A rat model of a repeat 70% major hepatectomy

BACKGROUND: This study investigated the effects of a repeat 70% major hepatectomy in a rat model. MATERIALS AND METHODS: The left lateral and median lobes of the livers of 80 seven-week-old male Wistar rats were excised during primary hepatectomy, removing a total of 70% of the liver. In 40 of the rats, the regenerated right lateral lobe, comprising 70% of the remnant liver, was excised during secondary hepatectomy 7 days after the initial procedure. The survival rate, posthepatectomized regeneration ratio, and laboratory blood data were compared between the groups that had undergone initial only and repeat hepatectomies. RESULTS: All of the rats survived for at least 7 days after each procedure. The remaining liver returned to up to about 90% of its original wet weight by 5 days in both groups. The serum glutamic-pyruvic transaminase levels peaked 12 h after hepatectomy, remained at a similar level at 36 h, and had normalized by 2 days. Serum total bilirubin levels were similar in both groups. The total cell numbers after 5 days were significantly higher in the initial hepatectomy group than in the repeat hepatectomy group. CONCLUSIONS: We established a rat model in which an initial 70% major hepatectomy was followed by a repeat 70% major hepatectomy of the regenerated liver. The time taken to restore the integrity of the liver was longer in the rats that underwent repeat hepatectomy. We believe that this model will be useful for investigating the regenerative ability of the liver after a second major hepatectomy.     

Multivariate analysis of liver regenerative capacity after hepatectomy in humans

Many factors affect liver regeneration after partial hepatectomy; however, those factors that are essential for regulation of liver regeneration in humans are not known. Using multiple regression analysis we conducted a study to determine essential factors involved in the speed of liver regeneration after hepatectomy. The subjects were 59 patients who underwent hepatic resection between January 1980 and December 1991. A regression equation for predicting regeneration speed (Y; cm³/day) during the 1st postoperative month was obtained by stepwise forward multiple regression analysis, using 11 explanatory parameters (Xi). The regeneration speed and the resection ratio (%; indicating the magnitude of resection) were calculated based on a computed tomography (CT) scan volumetric study. The degree of liver fibrosis, expressed as the fibrotic index (%), was morphometrically determined in Azan-Mallory stained sections. Of the 11 explanatory parameters, the resection ratio and the fibrotic index had a significant simple correlation with Y. The following regression equation was obtained: Y (cm³/day)=–1.1+3.7 × resection ratio –5.4 × alkaline phosphatase –3.7 × fibrotic index +1.2× total bilirubin –2.6 × glutamic pyruvic transaminase (multiple correlation coefficient, 0.82). We found that the extent of resection and the degree of fibrosis, as well as alkaline phosphatase, total bilirubin, and glutamic pyruvic transaminase, contributed to the speed of regeneration after partial hepatectomy.     

血晶素对大鼠70%肝脏切除后再生的影响

目的 探讨血晶素(Hemin)对大鼠70%肝脏切除术后肝脏再生的影响.方法 复制大鼠70%肝脏切除模型,随机分成血晶素治疗组和生理盐水对照组,在术后第1天、第2天、第3天和第7天测定比较肝重/体重、血清肿瘤坏死因子α(TNF-α)、肝脏组织中血晶素加氧酶1(HO-1)含量及肝细胞核增殖蛋白抗原(PCNA)表达指数.结果 术后第7天治疗组肝重/体重明显高于对照组(P<0.05),第3天开始肝细胞 PCNA表达指数较对照组升高,差异有统计学意义(P<0.01).治疗组术后肝脏组织中HO-1浓度比对照组高,血清TNF-α的含量比对照组低(P<0.05).结论 血晶素大鼠肝脏70%切除术后肝脏再生的速度明显提高,这可能跟HO-1表达升高有关.     

The role of polyamines in liver regeneration after hepatectomy with ischemic injury

A total of 175 rats were divided into: (1) a sham operation group, in which the liver was slightly mobilized after laparotomy; (2) a control group in which 68% of the liver was resected without the blockade of blood flow; (3) an ischemia + hepatectomy group, in which the vessels entering the right and caudate lobes were clamped for 30 min, and the nonischemic lobes were resected; (4) a DFMO + ischemia + hepatectomy group, in which the same procedure as for the ischemia + hepatectomy group was performed, but the animals received α-difluoromethylornithine (DFMO); (5) a DFMO + Put + ischemia + hepatectomy group, in which the animals underwent the same procedure, but were given putrescine (Put) in addition to DFMO. There were 6 to 7 rats in each of the five groups. The putrescine level and ornithine decarboxylase (ODC) activity were significantly higher in the ischemia + hepatectomy group than in the control group, but were markedly decreased in the DFMO + ischemia + hepatectomy group. However, the lipid peroxide level was significantly higher in the DFMO + ischemia + hepatectomy group than in the ischemia + hepatectomy group. The incorporation of [³H]thymidine in the DFMO + ischemia + hepatectomy group was significantly lower than that in the control group. The increase in the lipid peroxide level and the decrease in [³H]thymidine found in the DFMO + ischemia + hepatectomy group tended to be reversed by the administration of putrescine. These results suggest that putrescine suppressed the production of lipid peroxides and promoted DNA synthesis in regenerating the liver after ischemia-reperfusion injury.     

Effects of TVE application during 70% hepatectomy on regeneration capacity of rats

BACKGROUND: For adequate control of excess bleeding during liver resection, total vascular exclusion (TVE) is preferred by surgeons, especially when the tumor is located in the posterior liver lobes or near the cava. To the authors' knowledge, the effects of TVE technique on the postoperative liver regeneration process have not thus far been evaluated yet in the literature. This study was planned to compare the effects of liver resections performed either with portal pedicle clamping or with TVE on the regeneration process. MATERIALS AND METHODS: Seventy percent hepatectomy was performed with portal pedicle clamping (n=10, Group A) or with TVE (n=10, Group B) in rats. At 48 h after resection, sampling was performed for the measurement of serum transaminase, alkaline phosphatase (ALP), tissue malondialdehyde (MDA), and glutathione (GSH) levels. Liver regeneration rate, proliferating cell nuclear antigen (PCNA) labeling, and mitotic indices were also evaluated. RESULTS: Liver injury determinants (serum transaminases, ALP, and tissue MDA levels) were found significantly higher in group B than in group A. Liver regeneration rate, liver GSH levels, PCNA labeling index, and mitotic index were significantly lower in group B than in group A. CONCLUSIONS: The injury during TVE seems to be greater than during resection with portal pedicle clamping. The negative effect of this oxidative damage may influence the regenerative capacity of the remnant liver tissue.     

肝脏类器官构建及其对小鼠部分肝切除术后肝再生的作用#br#

目的 观察肝脏类器官对小鼠部分肝切除术后肝再生的作用。方法 体外构建肝脏类器官,通过形态学、PCR和免疫荧光对类器官进行初步鉴定。C57BL/6小鼠随机等分为对照组和治疗组,每组18只。对照组进行肝左叶、中叶切除术+肝包膜注射200 μL PBS;治疗组进行肝左叶、中叶切除术+肝包膜移植200 μL类器官悬液。建模成功后分别于术后第1、4、7天收集标本。通过血清生化检测、免疫组化和Western blotting评估肝脏类器官对小鼠肝部分切除术后肝再生的作用。结果 类器官体外培养3 d,从直径20 μm的囊性结构扩增到约125 μm的细胞团（P＜0.05）,直径扩增近6 倍。肝脏干细胞标志基因EPCAM、SOX9和CK19明显上调（P＜0.05）,传代前后基因保持稳定。免疫荧光显示CK8、Desmin、AFP和PCNA呈阳性。HE显示术后第4天,治疗组肝细胞形态大小基本恢复正常,形态较清晰,无炎症细胞浸润,无脂肪或气球样变。对照组小鼠肝细胞核仁染色加深,仍有炎性细胞浸润,部分区域存在肝细胞坏死区。免疫组化Ki67和Western blotting对增殖水平进行检测,结果显示治疗组增殖能力是对照组的3 倍。肝功能检测发现治疗组在术后第4天ALT、AST、TBIL和DBIL明显下降,ALB合成增加（P＜0.05）。结论 具有肝脏干细胞属性和增殖能力的肝脏类器官,能通过保护肝细胞、改善部分肝切除术后小鼠肝功能,发挥促进肝再生作用。     

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目的分析原发性肝癌规则性肝切除和非规则性肝切除的围手术期因素,探讨原发性肝癌治疗中二者手术适应证。方法回顾性分析中国人民解放军空军总医院1990-2010年原发性肝癌中274例规则性肝切除术和586例非规则性肝切除术病人的临床资料。结果统计分析表明,规则性肝切除与非规则性肝切除相比,对术前病人肝功能状态要求更加严格,术中切除肝体积以及出血量、输血量均较非规则性肝切除组显著增多,手术时间延长,术后并发症发生率增加。但实施规则性肝切除术病人的肿瘤体积明显大于非规则性肝切除病人,切除肝段数目大于三段者所占比例亦显著高于非规则性肝切除组。结论对于<5cm的肝癌病人,采用非规则性肝切除保留更多功能性肝实质,可能更有利于病人术后恢复,减少相关并发症的发生。     

The enhancement of tumor growth after partial hepatectomy and the effect of sera obtained from hepatectomized rats on tumor cell growth

In the process of liver regeneration, the participation of various types of growth stimulators and changes in immune responses have been reported. Here, we examined the growth of subcutaneously transplanted AH130 cells and Walker 256 cells after partial hepatectomy. In the case of tumor cells being transplanted on the same day as partial hepatectomy, the increase in tumor size in hepatectomized rats was significantly greater compared with that in non-treated rats or in those having undergone a simple laparotomy. When the transplantation of tumor cells was done on the 7th day after partial hepatectomy, however, the increase was less marked. We also examined the effect of serum obtained from rats after partial hepatectomy on thein vitro growth of these tumor cells. Growth enhancement was observed with medium containing serum drawn from rats 1 to 4 days after partial hepatectomy. These results suggest that the growth of tumor cells was stimulated during liver regeneration and that some humoral factors participated in the process. Furthermore, as the conditions of thein vitro method appear to mimic those of thein vivo method, thein vitro approach should be very useful for analysis of the factors responsible.     

乙酰肝素酶siRNA对部分肝切除大鼠术后肝再生的抑制作用

目的探讨乙酰肝素酶(HPSE)siRNA对部分肝切除大鼠术后肝再生的抑制作用。方法设计合成HPSE siRNA,以vivo-jetPEI-Gal为载体转染70%肝切除大鼠,以逆转录-聚合酶链反应(RT-PCR)检测转染后HPSE mRNA表达,以Western blot检测AFP、ALB、CK-18和CK-19蛋白表达,以原位末端标记法(Tunel)检测肝细胞凋亡,以免疫组化检测肝组织增殖细胞核抗原(PCNA)表达,并测定肝再生率。结果与各对照组相比,siRNA干扰组HPSE mRNA表达明显降低,AFP、ALB、CK-18和CK-19蛋白表达明显降低,肝细胞凋亡指数明显增高,增殖指数明显降低,肝再生率明显降低,差别显著(P0.05)。结论 siRNA沉默HPSE表达后,部分肝切除大鼠术后肝再生受到明显抑制,提示HPSE对肝再生具有调控作用。     

Increased intraabdominal pressure impairs liver regeneration after partial hepatectomy in rats

BACKGROUND: There are many experimental studies showing that increased intraabdominal pressure (IAP) reduces liver blood flow, leading to ischemia and portal venous congestion. But, there is no study evaluating the effect of increased IAP on liver regeneration. It is well known that acute liver ischemia and portal venous congestion impair liver regeneration. We, therefore, aimed to determine the effect of increased IAP on liver regeneration in this study. METHODS: Sprague-Dawley rats underwent partial hepatectomy with or without IAP of 12-14 mm Hg for 24 h or sham operation. Rats were randomly divided into six groups: two sham-operated groups, two hepatectomy groups, and two hepatectomy with increased IAP groups. Mitotic index, proliferating cell nuclear antigen (PCNA)-labeling index, and liver regeneration rate as liver regeneration parameters were studied on day 1 or on day 4 after operation. Additionally, serum aspartate transaminase (AST) level and histopathological changes in intestinal mucosa were studied. RESULTS: Hepatectomy with/without increased IAP groups had significantly higher serum AST levels than the sham-operated group on day 1. Serum AST level was found to be significantly higher in the hepatectomy with increased IAP group than in the other groups on day 4. Intestinal mucosal injury was found in the hepatectomy with increased IAP groups on days 1 and 4. Mitotic index and PCNA-labeling index were markedly higher in all hepatectomy with/without increased IAP groups than in the sham-operated groups. However, together with liver regeneration rate, both indices were significantly less in the hepatectomy with increased IAP groups than in the hepatectomy groups both on day 1 and on day 4. CONCLUSION: Maintenance of IAP between 12 and 14 mm Hg for 24 h impaired liver regeneration after partial hepatectomy in rats.     

Subtotal hepatectomy: a porcine model for the study of liver regeneration

BACKGROUND: This study aimed to devise a simple, reproducible method of subtotal hepatectomy in a large animal model. Such an experimental model could be useful in the investigation of liver regeneration and liver insufficiency after partial hepatectomy. Equally, this technique could be used for assessing the effect of artificial liver support systems on both liver function and regeneration. MATERIALS AND METHODS: Twenty pigs were subjected to either 70-80% liver resection (n = 11), or 85-90% liver resection (n = 9), using a simplified technique. RESULTS: Most tolerated the procedure well and showed restoration of full liver volume within 3 weeks. Three animals in the 90% resection group died with significantly raised levels of International Normalized Ratio (INR) and ammonia. CONCLUSIONS: These two techniques have been shown to be easily reproducible and well tolerated by the animals and allow easy assessment of liver function and regeneration in the postoperative period. The deaths in the 90% resection group supports the hypothesis that 90% partial hepatectomy represents a model of critical residual liver parenchyma.     

门冬氨酸-鸟氨酸在减轻肝切除术后肝功能损害中的临床研究

目的: 探讨门冬氨酸-鸟氨酸在减轻肝切除术后肝功能损害中的作用.方法: 将120例行肝切除术的病人按照切除范围分为右半肝切除组,左半肝切除组和左外叶切除组,随后每组再随机分成两组:对照组,术后行常规护肝治疗;实验组,术后除常规护肝治疗外,从术前第1天开始至术后第10天,加用门冬氨酸-鸟氨酸.检测两组术前和术后胆红素(TB)、门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和血氨(BA)水平.同时分析术中第一肝门阻断15 min以上和15 min以下患者的肝功能的恢复情况.结果: 第一肝门阻断15 min以上患者和右半肝切除病例中,实验组术后AST,ALT以及TB明显低于对照组,P<0.05,差异有统计学意义,并且术后1 w内肝功能恢复正常.在术中第一肝门阻断15 min以下组和左半肝切除和左外叶切除病例中,术后AST,ALT以及TB低于对照组,但P>0.05,差异无统计学意义.治疗组术后血氨均低于对照组,但与对照组相比较无显著性差异(P>0.05).结论: 门冬氨酸-鸟氨酸可减轻肝切除术后尤其是大范围肝切除术后肝功能的损害,对肝功能具有保护作用.     

A nonspecific colonic ulcer occurring after hepatectomy: Report of a Case

We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction.     

Serum endostatin levels and regenerative capacities of normal and cirrhotic livers following partial hepatectomy in mice: the response to different resection sizes

BACKGROUND: Angiogenesis has an important role in liver regeneration. Antiangiogenic response in remnant liver following resection and its relationship to regeneration is not well known. The aim of this study was to investigate the effect of hepatectomy size on serum endostatin levels, and the effect of endostatin levels to liver regeneration after partial hepatectomy in normal and cirrhotic mice. MATERIALS AND METHODS: Sixty noncirrhotic and 36 carbon tetrachloride-induced cirrhotic mice were included in the study. Noncirrhotic mice were randomly divided into four main groups: sham, 20%, 40%, and 70% hepatectomy groups. Similarly, cirrhotic mice were randomly divided into three main groups: sham, 20%, and 40% hepatectomy groups. The mice in each group were further divided into two subgroups to compare serum endostatin levels and liver regeneration indexes on days 1 and 14. Liver regeneration was evaluated by the proliferating cell nuclear antigen-labeling index. Serum endostatin level was measured to evaluate antiangiogenic response. RESULTS: Serum endostatin levels on the first day and 14th day increased significantly in correlation with the hepatectomy size, both in normal mice and cirrhotic mice (P < 0.05). In normal mice with high regeneration indexes that underwent 40% and 70% hepatectomies, there was a significant increase in serum endostatin levels on the 14th day compared with the first day (P < 0.05). However, the increase in mice that underwent 20% hepatectomies was not significant. After 20% and 40% hepatectomies, first day serum endostatin levels were significantly higher in cirrhotic mice compared with normal mice (P < 0.05), which was independent of regeneration. Nevertheless, after 40% hepatectomies, 14th day serum endostatin levels were significantly lower in cirrhotic mice compared with normal mice, attributable to the limited regeneration capacity of cirrhotic liver (P < 0.05). Regeneration capacity of cirrhotic liver was low at all times. CONCLUSIONS: The current study suggests that there is a significant relationship between serum endostatin levels and regeneration capacity after hepatectomy in normal mice. On the other hand, following resection of cirrhotic liver, regeneration capacity is depressed and high endostatin levels are independent of hepatic regeneration.     

Pancreatic injury after major hepatectomy: a study in a porcine model

Purpose

The aim of this study was to investigate the pathophysiology of pancreatitis after major hepatectomy.

Methods

The study used ten female pigs. Three served as sham animals (sham group) and were killed after laparotomy to obtain normal tissue samples. Seven animals were subjected to major hepatectomy (70–75%), using the Pringle maneuver for 150?min, after constructing a portacaval side-to-side anastomosis (hepatectomy group). Duration of reperfusion was 24?h.

Results

Pancreatic tissue sampled 24?h after reperfusion had increased necrosis and edema in comparison to sham group and to tissue sampled at 12?h. Tissue malondialdehyde (MDA) did not differ significantly between samples at 12 and 24?h but was increased in the hepatectomy group in comparison to sham animals. Percentage increase in portal MDA content during reperfusion was greater at 12?h of reperfusion in comparison to the increase after 24?h. Portal pressure increased significantly after 12?h of reperfusion. Serum amylase and C-peptide increased during reperfusion in comparison to baseline levels.

Conclusions

The findings suggest that intraoperative portal congestion is not the only cause of the development of pancreatitis after major hepatectomy. The oxidative markers suggest that reactive oxygen species produced during vascular control may be responsible as well.     

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目的 了解原发性肝癌病人行肝部分切除术后早期腹水形成的原因。方法 通过对69例原发性肝癌病人的临床资料回顾性研究，分析了术前、术中及术后有关指标，探讨其腹水形成的原因。结果 腹水形成的术前因素主要与血清白蛋白、前白蛋白含量、肝功能的Child分级及肝硬化类型等有关；要中与肝门阻断时间术中出血量、术中输血量、右肝韧带的离断等有关；术后主要与腹腔引流管的拔除时间有关。结论 为减少术后早期腹水形成，主要是要前有良好的肝功能储备，尽可能缩短手术时间，减少不必要的分离，尽早拔除腹腔引流管。     

标准化剩余肝体积与肝硬度比值预测肝脏切除术后肝功能不全的临床研究

目的 探讨应用标准化剩余肝体积与肝硬度值的比值预测肝脏切除术后肝功能不全的临床价值。方法 回顾性分析我院2015年1月~2021年6月行肝脏切除术患者61例的临床资料,术前采用CT或者MR进行肝脏增强扫描,检查图像进行三维重建。按照肝脏肿瘤的位置拟行解剖性左半肝脏或者右半肝脏切除术。并按照拟定的手术方案计算出全肝体积及剩余的肝脏体积,同时对61位患者行肝脏超声影像和瞬时弹性成像检查,检测出每位患者的肝脏硬度值（KPA）,计算出标准化剩余肝体积与肝硬度值的比值（SFLV/KPA）,并观测61位患者是否出现术后肝功能不全。把引起术后肝功能不全的可能相关因素进行单因素分析,得到与术后肝功能不全相关的影响因素,再通过二元logistics回归分析分析这些因素与术后肝功能不全的相关性,探讨标准化剩余肝体积与肝硬度值的比值（SFLV/KPA）预测肝脏切除术后肝功能不全的作用。并通过受试者工作特征曲线ROC曲线确定SFLV/KPA与术后肝功能不全的关系。结果 61例患者手术全部成功,术后有7例患者出现肝功能不全,无患者出现肝功能衰竭,无患者术后死亡。研究显示术中出血量、肝门阻断时间、SFLV/KPA、手术方式均是术后肝功能不全的影响因素。结论 通过受试者工作特征曲线ROC曲线,SFLV/KPA（标准化剩余肝体积/肝脏硬度值）比值大于30.6时,患者术后一般不出现肝功能不全,手术安全性更高。