (p < .01). No anastomosis leakage could be demonstrated in both groups in the cecum resection model. Conclusion: This study showed that, in these rat models, parecoxib might reduce PPA formation. Confirmation of the safety of parecoxib on intestinal anastomoses is required and should be investigated in further animal models. [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 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 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 detailLaparoscopic liver resection: a single center experience
SZECEL, Delphine ULg; DE ROOVER, Arnaud ULg; DELWAIDE, Jean ULg et al

in Surgical Endoscopy (2013), 27

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See detailIntraperitoneal Adhesions After Open or Laparoscopic Abdominal Procedure: An Experimental Study in the Rat.
Arung, Willy; Drion, Pierre ULg; Honoré, Pierre ULg et al

in Surgical Endoscopy (2013), 27

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See detailDonation after cardio-circulatory death liver transplantation.
Le Dinh; DE ROOVER, Arnaud ULg; KABA, Abdourahmane ULg 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 ▲]

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See detailIntraperitoneal Adhesions After Open or Laparoscopic Abdominal Procedure: An Experimental Study in the Rat.
Arung, Willy; Drion, Pierre ULg; CHERAMY-BIEN, Jean-Paul ULg 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 ▲]

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See detailCategories of donation after cardiocirculatory death.
DETRY, Olivier ULg; Le Dinh, Hieu ULg; NOTERDAEME, Timothée et al

in Transplantation Proceedings (2012), 44(5), 1189-95

The interest in donation after cardiocirculatory death (DCD) was renewed in the early 1990s, as a means to partially overcome the shortage of donations after brain death. In some European countries and in ... [more ▼]

The interest in donation after cardiocirculatory death (DCD) was renewed in the early 1990s, as a means to partially overcome the shortage of donations after brain death. In some European countries and in the United States, DCD has become an increasingly frequent procedure over the last decade. To improve the results of DCD transplantation, it is important to compare practices, experiences, and results of various teams involved in this field. It is therefore crucial to accurately define the different types of DCD. However, in the literature, various DCD terminologies and classifications have been used, rendering it difficult to compare reported experiences. The authors have presented herein an overview of the various DCD descriptions in the literature, and have proposed an adapted DCD classification to better define the DCD processes, seeking to provide a better tool to compare the results of published reports and to improve current practices. This modified classification may be modified in the future according to ongoing experiences in this field. [less ▲]

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See detailINTRA-TUMORAL HETEROGENEITY AND RATIONAL SELECTION OF ANTIGENS FOR TARGETED THERAPY OF LIVER METASTASES
Turtoi, Andrei ULg; Blomme, Arnaud ULg; Delvaux, David ULg et al

in Acta Chirurgica Belgica (2012, May), 112(3), 8953

Objectives: Targeted therapies of liver metastases are gaining a major stake in current and future treatment options. However, the malignant lesions are heterogeneous in nature offering niches for cancer ... [more ▼]

Objectives: Targeted therapies of liver metastases are gaining a major stake in current and future treatment options. However, the malignant lesions are heterogeneous in nature offering niches for cancer cells causing treatment resistance and relapse. Therefore, a rational strategy is needed to select targetable antigens that would overcome this intra-tumoral heterogeneity. Methods: After ethical committee approval, 48 fresh liver metastases of colorectal origin were prospectively collected from patients undergoing liver resection. Here we macroscopically divided the lesion in different zones and generated a unique quantitative picture of the proteome heterogeneity in colorectal carcinoma liver metastases. Particular focus was laid on accessible proteins, a protein subclass comprising cell membrane associated and extracellular proteins. Accordingly, the tissues were ex-vivo biotinylated, affinity purified and analyzed for each zone separately using nano-UPLC-MSe proteomics technique. In total over 1500 unique proteins were statistically divided into different patterns of expression. Results: We have generated a quantitative picture of the proteome heterogeneity in colorectal carcinoma liver metastases. The study offers insight into novel targets but also antigens against which the antibodies are already involved in clinical trials or treatment of liver metastases. Extensive clustering and validation experiments highlight novel markers that offer the potential to homogeneously cover the metastatic lesion and become better targets. Conclusions: Two such antigens, LTBP2 and TGFBI were selected for functional analysis in colorectal carcinoma cells. In vitro and in vivo experiments showed that in particular TGFBI is relevant for migration and proliferation capacity of colorectal cancer cells. The suppression of this protein led to significant inhibition of tumor growth, crystalizing it as bona fide target for the development of anti-metastases therapies. [less ▲]

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