Small-for-size Grafts Research Articles

Improvement of mouse cardiac function by hESC-derived cardiomyocytes correlates with vascularity but not graft size

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) has been shown to improve the function of the rodent heart 1 month after myocardial infarction (MI). However, the mechanistic basis and optimal delivery strategies are unclear. We investigated the influence of the number of injected cells, resulting graft size, and possible paracrine mechanisms in this process. MI was induced in NOD-SCID mice ( n = 84) followed by injection of enriched hESC-CM at different dosages, hESC-non-CM derivatives, culture medium, or no injection. Cardiac function was monitored for 12 weeks with 9.4 T MRI ( n = 70). Grafts were identified by epifluorescence of a transgenic GFP marker and characterized by immunofluorescence. Vascularity and paracrine effects were investigated immunohistochemically. Transplantation of differentiated hESCs improved short, mid-, and long-term cardiac performance and survival, although only cardiomyocytes formed grafts. A mid-term (4 weeks) cardiomyocyte-specific enhancement was associated with elevated vascular density around the graft and attenuated compensatory remodeling. However, increasing the number of hESC-CM for injection did not enhance heart function further. Moreover, we observed that small graft size was associated with a better functional outcome. HESC-CM increased myocardial vascularization and enhanced heart function in mice after MI, but larger graft size was associated with reduced functional improvement. Future studies should focus on advanced delivery strategies and mechanisms of action rather than increasing graft size.

Hepatic Regenerative Response in Small-Sized Liver Isografts in the Rat

To investigate hepatic regenerative response and associated mechanisms in different-size liver grafts in the rat. Rat models of different-size-graft liver transplantation (whole, 50%-size, or 30%-size) were established, with a sham operation group serving as a control. Portal pressure, graft injury, interleukin 6 (IL-6), signal transducer and activator of transcription (Stat3), mitogen-activated protein kinase (MAPK), cyclin D1, and proliferating cell nuclear antigen (PCNA) were all assessed. The portal pressure was significantly higher and hepatic injury more severe in the smaller sized groups than in the whole graft group, especially in the 30%-size grafts. Hepatic IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels in the two smaller sized groups were significantly higher than in the whole graft group, while IL-6 levels appeared to be negatively associated with graft sizes. Downstream markers of IL-6, Stat3 and MAPK phosphorylation, cyclin D1, and PCNA expression were also markedly increased in the small-sized grafts compared with the whole grafts, and appeared to positively correlate with early measurements of portal pressure and subsequent hepatic injury. Vigorous hepatic regeneration in small-for-size liver grafts may be associated with highly activated IL-6/Stat3 and MAPK signaling, which may in turn correlate with graft size, portal pressure, and hepatic injury.

Prevent Small-For-Size Syndrome Using Dual Grafts in Living Donor Liver Transplantation

The growing gap between the number of patients waiting for transplantation and available organs is still the main issue facing the transplant community. The major limitation of adult-to-adult living donor liver transplantation (LDLT) is the small-for-size problem because of the concern of donor safety. We report preliminary experiences for preventing small-for-size syndrome using dual grafts from one right lobe without the middle hepatic vein and one left lateral segment in adult-to-adult LDLT. One hundred ten cases of adult-to-adult LDLT were performed in West China Hospital of Sichuan University from January 2002 to August 2007, and there were 16 small-for-size (SFS) grafts in all grafts. Dual grafts LDLT was performed for six patients with end-stage liver disease, consisting of five cases from one right lobe without the middle hepatic vein and one left lateral segment, and one case from two left lobes. All living donors underwent a full recovery from the operation without persistent complications. Four recipients died of sepsis, one recipient received re-transplantation, and three recipients received transplenic artery embolization in the recipients with SFS grafts. All recipients with dual grafts displayed good graft function and a majority of grafts showed normal triangular-shape regeneration of their respective liver grafts. Only in one left lateral segment atrophy occurred, graft hepatectomy was not required. Dual grafts from one right lobe without the middle hepatic vein and one left lateral segment in adult-to-adult LDLT can prevent the small-for-size problem and yet secure the safety of the donors.

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

To investigate the tacrolimus dosage requirements and blood concentrations in adult-to-adult right lobe living donor liver transplantation (AALDLT) recipients with small-for-size (SFS) grafts. During January 2007 and October 2008, a total of 54 cases of AALDLT with an observation period of 6 mo were enrolled in this study. The 54 patients were divided into two groups according to graft-recipient body weight ratio (GRBW): SFS grafts group (Group S, GRBW < 0.8%, n = 8) and non-SFS grafts group (Group N, GRBW > or = 0.8%, n = 46). Tacrolimus 12-hour blood levels and doses were recorded during weeks 1, 2, 3 and 4 and months 2, 3, 4, 5 and 6 in group S and group N. Meanwhile, acute rejection rates, liver and renal function test results, and the number of potentially interacting medications were determined at each interval in the two groups. A comparison of tacrolimus dosage requirements and blood levels were made weekly in the first month post-surgery, and monthly from months 2 to 6. There were no differences in the demographic characteristics, acute rejection rates, liver and renal function test results, or the number of potentially interacting medications administered between the two groups. The tacrolimus dosage requirements in group S were significantly lower than group N at 2 wk (2.8 +/- 0.4 mg/d vs 3.6 +/- 0.7 mg/d, P = 0.006), 3 wk (2.9 +/- 0.7 mg/d vs 3.9 +/- 0.8 mg/d, P = 0.008), 4 wk (2.9 +/- 0.8 mg/d vs 3.9 +/- 1.0 mg/d, P = 0.023) and 2 mo (2.8 +/- 0.7 mg/d vs 3.8 +/- 1.1 mg/d, P = 0.033). Tacrolimus 12-h trough concentrations were similar between the two groups at all times except for 2 wk post-transplantation, when the concentrations were significantly greater in group S recipients than in group N recipients (11.3 +/- 4.8 ng/mL vs 7.0 +/- 3.8 ng/mL, P = 0.026). SFS grafts recipients have significantly decreased tacrolimus dosage requirements compared with non-SFS grafts recipients in AALDLT during the first 2 mo post-surgery.

Second Unrelated Donor (URD) Transplant as a Rescue Strategy for 122 Patients with Primary Non Engraftment: Results from the CIBMTR

Few data are available on the outcomes of patients who fail to engraft following URD transplantation. We describe the results of 122 patients reported to the National Marrow Donor Program (NMDP) between 1990 and 2005, who received a second bone marrow (BM) or peripheral blood (PB) URD transplant after failing to achieve an absolute neutrophil count of ≥ 500/mm3 without evidence of recurrent disease. Patients were transplanted for leukemia (n=83), myelodysplastic disorders (n=16), severe aplastic anemia (n=20) and other disease (n=3). The median age at first transplant was 29 years. Approximately one third were in each age range, < 20 (33%), 20–40 (37%) and >40 (29%). The initial transplant was BM in 84% of patients while 51% received BM for the subsequent transplant. One hundred ten of these patients received two transplants, 11 received three and one received 4 transplants. Twenty four used a different donor whereas 98 used the original donor for the second transplant; 28 of these used cells that had been cryopreserved at the initial transplant date. Nearly two thirds of the patients received reduced intensity conditioning or no conditioning for the second transplant. Sixty one percent had ATG as a component of their second transplant. The median interval from first transplant to second transplant was 48 (range, 18–126) days. The median nucleated cell dose was 2 × 108/kg (range, <1–23) for the first transplant and 2 × 108/kg (range, <1–50) for the second. The median follow up of survivors after second transplant was 77 (range, 2–144) months. Univariate probabilities of outcomes for these patients after second transplant were:OutcomeN evalProbability (95% CI)Neutrophil engraftment*122@ 28 days43 (34–52) %@100 days48 (39–57) %30 day mortality12239 (31–48) %100 day mortality12275 (67–82) %Overall survival (OS) @ 1 year12211 (6–17) %Treatment related mortality (TRM) @ 1 year*9986 (79–92) %Disease free survival (DFS) @ 1 year997 (2–12) %*cumulative incidenceOf the 122 patients analyzed, only 10 remain alive. The most common causes of death were graft failure or rejection (33%), organ failure/interstitial pnuemoniatis (22%), infection (15%), GVHD (14%) and recurrent disease (6%). Of the 37 patients who had persistent graft failure 21 (57%) died from infectious causes.We observed no differences between patients who received a graft from the same donor vs. different donor, fresh vs. cryopreserved cells, or small initial graft size vs. large initial graft size. Patients who received a T-cell depleted graft at the time of their first transplant had significantly worse survival at 1 year after their second transplant, 4% (95% CI, 0–11) compared to those patients who had a non T-cell depleted initial graft, 16% (95 % CI, 8–25)(P = 0.02). It appears that a second salvage transplant strategy may be effective in a small group of patients, although the overall DFS at 1 year of only 7% is disappointing. To improve these results, efforts might focus on early identification and treatment of those at highest risk for non engraftment to determine whether such a strategy can alter the natural history we have described.

Optimal Administration of Tacrolimus in Reduced-Size Liver

The optimal administration of immunosuppressants such as tacrolimus (Tac) for small-for-size (SFS) grafts, where the functional liver mass is small and must regenerate, has not been reported so far. The aim of this study is to clarify the characteristics of Tac metabolism according to liver volume. Seven-week-old male Wistar rats were randomly divided into three groups: (1) Tac administrated and 70% Hx group (Tac 70% Hx group), (2) Tac administrated and 90% Hx group (Tac 90% Hx group), and (3) vehicle administrated and 90% Hx group (control 90% Hx group). In both the Tac groups, Tac (0.3 mg/kg) was given daily for 3 days before operation, and daily after surgery until sacrifice (each time point; n = 5). The plasma concentration of Tac (trough level), as well as liver toxicity, were measured. The plasma concentration of Tac in the Tac 90% Hx group was significantly higher than in the Tac 70% Hx group from 24 to 72 h after operation. Furthermore, expression of CYP3AII mRNA was significantly lower in the Tac 90% Hx group than in the Tac 70% Hx group. Regarding the liver toxicity, there was no significant difference in both the Tac 90% Hx and the control 90% Hx groups. In this experimental study, the plasma concentration of Tac was dependent on the remnant liver volume. Therefore, special attention in regard to Tac administration should also be taken for patients with SFS grafts in living-donor liver transplantation (LDLT).

Current concept of small-for-size grafts in living donor liver transplantation

The extended application of living donor liver transplantation (LDLT) has revealed the problem of graft size mismatching called "small-for-size (SFS) graft syndrome." The initial trials to resolve this problem involved increasing the procured graft size, from left to right, and even extension to include a right lobe graft. Clinical cases of living right lobe donations have been reported since then, drawing attention to the risks of increasing the liver volume procured from a living donor. However, not only other modes of increasing graft volume such as auxiliary or dual liver transplantation, but also control of the increased portal pressure caused by an SFS graft, such as a portosystemic shunt or splenectomy, have been trialed with some positive results. To establish an effective strategy for transplanting SFS grafts and preventing SFS graft syndrome, it is essential to have precise knowledge and tactics to evaluate graft quality and graft volume, when performing these LDLTs with portal pressure control. We reviewed the updated literature on the pathogenesis of and strategies for using SFS grafts.

Effects of Prophylactic Splenic Artery Modulation on Portal Overperfusion and Liver Regeneration in Small-for-Size Graft

The small-for-size (SFS) syndrome is caused by excessive portal inflow into a small-sized liver graft. Various approaches for portal decompression have been used, but details of their impact on liver regeneration in SFS graft remain unclear. We examined the effect of prophylactic splenic artery modulation (SAM). We conducted a retrospective cohort study. The study group was 39 consecutive adult-to-adult living liver transplantation recipients, with a graft-to-recipient body weight ratio of less than 0.8. Patients were assigned into the non-SAM group (n=18, without any portal inflow attenuation) or SAM group (n=21, preoperative embolization in 15 patients and intraoperative ligation in 6 patients). Hepatic hemodynamics, graft function, liver regeneration, and outcome were evaluated. In the SAM group, the excessive portal flow was significantly reduced (P<0.01) and the effect of embolization on portal decompression was equivalent to that of ligation. In the acute postoperative phase, serum transaminases, interleukin-6, and tumor necrosis factor-alpha, were lower in the SAM group than in non-SAM group. In both groups, a negative correlation was observed between graft-to-recipient body weight ratio and liver regeneration rate at 2 weeks after living donor liver transplantation. Splenic artery modulation was advantageous for liver regeneration, and significantly improved clinical features, hyperbilirubinemia, and prolonged ascites. Small-for-size syndrome occurred in five patients of the non-SAM group, and only one of SAM group (P=0.038). In SFS graft with severe portal hypertension, prophylactic splenic embolization/ligation seems to relieve portal overperfusion injury and contributes in improvement of posttransplantation prognosis through liver regeneration.

Bone marrow stem cells for urologic tissue engineering

Experiments in rats and dogs have demonstrated the potential of bone marrow-derived mesenchymal stem cells (MSCs) for urinary tract tissue engineering. However, the small graft size in rats and a failure to identify the MSCs in engineered tissues made it difficult to assess the true potential of these cells. Our goals were to characterize MSCs from pigs, determine their ability to differentiate into smooth muscle cells (SMCs) and use them in an autologous augmentation cystoplasty. MSCs were isolated from pigs and analyzed for common markers of MSCs by flow cytometry. SMC differentiation was determined by immunoblotting. MSCs were isolated, genetically labeled, expanded in vitro, seeded onto small intestinal submucosa (SIS) and used for autologous bladder augmentation. Porcine MSCs are morphologically and immunophenotypically similar to human MSCs. Culturing MSCs at low density enhances proliferation rates. MSCs consistently differentiate into mature SMCs in vitro when maintained at confluence. Labeled MSCs grew on SIS over one week in vitro and survived a 2-week implantation as an autologous bladder augment in vivo. Some label-positive cells with SMC morphology were detected, but most SMCs were negative. Notably, many cells with a urothelial morphology stained positively. Porcine MSCs have similar properties to MSCs from other species and consistently undergo differentiation into mature SMC in vitro under specific culture conditions. Labeled MSCs within SIS may assist tissue regeneration in augmentation cystoplasty but may not significantly incorporate into smooth muscle bundles.

The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft

Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n=69), in which splenectomy was not performed, and the Sp (+) group (n=44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n=50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio<40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P=0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less.

Strategies for improving the outcomes of small-for-size grafts in adult-to-adult living-donor liver transplantation

Living-donor liver transplantation (LDLT) has been refined and accepted as a valuable treatment for patients with end-stage liver disease in order to overcome the shortage of organs and mortality on the waiting list. However, graft size problems, especially small-for-size (SFS) grafts, remain the greatest limiting factor for the expansion of LDLT, especially in adult-to-adult transplantation. Various attempts have been made to overcome the problems regarding SFS grafts, such as increasing the graft liver volume and/or controlling excessive portal inflow to a small graft, with considerable positive outcomes. Recent innovations in basic studies have also contributed to the treatment of SFS syndrome. Herein, we review the literature and assess our current knowledge of the pathogenesis and treatment strategies for the use of SFS grafts in adult-to-adult LDLT.

Aortic reconstruction with femoral-popliteal vein: Graft stenosis incidence, risk and reintervention

Management using femoral-popliteal vein (FPV) of aortic graft infections, failing aortofemoral bypass, and aortoiliac occlusive disease in young patients with a small aorta is now an accepted therapeutic method and is performed frequently at our institution. A high reintervention rate for FPV graft stenosis has recently been reported. The purpose of this study was to determine the incidence of FPV graft failure due to stenosis after neoaortoiliac system (NAIS) reconstruction, and to identify risk factors for this complication. A review was performed of 240 patients who underwent NAIS reconstruction at our institution between January 1991 and December 2005. All patients were entered into a prospective database and were evaluated for the incidence of vein graft stenosis requiring reintervention, risk factors for stenosis, and the rate and type of reintervention required to assist patency. Patients with occlusion are evaluated and reported, but excluded from detailed analysis. Risk factors assessed included gender, operative features, FPV size (diameter), smoking history, and medical comorbidities. Of the 240 NAIS procedures performed during this time period, 11 (4.6%) patients have required 12 graft revisions (one patient required a second intervention) for stenosis using open and endovascular techniques. Over the same time period, graft occlusion occurred in nine patients (3.8%). This provided a primary patency at 2 and 5 years of 87% and 82%, and an assisted primary patency rate of 96% and 94%. Mean time to revision was 23.5 months (range 5.5 to 83.5 months). Median FPV graft size in the nonrevised patients was 7.8 mm (range 4.0 to 11.4 mm), and 6.4 mm (range 4.7 to 8.7 mm) in the revised group (P = .006). Survival analysis revealed small vein graft size (<7.2 mm), coronary artery disease (CAD), and extensive smoking history as independent predictors of time to stenosis (P = .002, .02, .01, respectively), with multivariable analysis confirming these results (P = .002, .06, .012). Patients with CAD combined with small graft size were found to be at especially high risk for stenosis, with 8/36 (22.2%) requiring revision vs 3/184 (1.6%) of patients without both factors (P < .0001). FPV graft stenosis requiring revision after NAIS reconstruction is uncommon. Risk factors for stenosis include small graft size, history of CAD, and smoking. All patients merit aggressive counseling for smoking cessation, and patients exhibiting multiple risk factors should undergo close postoperative surveillance for graft stenosis.

Monitoring for HLA Antibodies in Cord Blood Transplantation.

Though graft rejection in hematopoietic cell transplantation (HCT) is presumed to be mediated primarily by host anti-donor T cells and natural killer cells, host antibodies which generate antibody dependent cellular cytotoxic reactions to donor antigens may also contribute. For patients undergoing HCT with a cord blood graft which is usually markedly mismatched to the recipient, alloimmunization is a potential significant issue. Cross-matching is not able to be performed secondary to limited cell numbers available from a cord blood graft. Delayed hematopoietic recovery and graft failure are known complications of cord blood transplantation (CBT), and though likely related primarily to small graft size and presence of primarily naïve immune cells in a cord blood graft, HLA antibodies may also contribute. At our center, we investigate recipient alloimmunity in all patients undergoing CBT to guide donor selection. Patients are first screened for the presence of antibodies against HLA antigens using an ELISA-based assay in which patient serum is tested against pools of purified class I and class II HLA antigens bound in wells of a plastic microtiter plate. Serum from patients noted to have evidence of HLA antibodies prompts further testing to identify the specific HLA antibodies using panels of color coded plastic microspheres each coated with a single purified class I or class II HLA antigen. To date, 4 of 29 patients screened have had evidence of HLA alloimmunization. Further investigation of antibody specificity in one patient undergoing double unit CBT demonstrated antibodies to HLA-Bw6, an epitope known to be present on one of the donor units. Because no other donors were available, the unit was used. Following a reduced intensity preparative regimen (RIT), the patient engrafted neutrophils on day 24 and platelets on day 42. However, the HLA-Bw6 positive unit was absent on all chimerism studies (beginning day 21 post transplantation). Three other patients with HLA alloimmunization did not have identifiable antibody specificity directed against mismatched HLA antigens, and engrafted neutrophils on days 25, 29, 25 and platelets on days 29, 41, and 102 respectively. To our knowledge, we are the first to report monitoring for alloimmunization in CBT and the first to describe the outcome of grafting a cord blood unit known to be HLA antibody incompatible with the patient. When patients undergo double unit CBT, cells from both units can generally be detected in the blood of the recipient during the first month, especially following RIT conditioning, but one unit eventually and consistently prevails (though predictive factors for the winning unit have not yet been satisfactorily described). In this case the compatible unit prevailed and there was no evidence at day 21 of cells from the antibody incompatible unit. Although we cannot attribute cause and effect to the anti-Bw6 alloantibody, it is interesting to note that all seven other patients transplanted on the same RIT protocol have demonstrated at least minimal bone marrow contributions to chimerism from both units at day 28. Hence, alloimmunization may be an important factor influencing graft rejection in CBT. CBT patients should likely be screened for HLA antibodies, and positive screenings warrant further investigation to avoid whenever possible donor/recipient mismatches against which the patient is sensitized. Ongoing monitoring will help clarify the clinical significance of this issue.

Improvement of recipient survival after small size graft liver transplantation in rats with preischemic manipulation or administering antisense against nuclear factor-?B

The survival rate of small size graft liver transplantation (SSGLT) in rats is inversely related to graft volume. The present study aims to evaluate the protective effects of preischemic manipulation (PIM) and oligodeoxynucleotide (ODN) antisense against NF-kappaB on graft failure and animal survival. The protective effects of PIM and NF-kappaB ODN antisense were investigated in a rat SSGLT model. The graft function and survival of recipient animals over 3 weeks were monitored, and in situ staining for apoptotic cells in the graft tissue was examined. Both PIM and NF-kappaB antisense treatment significantly improved the survival of small graft-transplanted rats compared with the SSGLT group, lowered serum levels of alanine and aspartate aminotransferases, as well as tumor necrosis factor-alpha (TNF-alpha) levels, and minimized apoptotic cell counts in the liver sections. Moreover, the enhanced activation of NF-kappaB in the SSGLT group was diminished in both PIM and NF-kappaB antisense-treated groups. The findings suggest that enhanced NF-kappaB activation and TNF-alpha production may be involved in the ischemia/reperfusion-associated small size graft injury, and that PIM and antisense against NK-kappaB are effective in the attenuation of the small size graft injury, and improve the recipient animal survival.

Pharmacokinetics of Cyclosporine A After Massive Hepatectomy: A Hint for Small-for-Size Graft in Living Donor Liver Transplantation

In living donor liver transplantation, graft size is very important, and various studies have been conducted regarding these problems in small-for-size (SFS) grafts. The administration of immunosuppressants for SFS graft, in which the functional liver mass is small and necessary for excessive liver regeneration, has not been reported so far. The aims of this study were to investigate the optimal administration of cyclosporine (CyA) and characteristics of metabolism of CyA, according to liver volume. Seven-week-old male Wister rats were randomly divided into four groups: two CyA-administered groups (CyA groups), 70% and 90% hepatectomy (Hx); and two control groups, 70% and 90% Hx. The 70% Hx and 90% Hx were used as the surrogate model of SFS for 30% and 10% graft models. In CyA groups, CyA (5 mg/kg/day) was given for 3 days before Hx and after surgery until sacrifice. Animals were sacrificed at 0, 12, 24, 48, and 72 hr after Hx. The blood concentration of CyA and the expression of the CYP3A2 gene were measured at each point in CyA groups, and liver regeneration was evaluated by measuring the ratio of remnant liver weight to body weight in each group. Regarding the blood concentration of CyA, no difference was recognized between 30% and 10% graft models except for 72 hr after Hx. As for liver regeneration, no significant difference was recognized. Regarding the expression of CYP3A2, no change was noted in the 30% graft model; on the other hand, CYP3A2 expression was reduced. Significant differences between the 30% and the 10% graft model were observed 48 and 72 hr after Hx. The blood concentration of CyA was not dependent on the volume of the liver graft.

Live Donor Liver Transplantation in Adults

Live donor liver transplantation (LDLT) was initiated in 1988 for children recipients. Its application to adult recipients was limited by graft size until the first right liver LDLT was performed in Hong Kong in 1996. Since then, right liver graft has become the major graft type. Despite rapid adoption of LDLT by many centers, many controversies on donor selection, indications, techniques, and ethics exist. With the recent known 11 donor deaths around the world, transplant surgeons are even more cautious than the past in the evaluation and selection of donors. The need for routine liver biopsy in donor evaluation is arguable but more and more centers opt for a policy of liberal liver biopsy. Donation of the middle hepatic vein (MHV) in the right liver graft was considered unsafe but now data indicate that the outcome of donors with or without MHV donation is about equal. Right liver LDLT has been shown to improve the overall survival rate of patients with chronic liver disease, acute or acute-on-chronic liver failure and hepatocellular carcinoma waiting for liver transplantation. The outcome of LDLT is equivalent to deceased donor liver transplantation despite a smaller graft size and higher technical complexity.

Factors influencing the survival of cryopreserved homografts. The second homograft performs as well as the first☆

To determine the life span of cryopreserved homografts implanted in the right ventricular outflow tract and the factors influencing it. From 1989 through 2003, we reconstructed the pulmonary valve with 301 homografts in 272 patients (median age 13 years; range 4 days-69 years). Indications were tetralogy of Fallot (136), truncus (23), Rastelli repair (11), double outlet ventricle (13), endocarditis (5), and the Ross operation (84). Median follow-up was 5.7 years (range 0-14). We analyzed possible predictors of graft replacement by simple and multiple Cox regression. Actuarial survival was 96+/-1.2% at 1, 95+/-1.4% at 5, and 94+/-1.5% at 10 years follow-up. Three homografts were explanted because of endocarditis (excluded from the analysis). Freedom from explantation was 99.6+/-0.4% at 1, 94.5+/-1.7% at 5, and 81.8+/-4.1% at 10 years. Variables, significantly related to explantation in the univariate analysis, were younger age, small graft size, implantation in a non-anatomical position, the aortic donor homograft, a shorter aortic cross-clamp time and the implantation of a second homograft. In the multiple model, non-anatomical position (P=0.001), smaller graft size (P<0.0001) or younger age (on square root scale, P<0.0001) and clamp time (P=0.01) remain as independent risk factors. Immunological variables, like blood group incompatibility, implantation of a second homograft and short warm ischemic time were not significant. The life span of a cryopreserved homograft is determined by graft size (correlates with age) and the non-anatomic position (correlates with indication). In a specific patient, the second homograft performs as well as the first.

Effects of Hemi-Portocaval Shunts For Inflow Modulation on the Outcome of Small-for-Size Grafts in Living Donor Liver Transplantation

Graft hyperperfusion in small-for-size grafts (SFSG) is considered the main causal factor of small-for-size syndrome (SFSS). We compared SFSG with a graft-to-recipient body ratio < or =0.8, with and without graft inflow modulation (GIM) by means of a hemi-portocaval shunt (HPCS). Thirteen patients underwent adult-to-adult living donor liver transplantation (AALDLT): G1, n = 5 [4 right livers (RL) and 1 left liver (LL)] without GIM, and G2, n = 8 (4 RL and 4 LL) with GIM. In G2 patients, portal vein flow (PVF) was significantly reduced by HPCS: 190 +/- 70 mL/min/100 g liver in G2 vs. 401 +/- 225 ml/min in G1 (p = 0.002). One- and 6-month post-transplantation graft volume/standard liver volume (GV/SLV) ratio was of 72% and 79.5% in G1; 80% and 101% in G2 (p = ns). SFSS was observed in three G1 recipients (who were retransplanted), but in none of the G2 patients. At 1-year, patient and graft survival was respectively of 40% and 20% in G1, 87.5% and 75% in G2 (p = 0.024 and 0.03). It is concluded that drastic reduction of PVF by means of HPCS improves overall patient and graft survival by averting the occurrence of SFSS. Graft inflow modulation through HPCS reduces the risk of complications when transplanting SFSG in adult recipients.

Impact of donor gender on male rat recipients of small-for-size liver grafts

The aim of this study was to assess the impact of donor gender on small-for-size (SFS) liver transplantation in male recipients using a rat model. Adult female or male Lewis rats were used as donors and male Lewis rats as recipients. Size-matched (SM) and SFS liver grafts from either male or female donors were transplanted into male recipients. Animals receiving SFS grafts were sacrificed at postoperative week 1, week 4, and week 12, respectively (n = 6-8 per group), those receiving SM grafts after 3 months. The cumulative survival rate (SVR) in the female-to-male (F-M) SFS group was significantly lower (62%; 13 of 21) compared with the male-to-male (M-M) group (90%; 18 of 20) (P < 0.05). Spontaneous death occurred in the F-M SFS combination either in the early postoperative period (<3 weeks) in animals with confluent hepatic necrosis or in the late postoperative period (>8 weeks) in animals with biliary obstruction. In contrast, no death was observed in the early posttransplantation period after M-M liver transplantation. The relative graft size in the SM F-M group was significantly higher (graft-to-recipient weight ratio [GRWR] 2.40% +/- 0.8%) than in the SFS M-M group (GRWR 1.35% +/- 0.2%; P < 0.001). Regardless of graft size, the outcome was worse in terms of SVR as well as regarding the incidence and severity of biliary complications in F-M compared with M-M liver transplantation. In conclusion, male recipients of female livers had a less favorable outcome irrespective of graft size. Confluent hepatic necrosis as well as biliary obstruction were perceived as consequence of a severe perfusion problem in F-M liver transplantation, which was possibly related to an enhancement of ischemia-reperfusion (I/R) injury by the lack of estrogen in male recipients of female grafts.

Critical progressive small-graft injury caused by intrasinusoidal pressure elevation following living donor liver transplantation

In adult-to-adult living liver transplantation, small-for-size graft syndrome sometimes occurs. The relationship between the hemodynamic changes and histologic findings has not been studied in patients with failure of small-for-size grafts. We analyzed the relationship between the postoperative hemodynamic changes and pathologic findings in patients with small-for-size grafts that ended in graft failure. From March 1999 to December 2002, adult-to-adult living-donor liver transplantation with small-size grafts (graft volume/standard liver volume less than 40%) was performed in eight patients. Three patients died from graft failure caused by overperfusion, which was diagnosed from pathologic findings. We analyzed the relation between hepatic hemodynamic parameters, such as portal venous blood velocity or splenic arterial pulsatility index, and histologic changes in patients with graft failure. Severe portal hyperperfusion (90 cm/sec at the umbilical portion) was observed on postoperative day 1. Among patients with graft failure, critical hemodynamic changes, such as sudden onset of extremely deteriorated portal venous blood flow, occurred during the early postoperative period (postoperative day 5, 3, 6, respectively). Histologic examination revealed vacuolar changes in the cytoplasm of hepatocytes, and submassive necrosis indicated intrasinusoidal pressure elevation. These changes were not observed in the biopsy obtained soon after reperfusion. In conclusion, critically decreased vascular beds may cause intrasinusoidal pressure elevation and sinusoidal circulatory disturbances.