Pure laparoscopic full-left living donor hepatectomy for calculated small-for-size LDLT in adults: proof of concept.

Adult-to-adult living donor liver transplantation (A2ALDLT) is an accepted mode of treatment for end-stage liver disease. Right-lobe grafts have usually been preferred in view of the higher graft volume, which lowers the risk of a small-for-size syndrome. However, donor left hepatectomy is associated with less morbidity than when it is compared to right hepatectomy. Laparoscopic donor hepatectomy (LDH) has been considered almost exclusively in pediatric transplantation. The results of laparoscopic left-liver graft procurement for calculated small-for-size A2ALDLT in four donors are presented. The graft-to-recipient body weight ratio was <0.8 in all recipients. The mean portal vein flow and the pressure and hepatic artery flows were measured at 190 ± 56 mL/min/100 g, 13 ± 1.4 mm/Hg and 109 ± 19 mL/min, respectively. No early postoperative donor complications were recorded. One graft was lost due to intrahepatic abscesses. Asymptomatic stenosis of a right posterior duct was treated with a Roux-en-Y loop 4 months later in one donor. We show that LDH of the full-left lobe is feasible. LDH is a very demanding operation, potentially decreasing donor morbidity. Standardization of this procedure, making it accessible to the growing number of experienced laparoscopic liver surgeons, could help renewing the interest for A2ALDLT in the Western world.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

The Eurotransplant donor risk index in liver transplantation: ET-DRI.

Recently we validated the donor risk index (DRI) as conducted by Feng et al. for the Eurotransplant region. Although this scoring system is a valid tool for scoring donor liver quality, for allocation purposes a scoring system tailored for the Eurotransplant region may be more appropriate. Objective of our study was to investigate various donor and transplant risk factors and design a risk model for the Eurotransplant region. This study is a database analysis of all 5939 liver transplantations from deceased donors into adult recipients from the 1st of January 2003 until the 31st of December 2007 in Eurotransplant. Data were analyzed with Kaplan-Meier and Cox regression models. From 5723 patients follow-up data were available with a mean of 2.5 years. After multivariate analysis the DRI (p < 0.0001), latest lab GGT (p = 0.005) and rescue allocation (p = 0.007) remained significant. These factors were used to create the Eurotransplant Donor Risk Index (ET-DRI). Concordance-index calculation shows this ET-DRI to have high predictive value for outcome after liver transplantation. Therefore, we advise the use of this ET-DRI for risk indication and possibly for allocation purposes within the Eurotrans-plant region.

[Current developments in liver transplantation in Germany: MELD-based organ allocation and incentives for transplant centres]. / Aktuelle Entwicklungen der Lebertransplantation in Deutschland: MELD-basierte Organallokation und "incentives" für Transplantationszentren.

Liver transplantation represents a successful and well-established therapeutic concept for patients with advanced liver diseases. Organ donor shortage continues to pose a significant problem. To ensure fair and transparent allocation of too few post-mortem grafts, the model of end-stage liver disease (MELD)-based allocation was implemented in December 2006. This has decreased waiting list mortality from 20 to 10 % but at the same time has reduced post OLT survival (1-year survival from almost 90% to below 80%), which is largely due to patients with a labMELD score > 30. Following MELD introduction the regular allocation threshold has increased from a matchMELD of initially 25 to meanwhile 34. At the same time the quality of donor organs has seen a continuous deterioration over the last 10 - 15 years: 63% of organs are "suboptimal" with a donor risk index of > 1.5. Moreover, the numbers of living-related liver transplantations have decreased. In Germany incentives for transplant centres are inappropriate: patients with decompensated cirrhosis, high MELD scores and high post-transplant mortality as well as marginal liver grafts are accepted for transplantation without the necessary consideration of outcomes, and against a background of the still absent publication and transparency of outcome results. The outlined development calls for measures for improvement: (i) the increase of donor grafts (e. g., living donation, opt-out solutions, non-heart beating donors), (ii) the elimination of inappropriate incentives for transplant centres, (iii) changes of allocation guidelines, that take the current situation and suboptimal donor grafts into account, and (iv) the systematic and complete collection of transplant-related data in order to allow for the development of improved prognostic scores.

Prospective evaluation of intraoperative hemodynamics in liver transplantation with whole, partial and DCD grafts.

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.

Infrarenal versus supraceliac aorto-hepatic arterial revascularisation in adult liver transplantation: multicentre retrospective study.

When the standard arterial reconstruction is not feasible during liver transplantation (LT), aorto-hepatic arterial reconstruction (AHAR) can be the only solution to save the graft. AHAR can be performed on the infrarenal (IR) or supraceliac (SC) tract of the aorta, but the possible effect on outcome of selecting SC versus IR reconstruction is still unclear. One hundred and twenty consecutive patients who underwent liver transplantation with AHAR in six European centres between January 2003 and December 2018 were retrospectively analysed to ascertain whether the incidence of hepatic artery thrombosis (HAT) was influenced by the type of AHAR (IR-AHAR vs. SC-AHAR). In 56/120 (46.6%) cases, an IR anastomosis was performed, always using an interposition arterial conduit. In the other 64/120 (53.4%) cases, an SC anastomosis was performed; an arterial conduit was used in 45/64 (70.3%) cases. Incidence of early (≤ 30 days) HAT was in 6.2% (4/64) in the SC-AHAR and 10.7% (6/56) IR-AHAR group (p = 0.512) whilst incidence of late HAT was significantly lower in the SC-AHAR group (4.7% (3/64) vs 19.6% (11/56) - p = 0.024). IR-AHAR was the only independent risk factor for HAT (exp[B] = 3.915; 95% CI 1.400-10.951; p = 0.009). When AHAR is necessary at liver transplantation, the use of the supraceliac aorta significantly reduces the incidence of hepatic artery thrombosis and should therefore be recommended whenever possible.

Induction of tolerance in solid organ transplantation: the rationale to develop clinical protocols in liver transplantation.

Minimization or withdrawal of immunosuppressive treatments after organ transplantation represents a major objective for improving quality of life and long-term survival of grafted patients. Such a goal may be reached under some clinical conditions, particularly in liver transplantation, making these patients good candidates for tolerance trials. In this context in liver transplantation, the central questions are (1) how to promote the natural propensity of the liver graft to be accepted, (2) which type of immunosuppressive drug should be used for induction and maintenance, and (3) which biomarkers could be used to discriminate tolerant patients from those requiring long-term immunosuppression. Induction therapies using aggressive T-cell-depleting agents may favor graft acceptance. However, persistent and/or rapidly reemerging cell lines, such as memory-type cells or CD8(+) T cells, could represent a significant barrier for induction of tolerance. The type of maintenance drugs also remains questionable. Calcineurin inhibitors may be eventually deleterious in the context of tolerance protocols, through inhibitory effects on regulatory T cells, that are not observed with rapamycin. In conclusion, significant efforts must be made to achieve reliable strategies for immunosuppression minimization or withdrawal after organ transplantation into the clinics.

Laparoscopic living donor hepatectomy for pediatric liver transplantation.

Living donor liver transplantation is a well established modality, especially for pediatric transplantation with excellent early graft function and long-term results. Left lateral sectionectomy through open approach is a well-standardized procedure. Considering our acquired experience in both laparoscopic liver resection and standard open surgery for live donation in pediatric and adult patients, we decided to offer, for the first time in Belgium, a laparoscopic approach for the left lateral sectionectomy to a young mother. The patient was a child 6-months old,affected by biliary atresia and rapidly deteriorating while waiting on a deceased donor liver graft. Surgical technique and key-points of this procedure in the living donor are hereby discussed.

Update on liver transplantation for cholangiocarcinoma : a review of the recent literature.

Cholangiocarcinoma (CC) represent 3% of all gastrointestinal tumours and can be classified anatomically in 3 types: intrahepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinomas. Resection is the treatment of choice but is only achieved in a few cases (<20%) because of invasion of the biliary tract and/or vascular structures. The outcome of advanced CC is poor with an overall survival (OS) of maximum 15 months with chemotherapy. In the 1990s, CC was regarded as a contraindication for liver transplantation (LT). LT has recently been proposed as potentially curative option for ICC and PCC. Careful patient selection has changed OS. This article provides an update on current status of LT for patients with unresectable CC.

Major hepatectomy for colorectal metastases: is preoperative portal occlusion an oncological risk factor?

BACKGROUND: This study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM). METHODS: Between 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed. RESULTS: 21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed. CONCLUSION: Unresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM.

Liver transplantation for hilar cholangiocarcinoma: a German survey.

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

The choice of recipient does not have a bearing on early outcome in liver transplant patients receiving grafts from non-heart-beating donors: a reappraisal?

INTRODUCTION: Donation after cardiac death has reemerged as a potential way of increasing the supply of organs for transplantation. We retrospectively reviewed the outcomes of non-heart-beating donor (NHBD) liver transplantation (OLT) experience and compared with standard heart-beating donation (HBD) at a single center. METHODS: From October 2003 to November 2006, 13/111 liver transplantations were performed in our institution with NHBD. Living donor liver transplantation, splitting procedures, combined, and pediatric liver transplantations were excluded from this analysis. RESULTS: Donor population was similar in both groups. The median warm ischemia time was 10 minutes (range 6 to 38). The median cold ischemia times 6 hours and 16 minutes (2.4 to 6.30 hours and 9 hours and 14 minutes (2.15 to 15.35 hours) for NHBD and HBD groups, respectively (P = .0002). In the NHBD groups, 4/13 (31%) grafts were retransplanted within 3 months, due to ischemic biliary lesions with severe cholestasis (n = 3) or due to the occurrence of primary nonfunction (n = 1). The retransplantation rate was significantly lower in the HBD group (11/98, 11%; P = .03). One-year patient and graft survivals were 62% and 54% versus 86% and 79%, respectively, for the NHBD and HBD groups (P = .107 and P = .003). CONCLUSION: Liver grafts procured from donors after cardiac death accounted for a significantly greater retransplantation rates, mainly due to nonanastomotic biliary strictures. This risk must be taken into account when transplanting such grafts. Based upon this experience, NHBD cannot rival HBD to be a comparable source of quality organs for liver transplantation.

Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation.

BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and interferon (IFN)-gamma are mediators of acute graft rejection after liver transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective role and correlate with graft acceptance. To test the hypothesis that infants aged <1 year have an immunological advantage with regard to graft acceptance because of a partially immature immune system with a physiological balance toward a Th2 cytokine profile, we conducted the present study. METHODS: We compared the T helper serum cytokine profiles in 105 infants and children after liver transplantation with or without acute graft rejection and analyzed the normal age-distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS: The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1 to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence of acute rejection in infants 0 to 12 months of age compared with children >1 year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1 cytokine concentrations and decreasing Th2 cytokine concentrations were found with increasing age. Patients with acute rejection had significantly higher values of Th1 cytokines compared with nonrejecting subjects, who had significantly higher concentrations of Th2 cytokines. A longitudinal analysis of serum cytokines from patients showed that changes of the cytokine patterns in the follow-up did not differ significantly from preoperative values, except in the 4 weeks posttransplant. CONCLUSIONS: We conclude from the data that the physiological balance toward a Th2 cytokine profile of infants in the first months of life predisposes to improved graft acceptance. Transplantation of children with biliary atresia as early as possible, avoiding Th1 stimulation by recurrent infections and vaccinations, may have a positive impact on overall tolerance.

Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: comparison with heterotopically transplanted liver grafts.

BACKGROUND: Hepatocyte transplantation using polymeric matrices is under investigation as an alternative therapy for metabolic liver diseases. Long-term engraftment of hepatocytes in polymers has been demonstrated. However, the metabolic activity of hepatocytes in such devices has never been assessed in direct comparison with liver grafts. METHODS: Hepatocyte and partial liver transplantation were evaluated in the scurvy-prone osteogenic disorder Shionogi rat model. Biodegradable poly glycolic acid matrices seeded with hepatocytes equivalent to 20% of the recipient's liver mass, or 20% liver grafts were heterotopically transplanted into ascorbic acid- (AsA) deficient recipients. Recipients of cell-free matrices or AsA-deficient liver grafts served as controls. Recipients were set on AsA-free diet after transplantation. Plasma AsA levels, AsA concentrations in liver and adrenal gland tissue, and body weight ratios were assessed and H&E histology was performed. RESULTS: Recipients from the control groups showed symptoms of scurvy at 1 month after cessation of AsA supply. Hepatocyte transplantation and auxiliary liver transplantation prevented symptoms of scurvy and increased plasma and tissue AsA levels and body weight ratios. AsA levels in recipients of 20% liver grafts were comparable to normal control animals. CONCLUSIONS: Hepatocytes transplanted in polymeric matrices are able to compensate for liver-based metabolic deficiencies. Hepatocyte transplantation improves plasma AsA levels in AsA-deficient recipients. However, auxiliary liver grafts are superior to hepatocyte grafts in improving metabolic parameters. Further research work is needed to increase the efficiency of liver cell transplantation with regard to a clinical application.

Selection of the living liver donor.

Living related liver transplantation offers several advantages in comparison to transplantation of cadaver organs. To achieve maximal donor safety evaluation, selection criteria and complications of the donor operation were retrospectively analyzed in living donors of segmental liver transplants. Seventy-three liver donor candidates were evaluated between October 1991 and June 1994. The median age of 42 mothers and 31 fathers was 31 years (range, 19-50 years). The median volume of the left lateral liver lobe comprised 230 ml (100-350 ml). Twenty-four of 73 (33%) donor candidates were not accepted for living donation. Rejection was due to unsuitability of the donor's liver as a graft (n = 13) or due to an increased risk for living donation (n = 11). Of 35 living donations performed so far, one was a full left hemihepatectomy and 34 were left lateral segmentectomies. The length of the donor operation was, on average, 4.3 hr. No heterologous blood was needed. Postoperative complications included death due to pulmonary embolism (n = 1), seizure due to a previously undiagnosed ependymoma (n = 1), bile duct injury (n = 1), incisional hernia necessitating late revision (n = 2), and duodenal ulcer (n = 2). Long-term follow-up revealed no persistent complications. Using our standardized protocol, 33% of young, presumably healthy donor candidates were rejected for living donation.

In situ splitting of the liver in the heart-beating cadaveric organ donor for transplantation in two recipients.

SLT presents an interesting concept to alleviate the organ shortage for children with end-stage liver disease. The procedure has, however, not gained wide acceptance. This is not only related to the complexity of the procedure, but also to the poorer results and the complications reported on the right side graft. We report on a first case in which we applied a new concept for splitting. The liver was split in situ in the heart-beating cadaveric donor with the aim of reducing the problems with the right side graft. This procedure makes splitting of the liver possible without submitting the recipient of the right side to increased risk. Therefore, in situ splitting of the liver has the potential of making splitting of liver grafts the rule rather than the exception, thus increasing the organ pool for small children presently carrying a high risk of dying on the waiting list.

One year of experience with extended application and modified techniques of split liver transplantation.

As organ donation rates decreased in Europe, the authors started a systematic approach of liver splitting in their center in 1994. During this 1-year experience, 73 cadaveric liver transplantations were performed in 66 patients. Sixteen of these transplantations were the result of split-liver transplantation (21.9% of grafts, 24.2% of patients). Patient and graft survival rates at 3 months were 81.2% and 75%, compared with 89.1% and 76.9 % for whole organs. Two modified techniques were developed, based on the technique of living related liver procurement, and applied in 10 cases. With these new techniques, patient and graft survival rates were 90% and 90%. This systematic approach allowed the total number of transplantations in our program to be maintained, despite the decrease in organ availability.