Ratio Of Graft Weight Research Articles

P9.15: What About the Heroes? Living Donor Liver Outcomes, From a Single Latin-American Center Experience Between 2009-2022

Background: The shortage of organs favors the need for considering the use of living donor´s grafts (LD) for liver transplantation (LT). Reports on long term donor outcomes are scarce. Our aim was to report the long term postoperative outcomes of all LD done in our center. Materials and methods: Retrospective observational study from 41 consecutive LD surgeries performed between 2009 and 2022 in a single center. Variables included were: donor (D) demographics, transplant indications, D-Recipient relationship, type of transplant, surgical approach, type of graft, operative time, days in ICU, length of hospital stay, graft weigh, estimated volume, graft/weight ratio (GRWR), postoperative complications using the Dindo- Clavien (DC) classification and mortality. As part of the evaluation, liver anatomy and volumetric assessment was done using CT-Scan and MRI. Biliary anatomy was studied with intraoperative cholangiography. Parenchymal transection was performed using CUSA. Statistical analyses were performed using SPSS v20.0. Results: Twenty four patients (58%) were woman. The mean donor age was 30(±7) years. Transplant indications were biliary atresia (N: 19, 46.3%); Alagille´s syndrome (N: 5, 12.2%), fulminant liver failure (N:5, 12.4%), primary biliary cholangitis (N:4, 9.8%), cryptogenic cirrhosis (N:2, 4.9%), colorectal CA liver metastasis (N:1, 2.4%), and others (N:5,12%). In 63% of cases the donors were parents, figure. Type of transplant was Adult-Pediatric (N: 35, 85%) and Adult-Adult (N: 6, 14%). Open surgery was used in (N: 38, 92%); using median laparotomy in 80% of cases (N: 33), 3 were hand assisted. Types of graft were: left lateral seccionectomy (N: 27, 66%), left lobe (N: 11, 26%) and right lobe (N:3, 8%). The median operative time was 302 (130-570) minutes. Mean graft weight was 309±177 grs, while the mean graft estimated volume calculated with the preoperative CT-Scan was of 342±174gr. Mean GRWR was 2.8±2. The overall complications rate was 12% (N: 5); minor complications were: intra-abdominal collections (N: 2, 4.9%; DC: IIIa and I), biliary fistula (N: 1, 2.4%; DC: I); while major complications were: one hemoperitoneum (DC IIIb) and one pyloric syndrome (DC IVa); all occurred within the first 30 pop. days. Mean ICU stay was 1±0.4 days; length hospital stay was 3±1 days. No postoperative deaths were observed.Conclusions: LD liver transplantation remains as a complex procedure, but the evolving experience, the sustained deficit of cadaveric organs, together with an acceptable morbidity, increases the team willingness to consider its use, in order to reduce the mortality in the waiting list.

Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling

Tumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10−/− and TLR4−/− mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4+ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.

Comparable short- and long-term outcomes in deceased-donor and living-donor liver retransplantation.

There is a big controversy over liver retransplantation, the only life-saving treatment for patients with a failing or failed liver graft. This retrospective study tried to determine if living-donor liver retransplantation (re-LDLT) is a justifiable alternative to deceased-donor liver retransplantation (re-DDLT). Anonymous data of liver transplant patients from January 2000 to April 2016 were reviewed. Recipients of retransplantation were divided into the re-DDLT and re-LDLT groups. The groups were compared in demographic characteristics, pre-retransplant and intraoperative details, and short- and long-term outcomes. Risk for living donors was examined. Twenty-nine patients had 33 re-DDLTs and 15 patients received re-LDLT. The re-LDLT group had lighter grafts (525 vs. 1295g, p≤0.001), a smaller ratio of graft weight to recipient standard liver volume (56.98 vs. 107.7%, p≤0.001), and shorter cold ischemia (106 vs. 451min, p≤0.001). The groups were otherwise comparable. Two patients in the re-DDLT group had Grade-5 complication. The groups were similar in patient survival (p=0.326) and graft survival (p=0.102). No living donors died, but three of them developed Grade-1 complications. With the required expertise, re-LDLT can produce results comparable to those of re-DDLT while keeping donor risk at bay. In places where the demand for deceased-donor liver grafts far outstrips supply, re-LDLT can be considered as an alternative to re-DDLT if the expertise is available and if the potential recipient benefits can balance out the potential donor risks.

Outcomes of right-lobe and left-lobe living-donor liver transplantations using small-for-size grafts.

AIMTo analyze the outcomes of living-donor liver transplantation (LDLT) using left-lobe (LL) or right-lobe (RL) small-for-size (SFS) grafts.METHODSProspectively collected data of adult patients who underwent LDLT at our hospital in the period from January 2003 to December 2013 were reviewed. The patients were divided into the RL-LDLT group and the LL-LDLT group. The two groups were compared in terms of short- and long-term outcomes, including incidence of postoperative complication, graft function, graft survival, and patient survival. A SFS graft was defined as a graft with a ratio of graft weight (GW) to recipient standard liver volume (RSLV) (GW/RSLV) of < 50%. The Urata formula was used to estimate RSLV.RESULTSTotally 218 patients were included for analysis, with 199 patients in the RL-LDLT group and 19 patients in the LL-LDLT group. The two groups were similar in terms of age (median, 53 years in the RL-LDLT group and 52 years in the LL-LDLT group, P = 0.997) but had significantly different ratios of men to women (165:34 in the RL-LDLT group and 8:11 in the LL-LDLT group, P < 0.0001). The two groups were also significantly different in GW (P < 0.0001), GW/RSLV (P < 0.0001), and graft cold ischemic time (P = 0.007). When it comes to postoperative complication, the groups were comparable (P = 0.105). Five patients died in hospital, 4 (2%) in the RL-LDLT group and 1 (5.3%) in the LL-LDLT group (P = 0.918). There were 38 graft losses, 33 (16.6%) in the RL-LDLT group and 5 (26.3%) in the LL-LDLT group (P = 0.452). The 5-year graft survival rate was significantly better in the RL-LDLT group (95.2% vs 89.5%, P = 0.049). The two groups had similar 5-year patient survival rates (RL-LDLT: 86.8%, LL-LDLT: 89.5%, P = 0.476).CONCLUSIONThe use of SFS graft in LDLT requires careful tailor-made surgical planning and meticulous operation. LL-LDLT can be a good alternative to RL-LDLT with similar recipient outcomes but a lower donor risk. Further research into different patient conditions is needed in order to validate the use of LL graft.

CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation

Liver graft injury and tumor recurrence are the major challenges of liver transplantation for the patients with hepatocellular carcinoma (HCC). Here, we aimed to explore the role and mechanism of liver graft injury mobilizing regulatory T cells (Tregs), which lead to late phase tumor recurrence after liver transplantation. The correlation among tumor recurrence, liver graft injury and Tregs mobilization were studied in 257 liver transplant recipients with HCC and orthotopic rat liver transplantation models. The direct roles of CXCL10/CXCR3 signaling on Tregs mobilization and tumor recurrence were investigated in CXCL10-/- and CXCR3-/- mice models with hepatic IR injury. Clinically, patients received the graft with graft weight ratio (GWR) <60% had higher HCC recurrence after liver transplantation than the recipients with GWR ⩾60% graft. More circulating Tregs and higher intragraft TLR4/CXCL10/CXCR3 levels were detected in recipients with GWR <60% graft. These results were further validated in rat transplantation model. Foxp3+ cells and expressions of TLR4, CXCL10, TGFβ, CTLA-4 and CD274 were increased in rat liver tumor tissues from small-for-size graft group. In mouse model, the mobilization and recruitment of Tregs were decreased in TLR4-/-, CXCL10-/- and CXCR3-/- mice compared to wild-type mice. Moreover, less CXCR3+ Tregs were recruited into liver in CXCL10-/- mice after hepatic IR injury. The knockout of CXCL10 and depletion of Tregs inhibited tumor recurrence after hepatic IR injury. CXCL10/CXCR3 signaling upregulated at liver graft injury directly induced the mobilization and intragraft recruitment of Tregs, which further promoted HCC recurrence after transplantation. There were positive correlation among tumor recurrence, circulating Tregs and liver graft injury after human transplantation for HCC patients. The knockout of CXCL10 decreased hepatic recruitment of CXCR3+ Tregs and late phase tumor recurrence after hepatic IR injury.

Technical refinement of hepatic vein reconstruction in living donor liver transplantation using left liver graft.

In adult living donor liver transplantation (LDLT), left liver graft is generally safer for the donor. The aim of this study was to demonstrate a technical refinement for achieving sufficient outflow using left liver graft. Forty-seven cases using left liver were divided into 2 groups according to the procedures of hepatic vein reconstruction: the side-clamp group (21 cases), and the cross-clamp group (26 cases), to sufficiently enlarge the diameter of the hepatic vein with excising the inferior vena cava (IVC). The liver function tests at 7 days after LDLT were not significantly different between the 2 groups, but the median amount of ascites was significantly greater in the side-clamp group (1250 ml; range, 484-3690) than in the cross-clamp group (582 ml; 190-2785). When we selected the patients with the ratio of graft weight to recipient standard liver volume less than 30%, the 1-year patient survival after transplantation was significantly better in the cross-clamp group than in the side-clamp group (90% in cross-clamp group vs. 71% in side-clamp group, P<0.05). In conclusion, hepatic vein reconstruction with cross-clamping of the IVC can secure a sufficient outflow in LDLT using left liver graft.

All-in-one sleeve patch graft venoplasty for multiple hepatic vein reconstruction in living donor liver transplantation

ObjectivesThis paper presents an innovative technique to address complex multiple hepatic vein (HV) reconstruction in right lobe graft living donor liver transplantation (RL-LDLT). MethodsA patient with hepatitis C virus-related cirrhosis underwent RL-LDLT. The graft had seven HVs, including: the right HV (17mm); one segment VII HV (11mm); two segment VI HVs (6mm and 16mm), and three segment V HVs. The graft weighed 663g (53% of standard liver volume; ratio of graft weight to recipient body weight: 0.96). Each HV had significant drainage territory requiring reconstruction. A cryopreserved iliac vein graft was used to create a sleeve patch to incorporate the HV openings. The holes were anastomosed to their corresponding HV tributaries using continuous 6–0 polydioxanone (PDS) sutures. Two of the three segment V HVs were combined using a smaller iliac vein patch, which was anastomosed in an end-to-side fashion to a previously harvested recipient umbilical vein interposition graft. The other end of the umbilical vein graft was anastomosed to the larger iliac vein sleeve patch. ResultsOverall, six HV openings were incorporated in one sleeve patch to allow a single wide anastomosis with the recipient inferior vena cava. Doppler ultrasound after reconstruction showed adequate flow patterns in all the HVs. ConclusionsAll-in-one sleeve patch graft venoplasty simplifies the reconstruction of multiple HVs and reduces warm ischaemia time in RL-LDLT with excellent outcomes.

Predicting the Ideal Serum Creatinine of Kidney Transplant Recipients by a Simple Formula Based on the Balance Between Metabolic Demands of Recipients and Renal Mass Supply From Donors

Serum creatinine (Scr) is the most frequently used test to estimate graft function after kidney transplantation. Our previous study demonstrated that the independent predictors of recipient posttransplantation Scr included the ratio of graft weight to recipient body weight, the ratio of graft weight to recipient body surface area (BSA), and the ratio of graft weight to recipient body mass index (BMI). A prospective analysis about the impact of the balance between metabolic demands and renal supply on posttransplantation Scr of recipients was previously reported. We plotted the scatter graph using the X-axis as the independent predictors of Scr by linear regression and the Y-axis as the recipient Scr. To generate the predictive formula of Scr, we calculated a fit of the line of plotted cases using a linear regression method with 2 regression lines for prediction of the upper and lower 95% confidence intervals. Each line was converted into a predictive formula: Scr = −0.0033* (Graft weight(g)/Recipient BSA(m 2))+1.75. Under 95% confidence, the Scr ranges from −0.0033* (Graft weight(g)/Recipient BSA(m 2))+1.07 to −0.0033* (Graft weight(g)/Recipient BSA (m 2))+2.44. Scr = −0.1049* (Graft weight(g)/Recipient body weight(kg))+1.72, which ranges from −0.1049* (Graft weight(g)/Recipient body weight(kg))+1.06 to −0.1049* (Graft weight(g)/Recipient body weight(kg))+2.37. Scr = −0.0158* (Graft weight(g)/Recipient BMI(kg/m 2))+1.56, which ranges from −0.0158* (Graft weight(g)/Recipient BMI(kg/m 2))+0.75 to −0.0158* (Graft weight(g)/Recipient BMI(kg/m 2))+2.26. Prediction of posttransplantation Scr may be achieved by measuring graft weight as well as recipient weight and height. When recipient Scr is significantly higher than that predicted by the formula, a clinician should suspect an underlying graft injury.

Graft size assessment by preoperative computed tomography in living related partial liver transplantation.

The size of segmental liver grafts assessed by preoperative computed tomography (CT) volumetry was evaluated in relation to surgical outcome in 14 living related partial liver transplantations (LRLTs). The aim was to show that graft size can be accurately assessed before operation and to estimate the lower safety limit of graft size in assessing subsequent graft function and survival. The relationship between calculated CT volume and weight of the liver was linear in the recipient (r = 0.97) and donor (r = 0.98). The mean(s.e.m.) modified liver weight ratio (MLWR; ratio of graft weight to recipient's expected liver weight based on body-weight) was 0.59(0.07) (range 0.27-1.09). Surgical complications related to an oversized graft and primary graft failure caused by a small-for-size graft were not observed. The lowest MLWR of any survivor was 0.27. These results suggest that a partial liver graft reduced to about 30 per cent of the recipient's expected liver weight can tolerate LRLT well.

The ???small for size??? liver syndrome

Small-for-size syndrome (SFSS) is a clinical syndrome described following liver transplantation (LT) and extended hepatectomy. New evidence has emerged documenting the importance of preoperative evaluation of functional liver mass, liver quality, influence of portal hypertension, and variations in surgical technique to improve outcome. SFSS is characterized by postoperative coagulopathy and liver dysfunction due to insufficient functional liver mass. Recent radiologic advances allow accurate preoperative estimation of total, graft, and remnant liver volume (RLV). In adult-to-adult living donor liver transplantation (LDLT), a graft-to-recipient body weight ratio > or = 0.8% or graft weight ratio > or = 30% are important to avoid SFSS. Minimal functional RLV following extended hepatectomy is > or = 25% in a normal liver, and > or = 40% with preoperative liver dysfunction. Preoperative portal vein or hepatic artery embolization to increase RLV and function after extended hepatectomy, and the increasing use of parenchymal-sparing segmental resections have improved outcome. In LT, the evolving use of split livers, LDLT and marginal grafts has resulted in increased recognition of SFSS. This has led to a renewed interest in defining the pathophysiology, and the development of new surgical techniques to reduce its incidence. Current radiologic imaging techniques can be used to evaluate liver volume and the risk of SFSS following LT and extended hepatectomy. Intraoperative techniques to predict postoperative dysfunction are emerging, and may be helpful in directing the use of pre-emptive surgical interventions. The future lies in the development of perioperative liver protection and support in predicted SFSS, and enhancement of healthy liver regeneration.

Left portahepatic shunt: A novel technique to decrease excessive portal venous inflow during live donor liver transplantation

A critical shortage of cadaveric livers and an increasing population on the waiting list have encouraged the development of living donor liver transplantation. Living donor liver transplantation accounts for approximately 10% of all liver transplants being performed. One problem unique to lobar transplantation relates to hepatic congestion and associated functional impairment of the transplanted lobe. This congestion is multifactorial and includes low graft-weight ratio, middle hepatic vein drainage problems, and excessive portal venous inflow. Increasing disparities of graft-weight ratios exaggerate the importance of the other two factors. Finally, animal data from asplanchnic and anhepatic models implicate the intestine as the source of tumor necrosis factor released into the circulation following portal unclamping. Tumor necrosis factor, in turn, leads to adhesion molecule upregulation and endothelial cell disruption and potentiates allograft dysfunction. Although veno-venous bypass may alleviate some of these problems, it does not prevent excessive mesenteric venous flows, nor does it prevent the tumor necrosis factor production associated with portal clamping during the portal anastomotic phase. We have recently developed the technique of temporary left portahepatic shunt. This allows portasystemic decompression during implantation and diverts mesenteric blood from the liver during the crucial period after unclamping. Early lobar congestion can be avoided, and the shunt may be left in place for as long as 2 hours while volume homeostasis is restored. This technique allows the tailoring of the portal flow to the graft size to avoid any liver congestion or dysfunction.

Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression.

To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes in right lobe live donor liver transplantation (LDLT). Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft injury after reperfusion is common, but the mechanism and degree of injury remain unclear. The hepatic sinusoidal injury in different graft sizes and its relationship with portal hemodynamics and intragraft gene response at the early phase after reperfusion have not been studied in right lobe LDLT. From May 2000 to November 2001, 40 adults receiving right lobe LDLT had portal pressure measured continuously before and after reperfusion. Liver biopsies were taken before and after reperfusion for detection of vasoregulatory genes (endothelin-1 and endothelial nitric oxide synthase) and heat shock genes (heat shock protein 70 and heme oxygenase-1), and electron microscope examination. Blood samples from the portal vein and suprahepatic inferior vena cava were taken for the measurement of plasma nitric oxide level. The recipients were grouped according to the ratio of graft weight to estimated standard liver weight: group 1 (n = 10), less than 40%; group 2 (n = 21), 40% to 60%; and group 3 (n = 9), more than 60%. The portal pressures recorded after reperfusion in group 1 were significantly higher within 30 minutes of reperfusion than those in groups 2 and 3. After reperfusion, the intragraft endothelin-1 mRNA level in group 1 increased by 161% of the basal level but decreased by 31.5% and 62% of the basal level in groups 2 and 3, respectively. The intragraft mRNA level of heme oxygenase-1 in groups 1 and 2 decreased by 75.5% and 25.3% of the basal level respectively but increased by 41% of basal level in group 3. The intragraft protein level of heat shock protein 70 decreased by 50 ng/mL after reperfusion in group 1 but increased by 12.4 ng/mL and 0.6 ng/mL in groups 2 and 3, respectively. The portal vein plasma nitric oxide level decreased more significantly after reperfusion in group 1 than in group 2. Electron microscope examination of liver biopsies in group 1 showed tremendous mitochondrial swelling as well as irregular large gaps between the sinusoidal lining cells. There were two hospital deaths in group 1 and none in the other two groups. Patients implanted with grafts less than 40% of standard liver weight suffered from transient portal hypertension early after reperfusion. The phenomenon was accompanied by intragraft upregulation of endothelin-1 and ultrastructural evidence of sinusoidal damage. The transient portal hypertension after reperfusion, subsequent endothelin-1 overexpression, and plasma nitric oxide level reduction, together with downregulation of heme oxygenase-1 and heat shock protein 70, may account for the small-for-size graft injury.

Small-for-size grafts in living-related liver transplantation

BACKGROUND: The problems associated with small-for-size grafts in living-related liver transplantation are not fully understood. STUDY DESIGN: A consecutive series of 79 patients underwent 80 living-related liver transplantation procedures, including one retransplant, at the University of Tokyo from January 1996 to January 2000. They were divided into two groups by graft size: graft weight/recipient standard liver volume ratios of 40% or less (n = 24), and more than 40% (n = 56). Preoperative status, mortality, morbidity, duration of hospital stay, and postoperative graft function were examined and compared between the groups. RESULTS: The rate of patients who were restricted to the intensive care unit preoperatively was comparable between the groups (33% versus 21%, p = 0.27). The mean standard liver volume ratios were 37% in the small graft group and 84% in the large group. Survival rates were 80% (5 of 24) for the small graft group, which was significantly lower than that for the large group (96%, 54 of 56, p = 0.02). The rate of acute rejection was comparable between the groups (33% versus 43%, p = 0.47). Vascular complication was observed in 17% of the small graft group patients and 23% of the large group (p = 0.77). No difference was observed in the frequency of bile leakage or bile duct stenosis (25% versus 21%, p = 0.77). Hyper-bilirubinemia and elongation of prothrombin time persisted longer in the small graft group than in the large group (p < 0.0001 for both). CONCLUSIONS: Our surgical results may suggest that a graft weight ratio of 40% or less provides a lower chance of survival after living-related liver transplantation.

Peri-operative blood lactate levels in recipients of living-related liver transplantation.

The role of changes in peri-operative blood lactate levels in recipients of living-related liver transplants has not yet been clarified. Forty-three recipients were included in this study. Blood lactate, plasma total bilirubin, aminotransferase, body temperature, and gastric mucosal PCO2 levels were measured at six time points during surgery: just before the initiation of surgery, just after dissection of the hepatic vasculature, at the end of the anhepatic phase, and 30, 60, and 120 min after reperfusion. We calculated the rate of lactate accumulation during the pre-anhepatic and anhepatic phases and the elimination rate during reperfusion (neohepatic phase), and examined the correlation between these results and the clinical findings. The rate of lactate elimination during the neohepatic phase was correlated with the ratio of graft weight to standard liver volume (P<0.0001). There was also a significant correlation between the rate of lactate accumulation during the pre-anhepatic phase and the preoperative total bilirubin levels (P=0.0008). Each pre-anhepatic, anhepatic, and neohepatic phase had a characteristic blood lactate profile. The graft size strongly affected lactate levels during the early neohepatic phase.

Minimum graft size for successful living donor liver transplantation.

The extension of living donor liver transplantation to adult recipients is limited by the adequacy of the size of the graft. We evaluate the effect of the graft size on the survival of the recipient in order to establish a clinical guide for the minimum requirement. The clinical records of 14 adults and 11 children (body weight 6.1-100 kg) who underwent living donor liver transplantation for chronic or acute liver failure were reviewed. The effect of the graft weight ratio (graft weight divided by standard liver weight of recipient) on graft function and survival was studied. The graft weight ratio ranged from 31 to 203%. The overall graft and patient survival rates were 84% at a median follow-up of 29 months. The survival rate was 95% for recipients with a graft weight ratio >40%, and 40% only for those with a ratio < or =40% (P = 0.016). It was 88% (7/8) when the ratio was >100%, 100% (5/5) when the ratio was 71 to 100%, 100% (7/7) when the ratio was 41 to 70%, and 40% (2/5) only when the ratio was < or =40%. When the graft weight ratio was < or =40%, early graft dysfunction was evident and contributed to the causes of death in three patients. Preoperative computed tomographic measurement of liver size of a living donor is essential. A graft that represented 40% or less of the recipient's standard liver weight should be regarded as a marginal graft with a lower success rate.