Small-for-size Syndrome Research Articles

Exogenous melatonin protects small-for-size liver grafts by promoting monocyte infiltration and releases interleukin-6.

Defective regeneration of small-for-size (SFS) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT) has protective effects on hepatic ischemia-reperfusion injury (IRI), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR+PH group: 60minutes liver ischemia (IR) plus 2/3 hepatectomy (PH); (II) IR+exPH group: 60minutes liver IR plus extended hepatectomy (exPH) associated with the SFS syndrome; (III) SFS-LT group: Arterialized 30% SFS liver transplant. Each group was divided into MLT or vehicle-treated subgroups. Hepatic injury, inflammatory signatures, liver regeneration, and animal survival rates were assessed. MLT reduced liver injury, enhanced liver regeneration, and promoted interleukin (IL) 6, IL10, and tumor necrosis factor-α release by infiltrating, inflammatory Ly6C+ F4/80+ monocytes in the IR+PH group. MLT-induced IL6 significantly improved hepatic microcirculation and survival in the IR+exPH model. In the SFS-LT group, MLT promoted graft regeneration and increased recipient survival along with increased IL6/GP130-STAT3 signaling. In IL6-/- mice, MLT failed to promote liver recovery, which could be restored through recombinant IL6. In the IR+exPH and SFS-LT groups, inhibition of the IL6 co-receptor GP130 through SC144 abolished the beneficial effects of MLT. MLT ameliorates SFS liver graft IRI and restores regeneration through monocyte-released IL6 and downstream IL6/GP130-STAT3 signaling.

Prediction of small for size syndrome after extended hepatectomy: Tissue characterization by relaxometry, diffusion weighted magnetic resonance imaging and magnetization transfer.

This study aimed to monitor the course of liver regeneration by multiparametric magnetic-resonance imaging (MRI) after partial liver resection characterizing Small-for-Size Syndrome (SFSS), which frequently leads to fatal post-hepatectomy liver failure (PLF).Twenty-two C57BL/6 mice underwent either conventional 70% partial hepatectomy (cPH), extended 86% partial hepatectomy (ePH) or SHAM operation. Subsequent MRI scans on days 0, 1, 2, 3, 5 and 7 in a 4.7T MR Scanner quantified longitudinal and transverse relaxation times, apparent diffusion coefficient (ADC) and the magnetization-transfer ratio (MTR) of the regenerating liver parenchyma. Histological examination was performed by hematoxylin-eosin staining. After hepatectomy, an increase of T1 time was detected being larger for ePH on day 1: 18% for cPH vs. 40% for ePH and on day 2: 24% for cPH vs. 49% for ePH. An increase in T2 time, again greater in ePH was most pronounced on day 5: 21% for cPH vs. 41% for ePH. ADC and MTR showed a decrease on day 1: 21% for ePH vs. 13% for cPH for ADC, 15% for ePH vs. 11% for cPH for MTR. Subsequently, all MR parameters converged towards initial values in surviving animals. Dying PLF animals exhibited the strongest increase of T1 relaxation time and most prominent decreases of ADC and MTR. The retrieved MRI biomarkers indicate SFSS and potentially developing PLF at an early stage, likely reflecting cellular hypertrophy with extended water content and concomitantly diluted cellular components as features of liver regeneration, appearing more intense in ePH as compared to cPH.

Impact of preserved collateral veins on small-for-size grafts in living donor liver transplantation.

Graft size is a critical issue in living donor liver transplantation (LDLT). We hypothesized that too much portal flow could possibly be diverted into pre-existing collateral veins, alleviating small-for-size syndrome (SFSS) in LDLT. This study evaluated the impact of the preserved collateral veins in the outcomes of LDLT using a small-for-size graft. For patient safety, a graft-to-recipient weight ratio (GRWR) <0.8% was strictly confined to patients with collateral veins (group A), and the patient group was compared in a 1:3 ratio to a matched group of patients with GRWR ≥0.8% (group B) using propensity score analysis. Forty and 120 patients were included in group A and B, respectively. No significant differences in baseline patient characteristics were observed between the two groups except for graft weight and GRWR. The lowest GRWR was 0.4%. The graft portal inflow showed no significant differences for 7 days after graft implantation, ranging from 1668 to 5100 mL/min. Small-for-size syndrome occurred in no patients (0.0%) in group A and in 10 (8.3%) in group B (P = 0.067). Overall survival rates at 1, 3, and 5 years were not different between the two groups (85.0%, 82.5%, and 82.5% vs. 92.5%, 86.7%, and 85.0%, respectively; P = 0.670). Pre-existing collateral veins saved during surgery may have a reserve buffer for excessive portal flow to obviate SFSS in LDLT.

Small-for-Size Syndrome: Bridging the Gap Between Liver Transplantation and Graft Recovery.

In living donor liver transplantation, optimal graft size is estimated from values like graft volume/standard liver volume and graft/recipient body weight ratio but the final functional hepatic mass is influenced by other donor and recipient factors. Grafts with insufficient functional hepatic mass can produce a life-threatening condition with rapidly progressive liver failure called small-for-size syndrome (SFSS). Diagnosis of SFSS requires careful surveillance for signs of inadequate hepatocellular function, residual portal hypertension, and systemic inflammation that suggest rapidly progressive liver failure. Early diagnosis, symptom control, and addressing the cause of SFSS may prevent the need for retransplantation. With increased attention to avoiding donor risk, intensivists will be confronted with more SFSS recipients. In this review, we aim to outline a systematic approach to the medical management of patients with SFSS by providing a concise synopsis of general supportive care-neurological, cardiovascular, and renal support, mechanical ventilation, nutritional support, infection control, and tailored immunosuppression-with an aim to avoid end-organ damage or death and a review of current interventions including liver support devices, portal flow modulating drugs, and other experimental interventions that aim to preserve existing hepatic mass and improve conditions for hepatic regeneration. We examine evidence for SFSS interventions to provide the reader with information that may assist in clinical decision making. Points of controversy in care are purposefully highlighted to identify areas where additional experimental work is still needed. A full understanding of the pathophysiology of SFSS and measures to support liver regeneration will guide effective management.

Is Portal Venous Pressure or Porto-systemic Gradient Really A Harbinger of Poor Outcomes After Living Donor Liver Transplantation?

Portal hyperperfusion as a cause of small for size syndrome (SFSS) after living donor liver transplantation (LDLT) remains controversial. Portal venous pressure (PVP) is often measured indirectly and may be confounded by central venous pressure (CVP). In 42 adult cirrhotics undergoing elective LDLT, PVP was measured by direct canulation of portal vein and porto systemic gradient (PSG) was obtained after subtracting CVP from PVP. None underwent portal inflow modulation. SFSS was looked in 27 patients after excluding 15 with technical complications. Clinical features of SFSS found in 6 patients, 5 with graft recipient weight ratio (GRWR)>0.8% and PVP<20mm of Hg. One with GRWR<0.8% could truly be labeled as SFSS. Incidence of SFSS was not higher in patients with elevated PVP>20mm of Hg (14.3% vs 0%, P=0.259) or PSG>13mm of Hg (33.3% vs 0%, P=0.111). Intensive care unit (ICU) stay was longer in patients with elevated PVP (14.55 vs 9.13 days, P=0.007) and PSG (16.8 vs 9.72 days, P=0.009). There was no difference in graft functions, post-operative complications and mortality in first month post-LDLT. Elevated PVP or PSG increased morbidity but neither predicted SFSS nor affected survival.

Small-for-size syndrome in live donor liver transplantation-Pathways of injury and therapeutic strategies.

Due to the severe organ shortage and the increasing gap between the supply and demand for donor grafts, live donor liver transplantation (LDLT) has become an accepted and alternative technique for the expansion of the donor pool. However, donor safety and good recipient outcomes must be balanced regarding risk stratification and decision-making within this patient population. Small-for-size syndrome (SFSS) is one of the complications encountered after LDLT, thus increasing the burden of optimizing donor graft selection and effective treatments during its occurrence. A graft-to-recipient weight ratio (GRWR) <0.8 predisposes the graft to SFSS. However, other factors may induce this complication even without a graft-to-patient size mismatch. Several strategies to prevent this complication include portal vein flow and liver outflow modulation, as well as pharmacological treatment. Also, as an entity with a multifactorial etiology, outcomes vary between right-lobe, left-lobe, and posterior-lobe donation among series encountered in the literature. In this review, we analyze the pathophysiology and classification of this complication, the state-of-the-art on management of SFSS, and the outcomes regarding the best treatment strategy on this patient population.

Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation.

AIMTo analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome (SFSS) after living donor liver transplantation (LDLT).METHODSThrough-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT (A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range (0-144 m).RESULTSSFSS was diagnosed in 20 (11.5%) of our recipients. While extra-small graft [small for size graft (SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis (P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis (P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10 (40%) SFSS vs 3/7 (42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe (RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10 (28.6%) SFSS vs 52/152 (34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference (P = 0.00).CONCLUSIONSFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention (i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).

Establishing a Porcine Model of Small for Size Syndrome following Liver Resection.

Background Small for size syndrome (SFSS) is responsible for a high proportion of mortalities and morbidities following extended liver resection. Aim The aim of this study was to establish a porcine model of SFSS. Methods Twenty-four Landrace pigs underwent liver resection with a remnant liver volume of 50% (group A, n = 8), 25% (group B, n = 8), and 15% (group C, n = 8). After resection, the animals were followed up for 8 days and clinical, laboratory, and histopathological outcomes were evaluated. Results The survival rate was significantly lower in group C compared with the other groups (p < 0.001). The international normalized ratio, bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase levels increased shortly after surgery in groups B and C, but no change was observed in group A (p < 0.05 for all analyses). The histopathological findings in group A were mainly mild mitoses, in group B severe mitoses and hepatocyte ballooning, moderate congestion, and hemorrhage, along with mild necrosis, and in group C extended tissue damage with severe necrosis, hemorrhage, and congestion. Conclusions Combination of clinical, laboratory, and histopathological evaluations is needed to confirm the diagnosis of SFSS. 75% liver resection in porcine model results in SFSS. 85% liver resection causes irreversible liver failure.

Graft inflow modulation in adult-to-adult living donor liver transplantation: A systematic review.

Small-for-size syndrome (SFSS) has an incidence between 0 and 43% in small-for-size graft (SFSG) adult living donor liver transplantation (LDLT). Portal hypertension following reperfusion and the hyperdynamic splanchnic state are reported as the major triggering factors of SFSS. Intra- and postoperative strategies to prevent or to reduce its onset are still under debate. We analyzed graft inflow modulation (GIM) during adult LDLT considering the indications, efficacy of the available techniques, changes in hemodynamics and outcomes. A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central. Treatment outcomes including in-hospital mortality and morbidity, re-transplantation rate, 1-, 3-, and 5-year patient overall survival and 1-, 3-, and 5-year graft survival rates, hepatic artery and portal vein flows and pressures before and after inflow modulation were analyzed. From 563 articles, 12 studies dated between 2003 and 2014 fulfilled the selection criteria and were therefore included in the study. These comprised a total of 449 adult patients who underwent inflow modulation during adult-to-adult LDLT. Types of GIM described were splenic artery ligation, splenectomy, meso-caval shunt, spleno-renal shunt, portocaval shunt, and splenic artery embolization. Mortality and morbidity ranged between 0 and 33% and 17% and 70%, respectively. Re-transplantation rates ranged between 0% and 25%. GIM was associated with good survival for both graft and recipients, reaching an 84% actuarial rate at 5 years. Through the use of GIM, irrespective of the technique, a statistically significant reduction of PVF and PVP was obtained. GIM is a safe and efficient technique to avoid or limit portal hyperperfusion, especially in cases of SFSG, decreasing overall morbidity and improving outcomes.

Left lobe living donor liver transplantation in adults: What is the safety limit?

Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL-LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥48 years (P = 0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL-LDLT. Within such high-risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. Liver Transplantation 22 1666-1675 2016 AASLD.

The beneficial role of simultaneous splenectomy after extended hepatectomy: experimental study in pigs

BackgroundThe role of hepatic hemodynamic modulation in the development of “small-for-size” syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. MethodsEighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out. Portal hemodynamics, liver function tests, histologic findings, injury and survival rates were compared between groups A and B. ResultsThe 7-d survival rate in the splenectomy group was significantly improved compared with group A (88.9% versus 44.4%, P < 0.05). Portal vein pressure, portal vein flow, and liver function tests in the splenectomy group were significantly lower than in group A immediately after splenectomy and postoperatively until the day of sacrifice. Histologic findings in group A clearly illustrate severe inflammation, bridging necrosis, ischemic cholangitis, and severe congestion, while in group B there were less serious histologic changes. ConclusionsOur experimental study indicates that perioperative portal modulation can successfully prevent the manifestation of SFSS after EH. Therefore, by focusing on “flow” rather than on “size,” researchers may understand better the pathophysiology of this syndrome.

Exploring Portal Vein Hemodynamic Velocities as a Promising, Attractive Horizon for Small-for-Size Syndrome Prediction After Living-Donor Liver Transplantation: An Egyptian Center Study.

Liver transplantation is the only definite treatment for patients with irreversible liver failure. This explored the impact of portal vein hemodynamic velocities on graft functions to determine the mean portal vein velocities that may increase small-for-size syndrome (SFSS) risk. The study was conducted with 123 cirrhotic patients who underwent living-donor liver transplantation (LDLT) at Kasr Alainy Hospital, Cairo, Egypt. Patients were submitted to full history, examination, pre-transplantation labs, and imaging. Intra-operative Doppler studies were performed after graft reperfusion. Post-operative (PO) Doppler was performed once a day over the first 2 weeks. Complete graft functions were obtained daily for patients. PVV (portal vein velocities) declined gradually but significantly after LT (intra-operative), and PO PVV were significantly higher in the SFSS group. The best cut-off values for prediction of SFSS with the use of intra-operative (before, during, and after) post-anastomotic PVV were 55.5, 106, and 126.5cm/s, respectively, and, for PO before and after anastomotic PVV, 48.6 and 71.1cm/s, respectively. There was a significant positive correlation between PO mean PVV and mean alanine transferase, total bilirubin, and international normalized ratio. PVV is a significant hemodynamic factor that influences graft functions. SFSS, which has a negative impact after LDLT, could be predicted by cut-off values for PVV, and therefore preventive measures such as splenectomy may be considered for its prevention.

A portal pressure cut-off of 15 versus a cut-off of 20 for prevention of small-for-size syndrome in liver transplantation: A comparative study.

Portal hypertension has recently been implicated in the pathogenesis of small-for-size syndrome (SFSS) in adult-to-adult living-donor liver transplantation (A-LDLT). The aim of our study is to compare the portal venous pressure (PVP) cut-off values of 15mmHg and 20mmHg in terms of prevention of SFSS in A-LDLT. Seventy-six patients underwent A-LDLT. A PVP <20mmHg at the end of the operation was targeted using graft inflow modulation. Patients were divided into two groups: group A, final PVP <15mmHg; and group B, final PVP 15-19mmHg. Peak serum bilirubin and peak international normalized ratio in the first month after A-LDLT, as well as hepatic encephalopathy, SFSS, 90-day morbidity, and mortality were observed in both groups. Final PVP was well controlled below 20mmHg in all patients (group A, n = 39; group B, n = 37). Six patients suffered SFSS in group B (16.2%) compared to one patient (2.6%) in group A (P = 0.04). Nine patients died in group B (24.3%), four of whom died of SFSS, compared to three patients in group A (7.7%) (P = 0.047). A PVP cut-off of 15mmHg seems to be a more appropriate target level than a cut-off of 20mmHg for prevention of postoperative SFSS in A-LDLT.

Portosystemic Shunts for "Too Small-for-Size Syndrome" After Liver Transplantation: A Systematic Review.

Portosystemic shunts (PSSs) modulate the portal hyperperfusion against small-for-size syndrome (SFSS) after split or living donor liver transplantation. To find out the results and the limitations of PSSs against SFSS. We searched PubMed and Cochrane databanks for systematic review and analyzed the indications, types, morbidities, and survivals of the PSSs at split or living donor liver transplantations. Total 66 patients were assessed in 16 studies. Main indications for PSS were graft recipient weight ratio (GRWRs) <0.8% and/or portal vein pressure >20mmHg. Five different types of PSSs were described but hemi-portocaval shunts were the most common one. The incidence of SFSS was 12%. Overall 90-day, 1-, and 3-year graft survivals were 80, 70, and 47%, respectively. GRWR <0.65% was found as the only significant parameter on graft survival. The 90-day, 1- and 3-year graft survivals for GRWR <0.65 and ≥0.65% patients were 62.5, 42.8, and 30.0 and 95, 94, and 67%, respectively (p=0.03, p=0.01, and p=0.18). PSSs can modulate the small graft size (GRWR<0.8%) and/or portal hypertension (>20mmHg) after split or living donor liver transplantations sufficiently. However, its protective effect is not unlimited. If the GRWR is below 0.65%, survival decreases significantly despite PSSs.

How far can we lower graft-to-recipient weight ratio for living donor liver transplantation under modulation of portal venous pressure?

Smaller size grafts for living donor liver transplantation (LDLT) can enhance donor safety and expand donor availability. We previously reported that modulation of portal venous pressure (PVP) was key for successful LDLT with small grafts, and that it actively lowered graft-to-recipient weight ratio (GRWR) for adult-to-adult LDLT. This retrospective study investigated the outcome of LDLT using small grafts with PVP modulation. This study analyzed 221 adult LDLT patients between March 2008 and December 2013 and divided them into 3 groups based on GRWR: large (L), GRWR ≥ 0.8% (n=154), medium (M), ≥0.7% GRWR < 0.8% (n=38); and small (S) GRWR < 0.7% (n=29). Donor and recipient factors, PVP, pressure gradient between PVP and central venous pressure (CVP), occurrence of small for size syndrome (SFSS), ascites, and posttransplant laboratory data were compared across the 3 groups. Patient and graft survival were compared using Kaplan-Meier methods. There was no difference in patient or graft survival between the 3 groups. Amount of posttransplant ascites and posttransplant International Normalized Ratio were similar, but the S and M groups had more prolonged cholestasis. SFSS was identified in 17%, 13%, and 13% in the S, M, and L groups, respectively (P=NS). Patients with a final PVP of ≤15mmHg had better survival than patients with a final PVP of >15mmHg (P<.001). Multivariate analysis showed that donor age >40years old, final PVP of >15mmHg, and pressure gradient of PVP-CVP >5mmHg were risk factors for inferior patient survival. We achieved satisfactory outcomes in LDLT with GRWR as low as 0.6% using PVP modulation. Thus, we currently set a lower limit of GRWR at 0.6% while protecting donor safety and expanding donor availability.

Early (&lt;6 months) Mortality after Adult to Adult Living Donor Liver Transplantation,Single Centre Experience: A Retrospective Cohort Study

Objectives: Both complications and mortality of recipients are annoying problems after living donor liver transplantation (LDLT). The aim to analyze early (<6 months) mortality of patients after adult to adult LDLT (A-ALDLT) in a single center. Methods: Between April 2003 and February 2013, we performed 167 A-ALDLT in National Liver Institute, Egypt. We retrospectively analyzed early mortality in recipients. Results: The overall incidence of early mortality was 34.1% (n=57), it was classified into in hospital (28.7%) and post-hospital discharge (5.4%) mortalities. The most frequent causes of in hospital and post hospital discharge mortalities were SFSS (10/48) and sepsis (5/9) respectively. On univariate analysis, the following factors were significant predictors of early mortality (Female gender, Lt Lobe graft, GRWR<0.8, mean blood transfusion 10.8 ± 9.8 units,(vascular, renal, chest, neurological, bacterial infection and small for size syndrome (SFSS)) complications. While on multivariate analysis by Cox regression, mean blood transfusion 10.8 ± 9.8 units, vascular and neurological complications were independent predictors. Conclusion: Reduction of blood transfusion units, prevention and management of vascular and neurological complications is required for better early outcome after A-A LDLT.

How Much Portal Vein Flow Is Too Much for Liver Remnant in a Stable Porcine Model?

BackgroundThere is increasing evidence that the occurrence of small-for-size syndrome (SFSS) depends on portal hemodynamics rather than graft size. The portal hyperperfusion has been regarded as the most important contributing factor to SFSS. However, it is unknown how much portal vein flow (PVF) or what limit of PVF the liver remnant can sustain in extreme hepatectomy. This study aimed to evaluate the limit of portal hyperperfusion in a stable porcine model. MethodsTwenty pigs were subjected to different liver resection volumes of 77%–82% (80% group; n = 6), 83%–87% (85% group; n = 7), and 88%–92% (90% group; n = 7). The survival rate, hemodynamic change, energy metabolism, lipopolysaccharide (LPS)/bacterial translocation, and injury and regeneration of the residual liver were observed after surgery. ResultsAll of the 80% group could sustain ∼4 times baseline PVF per unit volume, energy metabolism, and detoxifying functions, and survived to postoperative day (POD) 14. Only 3 animals in the 85% group, with ∼5.6 times baseline of PVF, were alive on POD 14, and in the 90% group, with >6 times baseline of PVF, undergoing severe hyperperfusion injury and LPS/bacterial translocation, none survived to POD 14. ConclusionsThe deaths of animals in the 85% group supports the hypothesis that the remnant vascular bed with 15% of liver volume represents a critical residual liver parenchyma in pigs, the safe minimum residual liver volume should be >15% of liver volume, indicating that the liver remnant can regenerate successfully in ∼5.6 times baseline of PVF, whereas it fails to regenerate in >5.6 times baseline of PVF.

Small for Size and Flow (SFSF) syndrome: An alternative description for posthepatectomy liver failure

Small for Size Syndrome (SFSS) syndrome is a recognizable clinical syndrome occurring in the presence of a reduced mass of liver, which is insufficient to maintain normal liver function. A definition has yet to be fully clarified, but it is a common clinical syndrome following partial liver transplantation and extended hepatectomy, which is characterized by postoperative liver dysfunction with prolonged cholestasis and coagulopathy, portal hypertension, and ascites. So far, this syndrome has been discussed with focus on the remnant size of the liver after partial liver transplantation or extended hepatectomy. However, the current viewpoints believe that the excessive flow of portal vein for the volume of the liver parenchyma leads to over-pressure, sinusoidal endothelial damages and haemorrhage. The new hypothesis declares that in both extended hepatectomy and partial liver transplantation, progression of Small for Size Syndrome is not determined only by the "size" of the liver graft or remnant, but by the hemodynamic parameters of the hepatic circulation, especially portal vein flow. Therefore, we suggest the term "Small for Size and Flow (SFSF)" for this syndrome. We believe that it is important for liver surgeons to know the pathogenesis and manifestation of this syndrome to react early enough preventing non-reversible tissue damages.

Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study.

Background and aimsLiving donor liver transplantation (LDLT) is widely performed for patients to resolve the critical shortage of organs from cadavers. Despite rapid implementation of the procedure, both complications and mortality of LDLT are annoying problems. The aim of this study was to analyze complications and mortality of patients after adult to adult LDLT (A-ALDLT) in a single center. Methods: Between April 2003 and November 2013, 167 (A-ALDLT) recipients in National Liver Institute, Egypt were included. We retrospectively analyzed complications and mortality in them.ResultsThe overall incidence of complications was 86.2% (n = 144) and classified as biliary 43.7% (n = 73), vascular 21.6% (n = 36), Small for size syndrome (SFSS) 12.6% (n = 21), Gastrointestinal tract (GIT) 19.8% (n = 33), wound 12.6% (n = 21), chest 19.8% (n = 33), neurological 26.3% (n = 44), renal 21% (n = 35), intra abdominal collection 21.6% (n = 36), recurrent hepatitis C virus (HCV) 16.8% (n = 28), recurrent hepatocellular carcinoma (HCC) 2.4% (n = 4), acute rejection 19.2% (n = 32). 65 (45.1%) of 144 complicated patients died, while 10 (43.5%) of 23 non complicated died. The incidence of whole, in hospital and late mortalities were 44.9%, 28.7% and 16.2% respectively. Conclusions: Mortality was higher among complicated cases where vascular complications and SFSS had significant effect on it so prevention and treatment of them is required for improving outcome.

Which is the best route of administration for cell therapy in experimental model of small-for size syndrome in rats?

To evaluate which is the best route of administration for cell therapy in experimental rat model of small-for size syndrome. A total of 40 rats underwent partial hepatectomy (70%) that induces the small-for-size syndrome and were divided into four groups of route administration: intravenous, intraperitoneal, enteral and tracheal. The small-for-size syndrome model was designed with extended partial hepatectomy (70%). The animals were divided into four groups of routes administration: intravenous (n=10) - intravenously through the dorsal vein of the penis; intraperitoneal (n=10) - intraperitoneally in the abdominal cavity; enteral (n=10) - oroenteral with the placement of a number 4 urethral probe and maintained at third duodenal portion; tracheal (n=10) - after tracheal intubation. We track the animals and monitor them for 21 days; during this follow-up we evaluated the result of cell therapy application tracking animals using ultrasound, radiography and PET-scan. Statistical analysis was performed using GraphPad Prism Software(r). Differences were considered significant with the p<0.05. Data are presented as the median and variation for continuous variables. Comparisons between groups were made using analysis of the imaging test by the researchers. All four groups underwent partial hepatectomy of 70% liver tissue targeting the same weight of resected liver. Initially the PET-scan tests showed similarity in administered cells by different routes. However, in few days the route of intravenous administration showed to be the most appropriated to lead cells to the liver followed by enteral. The tracheal and peritoneal routes were not as much successful for this goal. The intravenous route is the best one to cell therapy in experimental rat model of small-for size-syndrome.