间歇性全入肝血流阻断与区域性入肝血流阻断腹腔镜肝切除术治疗原发性肝癌患者术后恢复研究*

目的 探讨采取间歇性全入肝血流阻断与区域性入肝血流阻断腹腔镜肝切除术(LH)治疗原发性肝癌(PLC)患者术后恢复情况。方法 2016年3月～2021年3月我院诊治的128例PLC患者,均接受LH手术治疗,其中57例在术中采取间歇性全入肝血流阻断法,另71例采取区域性入肝血流阻断法。监测平均动脉压(MAP)和心率(HR),使用多普勒超声检测门静脉血流速度(PVV)。结果 区域血流阻断组术中出血量和肝血流阻断时间分别为(305.4±58.6)mL和(0.0±0.0)min,显著少于或短于全肝血流阻断组【分别为(382.5±60.3)mL和(24.2±7.5)min,P＜0.05】;在术后7 d,区域血流阻断组血清总胆红素水平为(16.4±8.5)μmol/L,血清白蛋白水平为(35.6±5.3)g/L,与全肝血流阻断组【分别为(25.7±7.2)μmol/L和(32.4±4.9)g/L】比,差异显著(P＜0.05);区域血流阻断组MAP、HR和PVV分别为(85.6±2.3)mmHg、(78.7±8.3)次/min和(20.3±0.2)cm/s,与全肝血流阻断组【分别为(86.8±2.5)mmHg、(79.6±8.1)次/min和(20.1±0.3)cm/s】比,差异无统计学意义(P＞0.05);术后,区域血流阻断组腹腔内出血、胆汁漏、胸腔积液和肺部感染发生率分别为1.4%、8.5%、14.1%和5.6%,与全肝血流阻断组(分别为3.5%、10.5%、22.8%和10.5%)比,差异无统计学意义(P＞0.05)。结论 采取区域性入肝血流阻断LH治疗PLC患者有较好的手术和术后恢复效果,能够有效降低术中出血量,减少肝血流阻断时间,减轻术后肝功能损伤。     

Continuous normothermic hemihepatic vascular inflow occlusion over 60 min for hepatectomy in patients with cirrhosis caused by hepatitis B virus

Aim: To evaluate the safety of remnant liver in cirrhotic patients who had undergone irregular hepatectomy with continuous normothermic hemihepatic vascular inflow occlusion for over 60 min. Methods: A group of 133 cirrhotic patients who had hepatitis B virus accompanied by hepatocellular carcinoma and had undergone irregular hepatectomy by hemihepatic vascular inflow occlusion was studied. According to the time of hemihepatic vascular inflow occlusion, patients were assigned either to the control group, treatment(60) group, or treatment(90) group. The quantity of blood loss and blood transfusion, routine liver biochemistry and postoperative complications were retrospectively analyzed. Results: The data showed that there were no significant differences in postoperative complications between the three groups. Compared to the preoperative day, the levels of aspartate transaminase (AST), alanine transaminase (ALT), prothrombin time (PT) and serum bilirubin on postoperative days 1 and 3 were significantly increased in all three groups and the levels of albumin and platelet were significantly decreased on postoperative day 1. Duration of hospital stay and the levels of ALT and AST on postoperative days 1, 3 and 7 were higher in the treatment(90) group than in the control group and treatment(60) group (P < 0.05). However, no significant differences were displayed in the length of hospital stay and the levels of AST, ALT, PT, albumin, platelet count and serum bilirubin on postoperative days 1, 3 and 7 between the control group and the treatment(60) group (P > 0.05). Conclusion: Hemihepatic vascular inflow occlusion over 60 min is a possible method for irregular hepatectomy in patients with cirrhosis caused by the hepatitis B virus. However, caution must be exercised in utilizing this method where the time of vascular occlusion is over 90 min.     

不阻断肝血流在原发性肝癌肝切除术中的应用

目的探讨原发性肝癌患者行肝切除术中不阻断肝血流对肝功能及术后恢复的影响。方法将2010年6月-2013年6月福建省立医院收治的80例行肝切除术的原发性肝癌患者依据肝血流阻断方法的不同分为3组:第一肝门阻断组(Pringle组,n=24)、半肝血流阻断组(HVC组,n=24)及不阻断肝血流组(n=32)。分别比较不阻断肝血流组与Pringle组和HVC组患者的手术时间、术中出血量、术后肝功能变化、手术并发症及术后住院时间。计量资料和计数资料分别采用方差分析及卡方检验,方差分析中多重比较采用Dunnett-t检验。结果 3组患者手术时间、出血量差异均无统计学意义(F值分别为2.45,0.34,P值均0.05)。术后1及7 d血清TBil及ALT恢复情况,不阻断肝血流组[1 d,TBil:(22.4±9.4)μmol/L,ALT:(287.4±165.7)U/L;7 d,TBil:(17.1±6.6)μmol/L,ALT:(86.2±54.5)U/L]优于Pringle组[1 d,TBil:(33.5±11.9)μmol/L,ALT:(429.5±137.8)U/L;7 d,TBil:(24.5±7.0)μmol/L,ALT:(145.5±43.6)U/L]及HVC组[1d,TBil:(29.1±8.3)μmol/L,ALT:(390.2±176.6)U/L;7 d,TBil:(21.5±7.5)μmol/L,ALT:(121.5±56.8)U/L](P值均0.05)。血清Alb恢复情况,术后1 d,不阻断肝血流组[(29.3±2.8)g/L]优于Pringle组[(27.3±3.3)g/L](P值均0.05),但与HVC组[(27.8±2.5)g/L]相比,差异无统计学意义(P0.05);术后7 d,3组患者差异均无统计学意义(P值均0.05)。不阻断肝血流组术后住院时间[(10.3±2.1)d]较Pringle组[(12.7±2.6)d]和HVC组[(12.0±2.2)d]显著缩短(P值均0.05)。结论不阻断肝血流较第一肝门阻断、半肝血流阻断,不增加手术时间及术中出血量,且具有肝损伤较轻及术后恢复快的优点。     

Pringle肝门阻断术对老年患者术中末梢灌注指数及无创血红蛋白准确性的影响

目的探讨Pringle肝门阻断术对老年患者术中末梢灌注指数(PI)及无创脉搏血红蛋白(SpHb)准确性的影响。方法入选2013年6月至2014年1月期间华中科技大学同济医学院附属同济医院收治的60岁患者43例,全麻下行择期肝脏手术。于Pringle肝门阻断前后记录同一时间的PI、SpHb和有创血红蛋白(Hb)。Bland-Altman分析和线性回归模型评估Pringle肝门阻断前后的PI和SpHb测量误差(SpHb与有创Hb差值的绝对值)。结果肝门阻断前后分别收集有效试验数据:44对和73对。肝门阻断前PI1.4的数据占77.3%,SpHb测量误差≤1 g/dl的数据占75.0%,SpHb偏倚值为0.62 g/dl,95%CI为-1.15~2.38 g/dl。肝门阻断后PI1.4的数据占67.1%,SpHb测量误差≤1 g/dl的数据占35.6%,SpHb偏倚值为1.12 g/dl,95%CI为-0.98~3.23 g/dl。PI与SpHb测量误差呈显著负相关(r=-0.32,P0.05)。结论 Pringle肝门阻断术通过降低老年患者的PI,增加了SpHb的测量误差;阻断后指导输血应当参考有创Hb的测量值。     

Effect of in situ hypothermic perfusion on intrahepatic pO2 and reactive oxygen species formation after partial hepatectomy under total hepatic vascular exclusion in pigs

Abstract: Aim: This study examined attenuation of ischemia and reperfusion (I/R) induced liver injury during liver resections by hypothermic perfusion of the liver under total hepatic vascular exclusion (THVE). Method: Reactive oxygen species (ROS) formation, microcirculatory integrity and endothelial cell damage were investigated. Left hemihepatectomy (LHX) was performed without in situ perfusion (control‐LHX, n = 5) or with concomitant in situ perfusion with hypothermic (4 °C) Ringer‐glucose (cold‐LHX, n = 5) or normothermic (38 °C) Ringer‐glucose (warm‐LHX, n = 5). Glutathione (GSH) and malondialdehyde (MDA) concentrations, tissue pO₂ levels and hyaluronic acid (HA) uptake capacity were determined. Results: After cold, warm and control‐LHX, 24 h survival was 5/5, 0/5 and 3/5, respectively. GSH levels were best preserved after cold‐LHX during reperfusion. MDA levels increased in all groups without significant differences between the groups during reperfusion. Tissue pO₂ levels increased after cold‐LHX whereas after warm‐LHX and control‐LHX, pO₂ levels decreased during reperfusion. HA uptake capacity remained normal after cold‐LHX. After warm‐LHX and control‐LHX, HA uptake capacity decreased after 6 h of reperfusion but recovered after 24 h of reperfusion in the control‐LHX group. Conclusion: Moderate hypothermic perfusion protects the liver from I/R injury during LHX under THVE. This protective effect depended on maintenance of liver microcirculation rather than a reduction in ROS formation.     

不同肝血流阻断方案对手术切除原发性大肝癌患者治疗效果比较

目的 探讨不同肝血流阻断方法对外科手术切除原发性大肝癌患者疗效的影响。方法 2014年5月~2016年5月收治的172例原发性大肝癌患者,分别采用肝门阻断（n=52）、半肝阻断（n=44）和联合阻断（n=76）血流行肝癌切除术。结果 三组患者的基本资料比较差异无统计学意义（P>0.05）;三组血流阻断时间、手术用时和切除肝量差异均无统计学意义（P>0.05）,肝门阻断组出血量为（736.38±498.36） ml,显著多于半肝阻断组[（472.56±111.89） ml或联合阻断组的（356.14±132.53） ml,P<0.05],肝门阻断组输血量为（586.54±132.58） ml,显著多于半肝阻断组[（427.95±210.47） ml或联合阻断组的（184.38±72.54） ml,P<0.05];术后7 d,肝门阻断组血清ALT水平为（73.02±43.41） U/L,显著高于半肝阻断组[（55.89±40.82） U/L或联合阻断组的（52.01±33.81） U/L,P<0.05];三组手术并发症以肺部感染、切口感染、胆瘘、腹腔积液为主,但其发生率差异无统计学意义（P>0.05）;联合阻断组1 a生存率为96.1%,肿瘤复发率为2.6%,显著低于肝门阻断组的75.0%和15.4%或半肝阻断组的68.2%和20.5%（P<0.05）。结论 Pringle法联合肝下腔静脉阻断术阻断血流在切除原发性大肝癌患者外科手术过程中可以有效降低术中出血量,促进患者术后恢复,或许还能提高生存率。     

Safe upper limit of intermittent hepatic inflow occlusion for liver resection in cirrhotic rats

AIM To evaluate the effects of varying ischemicdurations on cirrhotic liver and to determine the safeupper limit of repeated intermittent hepatic inflowocclusion.METHODS Hepatic ischemia in cirrhotic rats was inducedby clamping the common pedicle of left and median lobesafter non-ischemic lobes resection.The cirrhotic ratswere divided into six groups according to the duration andform of vascular clamping:sham occlusion(SO),intermittent occlusion for 10(IO-10),15(IO-15),20(IO-20)and 30(IO-30)minutes with 5 minutes of reflow andcontinuous occlusion for 60 minutes(CO-60).All animalsreceived a total duration of 60 minutes of hepatic inflowocclusion.Liver viability was investigated in relation ofhepatic adenylate energy charge(EC).Triphenyltetrazollum chloride(TTC)reduction activitieswere assayed to qualitatively evaluate the degree ofirreversible hepatocellular injury.The biochemical andmorphological changes were also assessed and a 7-daymortality was observed.RESULTS At 60 minutes after reperfusion following atotal of 60 minutes of hepatic inflow occlusion,EC valuesin IO-10(0.749±0.012)and IO-15(0.699±0.002)groupswere rapidly restored to that in SO group(0.748±0.016),TTC reduction activities remained in high levels(0.144±0.002mg/mg protein,0.139±0.003mg/mg protein and0.121±0.003mg/mg protein in SO,IO-10 and IO-15groups,respectively).But in IO-20 and IO-30 groups,EClevels were partly restored(0.457±0.023 and 0.534±0.027)accompanying with a significantly decreased TTCreduction activities(0.070±0.005mg/mg protein and0.061±0.003mg/mg protein).No recovery in EC values(0.228±0.004)and a progressive decrease in TTCreduction activities(0.033±0.002mg/mg protein)wereshown in CO-60 group.Although not significantlydifferent,the activities of the serum aspartateaminotransferase(AST)on the third postoperative day(POD_3)and POD_7 and of the serum alanineaminotransferase(ALT)on POD_3 in CO-60 group remained higher than that in intermittent occlusion groups.Moreover,a 60% animal mortality rate and more severemorphological alterations were also shown in CO-60group.CONCLUSION Hepatic inflow occlusion during 60 minutesfor liver resection in cirrhotic rats resulted in lesshepatocellular injury when occlusion was intermittentrather than continuous.Each period of 15 minutes was thesafe upper limit of repeated intermittent vascularocclusion that the cirrhotic liver could tolerate withoutundergoing irreversible hepatocellular injury.     

Gastric mucosal blood flow and hepatic perfusion index in patients with portal hypertensive gastropathy

Endoscopic laser Doppler velocimetry is a simple non-invasive method to measure gastric mucosal blood flow. The present study is an attempt to determine a correlation, if any, between gastric mucosal blood flow and the hepatic perfusion index in patients with portal hypertensive gastropathy and their relationship to the severity of liver disease. Thirty patients with portal hypertensive gastropathy due to cirrhosis of the liver (eight class A, 13 class B, nine class C, according to Child-Pugh Classification) and six normal subjects were recruited into the study. In all subjects, the gastric mucosal blood flow and venous vasomotor reflex response was measured at two sites: the lesser and greater curvature, using endosoopic laser Doppler velocimetry. The hepatic perfusion index was measured using dynamic liver scintigraphy. The hepatic perfusion index (ratio of arterial/portal venous perfusion) in normal subjects and patients with portal hypertensive gastropathy belonging to Child-Pugh class A, B and C were 0.36 ± 0.02, 0.53 ± 0.08, 0.62 ± 0.14 and 1.04 ± 0.28, respectively. The gastric mucosal blood flow was similar in Child's A, B and C cases, while the venous vasomotor reflex response was reduced according to the Child-Pugh score (Child's A 37.4 ± 5.4%, normal control 62.3 ± 10.9%, Child's B 38.3 ± 18.2%, Child's C 22.5 ± 15.2%) and was statistically significant. The gastric mucosal blood flow and hepatic perfusion index are inversely correlated. The hepatic perfusion index altered with grading of cirrhotic change. This study confirms that the severity of portal hypertensive gastropathy is correlated with Child-Pugh score.     

Ex vivo extended left hepatectomy with caval preservation, temporary portacaval shunt, and reconstruction of the right hepatic vein outflow using a reversed portal vein bifurcation graft

Liver resections that require ex vivo techniques occur rarely, but when done are generally performed on veno-veno bypass to maintain venous return and decompress the portal circulation during the anhepatic phase of the procedure. We describe an ex vivo extended left hepatectomy that was performed with preservation of the inferior vena cava and the use of a temporary portacaval shunt to eliminate the need for veno-venous bypass. Ex vivo resection allowed reconstruction of right hepatic vein branches, using the patient's reversed portal vein bifurcation as a graft to provide venous outflow.     

Histidine-tryptophan-ketoglutarate solution versus University of Wisconsin solution in adult-to-adult living donor liver transplantation: A propensity score matching analysis from mainland China

To compare the difference between University of Wisconsin (UW) solution and histidine-tryptophan-ketoglutarate (HTK) solution in adult living donor liver transplantation (LDLT).This study included LDLT patients at the Liver Transplantation Center of West China Hospital of Sichuan University from November 2001 to June 2018. These patients were classified into 2 groups depending on the use of the different preservation solutions, and the confounding factors between the 2 groups were eliminated by propensity score matching. Finally, the incidence of complications; serum examination at postoperative days 1, 3, 5, 7, 14, 21, and 30; and the overall survival rate of the 2 groups were compared to observe whether there were any differences between the 2 preservation solutions.Of the 298 patients we screened, 170 were treated with UW solution and 128 with HTK solution. After propensity score matching, 106 pairs of patients were selected. In the comparison of the 2 groups, the length of intensive care unit stay in the UW group was significantly longer than that in the HTK group (P = .022), but there was no difference in the total length of hospital stay between the 2 groups (P = .277). No statistically significant difference was observed in the 2 groups in terms of the incidence of complications or postoperative examinations. However, the incidence of early allograft dysfunction in the HTK group was slightly lower than that in the UW group (HTK: UW = 14.1%: 20.7%), although the difference was not statistically significant. In terms of the overall survival rate, the 1, 3, and 5-year survival rates of the HTK group were 85.5%, 70.2%, and 65.1%, respectively, while the 1, 3, and 5-year survival rates of the UW group were 83.1%, 67.2%, and 59.8%, respectively, and there was no significant difference between the 2 groups.In conclusion, our study shows that UW solution and HTK solution are equivalent in perioperative safety, the recovery of transplanted liver function, the occurrence of postoperative complications and overall survival and can be safely and effectively applied in adult LDLT. If economic factors are taken into account, HTK can save costs to a certain extent.     

Complex liver resection under hepatic vascular exclusion and hypothermic perfusion with versus without veno-venous bypass: a comparative study

BackgroundWhile hypothermic liver perfusion has been shown to improve parenchymal tolerance to complex resections in patients requiring prolonged hepatic vascular exclusion (HVE), the benefit of associated veno-venous bypass (VVB) in this setting remains poorly evaluated.MethodsAll patients undergoing liver resection requiring HVE and hypothermic liver perfusion for at least 55 min between 2006 and 2017 were retrospectively reviewed. Perioperative outcomes were compared between patients with (VVB+) or without VVB (VVB?).ResultsTwenty-seven patients were analyzed, including 13 VVB+ and 14 VVB?. Median HVE duration was similar in VVB+ and VVB? patients (96 vs. 75 min, respectively). VVB+patients had longer operative time (460 vs. 375 min, p = 0.023) but less blood loss (p = 0.010). Five (19%) patients died postoperatively from liver failure or sepsis, without difference between groups. Postoperative major morbidity rate was similar between VVB+ and VVB? patients (30% vs. 50%, respectively) such as rates of liver failure, haemorrhage, renal insufficiency and sepsis, but VVB? patients experienced more respiratory complications (64% vs. 15%, p = 0.012).ConclusionDuring liver resection under HVE and hypothermic liver perfusion, use of VVB allows for reducing blood loss and postoperative respiratory complications. VVB should be recommended in case of liver resection with prolonged HVE.     

Correlation of transcutaneous hepatic near-infrared spectroscopy readings with liver surface readings and perfusion parameters in a piglet endotoxemic shock model.

PURPOSE: To determine whether transcutaneous liver near-infrared spectrophotometry (NIRS) measurements correlate with NIRS measurements taken directly from the liver surface, and invasive blood flow measurements. PROCEDURE: Laparotomy was performed in 12 Yorkshire piglets, and ultrasound blood flow probes were placed on the hepatic artery and portal vein. Intravascular catheters were inserted into the hepatic and portal veins for intermittent blood sampling, and a pulmonary artery catheter was inserted via the jugular vein for cardiac output measurements. NIRS optodes were placed on skin overlying the liver and directly across the right hepatic lobe. Endotoxemic shock was induced by continuous infusion of Escherichia coli lipopolysaccharide O55:B5. Pearson's correlations were calculated between the NIRS readings and the perfusion parameters. FINDINGS: After endotoxemic shock induction, liver blood flow, and oxygen delivery decreased significantly. There were statistically significant correlations between the transcutaneous and liver-surface NIRS readings for oxyhemoglobin, deoxyhemoglobin, and cytochrome c oxidase concentrations. There were similar significant correlations of the transcutaneous oxyhemoglobin with both the mixed venous and hepatic vein saturation, and mixed venous and hepatic vein lactate. CONCLUSIONS: Transcutaneous NIRS readings of the liver, in an endotoxemic shock model, correlate with NIRS readings taking directly from the liver surface, as well as with global and specific organ-perfusion parameters.     

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model

BACKGROUND: Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he-patocellular carcinoma (HCC). Pre-carcinoma and early HCC nodules are dififcult to differentiate by observing only their hemodynamics changes. The present study aimed to investi-gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nod-ules using CT perfusion and receiver operating characteristic (ROC) curves.
METHODS: Male Wistar rats were randomly divided into con-trol (n=20) and experimental (n=70) groups. Diethylnitrosa-mine (DEN) was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion (HPP), hepatic arterial frac-tion (HAF), hepatic arterial perfusion (HAP), hepatic blood volume (HBV), hepatic blood lfow (HBF), mean transit time (MTT) and permeability of capillary vessel surface (PS) data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats (control, pre-carcinoma and early HCC groups) using the Kruskal-Wallis test and analyzed with ROC curves. Histo-logical examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.
RESULTS: For HPP, HAF, HBV, HBF and MTT, there were signiifcant differences among the three groups (P<0.05). HAF had the highest areas under the ROC curves: 0.80 (control vs pre-carcinoma groups) and 0.95 (control vs early HCC groups) with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 (control vs pre-carcinoma groups) and 0.92 (control vs early HCC groups) with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively.
CONCLUSIONS: CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.     

Effect of atrial natriuretic peptide on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model

AIM： To evaluate the effect of ANP on warm I/R injury in a porcine THVE model.
METHODS： Miniature pigs （mini-pigs） weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP （0.1 μg/kg per min） was administered to the ANP group （n = 7）, and vehicle was administered to the control group （n = 7）. Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood flow （HTBF） was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups.
RESULTS： The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were significantly different between the two groups （60 min： 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 〈 0.05, 120 rain： 673.6± 148.2 vs 281.1±44.8, P = 0.004 〈 0.01）. No significant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant. A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group （0min： 2.92± 1.1 vs 6.38 ±1.1,,P= 0.011 〈 0.05）.
Histological tissue damage was milder in the ANP group than in the control group.
CONCLUSION： Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.