Lars Mueller

Portal Vein Embolization vs. Portal Vein Ligation for Induction of Hypertrophy of the Future Liver Remnant

The objective of this study was to assess the efficacy of right portal vein embolization (PVE) vs. right portal vein ligation (PVL) for induction of hypertrophy of the left lateral liver lobe before extended right hepatectomy. Thirty-four patients with primary or secondary liver tumors and estimated remnant functional liver parenchyma of less than 0.5% of body weight underwent either right PVE (transcutaneous, n= 10; transileocolic, n =7) or right PVL (n=17). Liver volume was assessed by CT scan before occlusion of the right portal vein and prior to resection. There were no deaths. The morbidity rate in each group was 5.8% (PVE, 1 abscess; PVL, 1 bile leak). The increase in liver volume was significantly higher after PVE compared with PVL (188±81 ml vs. 123±58 ml) (P= 0.012). Postoperative hospital stay was significantly shorter after PVE in comparison to PVL (4±2.9 days vs. 8.1±5.1 days;P<0.01). Curative liver resection was performed in 10 of 17 patients after PVE and 11 of 17 patients after PVL. PVE and PVL were found to be feasible and safe methods of increasing the remnant functional liver volume and achieving resectability for extended liver tumors. PVE results in a significantly more efficient increase in liver volume and a shorter hospital stay.

Evolution of Donor Morbidity in Living Related Liver Transplantation: A Single-Center Analysis of 165 Cases

Objective:During the last 14 years, living donor liver transplantation (LDLT) has evolved to an indispensable surgical strategy to minimize mortality of adult and pediatric patients awaiting transplantation. The crucial prerequisite to performing this procedure is a minimal morbidity and mortality risk to the healthy living donor. Little is known about the learning curve involved with this type of surgery. Patients and Methods:From January 1991 to August 2003, a total of 165 LDLTs were performed in our center. Of these, 135 were donations of the left-lateral lobe (LL, segments II and III), 3 were of the left lobe (L, segments II–IV), 3 were full-left lobes (FL, segments I–IV), and 24 were of the full-right lobe (FR, segments V–VIII). We divided the procedures into 3 periods: period 1 included the years 1991 to 1995 (LL, n = 49; L, n = 2; FR, n = 1), period 2 covered 1996 to 2000 (LL, n = 47), and period 3 covered 2001 to August 2003 (LL, n = 39; FR, n = 23; FL, n = 3; L, n = 1). Perioperative mortality and morbidity were assessed using a standardized classification. Length of stay in intensive care unit, postoperative hospital stay, laboratory results (bilirubin, INR, and LFTs), morbidity, and the different types of grafts in the 3 different periods were compared. Results:One early donor death was observed in period 1 (03/07/93, case 30; total mortality, 0.61.%). Since 1991, the perioperative morbidity has continually declined (53.8% vs. 23.4% vs. 9.2%). In period 1, 28 patients had 40 complications. In period 2, 11 patients had 12 complications, and in period 3, 6 patients had 9 complications. Within the first period, 1 donor underwent relaparotomy because of bile leakage. Postoperative hospital stay was 10 days, 7 days, and 6 days, respectively. Donation of the full right lobe, in comparison with that of the left lateral lobe, resulted in a significantly diminished liver function (bilirubin and INR) during the first 5 days after donation but did not increase morbidity. One donor from period 1 experienced late death caused by amyotrophic lateral sclerosis. Conclusions:In a single center, morbidity after living liver donation strongly correlates to center experience. Despite the additional risks associated with temporary reduction of liver function, this experience enabled the team to bypass part of the learning curve when starting right lobe donation. Specific training of the surgical team and coaching by an experienced center should be implemented for centers offering this procedure to avoid the learning curve.

Is There Still a Need for Living-related Liver Transplantation in Children?

ObjectiveTo assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). Summary Background DataThe concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. MethodsOutcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. ResultsAfter a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. ConclusionsThe short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

One Hundred Thirty-Two Consecutive Pediatric Liver Transplants Without Hospital Mortality: Lessons Learned and Outlook for the Future

Objective:Orthotopic liver transplantation (OLT) has become an established procedure for the treatment of pediatric patients with end-stage liver disease. Since starting our program in 1989, 422 pediatric OLTs have been performed using all techniques presently available. Analyzing our series, we have concluded that the year of transplantation is the most important prognostic factor in patient and graft survival in a multivariate analysis. Methods:From April 2001 to December 1, 2003, 18 whole organs (14%), 17 reduced-size organs (13%), 53 split organs (42%; 46 ex situ, 7 in situ), and 44 organs from living donors (33%) were transplanted into 115 patients (62 male and 53 female). One hundred twelve were primary liver transplants, 18 were retransplants, one third and one fourth liver transplants. Of the 132 OLTs, 26 were highly urgent (19.7%). The outcome of these 132 OLTs was retrospectively analyzed. Results:Of 132 consecutive pediatric liver transplants, no patients died within the 6 months posttransplantation. Overall, 3 recipients (2%) died during further follow-up, 1 child because of severe pneumonia 13 months after transplantation and the second recipient with unknown cause 7 months postoperatively, both with good functioning grafts after uneventful transplantation. The third had a recurrence of an unknown liver disease 9 months after transplantation. The 3-month and actual graft survival rates are 92% and 86%, respectively. Sixteen children (12%) had to undergo retransplantation, the causes of which were chronic rejection (3.8%), primary nonfunction (3.8%), primary poor function (PPF; 1.5%), and arterial thrombosis (3%). The biliary complication rate was 6%; arterial complications occurred in 8.3%; intestinal perforation was observed in 3%; and in 5%, postoperative bleeding required reoperation. The portal vein complication rate was 2%. Conclusions:Progress during the past 15 years has enabled us to perform pediatric liver transplantation with near perfect patient survival. Advances in posttransplant care of the recipients, technical refinements, standardization of surgery and monitoring, and adequate choice of the donor organ and transplantation technique enable these results, which mark a turning point at which immediate survival after transplantation will be considered the norm. The long-term treatment of the transplanted patient, with the aim of avoiding late graft loss and achieving optimal quality of life, will become the center of debate.

Long-term Outcome of Split Liver Transplantation Using Right Extended Grafts in Adulthood: A Matched Pair Analysis

Objective:Shortage of suitable organs led to the development of alternative techniques in liver transplantation. Split liver transplantation (SLT) is well established in pediatric patients. SLT is not completely accepted in adult recipients due to potential increased risk of complications. Despite satisfying results of short-term outcome, there is a leak on information of the long-term outcome. Therefore, we compared the outcome after transplantation of the right extended liver lobe with whole liver transplantation (WLT) using a matched pairs analysis. Patients and Methods:From the period of January 1993 to February 2005, 70 SLT recipients were matched with 70 WLT recipients of whole livers. Matching criteria were: 1) indication for transplantation, 2) United Network for Organ Sharing (UNOS) status, 3) recipient age, 4) donor age, 5) cold ischemic time, and 6) year of transplantation. The outcome was analyzed retrospectively. Results:Mean follow-up was 36 months. The 2- and 5-year patient survival rates after SLT and WLT were 86.3% and 82.6%, and 78.4% and 75.6%, respectively (log rank, P = 0.2127). Two- and 5-year graft survival rates were 77.3% and 77.3% after SLT and 71.9% and 65.8% after WLT, respectively (log rank, P = 0.3822). The total biliary complication rate was 11.4% in the SLT group versus 10.0% in the WLT group in the short-term course, while it was 8.5% after SLT and 10.0% after WLT in the long-term course. We did not observe significant differences between the groups in term of short- and long-term morbidity. Conclusion:Transplantation of the right extended lobe deriving from left lateral splitting of deceased donor livers is followed by the same long-term patient and graft survival, which is known from WLT. There were no differences in the complication rates even in long-term outcome implementing that SLT does not put the adult recipient to an increased early and late risk. Transplantation of the extended right liver lobe provides a safe and efficient procedure in adult patients to expand the number of available grafts.

Comparative study of portal vein embolization versus portal vein ligation for induction of hypertrophy of the future liver remnant using a mini-pig model.

Summary Background Data:The extent of hepatectomies is limited by the functional reserve of the remnant liver. The introduction of preoperative portal vein occlusion techniques to induce a preoperative hyperplasia of the future liver remnant has reduced the risk of postoperative liver failure. However, it has remained a matter of debate whether partial portal vein embolization (PVE) or suture ligation of the portal branches during exploration is the preferred technique. We compared both techniques under standardized experimental conditions in a large animal model by means of effectiveness and pathophysiologic differences. Methods:Thirteen mini-pigs underwent portal vein ligation (PVL), 11 mini-pigs underwent PVE of 75% of the liver volume, and 6 underwent a sham operation. The animals were killed after 28 days. Laboratory liver function and damage parameters, lobar liver-to-body weight indices, portal and arterial flow alterations, and histologic changes were assessed. Ex situ arteriograms and portograms were performed to examine adaptive changes in the macroarchitecture of both vascular systems. Results:The liver-to-body weight index of the nonoccluded lobe was highest after PVE (0.85) versus 0.6 (P < 0.05) after PVL. There was no significant reduction in global serum parameters reflecting total liver function. After 4 weeks, the PVL group consistently exhibited hepatopetal portal flow in the ligated lobes, which was present but significantly decreased after PVE. The ex situ angiography after PVE and PVL revealed the development of portal neocollaterals in the portal-occluded liver parts. Conclusions:Both PVL and PVE are able to induce hypertrophy of the future liver remnant. In comparison, PVE is the more effective technique to increase the future liver remnant. This is due to a more effective, durable occlusion of the portal branches. Formation of collaterals between occluded and nonoccluded liver parts seems to be the cause of inferior regeneration in the ligation group.

Technical Refinements and Results in Full-Right Full-Left Splitting of the Deceased Donor Liver

Objective:Splitting of the liver at the line of Cantlie of otherwise healthy people is accepted worldwide as a reasonable procedure for the donors in adult living donor liver transplantation. A similar operation is still considered as experimental if performed in the deceased donor liver. The aim of this study is to evaluate the technical evolution and the results of this variant splitting technique. Patients and Methods:From January 1999 to August 2004, a total of 35 transplants of hemilivers from deceased donors (segments V–VIII: n = 16 and segments (I)II–IV: n = 19) were performed in our center. Seven splits were performed in situ and 12 ex situ. Splitting of the vena cava was applied in 18 splits and splitting of the middle hepatic vein in 8. Seven adults and 12 adolescents received the left hemiliver with a mean age of 12 years (range, 3–64 years), of whom 21% were UNOS status 1. Recipients of right hemilivers were exclusively adults with a mean age of 48 years (range, 31–65 years), none of them were high urgent. The outcome of these 35 recipients of hemilivers was prospectively evaluated. Results:Mean deceased donor age was 27 years (range, 12–57 years), the donors body weight ranged between 55 kg and 100 kg. The mean weight of the right and left hemilivers was 1135 g (range, 745–1432 g) and 602 g (range, 289–1100 g), respectively. The mean graft recipient weight ratio in left and right hemiliver group was 1.46% (range, 0.88%–3.54%) and 1.58% (range, 1.15%–1.99%), respectively. Median follow-up was 27.4 months (range, 1–68.3 months). Four patients died (actual patient survival FR group: 87.5% versus FL group: 89.5%), 3 due to septic MOF and 1 due to graft versus host disease. In each of the 2 groups, 2 recipients had to undergo retransplantation, which resulted in an actual right and left hemiliver survival rate of 75% and 84%, respectively. The causes for retransplantation were primary nonfunction in 2 left hemilivers, chronic graft dysfunction in 1 right hemiliver, and recurrence of the primary disease in 1 recipient of a right hemiliver. Primary poor function was observed in 1 recipient of a right hemiliver. Early and late biliary complications occurred in both right and left hemiliver groups at the rate of 37.5% (n = 6) and 21% (n = 4), respectively. Arterial, portal, and venous complications were not observed in either group. Conclusion:The technical development of splitting along Cantlies line is almost complete with the last challenge being the reduction of biliary complications. The key to success is the choice of adequate deceased donors and recipients. Full-right full-left splitting is safely possible and should be considered as a reasonable instrument to alleviate mortality on the adult waiting list and to reduce the need for adult and adolescent living donation.

The induction of the immediate-early-genes Egr-1, PAI-1 and PRL-1 during liver regeneration in surgical models is related to increased portal flow

BACKGROUND The environmental triggers which control liver regeneration following partial hepatectomy (PH) are not clear. With respect to haemodynamic changes, the model of rat portal branch ligation (PBL) provides the unique opportunity to discriminate transcriptional events, which selectively result from increased portal flow. AIMS The potential role of portal over-flow on early expression of early growth response gene-1 (Egr-1), type-1 plasminogen activator inhibitor (PAI-1) and phosphatase of regenerating liver-1 (PRL-1) was analysed by a comparative experimental study using PBL and PH. METHODS Operative procedures were carried out in male Wistar rats. Growth kinetics were measured by liver weight indices. S-phase-specific mRNA-levels of H2B-histone protein (H2B), as well as expression analysis of Egr-1, PAI-1 and PRL-1 were examined by Northern blot experiments. RESULTS Growth patterns did not differ significantly between PBL and PH, whereas peak H2B expression occurred earlier after PH. Egr-1 and PAI-1 were specifically induced during the first few hours in the hyper-perfused lobes following PBL and PH. PRL-1-expression selectively peaked 3h after PH and PBL in the hyper-perfused lobes. CONCLUSIONS Increased portal flow after PBL and PH was associated with induction of Egr-1, PAI-1 and PRL-1. Thus, haemodynamic changes affect the molecular immediate-early response during liver regeneration.

Pediatric transplantation: the Hamburg experience.

Background. Since starting our program in 1989, 455 pediatric orthotopic liver transplantations have been performed using all techniques. In April 2001, we experienced our last in-hospital death of a pediatric liver-transplant recipient. Since then, all our liver-transplant children (n=170) were able to be discharged from the hospital. The aim of this study is to analyze the actual status of pediatric liver transplantation at the University of Hamburg and to find future perspectives to improve the results after pediatric liver transplantation. Methods. From May 4, 2001 until September 8, 2004, 22 (13%) whole organs, 18 (11%) reduced-size organs, 79 (47%) split organs, and 51 (30%) organs from living donors were transplanted into 142 patients. One hundred forty-one were primary liver transplants, 25 retransplants, 3 third, and 1 fourth liver transplants. Of the 170 orthotopic liver transplantations (OLT), 31 (18%) were highly urgent (United Network of Organ Sharing [UNOS] I). Results. After 170 consecutive pediatric liver transplants, no patients died during the hospital course (100% patient survival<3 months), but overall, 5 (2.9%) recipients died during further follow-up. The 3-month and actual graft survival rates are 93% and 85%, respectively. Twenty (11.8%) children had to undergo retransplantation. However, patient survival was not sustained by longer graft survival. Analyzing our series, we see that graft survival after reduced-size liver transplantation showed a significantly lower rate versus living-donor liver transplantation. Conclusion. The learning curve in pediatric liver transplantation has reached a turning point where immediate patient survival is considered the rule. The challenge is to increase graft survival to the same level. The long-term management of the transplant patients, with the aim of avoiding late graft loss and achieving excellent quality of life, will become the center of the debate.

Sustained function in atrophying liver tissue after portal branch ligation in the rat

BACKGROUND Preoperative segmental portal vein occlusion has become a common method to prevent liver failure after extended hepatic resection. To date, it is not elucidated whether atrophy by portal deprivation with concomitant contralateral regeneration leads to impaired liver function. We addressed this question by examining the expression of liver function proteins related to glucose homeostasis and acute-phase response in a corresponding animal model. MATERIALS AND METHODS Male Wistar rats were subjected to either portal branch ligation (PBL), partial hepatectomy (PH), or sham operation (SO). The mRNA expression and chronological distribution of glucose-6-phosphatase (G6P), glucagon receptor (GR), glceraldehyd-3-phosphate-dehydrogenase (GAPDH), albumin, fibronectin, and C1-esterase-inhibitor (C1-Inh) genes were examined by Northern-blot hybridizations. Determinations of serum-glucose and glycogen staining by periodic acid and Schiff were performed to analyze changes in glucose mobilization and storage. RESULTS In regenerating liver tissue after PH and PBL, we detected a selective reduction of transcripts encoding G6P during the prereplicative period 6 and 12 h after surgery and a contemporary drop in serum glucose levels. This impairment proved to be more distinct after PH than after PBL. Compared with the residual liver after PH, the level of glycogen disappearance was lower after PBL in the regenerating lobe. In the portal-deprived liver tissue, the expression of genes coding for G6P, GR, GAPDH, albumin, fibronectin, and C1-Inh was not altered compared with the SO group. CONCLUSIONS Overall, portal-deprived liver tissue undergoing atrophy retains its liver-specific differentiation and function and helps to maintain homeostasis during the fast regeneration of the non-occluded liver lobe.