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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 detailIs there a role for intra-arterial therapy or isolated liver perfusion?
DETRY, Olivier ULg

Conference (2014, October 10)

IS THERE A ROLE FOR INTRA-ARTERIAL THERAPY OR ISOLATED LIVER PERFUSION? Pr Olivier Detry, Dpt of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, The liver is the most common ... [more ▼]

IS THERE A ROLE FOR INTRA-ARTERIAL THERAPY OR ISOLATED LIVER PERFUSION? Pr Olivier Detry, Dpt of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, The liver is the most common visceral site of colorectal cancer (CRC) metastasis and recurrence. Approximately 25% of CRC patients present with synchronous hepatic metastases at time of initial diagnosis, and further 50% will develop metachronous metastases during the course of their illness. Unfortunately, only 25% of patients with hepatic CRC metastases are suitable for R0 resection at time of diagnosis or after chemotherapy. Intra‐arterial locoregional therapies are evolving tools in the management of CRC liver metastases. Although these therapies were initially used for salvage and palliation, they are becoming therapeutic options earlier in the course of disease in selected populations, to increase the rate of curative surgical resection, and to improve survival and quality of life. Furthermore, intra‐arterial therapies may serve as viable first‐line treatments for the large majority of patients who present with unresectable liver metastases, and as neoadjuvant chemotherapy prior to hepatectomy to minimize systemic effects. Hyperthermic isolated liver perfusion (HILP) has also been proposed by some groups as a mean to treat patients with unresectable liver metastases. Significant anti-tumoral effect has been demonstrated but HILP is a complicated procedure with a high morbidity. There remains a lack of robust, prospective randomized data for fair and balanced comparisons to be made between locoregional and modern systemic therapeutic modalities, as well as between locoregional therapies. Future RCTs addressing overall patient survival, tumor response and toxicity are required before any of these locoregional intra‐arterial treatments can be definitively recommended as the standard of care for hepatic colorectal liver mestastases. At the CHU of Liege, intra-arterial chemotherapy is now the usual way of administrating chemotherapy in patients with multiple CRC metastases limited to the liver after R0 liver resection. [less ▲]

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See detailOrthotopic liver transplantation for hepatocellular car- cinoma after successful downstaging: results from the Belgian multicentre cohort
Schreiber, J.; Lerut, J; Verslype, C et al

in Hepatology (Baltimore, Md.) (2014, October), 60(S1), 468550

Purpose: Successful downstaging of hepatocellular carcinoma (HCC) into the Milan criteria (MC) remains a controversial indication for orthotopic liver transplantation (OLT). In Belgium, successful ... [more ▼]

Purpose: Successful downstaging of hepatocellular carcinoma (HCC) into the Milan criteria (MC) remains a controversial indication for orthotopic liver transplantation (OLT). In Belgium, successful downstaging of HCC is an accepted non-standard- ized exception (NSE) for liver allocation. This NSE group rep- resents a unique cohort to analyse if OLT can be safely offered to patients with those extended allocation criteria. The aim of this study is to compare the overall and recurrence free survival after cadaveric OLT between patients with successful downstaging (MILDOWN) and patients always inside the MC (MILIN) from all Belgian transplant centres. Methods: We ret- rospectively analysed all patients listed for OLT with HCC and underlying cirrhosis between 12/2006 and 12/2011 from all Belgian liver transplant centres. Successful downstaging was defined as bringing a patient who was outside the MC into the MC after locoregional therapy (LRT). Results: Overall 381 patients were listed in Belgium during the study period. Of these, 320 received OLT. 248 were MILIN, 62 were MIL- DOWN and 10 were transplanted outside MC. Downstaging treatment included transarterial chemoembolization (TACE; n=26), radiofrequency (RF; n=9), transarterial radioembolisa- tion (TARE; n=4), resection (n=3), percutaneous ethanol injec- tion (n=2) and a combination of the above-mentioned therapies in 18 cases. In the MILIN group 67.3% received locoregional therapy before transplantation, with no significant differences in the distribution of treatment type compared to the MIL- DOWN group. At listing there were no significant differences between the MILIN and MILDOWN group for age, gender and underlying liver disease. Median time on waiting list between the two groups was similar (120 days vs. 115.5 days). Overall survival at 1 year was not significantly different between MILIN and MILDOWN (87.1% vs. 79%; p=0.120). 1.6% of patients were lost to follow-up in both groups. Although not significant, recurrence free survival at 1 year tended to be higher in the MILIN group than in the MILDOWN group (83.9% vs. 74.2%; p=0.073). Conclusion: In this large Belgian multicentre cohort, overall and recurrence free survival at 1 year are not signifi- cantly different between patients who have been downstaged successfully and patients who were always inside the Milan criteria. However, a longer follow up period will define, if the trend of lower survival in the successfully downstaged group becomes significant. Factors associated with HCC recurrence have to be identified. [less ▲]

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See detailPREVENTION OF INCISIONAL HERNIA AFTER MIDLINE LAPAROTOMY FOR ABDOMINAL AORTIC ANEURYSM TREATMENT: A RANDOMIZED CONTROLLED TRIAL
Muysoms, F; Vierendeels, T; Huyghe, M et al

Conference (2014, September 11)

Background: The incidence of incisional hernias (IH) after open abdominal aortic aneurysm (AAA) repair is high. Prophylactic mesh augmentation (PMA) during laparotomy closure has been proposed in high ... [more ▼]

Background: The incidence of incisional hernias (IH) after open abdominal aortic aneurysm (AAA) repair is high. Prophylactic mesh augmentation (PMA) during laparotomy closure has been proposed in high-risk patients. Methods: A multicenter prospective randomized controlled study was conducted on patients undergoing elective repair of AAA through midline laparotomy (Clinical.Trials.gov: NCT00757133). In the study group a retro-muscular PMA was performed with a large-pore polypropylene mesh (Ultrapro™, width 7.5 cm). The primary endpoint was the incidence of IH at 24 months. Results: Between February 2009 and January 2013, 120 patients were recruited at 8 Belgian centers. Patients' characteristics at baseline were similar between the groups. Operative and postoperative characteristics showed no difference in morbidity or mortality. A highly significant reduction of IH incidence was found after PMA compared to conventional closure, respectively 0% (CI: 0 % - 5.5%) versus 27.6% (CI: 16.7% - 40.9%) (P<0.0001; Fisher's exact test). The estimated "freedom of IH" curves (Kaplan-Meier estimate) were significantly different across study arms (X2=18.93, P<0.0001; Mantel-Cox test). No adverse effects were observed, apart from an increased mean (SD) time to close the abdominal wall for PMA: 46.2 min (18.6) versus 29.6 min (18.5) (P<0.001; Mann-Whitney U test). Conclusion: Prophylactic retro-muscular mesh augmentation of a midline laparotomy in AAA patients is safe and effectively prevents the development of IH, with an extra time investment of 17 minutes. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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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 detailCinacalcet treatment at the time of transplantation is associated with a significant risk of delayed graft function in kidney transplant recipients
Jouret, François ULg; WEEKERS, Laurent ULg; GROSCH, Stéphanie ULg et al

in Transplant International (2014, May), 27(S1), 167

The calcium-sensing receptor (CaSR) has been implicated in the ischemia/ reperfusion (I/R) cascade in heart, liver and brain. Renal I/R occurs at the time of transplantation (Tx), with a deleterious ... [more ▼]

The calcium-sensing receptor (CaSR) has been implicated in the ischemia/ reperfusion (I/R) cascade in heart, liver and brain. Renal I/R occurs at the time of transplantation (Tx), with a deleterious impact on early graft function. Here, we retrospectively investigated if the use of cinacalcet, a CaSR agonist, in kidney transplant recipients (KTR) influences early graft recovery. All KTR from 2007 to 2012 in our Academic Hospital were prospectively included in a database. Patients actively treated with cinacalcet on the day of Tx were retrospectively identified from this database and matched with controls on (i) type of donor (living [LD], deceased after brain or circulatory death [DCD]); (ii) cold ischemic time (CIT) ` 1 h; (iii) residual diuresis (` 500 ml); and (iv) donor age (` 5 years). Delayed graft function (DGF) was defined as dialysis requirement after Tx. Baseline characteristics were compared between groups with student’s t-test or Chi-2 as appropriate. The endpoint was the percentage of DGF in both groups. Among 337 KTR, 36 (10.7%) were treated with cinacalcet at Tx. Control group included 61 patients. Characteristics of patients and donors are summarized in the table. DGF occurred in 42 and 23% of cinacalcet-treated and control groups, respectively (p = 0.05). These retro- spective observations suggest that CaSR activation at the time of Tx impairs early graft recovery. [less ▲]

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See detailWhat you should know before starting minimal invasive liver resection: an overview
DETRY, Olivier ULg

in Acta Chirurgica Belgica (2014, May), 114(3), 117

Laparoscopic liver surgery has evolved over the last 2 decades. Advancements in surgical technology, surgical technique, and postoperative care have aided in lifting barriers to laparoscopic liver ... [more ▼]

Laparoscopic liver surgery has evolved over the last 2 decades. Advancements in surgical technology, surgical technique, and postoperative care have aided in lifting barriers to laparoscopic liver resections (LLR). LLR might decrease morbidity and hospitalisation stay compared to open approach, and importantly in liver surgery, may decrease postoperative costal pain. However, in hepatic surgery as in all abdominal procedures, laparoscopic approach is a mean but not a goal. The possibility of LLR should neither modify indications for surgery nor the type of resection. Physiologic modifications induced by CO2 pneumoperitoneum should be known by the surgical and anaesthetic team involved in LLR. Pneumoperitoneum decreases cardiac output, and this decrease could be worsened by the reverse Trendelenburg position and by hepatic hilar clamping. CO2 pneumoperitoneum decreases hepatic blood flow. This is a clear advantage for limiting blood loss during LLR, but this also might increase liver ischemia during Pringle liver hilum clamping, a manoeuvre that should be avoided in LLR. Low venous pressure might decrease blood loss by the small supra hepatic veins, but may also further decrease cardiac output. Several devices may be used for liver section, without evidence of the superiority of one device compared to others. Endo GIA might be very helpful to control the major liver vessels, as branches of portal vein or suprahepatic veins. Significant CO2 embolism is a rare complication, and conversion to open approach for haemorrhage should be performed only if blood loss is controlled. Up to now, there is no clear scientific evidence that laparoscopic approach provides any advantage compared to open approach. SILS, LESS or even robotic approaches should only considered as purely experimental. Current barriers to LLR will continue to fall in the future. [less ▲]

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See detailMSC in clinics: Liver Transplantation
DETRY, Olivier ULg

Conference (2014, March 21)

For several years, mesenchymal stem cells (MSC) have been evaluated in vivo and in vitro for their immunomodulatory, anti-inflammatory, anti- ischemia-reperfusion injury and “tissue repair” properties ... [more ▼]

For several years, mesenchymal stem cells (MSC) have been evaluated in vivo and in vitro for their immunomodulatory, anti-inflammatory, anti- ischemia-reperfusion injury and “tissue repair” properties. These characteristics could make them interesting in various clinical applications, and particularly in organ transplantation. Taking advantage of our centre expertise and experience concerning MSC use in graft-versus-host disease after bone marrow transplantation and using already functioning GMP-compliant laboratory able to produce clinical-grade MSC, we initiated in 2011 a first trial exploring safety and tolerability of third party MSC infusions after kidney or liver transplantation in a prospective phase I-II study. In this study, after successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppressive treatment (tacrolimus, mycophenolate, steroids) receive an intravenous infusion of 1.5 - 3x106/kg of third-party MSC, on post-operative day 3+/-2. These patients are prospectively compared to the same number of liver and kidney transplant recipients who meet inclusion criteria but do not receive MSC infusion. Safety is assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential is evaluated by rejection episode rates, graft/patient survivals, immunohistology of 3-month (kidney) and 6-month (liver) graft biopsies, and in vitro evaluation of recipient immunity profile. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression is attempted in recipients who received MSC. Inclusion of liver patients is now complete, and to date 3 kidney patients received MSC. Primary results will be presented, and complete 6-month liver results are expected for the end of 2014. The next step will be to assert the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. [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 detailOrganized proteomic heterogeneity in colorectal liver metastases and implications for therapies
Turtoi, Andrei ULg; Blomme, Arnaud ULg; Debois, Delphine ULg et al

in Acta Gastro-Enterologica Belgica (2014, March), 77(1), 07

Introduction : Tumor heterogeneity is a major obstacle for developing effective anti-cancer treatments. Recent studies have pointed at large stochastic genetic heterogeneity within cancer lesions, where ... [more ▼]

Introduction : Tumor heterogeneity is a major obstacle for developing effective anti-cancer treatments. Recent studies have pointed at large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Aim : Because to date no similar information is available at the protein (phenotype) level, we aimed at characterising the proteomic heterogeneity in human colorectal carcinoma (CRC) liver metastases. Methods & Results : We employed MALDI imaging-guided proteomics and explored the heterogeneity of extracellular distribution of over 1000 proteins we found unexpectedly that all liver metastasis lesions displayed a reproducible, zon- ally delineated, pattern of functional and therapeutic biomarker heterogeneity. Peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed 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. Conclusions : proteome heterogeneity has a distinct, organized, pattern. This particular hallmark can now be used as a part of the strategy for developing rational therapies based on multiple sets of targetable antigens. [less ▲]

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See detailTGF-B induced protein IG-H3 is essential for the growth of human liver metastases
Castronovo, Vincenzo ULg; Blomme, Arnaud; Delvenne, Philippe ULg et al

in Acta Gastro-Enterologica Belgica (2014, March), 77(1), 05

Introduction : Transforming growth factor-beta-induced protein ig-h3 (TGFBI) is extracellular matrix component known to be important for cell-collagen interaction. We and others have reported elevated ... [more ▼]

Introduction : Transforming growth factor-beta-induced protein ig-h3 (TGFBI) is extracellular matrix component known to be important for cell-collagen interaction. We and others have reported elevated expression of TGFBI in sev- eral human cancers, where its role remains controversial. Aim Current study aims at clarifying the function of TGFBI to date. Methods &Results : CRC-LM and in liver metastases originating from breast, lung and pancreatic tumors. We have next focused on func- tional aspects and have silenced TGFBI expression in SW1222 human colorectal carcinoma cells. The suppression of TGFBI protein led to a marked decrease in cell migration (-70%) and proliferation (-30%) in vitro. To study the effects in vivo we have developed a novel animal model of colorectal carcinoma based on chicken chorioallantoic membrane (CAM) that mimics human CRC-LM. TGFBI silencing resulted in 50% reduction of tumor volume in the CAM tumor model. Notably, the tumors displayed a marked inhibition of vascularization, suggesting an additional anti-angiogenic effect. Indeed, SW1222 cells silenced for TGFBI expression secreted lower levels of VEGFA in vitro. Finally, we have investigated if TGFBI can be used as systemically reachable target for antibody-drug delivery. For this purpose we have The in vivo data demonstrated that TGFBI is an accessible tumor target. Conclusions : Taken together, the present study shows that TGFBI is essential for promoting the development of CRC- LM and therefore represents a promising target for designing novel therapeutic approaches. [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 detailDoes comfort therapy during controlled donation after circulatory death shorten the life of potential donors?
LEDOUX, Didier ULg; DELBOUILLE, Marie-Hélène ULg; DE ROOVER, Arnaud ULg et al

in Clinical transplantation (2014), 28(1), 47-51

INTRODUCTION: Controlled donation after circulatory death (DCD) remains ethically controversial. The authors developed a controlled DCD protocol in which comfort therapy is regularly used. The aim of this ... [more ▼]

INTRODUCTION: Controlled donation after circulatory death (DCD) remains ethically controversial. The authors developed a controlled DCD protocol in which comfort therapy is regularly used. The aim of this study was to determine whether this policy shortens the DCD donors' life. METHODS: The authors retrospectively analyzed prospectively collected data on patients proposed for DCD at the University Hospital of Liege, Belgium, over a 56-month period. The survival duration of these patients, defined as duration between the time of proposal for DCD and the time of circulatory arrest, was compared between patients who actually donated organs and those who did not. RESULTS: About 128 patients were considered for controlled DCD and 54 (43%) became donors. Among the 74 non-donor patients, 34 (46%) objected to organ donation, 38 patients (51%) were denied by the transplant team for various medical reasons, and two potential DCD donors did not undergo procurement due to logistical and organizational reasons. The survival durations were similar in the DCD donor and non-donor groups. No non-donor patient survived. CONCLUSIONS: Survival of DCD donors is not shortened when compared with non-donor patients. These data support the ethical and respectful approach to potential DCD donors in the authors' center, including regular comfort therapy. [less ▲]

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