Retrospective analysis of Belgian experience with intestinal transplantation

Conference (2013, March 21)

Aim: The only alternative to Total Parenteral Nutrition (TPN) for complicated intestinal failure is Intesti- nal Transplantation (ITx) which is perceived as a high-risk procedure with inferior results ... [more ▼]

Aim: The only alternative to Total Parenteral Nutrition (TPN) for complicated intestinal failure is Intesti- nal Transplantation (ITx) which is perceived as a high-risk procedure with inferior results compared to other organ Tx. Therefore ITx has been rarely applied in Belgium. In a multicenter retrospective review, we analyzed the overall Belgian experience with ITx. Methods: The Belgium Liver Intestine Committee organized a survey among all Belgian Tx centers, based on the patient-specific data form of the international ITx registry. Overall activity and indications were reviewed. Patient/graft survival was calculated (Kaplan-Meier). Nutritional (TPN) independence and Quality of Life (QoL) (Karnofsky score) were analyzed. Results: 21 ITx were performed in 20 patients (03/99-11/12), distributed among 5 centers: KUL (12), ULg (5), UZG (2), UCL (1), UZA (1). Median age was 38y(8mo-56y). Male/female ratio was 10/10. 5 were pediatrics (<18y) and 15 adults. Indications were anatomical or functional short bowel syndrome: intestinal ischemia(5), volvulus(5), Crohn(2), chronic intestinal pseudo-obstruction(2), splanchnic thrombosis(2), Churg-Strauss(1), necrotizing enterocolitis(1), microvillus inclusion(1), intestinal atresia(1) and chronic rejection of a first ITx(1). Most patients also suffered from TPN-associated com- plications (infection/shortage of venous access or liver failure). An isolated small bowel was trans- planted in 9 patients (plus kidney Tx in 2; plus pancreas Tx in 1); 10 received a combined liver and ITx; 2 received a multivisceral Tx. At time of Tx, 11 patients were hospitalized and 10 at home. 20 grafts were procured from deceased donors; one segmental intestinal graft was procured from a living donor. ABO blood group was identical in 63%, compatible in 37%. Median cold ischemia time was 5h30 ́(3h17 ́-9h31 ́). All patients received tacrolimus-based immunosuppression. Basiliximab (anti-IL2 receptor antibody) induction was administered in 16 patients. In 11 patients donor specific blood was transfused as part of an immunomodulatory protocol. 5-year patient and graft survival is 59% and 55.6%, respectively. 8 patients died: 6 to sepsis, 1 to intracerebral hemorrhage; 1 sudden death re- mained unexplained. 1 patient developed postTx lymphoma. 2 chronic rejections occured for which one reTx was performed. Of 12 survivors (median follow-up 1870 days), 11 are nutritionally independent (TPN-free) and 10 have a Karnofsky score >90%. Conclusions: ITx has come of age in Belgium. During the last 13 years, 21 ITx were performed in 5 centers. A 5-year patient/graft survival of 59%/55.6% is achieved, which is similar to results reported by the International ITx registry. In Belgium, awareness should grow that ITx represents a life-saving (and QoL improving) treatment in selected patients with reduced life expectancy due to significant complica- tions from TPN and intestinal failure. [less ▲]

Is ultra-short cold ischemia the key to IBDL avoidance in DCD-LT?

Poster (2013, February 08)

Do Maastricht category III donation after cardiovascular death (DCD) donors experience end-of-life shortening?

Poster (2013, February 08)

Donation after cardio-circulatory death liver transplantation.

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 ▲]

INTRA-TUMORAL HETEROGENEITY AND RATIONAL SELECTION OF ANTIGENS FOR TARGETED THERAPY OF LIVER METASTASES

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 ▲]

Results of kidney transplantation from controlled donors after cardio-circulatory death: a single center experience

in Acta Chirurgica Belgica (2012, May), 112(3), 667

Objectives: The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio-circulatory death (DCD). Primary end-points were graft and patient survival ... [more ▼]

Objectives: The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio-circulatory death (DCD). Primary end-points were graft and patient survival, and post-transplant complications. The influence of delayed graft function (DGF) on graft survival and DGF risk factors were analyzed as secondary end-points. Methods: This is a retrospective mono-center review of a consecutive series of 80 DCD-KT performed at the University Hospital of Sart Tilman, University of Liège, between Jan 2005 and Dec 2011. Mean patient follow-up was 28.5 months. Results: Overall graft survival was 93.7%, 89.5%, 85% and 81.3% at 3 months, 1 year, 3 and 5 years, respectively. Death-censored graft survival at the corresponding time points was 93.7%, 93.7%, 90.8% and 90.8%. Main cause of graft loss was patient’s death with a functioning graft. No primary non-function grafts were encountered. Renal graft function was suboptimal at hospital discharge, but nearly normalized at 3 months. DGF was observed in 36% of all DCD-KT. DGF significantly increased post-operative length of hospitalization, but had no deleterious impact on graft function or survival. Donor body mass index (BMI) ≥30 kg/m2, recipient BMI ≥30 kg/m2 and pre-transplant dialysis duration significantly increased the risk of DGF in a multivariate logistic regression analysis (p < 0.05). Conclusions: Despite a higher rate of DGF, controlled DCD-KT offers a valuable contribution to the pool of deceased donor kidney grafts, with comparable mid-term results to those procured after brain death. [less ▲]

Laparoscopic liver resection: a single center experience

in Acta Chirurgica Belgica (2012, May), 112(3), 631

Results of kidney transplantation from controlled donors after cardio-circulatory death: a single center experience.

in Transplant International (2012), 25

The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio-circulatory death (DCD). Primary end-points were graft and patient survival, and post ... [more ▼]

The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio-circulatory death (DCD). Primary end-points were graft and patient survival, and post-transplant complications. The influence of delayed graft function (DGF) on graft survival and DGF risk factors were analyzed as secondary end-points. This is a retrospective mono-center review of a consecutive series of 59 DCD-KT performed between 2005 and 2010. Overall graft survival was 96.6%, 94.6%, and 90.7% at 3 months, 1 and 3 years, respectively. Main cause of graft loss was patient's death with a functioning graft. No primary nonfunction grafts. Renal graft function was suboptimal at hospital discharge, but nearly normalized at 3 months. DGF was observed in 45.6% of all DCD-KT. DGF significantly increased postoperative length of hospitalization, but had no deleterious impact on graft function or survival. Donor body mass index >/=30 was the only donor factor that was found to significantly increase the risk of DGF (P < 0.05). Despite a higher rate of DGF, controlled DCD-KT offers a valuable contribution to the pool of deceased donor kidney grafts, with comparable mid-term results to those procured after brain death. [less ▲]

Delayed graft function does not harm the future of donation-after-cardiac death in kidney transplantation.

in Transplantation Proceedings (2012), 44(9), 2795-802

INTRODUCTION: Delayed graft function (DGF) occurs more frequently in kidney transplants from donation after cardiac death (DCD) than from donation after brain death (DBD). We investigated the effect of ... [more ▼]

INTRODUCTION: Delayed graft function (DGF) occurs more frequently in kidney transplants from donation after cardiac death (DCD) than from donation after brain death (DBD). We investigated the effect of DGF on posttransplantation outcomes among grafts from controlled DCD kidneys. PATIENTS AND METHODS: This single-center retrospective study recruited 80 controlled DCD kidneys transplanted from January 2005 to December 2011. Mean patient follow-up was 28.5 months. RESULTS: There were no primary nonfunction grafts; the DGF rate was 35.5%. Overall graft survival rates between groups with versus without DGF were 92.4% and 95.2% at 1 year, 92.4% and 87.1% at 3 years, and 84.7% and 87.1% at 5 years, respectively (P = not significant (NS)). Patients with versus without DGF showed the same survival rates at the corresponding time 92.4% vs 97.2%, 92.4% vs 93.9%, and 84.7% vs 93.9% (P = NS). Estimated glomerular filtration rate was significantly lower in the DGF compared with the non-DGF group at hospital discharge (29 vs 42 mL/min; P = .00) and at 6 months posttransplantation (46 vs 52 mL/min; P = .04), but the difference disappeared thereafter: 47 vs 52 mL/min at 1 year, 50 vs 48 mL/min at 3 years, and 54 vs 53 mL/min at 5 years (P = NS). DGF did not increase the risk of an acute rejection episode (29.6% vs 30.6%; P = NS) or rate of surgical complications (33.3% vs 26.5%; P = NS). However, DGF prolonged significantly the length of hospitalization in the DGF versus the non- DGF group (18.9 vs 13 days; P = .00). Donor body mass index (BMI) >/= 30 kg/m(2), recipient BMI >/=30 kg/m(2), and pretransplantation dialysis duration increased the risk of DGF upon multivariate logistic regression analysis. CONCLUSIONS: Apart from the longer hospital stay, DGF had no deleterious impact on the future of kidney allografts from controlled DCD, which showed comparable graft and patient survivals, renal function, rejection rates, and surgical complications as a group without DGF. Therefore, DGF should no longer be considered to be a medical barrier to the use of kidney grafts from controlled DCD. [less ▲]

MULTICENTER BELGIAN SURVEY ON DONOR MORBIDITY AND MORTALITY IN ADULT-TO-ADULT LIVING DONOR LIVER TRANSPLANTATION

in Transplant International (2011, September), 24(2), 13-13