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: 8 (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: 44 (13 ULg)
Feasibility and accessibility to the laparoscopic procedures in University Hospital of Kinshasa
; ; et al
in Surgical Endoscopy (2013), 27Detailed reference viewed: 22 (2 ULg)
Laparoscopic liver resection: a single center experience
SZECEL, Delphine ; DE ROOVER, Arnaud ; DELWAIDE, Jean et al
in Surgical Endoscopy (2013), 27Detailed reference viewed: 29 (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: 23 (0 ULg)
La transplantation d'organes au CHU de Liège - Rapport d'activité 2012
DETRY, Olivier ; MEURISSE, Michel
Report (2013)Detailed reference viewed: 22 (3 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: 47 (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: 26 (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: 29 (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: 83 (10 ULg)
Strategies to decrease bleeding and biliary fistula
Conference (2012, September 21)Detailed reference viewed: 6 (3 ULg)
Donation after cardio-circulatory death liver transplantation.
; DE ROOVER, Arnaud ; KABA, Abdourahmane et al
in World Journal of Gastroenterology (2012), 18(33), 4491-506
The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ ... [more ▼]
The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT. [less ▲]Detailed reference viewed: 27 (5 ULg)
Intraperitoneal Adhesions After Open or Laparoscopic Abdominal Procedure: An Experimental Study in the Rat.
; Drion, Pierre ; CHERAMY-BIEN, Jean-Paul et al
in Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. (2012), 22(7), 651-657
Abstract Background: Adhesion formation is common after abdominal surgery. The incidence and severity of adhesion formation following open or laparoscopic surgery remain controversial. The role of CO(2 ... [more ▼]
Abstract Background: Adhesion formation is common after abdominal surgery. The incidence and severity of adhesion formation following open or laparoscopic surgery remain controversial. The role of CO(2) pneumoperitoneum is also widely discussed. This study aimed to compare adhesion formation following peritoneal injury by electrocoagulation performed through open or laparoscopic procedures in a rat model. Materials and Methods: Sixty male rats were randomized to undergo a 1.5-cm peritoneal injury with unipolar cautery under general anesthesia: open surgery (Group A, n=20), laparoscopic surgery with CO(2) pneumoperitoneum (Group B, n=20), and laparoscopic surgery with air pneumoperitoneum (Group C, n=20). Duration of the procedures was fixed at 90 minutes in all groups, and pneumoperitoneum pressure was kept at 10 mm Hg. Ten days later, the animals underwent a secondary laparotomy to score peritoneal adhesions using qualitative and quantitative parameters. Results: Forty-five rats developed at least one adhesion: 95% in Group A, 83% in Group B, and 55% in Group C (P<.01; Group C versus Group A, P<.01). According to number, thickness, tenacity, vascularization, extent, type, and grading according to the Zuhkle classification, no significant difference was observed between Groups A and B. The distribution of adhesions after open surgery was significantly different than after laparoscopic surgery (P<.001). It is interesting that Group C rats developed significantly fewer adhesions at the traumatized site, and their adhesions had less severe qualitative scores compared with those after open surgery (P<.01). Conclusions: In this animal model, CO(2) laparoscopic surgery did not decrease the formation of postoperative adhesion, compared with open surgery. The difference with the animals operated on with air pneumoperitoneum emphasizes the role of CO(2) in peritoneal injury leading to adhesion formation. [less ▲]Detailed reference viewed: 30 (3 ULg)
Liver transplantation for unresectable hepatocellular carcinoma in normal livers.
; ; et al
in Journal of Hepatology (2012), 57(2), 297-305
BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for ... [more ▼]
BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation <12months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC. [less ▲]Detailed reference viewed: 19 (2 ULg)
Categories of donation after cardiocirculatory death.
DETRY, Olivier ; Le Dinh, Hieu ; 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 ▲]Detailed reference viewed: 33 (3 ULg)
Imaging Guided Proteomics Unveils Heterogeniety in Colorectal Carcinoma Liver Metastases – Implications for Targeted Therapies.
; Turtoi, Andrei ; Delvaux, David et al
in Proceedings Giga Day 2012 (2012, May 04)Detailed reference viewed: 47 (22 ULg)
INTRA-TUMORAL HETEROGENEITY AND RATIONAL SELECTION OF ANTIGENS FOR TARGETED THERAPY OF LIVER METASTASES
Turtoi, Andrei ; Blomme, Arnaud ; Delvaux, David 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 ▲]Detailed reference viewed: 78 (22 ULg)
Liège experience in donation after cardiac death liver transplantation: 2003-2011
Le Dinh, Hieu ; DELWAIDE, Jean ; MONARD, Josée et al
in Acta Chirurgica Belgica (2012, May), 112(3), 6811
Objectives: Results of DCD-LT at the University Hospital of Liège were evaluated from 2003 to 2011. Methods: Medical records of 56 DCD liver recipients were retrospectively reviewed with regard to patient ... [more ▼]
Objectives: Results of DCD-LT at the University Hospital of Liège were evaluated from 2003 to 2011. Methods: Medical records of 56 DCD liver recipients were retrospectively reviewed with regard to patient and graft survivals and biliary complications. Mean follow-up was 26.4 months. Mean donor age was 56.3±14.5 years (25 - 83). Donor causes of death were due to anoxia (51.8%), stroke (32.1%) and head trauma (14.3%). Mean WIT, CIT and suture time were 20.5±7.1min (10 – 39), 265.6±85.1min (105 – 576), and 40.8±7.8 min (25 – 61), respectively. 95% of liver grafts were locally shared. HTK was the most commonly used perfusion solution (86%). Mean recipient age was 56.6±10.5 years (29 – 73). Indications for LT included ESLD (53.6%) and HCC (46.6%). Mean MELD score at transplant was 15.6±6.1points (6 – 40). Results: No primary non-function grafts. Mean peak serum AST and bilirubin levels were 2520±3621UI/L and 50.2±49.2mg/L, respectively. Eight patients (14.3%) developed biliary complications. No intra-hepatic bile duct strictures or re-transplantation. Global patient and graft survival was 92.6% at 3 months, 92.6% at 1 year, 73.8% at 3 years and 60% at 5 years. Death-censored patient and graft survival at the corresponding time points was 92.6%, 92.6%, 87.7% and 87.7%. Thirteen liver grafts were lost during follow-up exclusively due to recipient deaths. The rate of HCC recurrence was 33.3%. Conclusions: Controlled DCD donors are a valuable source of transplantable liver grafts. Primary results are encouraging and apparently as good as those from brain-dead donation LT essentially due to short WIT and CIT. [less ▲]Detailed reference viewed: 69 (2 ULg)