Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study.

BACKGROUND: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions. METHODS: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed. RESULTS: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047). CONCLUSION: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.

Assessment of the Clinical Impact of a Liver-Specific, BCAA-Enriched Diet in Major Liver Surgery.

BACKGROUND: The relationship between nutrition and liver disease is relevant for the outcome after surgery. Patients with liver cirrhosis characteristically show protein-energy malnutrition with decreased levels of branched-chain amino acids (BCAA) and increased levels of aromatic amino acids. MATERIALS AND METHODS: We conducted a prospective controlled clinical trial including 57 patients after liver transplantation or major liver resection surgery in order to test the effect of early postoperative nutrition on the outcome and nutrition profile of these patients. The test group received a dietetic program composed of ingredients naturally rich in BCAA (BCAA group), and the control group received standard hospital meals. Patient survival, liver function tests, subjective well-being, and a nutritional status including amino acid profiles were analyzed immediately and 14 days after major liver surgery (secondary end points). General health and well-being were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (primary end point). RESULTS: In-depth analysis of amino acid profiles was performed for patients undergoing liver resection (n = 21) and liver transplantation (n = 36). Interestingly, amino acid profiles did not correlate with body mass index or the Model for End-Stage Liver Disease score. Patients scheduled for liver transplantation showed significantly lower levels of BCAA pretransplant compared to patients undergoing liver resection. Patients in the liver resection subgroup were more likely to benefit from the BCAA cuisine in terms of significantly higher food intake and subjective rating. The clinical liver function tests, however, did not show statistical difference between the BCAA group and the control group in the examination period of 14 days. CONCLUSION: Our specifically designed BCAA-enriched diet resulted in greater patient satisfaction and compliance with nutrition. A larger trial or longer-term follow-up may be required to identify an effect on survival, recovery, surgical complications, protein profiles, and amino acid profiles.

Open Management of the Renal Vein Is a Safe Modification in Right-Sided Laparoscopic Living Donor Nephrectomy to Maximize Graft Vein Length.

BACKGROUND: The primary objective in living donor kidney transplantation is donor safety. In laparoscopic living donor nephrectomy, most centers prefer the left kidney for donation given the shorter renal vein, higher rate of thromboses, and more difficult surgical procedure for right kidney retrieval. The goal of this study was to demonstrate the feasibility of a hybrid technique using a Satinsky clamp in right-sided living donor nephrectomy to obtain maximal renal vein and to compare the outcome with standard left-sided laparoscopic donor nephrectomies. MATERIAL AND METHODS: Between 2005 and 2013, 77 patients underwent a left (group L) and 54 a right (group R) living donor nephrectomy. In group R, after laparoscopic dissection and mobilization of the right kidney, two 12-mm trocar incisions in the right upper quadrant were connected in a 5-7 cm subcostal incision. The caval vein was partially clamped under direct vision prior to dissection of the renal vein. The venotomy was then closed with a running 4-0 Prolene suture. The two groups were compared with regard to surgical complications, graft function, and graft survival. RESULTS: Using this technique, no significant difference with regard to complications or graft function was observed. Serum creatinine at discharge in donor group L was 1.23 (±0.43) mg/dL and in donor group R 1.21 (±0.37) mg/dL (P = .71). Graft survival at one year was 100% in both groups. CONCLUSION: Open management of the renal vein is a safe alternative in laparoscopic right-sided donor nephrectomy and ensures maximal length of the vein.

Outcomes of pancreas retransplantation in patients with pancreas graft failure.

BACKGROUND: Pancreas retransplantation is still a controversial option after loss of a pancreatic graft. This article describes the experience of pancreas retransplantation at a high-volume centre. METHODS: This was a retrospective observational study of all pancreas retransplantations performed in a single centre between 1997 and 2013. Pancreatic graft loss was defined by the return to insulin dependence. Risk factors for graft loss as well as patient and graft survival were analysed using logistic and time-to-event regression models. RESULTS: Of 409 pancreas transplantations undertaken, 52 (12·7 per cent) were identified as pancreas retransplantations. After a median follow-up of 65·0 (range 0·8-174·3) months, 1- and 5-year graft survival rates were 79 and 69 per cent respectively, and 1- and 5-year patient survival rates were 96 and 89 per cent. During the entire follow-up, 22 grafts (42 per cent) were lost. Patient survival was not associated with any of the donor- or recipient-related factors investigated. Five-year graft survival was better after simultaneous kidney-pancreas retransplantation than pancreas retransplantation alone: 80 per cent (16 of 20) versus 63 per cent (20 of 32) (P = 0·226). Acute rejection (odds ratio 4·49, 95 per cent c.i. 1·59 to 12·68; P = 0·005) and early surgical complications (OR 3·29, 1·09 to 9·99, P = 0·035) were identified as factors with an independent negative effect on graft survival. CONCLUSION: Pancreas retransplantation may be considered for patients whose previous graft has failed.

Integrating interventional oncology in the treatment of liver tumors.

BACKGROUND: Percutaneous ablation techniques offer a vast armamentarium for local, minimally invasive treatment of liver tumors, nowadays representing an established therapeutic option, which is integrated in treatment algorithms, especially for non-resectable liver tumors. The results of ablative treatment compare very well to surgical treatment in liver lesions, and confirm that these techniques are a valuable option for bridging for transplantation. Different techniques have been established to perform tumor ablation, and the feasibility varies according to the procedure and technical skills of the operator, depending on the size and location of the liver lesion. In recent years, stereotactic multi-needle techniques using 3D trajectory planning, general anesthesia, and tube disconnection during needle placement have had a strong impact on the application range of ablation for liver tumors. CONCLUSION: It is well known that creating a sufficient ablation margin and overlapping ablation zones is one key issue to enable ablation of large liver lesions with tumor-free margins (A0 ablation in analogy to R0 resection). Image fusion during treatment and follow-up assure highly accurate staging procedures and interventional planning. NOVEL ASPECTS: Review on the standards in ablation techniques for the treatment of liver tumors. Update on different ablation techniques, indications, and contraindications for percutaneous liver tumor treatment. Summary of recently published reports on liver tumor ablation.

Rapamycin and CTLA4Ig synergize to induce stable mixed chimerism without the need for CD40 blockade.

The mixed chimerism approach achieves donor-specific tolerance in organ transplantation, but clinical use is inhibited by the toxicities of current bone marrow (BM) transplantation (BMT) protocols. Blocking the CD40:CD154 pathway with anti-CD154 monoclonal antibodies (mAbs) is exceptionally potent in inducing mixed chimerism, but these mAbs are clinically not available. Defining the roles of donor and recipient CD40 in a murine allogeneic BMT model, we show that CD4 or CD8 activation through an intact direct or CD4 T cell activation through the indirect pathway is sufficient to trigger BM rejection despite CTLA4Ig treatment. In the absence of CD4 T cells, CD8 T cell activation via the direct pathway, in contrast, leads to a state of split tolerance. Interruption of the CD40 signals in both the direct and indirect pathway of allorecognition or lack of recipient CD154 is required for the induction of chimerism and tolerance. We developed a novel BMT protocol that induces mixed chimerism and donor-specific tolerance to fully mismatched cardiac allografts relying on CD28 costimulation blockade and mTOR inhibition without targeting the CD40 pathway. Notably, MHC-mismatched/minor antigen-matched skin grafts survive indefinitely whereas fully mismatched grafts are rejected, suggesting that non-MHC antigens cause graft rejection and split tolerance.