Selective and unselective clamping in liver surgery]

Liver surgery requires a reduction in the operative blood loss to avoid postoperative liver failure. We carried out elective hepatic resection in 229 patients with Pringle's maneuver, which involves complete, intermittent clamping of the hepatic flow, and in 56 patients with selective vascular occlusion. Twenty-seven donors for living-related liver transplantation were also included in the latter series. The clinical outcomes were evaluated based on clamping method used. The cumulative clamping time and amount of blood loss were 64 +/- 46 min (mean +/- SD) and 828 +/- 665 ml in the Pringle's maneuver group and 88 +/- 44 min and 907 +/- 555 ml in the selective vascular occlusion group. Laboratory data showed good tolerance of vascular clamping in both groups, and serum aspartate aminotransferase levels returned to the baseline within one week. Operative morbidity rates were 23% and 27%, respectively, and no operative deaths occurred in this series. In living-related liver transplantation, modified selective vascular occlusion can preserve graft viability, as verified by the fact that all the recipients in this series had a good postoperative course, except for one death and one graft loss. In conclusion, intermittent total or selective vascular clamping is indispensable procedure during hepatic resection.     

选择性与全肝人肝血流阻断法在肝切除术应用的随机对照研究

目的 比较3种入肝血流阻断方法,即Pringle法(A组)、半肝阻断法(B组)、单纯门静脉阻断法(C组)在肝切除术中的应用效果.方法 采用随机对照研究的方法,将行肝切除术的患者随机分为3组,采用不同的阻断方法,对3组手术前后肝功能变化及术中出血及术后并发症进行比较.结果 B组中1例因分离单侧肝门困难而改用Pringle法;179例患者无围手术期死亡;术中出血量3组间较差异无统计学意义;术后第1、3、7天B组和C组的肝功能改变(总胆红素、丙氨酸氨基转移酶及蛋白水平等)组间比较无统计学意义,两组与A组比较有统计学意义.结论 3种入肝血流阻断方法在切肝过程中,控制术中出血效果满意,切肝过程中采用选择性入肝血流阻断较Pringle法对术后肝功能损伤较小.     

Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver

OBJECTIVE: To compare protection of the liver by ischemic preconditioning and intermittent inflow occlusion in a mouse model of prolonged periods of ischemia. SUMMARY BACKGROUND DATA: Preconditioning (short ischemic stress prior to a prolonged period of ischemia) and intermittent inflow occlusion protect the liver against reperfusion injury. This is the first study comparing these two modalities with continuous inflow occlusion (control). METHODS: Mice were subjected to 75 or 120 minutes of 70% hepatic ischemia and 3 hours of reperfusion. Each ischemic period was evaluated using three different protocols: continuous ischemia (control), preconditioning (10 minutes ischemia and 15 minutes reperfusion) prior to the prolonged ischemic insult, and intermittent clamping (cycles of 15 minutes ischemia and 5 minutes reperfusion). Organ injury was evaluated using serum levels of aspartate aminotransferase (AST), hematoxylin and eosin staining, and specific markers of apoptosis (cytochrome C release, caspase 3 activity, and TUNEL staining). Animal survival was determined using a model of total hepatic ischemia. RESULTS: Intermittent inflow occlusion and ischemic preconditioning were both protective against ischemic insults of 75 and 120 minutes compared with controls (continuous ischemia only). Protection against 75 minutes of ischemia was comparable in the intermittent clamping and the ischemic preconditioning group, whereas intermittent clamping was superior at 120 minutes of ischemia. One hundred percent animal survival was observed after 75 minutes of total hepatic ischemia using both protective protocols, whereas all animals subjected to continuous ischemia died after surgery. After 120 minutes of ischemia, intermittent inflow occlusion was associated with better animal survival (71%) compared with preconditioning (14%). CONCLUSIONS: Preconditioning and intermittent clamping are both protective against prolonged periods of ischemia. In the clinical setting, preconditioning is superior for ischemic periods of up to 75 minutes because it is not associated with blood loss during transection of the liver. However, for prolonged ischemic insults exceeding 75 minutes, intermittent clamping is superior to preconditioning.     

连续性半肝血流阻断与间歇性全肝血流阻断肝切除的临床分析

目的 评价在肝切除术中连续性半肝血流阻断(hemihepatic inflow occlusion,HH)与间歇性全肝血流阻断(total hepatic inflow occlusion,TH)的安全性和有效性.方法 将80例肝肿瘤患者分为HH组(40例)和TH组(40例).术中施行肝切除时,HH组患者采用连续阻断血流的方式,TH组患者采用阻断血流20 min、复流5 min的阻断方式.测量2组患者的术中出血量和肝断面面积,术后1、3、7 d测定肝功能,并记录术后并发症情况.结果 HH组比TH组的肝总缺血时间长,分别为[(42±13)min,(31±13)min,P=0.00],HH组的手术时间(236±49)min比TH组(204±38)min的时间长(P=0.02).两组患者断肝出血量分别为(500±269)ml与(416±235)ml,差异无统计学意义(P=0.14),术后第1天ALT与AST升高水平比较,二组差异无统计学意义[(ALT:(677 ±572)IU/L,(577±327)IU/L,P=0.12;AST:(591±468)IU/L,(512±301)IU/L,P=0.66)].两组患者术后并发症发生率相近(分别为22.5%和20.0%,P=0.35).结论 在肝切除中,连续性半肝血流阻断与间歇性全肝血流阻断同样安全和有效.     

“Time is tissue”—A minireview on the importance of donor nephrectomy,donor hepatectomy,and implantation times in kidney and liver transplantation

Donor organs are exposed to sequential temperature changes during the transplantation process. The role of donor warm ischemia and cold ischemia times on post-transplant outcomes has been extensively studied. Much less attention has been paid to the transient ischemia occurring during donor organ removal and implantation. Recently, it has become clear that prolonged donor nephrectomy and implantation time are independently associated with delayed graft function after kidney transplantation. In addition, implantation time correlates with post-transplant kidney graft function, histology, and survival. Similar detrimental associations of donor hepatectomy and implantation time with early allograft dysfunction, ischemic cholangiopathy, and graft and patient survival after liver transplantation have been demonstrated. This review details kidney and liver temperature changes occurring during procurement and transplantation. It summarizes the effects of the ischemia the kidney and liver sustain during these phases on short- and long-term post-transplant outcomes, advocating the standardized reporting of donor hepatectomy, donor nephrectomy, and implantation times in (inter)national registries. The review also explores strategies to protect the graft from this ischemic injury.     

Effects of pirfenidone on endotoxin-induced liver injury after partial hepatectomy in rats

BACKGROUND: In living donor liver transplantation, restrictions on graft size are a serious obstacle to expand indications for adult recipients. The sequence of gram-negative infection, septicemia, and multiple-organ failure is a common cause of early mortality after liver transplantation. An effective therapy has not been established for endotoxemia following extended hepatectomy in donors or small-for-size grafts in recipients. Pirfenidone (PFD), a new experimental antifibrotic agent, was used to ameliorate on endotoxin-induced liver injury following partial hepatectomy. METHODS: Male Sprague-Dawley rats were intravenously administered lipopolysaccharide (LPS) 48 hours after 70% hepatectomy. Prior to LPS administration, PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally twice. RESULTS: The survival rate of the PFD-treated group was markedly improved compared with that of the controls. PFD prevented the increases in the activities of serum enzymes (aspartate transaminase [AST], alanine transaminase [ALT], and lactate dehydrogenase [LDH]) and total bilirubin. The serum and liver tissue levels of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma, and interleukin-6, were significantly lower among the PFD than the control group. Furthermore, the degree of necrosis in the remnant liver was significantly decreased in the PFD-treated rats compared with controls. CONCLUSION: These results indicate that PFD alleviates endotoxin-induced liver injury after partial hepatectomy through the inhibition of production of inflammatory cytokines in the residual liver. PFD may be useful to prevent endotoxin-induced liver injury after hepatectomy.     

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in pigs

OBJECTIVE: To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy model in pigs after prolonged continuous or intermittent vascular inflow occlusion in the liver. SUMMARY BACKGROUND DATA: Massive intraoperative blood loss during liver resections can be prevented by temporary vascular inflow occlusion, consequently leading to ischemia and reperfusion injury in the remnant liver. Previously, in a pig liver resection model in which only limited I/R injury was induced during brief (90 min) vascular inflow occlusion, the authors demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to intermittent (INT). This liver resection study on pigs was undertaken to assess I/R injury after prolonged (120 min) CNT or INT occlusion. METHODS: In pigs (37.0 +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6 hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver resection was performed in control experiments (n = 6). Microvascular damage was assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2 during reperfusion. Hepatocellular damage was tested by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH). RESULTS: Hyaluronic acid uptake after 6 hours of reperfusion, compared to preischemic uptake, was unaltered in the control group, but was significantly reduced in both resection groups. However, more HA was taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%, respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6 hours of reperfusion more closely returned to preischemic configuration in the INT group than in the CNT group, indicating reduced microcirculatory disturbances after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was significantly increased in both CNT and INT groups. Lower AST levels, however, were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and 603.3 +/- 132.4 U/l, respectively; p = 0.06). CONCLUSIONS: Intermittent hepatic vascular inflow occlusion during prolonged liver ischemia in pigs resulted in less microcirculatory and hepatocellular injury, compared to continuous occlusion. Intermittent clamping is preferable when prolonged periods of vascular inflow occlusion are applied during liver resections.     

药物预处理和缺血预处理对供肝保护作用的比较研究

目的 寻找有效的砬轻供肝缺血再灌注损伤的途径。方法 建立大鼠肝脏原位隔离冷灌注模型模拟整个肝移植过程,对供肝分别作药物预处理和缺血预处理,比较正常肝,预处理供肝,末预处理供肝的ＰＣＮＡ,ＡＳＴ,ＡＬＴ,ＬＤＨ值。结果 与正常肝相比,药物预处理供肝、缺血预处理供肝、未预处理供肝肝损害程度依次加重。结论 预处理确实对供肝缺血再灌注损伤有保护作用;药物预处理的效果可能优于缺血预处理。     

A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection

OBJECTIVE: To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery. SUMMARY BACKGROUND DATA: IP and IC are distinct protective approaches against ischemic injury. Since both strategies proved to be superior in randomized controlled trials (RCTs) to continuous inflow occlusion alone, we designed a RCT to compare IP and IC in patients undergoing major liver resection. METHODS: Noncirrhotic patients undergoing major liver resection were randomized to receive IP with inflow occlusion (n = 36) or IC (n = 37). Primary endpoints were postoperative liver injury and intraoperative blood loss. Postoperative liver injury was assessed by peak values of AST (alanine aminotransferase) and ALT (aspartate aminotransferase), as well as the area under the curve (AUC) of the postoperative transaminase course. Secondary endpoints included resection time, the need of blood transfusion, ICU, and hospital stay as well as postoperative complications and mortality. RESULTS: Both groups were comparable regarding demographics, ASA score, type of hepatectomy, duration of inflow occlusion (range, 30-75 minutes), and resection surface. The transection-related blood loss was 146 versus 250 mL (P = 0.008), and when standardized to the resection surface 1.2 versus 1.8 mL/cm (P = 0.01) for IP and IC, respectively. Although peak AST, AUCAST, and AUCALT were lower for IC, the differences did not reach statistical significance. Overall (42% vs. 38%) and major (33 vs. 27%) postoperative complications as well as median ICU (1 vs. 1 day) and hospital stay (10 vs. 11 days) were similar between both groups. CONCLUSIONS: Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection. However, IP is associated with lower blood loss and shorter transection time. Therefore, both strategies can be recommended for noncirrhotic patients undergoing liver resection.     

Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial

OBJECTIVE: To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections. SUMMARY BACKGROUND DATA: Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia. PATIENTS AND METHODS: Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded. RESULTS: No differences were observed in the amount of hemorrhage (671 +/- 533 mL versus 735 +/- 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 +/- 4.6 versus 4.5 +/- 2.7 mukat/L, P = 0.01) and AST (10.2 +/- 8.7 versus 4.9 +/- 2.1 mukat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity. CONCLUSIONS: Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.     

Role of platelet-activating factor in hepatectomy with Pringle's maneuver

BACKGROUND: Interruption of hepatic inflow is commonly used to reduce blood loss during extensive liver resection, but may cause liver dysfunction. The present study investigated the effects of platelet-activating factor (PAF) antagonist E5880 on total liver warm ischemia and 70% hepatectomy. METHODS: Rabbits were used in this study and were divided into four groups: group 1, those treated with only 70% hepatectomy; group 2, those treated with only 20 min Pringle's maneuver; group 3, those treated with both Pringle's maneuver and 70% hepatectomy without pretreatment; and group 4, those pretreated with PAF antagonist E5880 (0.3 mg/kg) followed by Pringle's maneuver and 70% hepatectomy. The remnant liver function was then evaluated after reperfusion. RESULTS: Seven-day survival rates in both groups 1 and 2 were 100%. E5880 treatment significantly increased 7-day survival rate (group 4: 38% vs group 3: 0%, P < 0.05) after a combination of Pringle's maneuver and 70% hepatectomy. The elevations of serum liver enzymes (GOT, GPT, mGOT, and LDH) were significantly inhibited in group 4 at 1 and 4 h after reperfusion. Portal venous pressure and the energy charge of liver were also significantly improved in group 4, compared with those in group 3. Endothelin-1 levels of arterial and portal venous blood progressively increased after reperfusion; however, there were no significant differences between the two groups. Leukocyte infiltration into the liver was significantly inhibited in group 4. CONCLUSION: E5880 pretreatment has protective effects on liver function after 70% hepatectomy with Pringle's maneuver in rabbits.     

丹参对大鼠供肝冷保存缺血再灌注损伤中肝细胞凋亡的影响

目的 探讨丹参对大鼠原位肝移植供肝冷保存缺血再灌注损伤中肝细胞凋亡的影响.方法 将40只SD大鼠分为对照组、实验组及假手术组,建立原位肝移植模型.供肝灌注冷保存以4℃乳酸林格氏液为基液,实验组加丹参注射液(60 ml/L),对照组不加丹参.保存5 h后植入受体.移植后6 h处死大鼠取样,检测血浆中ALT、AST水平;采用TUNEL法检测移植术后肝细胞凋亡情况;流式细胞仪检测凋亡相关基因Bcl-2、FasL蛋白的表达;光镜下观察移植肝脏病理形态学的改变.结果 再灌注后实验组ALT、AST显著低于对照组.与对照组比较,实验组肝细胞凋亡指数明显下降(F=133.802,P<0.05);肝组织中Bcl-2蛋白表达增加(F=91.063,P<0.01);FasL蛋白表达无明显变化(F=1.329,P>0.05);实验组与对照组比较肝组织形态学的再灌注损害程度明显减轻.结论 丹参可通过促进抑制凋亡基因Bcl-2蛋白的表达来抑制冷保存再灌注导致的肝细胞凋亡,对原位肝移植肝脏的缺血再灌注损伤有保护作用.     

Insulin in University of Wisconsin solution exacerbates the ischemic injury and decreases the graft survival rate in rat liver transplantation

BACKGROUND: Insulin keeps the liver in a metabolically vigorous state. However, organ preservation aims to decrease the metabolic rate. The objective of this study was to clarify the effect of insulin used in University of Wisconsin (UW) preservation solution on the liver graft. METHODS: The liver grafts were preserved by UW solution with or without insulin for 7, 9, and 24 hr, respectively. The influence of insulin was studied by 7-day survival rate, liver function, morphology, and intragraft gene expression 24 hr after transplantation. Morphology was studied on the preserved grafts. RESULTS: The morphology of the graft in the insulin group showed more severe ischemia-reperfusion injury. The 7-day graft survival rates of the 7-hr subgroups with and without insulin were 55% and 93%, respectively (P=0.02). In the 9-hr subgroups, the survival rates were 0% and 78%, respectively (P=0.002). The serum levels of aspartate aminotransferase (AST) (P=0.008) and alanine aminotransferase (ALT) (P=0.032) were higher in the 7-hr subgroup with insulin. The same trend was found in the 9-hr subgroups (AST, P=0.016; ALT, P=0.016). The expression level of 215 genes were much lower at 24 hr after transplantation in the grafts preserved with insulin than in those preserved without insulin, and most of the genes were related to metabolic activities. CONCLUSIONS: Insulin in UW solution may exacerbate graft ischemic injury and decrease the graft survival rate in rat liver transplantation. Insulin, in the absence of glucose in UW solution, may exhaust the metabolic activity of the liver graft. It is harmful rather than helpful for isolated rat liver grafts preserved in UW solution.     

Expression of IL-8 during reperfusion of renal allografts is dependent on ischemic time

BACKGROUND: Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion. METHODS: This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR. RESULTS: Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies. CONCLUSIONS: The expression of chemokines directing neutrophil and macrophage recruitment increases during reperfusion of living and cadaveric donor renal allografts. Expression levels of IL-8 correlate with the ischemic time imposed on the renal graft. Early tissue injury may be attenuated by strategies antagonizing chemokines directing the recruitment of neutrophils and macrophages into kidney grafts.     

Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.     

Efficacy of PGI2 analog in preventing ischemia reperfusion damage of liver grafts from living donors

In living-related transplantation, warm ischemia/reperfusion damage (IRD) of liver grafts is inevitable during harvesting. In this study, we investigated the effects of prostacyclin (PGI₂) on IRD of liver grafts in the rat liver transplant model. Donor rats underwent 30-min warm ischemia of part of the liver (right lateral and medial lobes). After 10 min of reflow, the ischemic partial livers were flushed with Ringer's lactate and immediately transplanted into untreated recipients. Donor animals were divided into two groups: group I received vehicle, and group II received PGI₂ analog OP-41483 (OP, 500 ng/kg per min, i. v.) during the donor operation. One-week survival was studied and cellular adenine nucleotide levels of donor livers were assayed by high-performance liquid chromatography (HPLC). Donor treatment with PGI₂ analog group II significantly improved 1-week survival (86%), in comparison with the controls group I (25%). The levels of total adenine nucleotides (TAN, μmol/g dry wt) of the grafts just before implailtation were well maintained by PGI2 treatment (12.22), as compared with the controls (10.36). In summary, PGI2 treatment of the donor maintained high energy metabolism of the liver graft after IRD and improved the survival of recipients after transplantation. Our study suggested that PGI₂ treatment of donors improves viability in liver grafts from living donors thus and increases graft availability for transplantation.     

Segmental liver transplantation from living donors. Report of the technique and preliminary results in dogs

A technique of orthotopic liver transplantation using a segmental graft from living donors was developed in the dog. Male mongrel dogs weighing 25-30 kg were used as donors and 10-15 kg as recipients. The donor operation consists of harvesting the left lobe of the liver (left medial and left lateral segments) with the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The grafts are perfused in situ through the left protal branch to prevent warm ischemia. The recipient operation consists of two phases: total hepatectomy with preservation of the inferior vena cava using total vascular exclusion of the liver and veno-venous bypass, implantation of the graft in the orthotopic position with anastomosis of the left hepatic vein to the inferior vena cava and portal, arterial and biliary reconstruction. Preliminary experiments consisted of four autologous left lobe transplants and nine non survival allogenic left lobe transplants. Ten survival experiments were conducted. There were no intraoperative deaths in the donors and none required transfusions. One donor died of sepsis, but all the other donor dogs survived without complication. Among the 10 grafts harvested, one was not used because of insufficient bile duct and artery. Two recipients died intraoperatively of air embolus and cardiac arrest at the time of reperfusion. Three dogs survived, two for 24 hours and one for 48 hours. They were awake and alert a few hours after surgery, but eventually died of pulmonary edema in 2 cases and of an unknown reason in the other. Four dogs died 2-12 hours postoperatively as a result of hemorrhage for the graft's transected surface. An outflow block after reperfusion was deemed to be the cause of hemorrhage in these cases. On histologic examination of the grafts, there were no signs of ischemic necrosis or preservation damage. This study demonstrates the technical feasibility of living hepatic allograft donation. It shows that it is possible, in the dog, to safely harvest non ischemic segmental grafts with adequate pedicles without altering the vascularization and the biliary drainage of the remaining liver. We propose that this technique is applicable to human anatomy.     

Ischaemic preconditioning of the liver before transplantation

PURPOSE: Assessment of the effect of a short ischaemic time prior to liver transplantation on the liver graft. METHODS: White X Landrace pigs (N=10) were subjected to liver transplantation. Before being removed from the donor animal, the livers were randomised into two groups: group 1--pre-procurement ischaemia (15 minutes' temporary arrest of portal venous and hepatic arterial inflow to the liver, followed by reperfusion of these vessels for a period of 15 minutes); group 2--no prior inflow occlusion (control group). In group 1 a spleno-jugular bypass was established to prevent venous congestion, portal venous hypertension, intestinal oedema and bacterial translocation. The livers were perfused with Eurocollins solution (4 degrees C), after which they were stored on ice for a period of 3 hours' cold ischaemic time. Hepatocellular injury was assessed according to liver cell function tests (aspartate aminotransferase, AST), biochemical indicators of reperfusion injury (malondialdehyde) and histopathology. RESULTS: There was a significant rise of AST in both groups 1 hour after transplantation (from 51 +/- 27 IU/l to 357 +/- 152 IU/l in group 1 and from 29 +/- 10 IU/l to 359 +/- 198 IU/l in group 2). AST levels were marginally lower in group 1 at 2 and 4 hours after transplantation. There was also a rise in malondialdehyde levels in both groups at 5, 20, 40 and 60 minutes after transplantation. Levels of malondialdehyde were lower in the primed group at 5, 20 and 40 minutes, while the levels at 60 minutes after transplantation were comparable. Histological changes, as measured by vacuolisation, neutrophil infiltration and hepatic cell necrosis, were less in livers transplanted after ischaemic preconditioning, although the difference was not significant. CONCLUSIONS: Ischaemic preconditioning of the donor liver seems to decrease hepatocellular damage, reperfusion injury and histological changes in the liver after transplantation. Further studies with larger numbers are indicated.     

Evaluation of a protease inhibitor in the prevention of ischemia and reperfusion injury in hepatectomy under intermittent Pringle maneuver

BACKGROUND: The severity of ischemia and reperfusion (I/R) injury is an important determinant of patient outcome in hepatic surgery. The aim of this study was to investigate the efficacy of a protease inhibitor in alleviating I/R injury to human liver in the setting of hepatectomy under intermittent Pringle maneuver. METHODS: Sixty patients who underwent liver resection under conditions of intermittent inflow occlusion were randomly assigned to 2 groups (n = 30 each) according to the use of a synthetic protease inhibitor (gabexate mesilate or GM). GM was administered intravenously at a dosage of 2.0 mg/kg/h starting 12 hours before surgery until postoperative day 2. Preoperative and intraoperative clinical variables and postoperative outcomes were evaluated. The plasma levels of a cytokine, interleukin (IL)-6, as well as laboratory biochemical liver function parameters were analyzed to evaluate hepatic I/R injury. RESULTS: The 2 groups of patients were comparable with regard to hepatic inflow occlusion time, extent of liver resection, and background liver histology. The preoperative administration of GM (GM group) substantially alleviated hepatic I/R injury compared with the untreated control group; postoperative serum transaminase levels were significantly decreased in association with marked suppression of IL-6 levels in blood circulation during surgery. This was accompanied by a lower incidence of postoperative complications. The patients without postoperative complications had significantly lower activities of plasma IL-6 at 24 hours after surgery. CONCLUSIONS: This prospective randomized study demonstrated the hepatoprotective effect of a synthetic protease inhibitor in the setting of hepatectomy under the intermittent Pringle maneuver.     

Histidine-tryptophan-ketoglutarate versus University of Wisconsin solution in living donor liver transplantation: Results of a prospective study

The grafts obtained from a living donor hepatectomy are perfused on the back table with either University of Wisconsin solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK). The efficacy and safety of these solutions have been studied in cadaveric liver transplantation, however, there is no study comparing the two solutions in adult-to-adult living donor liver transplantation. In this study, UW and HTK were used in the perfusion of right living donor grafts. The grafts were perfused with a predetermined sequence and volume of one of the solutions. Liver biochemistries, complications, and graft and patient survival were analyzed. From January 2001 to September 2002, 30 grafts were alternately perfused with either UW (UW group) or HTK (HTK group). The perfusion was performed first via the artery and then via the portal vein with a predetermined volume. At a mean follow-up of 13 ± 7 months, no significant statistical difference between groups UW and HTK in posttransplantation liver biochemistries, complications, or patient and graft survival (84% and 80%, respectively) was observed. In conclusion, UW and HTK are equally effective and safe in the perfusion of the living donor liver grafts. HTK has a slight practical advantage over UW because it does not need to be flushed away before reperfusion of the graft and is less expensive. (Liver Transpl 2003;9:822-826.)