Advances in the study of small-for-size syndrome / 中华肝胆外科杂志

Small-for-size syndrome is one of the most common and dangerous complications of partial liver transplantation. With the accumulation of clinical experiences and basic researches developed in recent years, new knowledge about the pathogenesis, pathophysiological process, prevention and treatment of small-for-size syndrome has been established. This article summarizes the progress of research on the small-for-size syndrome in recent years to help better diagnosis, prevention and treatment, thus improving the prognosis and long-term survival of patients.

Perioperative management of split liver transplantation / 器官移植

In the context of shortage of donor livers, split liver transplantation has achieved the goal of "one donor liver for two recipients", which effectively alleviates the shortage of donor livers and has promising development prospect. With the advancement of liver transplant techniques, split liver transplantation may yield clinical prognosis equivalent to total liver transplantation. However, perioperative management of split liver transplantation still encounters multiple challenges, with demanding techniques requirement and high-risk postoperative complications. Besides, there is a possibility of dividing one high-quality donor liver into two marginal donor livers, which will affect the development of liver transplantation. In this article, perioperative management of split liver transplantation was discussed from the perspectives of preoperative evaluation, recipient management and postoperative complication management, aiming to provide reference for promoting the development of split liver transplantation and enhancing clinical prognosis of recipients after split liver transplantation.

Impact of graft/recipient weight ratio on the prognosis of infants with whole liver transplantation / 中华器官移植杂志

Objective:To explore the impact of graft recipient weight ratio(GRWR)on pediatric whole liver transplantation in infants aged under 1 year.Methods:From January 2014 to December 2019, clinical data were retrospectively reviewed for 140 children aged under 1 year with whole liver transplantation.They were divided into 3 groups of low GRWR(GRWR<2.5%, 48 cases), middle GRWR(2.5%≤GRWR<5%, 73 cases)and high GRWR(GRWR≥5%, 19 cases). Basic profiles, major postoperative complications and survival rate of graft/recipient were compared.Results:There were 62 males and 78 females with an average age of (7.34±1.81)months and an average weight of(6.81±1.09)kg.The median GRWR was 3.27%(1.33%~8.12%). The higher level of GRWR, the greater age, weight and graft weight of donor in three groups and there was statistical difference ( P<0.05); operative duration, postoperative ICU stay and hospital stay were longer in low GRWR group than those in middle GRWR group and there was statistical difference( P<0.05); The incidence of postoperative hepatic artery thrombosis was higher in low GRWR group than that in middle GRWR group(31.3%vs 8.2%)and there was statistical difference( P<0.05); 4 cases of small-for-size syndrome occurred in low GRWR group, it was significantly different from the other two groups and there was statistical difference( P<0.05); the median follow-up period was(50.7±23.4)months.The survival rates of grafts at 3-month and 1/5-year were 89.6%, 91.8%, 100%; 87.5%, 87.7%, 100%; 87.5%, 87.7%, 100%and there was no inter-group difference( P>0.05). The survival rates of recipients at 3 months, 1 year and 5 years post-operation were 93.8%, 91.8%, 100%; 91.7%, 87.7%, 100%; 91.7%, 87.7%, 100%and there was no inter-group difference( P>0.05). Conclusions:Different from pediatric living donor transplantation, GRWR≥5%does not affect the survival rate of recipient/graft during whole liver transplantation.And GRWR<2.5%may boost the postoperative incidence of hepatic artery thrombosis and small liver syndrome.

Clinical application of split liver transplantation technique / 器官移植

Currently, multiple difficulties exist in clinical liver transplantation, such as shortage of donor liver, increasing quantity of patients waiting for liver transplantation and lack of matching donors, etc. Some children and adult patients have little chance of undergoing liver transplantation, which also limits the development of liver transplantation. In this context, split liver transplantation emerges, in which 1 donor liver can be applied to 2 or even more recipients. It may effectively increase the utilization rate of donor liver and alleviate the shortage of donor liver. With the development of split liver transplantation, the survival rate of split liver transplantation is comparable to that of total liver transplantation. Multiple transplantation centers have routinely adopted split liver transplantation. In this article, the development of split liver transplantation, the selection and matching of donors and recipients, the split and reconstruction techniques of donor liver and postoperative complications were reviewed, aiming to provide reference for subsequent development of split liver transplantation in clinical practice and increase the chance of liver transplantation for more patients diagnosed with end-stage liver diseases.

"""Irrigation method"" in prevention and treatment of portal vein hypertension after small-for-size liver transplantation" / 中华肝胆外科杂志

Objective To investigate effective approach to decrease portal venous hypertension and high perfusion of portal vein caused by small-for-size (SFS) liver graft transplantation with the aim of improving hepatocellular microcirculation.Methods Rat models with SFS liver graft (n =62) were well estab lished and divided into SFS group and trans-portal intrabepatic portosystemic shunt (TPIPSS) group.Hemodynamic parameters,histopathologically morphologic changes,postoperative complications,accumulated survival rate were recorded and analyzed.Venous filling time after liver reperfusion,hemodynamic parameters were evaluated using t test and Kruskal-Wallis test.Kaplan-Meier method was performed for survival analysis.Results Venous filling time after liver reperfusion was remarkably prolonged with the application of multihole cone-shaped tubes.Compared with SFS group,the filling time was 4-second longer in TPIPSS.At each endpoints of reperfusion within 90 mins,the portal vein pressures were lowered in the TPIPSS group than those of SFS group.Liver grafts were present with more regular structures in TPIPSS group,with no sign of hepatic sinusoid congestion or irregular clearance extension.In the aspect of postoperative complications,all the rat receivers showed ascites in the SFS group.Nevertheless,there was no ascites observed in TPIPSS rats,and 50％ rats (5/10) experienced clinical manifestations of hepatic encephalopathy.Persistent fever over 7 days was showed in 10％ rats (1/10) of SFS group and 40％ rats (4/10) of TPIPSS group,respectively.The mean survival was superior in TPIPSS group (37.2 ± 23.5) d than SFS group (17.7 ± 13.5) d,P ＜ 0.05.Conclusion TPIPSS could be a safe and feasible approach to improve portal venous hypertension caused by SFS liver graft and hepatocellular reperfusion.

Effect of continuous low-dose infusion of adenosine into hepatic artery on hepatic arterial flow of liver graft / 中华肝胆外科杂志

Objective To assess the effect of continuous low-dose infusion of adenosine on hepatic arterial flow (HAF) of patients with liver graft during surgery.Methods From Jan 2009 to Aug 2009,44 patients underwent orthotopic liver transplantation (OLT).10 patients were enrolled to receive adenosine treatment and 34 patients served as controls.Following arterial reperfusion,a 16G central venous catheter was placed into the gastroduodenal artery and adenosine was continuously infused at doses ranging from 0.7 to 4.2 μg · kg-1 · min-1 for 30 min.HAF and portal vein flow (PVF) were measured using a real-time time flow meter prior to,during and 10 min after adenosine infusion.Data on gender,age,postoperative hospital stay,ICU stay,hepatic biochemical indicators and 1-year survival rate were compared between the two groups.Results Adenosine significantly increased HAF at doses from 1.4 to 2.8 μg · kg-1 · min-1 Doses ＞2.8 μg · kg-1 · min-1 did not further increase HAF.HAF increased by 150.3％ ± 161.2％ (P ＜0.05) while PVF showed no significant changes (P ＞ 0.05) during adenosine infusion.No significant differences were found on MAP [(85.6 ± 13.0) vs 84.0 ± 13.6,P ＞0.05] and HR [(74.5 ± 10.0) vs (74.1 ± 9.6),P ＞ 0.05] before and after adenosine infusion.In addition,there were no significant differences between the adenosine group and the control group on patients' gender,age,postoperative hospital stay,ICU stay,hepatic biochemical indicators and 1-year survival rate.Conclusion This pilot study concluded that adenosine administration directly into the HA significantly increased HAF of liver grafts without systemic side effects.

Procedures to prevent development of small-for-size syndrome during living donor liver transplantation / 中华器官移植杂志

Objective Small-for-size syndrome (SFSS) is a common and serious problem after living donor liver transplantation (LDLT) of small grafts.To prevent SFSS by selecting large enough graft,enlarging outflow tract,and controlling the portal vein pressure and flow during LDLT.Methods 113 adult LDLT recipients were reviewed from Dec.1,2007 to Nov.30,2009.Enlarging the portal outflow tract by the incision of the anterior rim of the orifice of the right hepatic vein (RHV),modificating graft inflow,and selecting large enough graft were done to prevent SFSS.The relationship between the patients' GRWR,portal vein flow,portal vein pressure and the occurrence of SFSS was analyzed.Results All patients received the outflow orifice modification.The portal vein pressure and the portal vein flow were decreased after spleen artery ligation.No SFSS ocurred.Conclusion Selecting large enough liver graft,and enlarging portal vein inflow and outflow were safe for the LDLT recipients,and can effectively prevent SFSS.

Relationship between hepatic arterial buffer response and early biliary complications and small-for-size syndrome after living donor liver transplantation / 中华肝胆外科杂志

Objective To study the relationship between hepatic arterial buffer response (HABR),recovery of liver function,early biliary complications and small-for-size syndrome (SFSS).Methods Early hepatic hemodynamic parameters (including hepatic arterial flow (HAF),portal venous flow (PVF) were measured using duplex Doppler sonography in 34 patients who received living donor liver transplantation (preoperatively n＝26,intraoperatively n=26) and on postoperative days 1,2,3,and 7.Alanine aminotransferase (ALT),aspartate aminotransferase (AST) and total bilirubin (TBIL) level were measured preoperatively and on postoperative days 1,2,3,7,14,21,and 28.If TBIL level was elevated,we used B ultrasonography or CT and even ERCP to diagnose early biliary complications.The days taken for AST,AI T and TBIL to recover and the number of patients with early (＜60 days) biliary complications (bile leakage or bile stricture) and with small-for-size syndrome (SFSS) were recorded.Results Passive hepatic artery buffer response (HABR) was present in 11 patients early after living donor liver transplantation (group 1) and it disappeared in 23 patients (group 2).The recovery in days taken for normalization of AST (10.6± 8.8),AIT (11.6±9.0) and TBlL (average of 29) in group 1 were shorter than in group 2.However,the differences did not reach statistics difference (P＞0.05).The overall incidences of early biliary complications and small-for-size syndrome (SFSS) in group 1 were significantly lower than in group 2 (P=0.04).The survival rate in group 1 was 82 ％,compared with 74 ％ in group 2.Conclusions Passive hepatic arterial buffer response (HABR) disappeared in some patients early after living donor liver transplantation.There were high incidences of early biliary complications and small-for-size syndrome (SFSS) in these patients.Measurcment of hepatic buffer response in the early stage after living donor liver tranaplanta tion is valuable for predition of early biliary complications and small-for-size syndrome (SFSS),thus helping to prevent failure in transplantation.

Establishment and evaluation of models for small-for-size graft injury without veno-venous bypass in miniature pigs / 中华肝胆外科杂志

Objective To establish small-for-size (SFS) graft injury models in miniature pigs with high standardization, reproducibility and similarity to clinical situation. Methods Ba-Ma miniature pigs were introduced in this study and orthotopic liver transplantations (OLTs) were performed in 12 pigs with 30% liver volume allogeneil grafts (small portion of right paramedian lobe, right lateral lobe and caudate lobe) without veno-venous bypass. The profiles of intra-operational hemodynamics and metabolism were investigated. Animals were observed for 7 days with daily serum biochemistry and coagulation function exam. The survival rate related to operation itself and the SFS grafts were respectively calculated as well as the graft regenerative ratio at post-operational day (POD) 7. Results Graft weight as a percentage of the recipient's native liver weight (GW/RLW) and the total body weight (GW/BW) were (28. 63±4. 42)% and (0. 73±0.06)%. The mean operation time, anhepatic phase, and the time of blockage of infra-hepatic IVC were (191. 7±14. 2) min, (28. 3±3. 6) min, and (45. 0±5. 8) min. The survival rate related to the operation itself and the SFS graft were 83. 33% (10/12) and 40% (4/10), and the graft regenerative ratio at POD7 was (278. 06±42. 95) %. Contrast to the remarkable increase of heart rate and serum potassium during anhepatic phase, the mean arterial pressure, central venous pressure, rectal temperature, PH value and buffer excess had a significant decrease (P<0.01) with a gradual recovery after reperfusioa Serum ALT, AST, PT, Cr, and TB were significantly increased with a peak level at POD1 for the former 4 and POD2 for TB, and then began to decrease and favorably recovered at POD7, but TB, PT, and AST levels were still high when compared to those of prereperfusion (P<0. 05). Conclusion This model of OLT performed with 30% liver volume graft without veno-venous bypass was an ideal large animal model for series studies related to SFS graft injury.

Advances in small-for-size syndrome / 中华肝胆外科杂志

The small-for-size syndrome (SFSS) is widely recognized as one of the most serious clinical complications. It substantially contributes to a poor prognosis after adult living donor liver transplantation. Currently, there is still no consensus on the exact definition and pathogenesis of SFSS. We reviewed the progress on research of pathogenesis of SFSS and put forward some relevant preventive and treatment measures, including donor selection, graft assessment, reduction of high portal vein perfusion, dual grafts technology, advanced molecular medicine and other innovative approaches. Also, we offered some relevant insights into the future research directions of SFSS.

Modulation of portal vein hemodynamics by selective splenectomy to prevent small-for-size syndrome in living donor liver transplantation / 中华肝胆外科杂志

ObjectiveTo investigate the effects of selective splenectomy on modulation of portal vein flow and prevention of small-for-size syndrome (SFSS) in living donor liver transplantation.MethodsTwenty six recipients who received LDLT from September 2007 to March 2008 were reviewed.The data of the portal vein flow of these recipients were collected during the operation.Simultaneous splenectomy was performed in patients with portal blood flow ＞250 ml/(min · 100g).No splenectomy was performed when the portal blood flow was less than 250 ml/(min · 100g).The effect of selective splenectomy on modulation of portal vein flow and whether splenectomy prevented the occurrence of SFSS were analyzed.ResultsThe portal vein flow decreased significantly after splenectomy in 8 patients who received splenectomy (P＜0.01),No SFSS occurred in the patients with or without splenectomy.Actual graft-to-recipient weight ratio (GRWR) of patients with splenectomy was significantly smaller than those with no splenectomy (P=0.044).The portal vein flow of patients with splenectomy was much higher than those with no splenectomy (P＜0.01).ConclusionAccording to the portal blood flow,selective splenectomy in LDLT decreased the portal vein flow and prevented the incidence of SFSS.

Protective effects of splenectomy of small-for-size syndrome in rat models / 中华器官移植杂志

Objective To explore the role of splenectomy in the prevention and treatment of small-for-size liver in rat models, as well as its pathophysiologic mechanism in the development of a small-for-size syndrome (SFSS). Methods The models of sham-operation and 80 % partial hepatectomy (PH) were used in rats. In the experiment group splenectomy was performed following 80% PH. The concentrations of serum tumor necrosis factor (TNF-α), the content of NF-cB p65 in liver nuclear extracts, the expression of TNF-α, intercellular adhesion molecular (ICAM-1), and proliferating cell nuclear antigen (PCNA) transcripts, the activities of serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), total bilirubin (TB), albumin (Alb) cholinesterase (CHE), and liver myeloperoxidase (MPO) were analyzed. Portal venous pressures (PVP),incidence of SFSS,and one-wk survival rate were measured. Results In the control rats,The PVP was obviously elevated immediately after PH. The level of NF-κB p65 was obviously increased at the first h and peaked at about 3rd h postoperatively. The transcription of TNF-α and ICAM-1 and the release of serum TNF-α were significantly increased 3 h after PH. Capillary endothelial cells of the livers strongly expressed ICAM-1 24 h after PH. Splenectomy significantly reduced the PVP and the content of NF-κB p65 in the livers in concurrence with the expression of TNF-α and ICAM-1 gene as well as the activity of MPO at the corresponding time points after PH (P＜0. 05), while increased the expression of PCNA gene (P＜0. 05). Administration of splenectomy resulted in a statistically significant decrease in AST, ALT, LDH, TB, the incidence of SFSS and increase in one-wk survival rate (P ＜ 0.05 ). Conclusion Splenectomy alleviates liver injury and promotes liver regeneration in small-for-size liver rats by reducing portal vein perfusion and pressure,and suppressing NFκB activation and subsequent expression of proinflammatory mediators.

The Role of Splenectomy in the Prevention and Treatment of Small-for-size Syndrome / 中国医科大学学报

Objective To explore the pathophysiologic mechanism of the development of a small-for-size syndrome(SPSS) and the role of splenectomy in the prevention and treatment of SFSS.Methods The rat models of sham-operation and 80% partial hepatectomy were established.Totally 144 rats were randomly divided into 3 groups:1)splenectomy group:splenectomy was performed following 80% partial hepatectomy;2)control group:80% partial hepatectomy was performed;3)sham group:no hepatectomy was performed.After the operation,we examined the portal venous pressures(PVP),tumor necrosis factor(TNF-α) and proliferating cell nuclear antigen(PCNA) expression,the activity of myeloperoxidase(MPO),liver function and explored the prevalence of SFSS.Results Compared with the sham group,the PVP of the rats in the control group obviously elevated after hepatectomy,and the expression level of TNF-a and the activity of MPO in the liver significantly increased(P<0.05).Compared with the control group,the PVP,the expression of TNF-a in the livers and the activity of MPO at the corresponding time points after hepatectomy in the splenectomy group significantly decreased,while the expression of PCNA in-creased(P<0.05).Administration of splenectomy resulted in a statistically significant decrease in aspartate transaminase(AST),alanine transaminase(ALT),lactate dehydrogenase(LDH),total bilirubin.and the incidence of SFSS(P<0.05).Conclusion Splenectomy could alleviate liver injury,promote liver regeneration in small-for-size liver rats by reducing portal vein perfusion and pressure and the subsequent expression of proinflammatory mediators.

Current status of small-for-size syndrome / 中华肝胆外科杂志

With the worldwide increase in adult-to-adult live donor liver transplantation, more profound basic and clinical medical research has ensued to solve the key problem of graft failure following liver transplantation. The present status of the study of small-for-size liver syndrome was summarized. Its definition, risk factors, pathogenesis,clinical manifestations, prevention and treatment were included.

"Small-for-size Graft" and "Small-for-size Syndrome" in Living Donor Liver Transplantation

The indications for living donor liver transplantation (LDLT) were successfully expanded from pediatric to adult cases last 15 years. During this process, graft type has been shifted from left side liver to right side liver. Although the introduction of right lobe graft can successfully increase the actual graft size in LDLT, problem related to "small-for-size grafts" have gradually come to light. "Small-for-size syndrome", such as poor bile production, delayed synthetic function, prolonged cholestasis, and intractable ascites, leading to septic complications and higher mortality, are neither specific nor inevitable in low-weight liver grafts. Many factors other than actual graft weight contribute to the occurrence of "small-for-size syndrome". In the clinical setting, surgical modification targeting portal hemodynamics and tissue congestion is a key to overcome "small-for-size syndrome". Until now, several therapeutic options were reported, but further elucidation of the pathogenesis in "small-for-size syndrome" will be a solution for improving the outcomes in adult-to-adult LDLT.