Preparatory hepatic resection with right hepatic vein reconstruction for paracaval liver tumor

A liver tumor in the paracaval portion was very difficult to resect because of its anatomical situation. We therefore employed a technique using right hepatic vein (RHV) resection and reconstruction following the resection of segments VII/VIII with the paracaval portion. The patient was a 70‐year‐old man who had a hepatocellular carcinoma in the paracaval portion, and the root of the RHV was compressed by the tumor. Computed tomography (CT) during arterioportography under temporary balloon occlusion of the RHV demonstrated hypoattenuation of the entire posterior segment, meaning that RHV reconstruction following the resection of segments VII/VIII with RHV resection would be necessary. We performed the above‐mentioned operation without any trouble. On mobilizing segments VI/V to the caudal direction after dissecting the distal RHV, the paracaval Glissons were easily exposed and dissected anteriorly from the first order of the right Glissonean sheath. Our preliminary surgical technique, based on IVR‐CT, could provide a better surgical field and result in decreased operating time and decreased blood loss in paracaval liver malignancy.     

Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis

Objective: A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM).Methods: A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival.Results: Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified.Conclusion: A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.     

Effect of granulocyte-macrophage colony-stimulating factor on hepatic regeneration after 70% hepatectomy in normal and cirrhotic rats

BackgroundPost-hepatectomy liver insufficiency is one of the most serious postoperative problems and its prevention is important after major hepatic resection, especially in the cirrhotic liver. Some growth factors and cytokines appear to play important roles in liver regeneration. In the present study we have investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hepatic regeneration after 70% partial hepatectomy (PH) in cirrhotic and non-cirrhotic rats.MethodsA rat model of liver cirrhosis was prepared using thioacetamide (TAA) (a dose of 20 mg/100 g body w, intra-peritoneally) on three days a week for 12 weeks. Adult male rats were divided into four groups:Group 1 (n=10) no cirrhosis and no GM-CSF; Group 2 (n=10) no cirrhosis and GM-CSF; Group 3 (n=10) cirrhosis and no GM-CSF; and Group 4 (n=10) cirrhosis and GM-CSF. All the rats underwent a 70% hepatectomy, and GM-CSF was administrated immediately after operation in Groups 2 and 4. On postoperative days 2 and 7, fresh samples from the remnant liver were obtained to evaluate its regenerative capacity.The liver regenerative process was estimated by DNA synthesis, using flow cytometry.ResultsProliferation index (PI) of hepatocytes at 48 h was higher in Group 4 rats than Group 3 rats (p<0.05). On postoperative day 7, PI was elevated in Group 3 rats compared with Group 4 rats, but this difference was not statistically significant. In non-cirrhotic rats given GM-CSF, PI was increased compared with Group 1 rats at day 2 (p<0.05), but not at day 7.ConclusionsThe findings suggest that the proliferative capacity of liver cells is impaired and delayed after 70% PH in cirrhotic rat liver. GM-CSF administration might enhance the liver PI in both normal and TAA-induced cirrhotic rats.     

大黄对暴发性肝衰竭大鼠肝损伤及肝再生的影响

[目的]探讨大黄对暴发性肝衰竭(FHF)大鼠肝损伤及肝再生的影响.[方法]Wistar大鼠随机分4组:正常对照(对照)组、模型(FHF)组、大黄组、促肝细胞生长素(PHGF)组.FHF、大黄组和PHGF组动物模型采用皮下注射(sc)硫代乙酰胺(TAA)600 mg/kg体重,2次,每次间隔24 h,复制FHF动物模型.大黄组和PHGF组动物除予TAA外,于实验前3天至实验结束分别sc大黄注射液1 ml/100 g和PHGF 1 ml/100g,对照组和FHF组同时sc 0.85%氯化钠液1 ml/100g.FHF组、大黄组和PHGF组,于第2次注射TAA后24 h,随机各取8只,腹主动脉取血测肝功能.迅速取肝组织,用10%甲醛液固定,石蜡切片,检测肝细胞有丝分裂指数(MI)和增殖细胞核抗原(PCNA).[结果]大黄具有降低FHF大鼠丙氨酸氨基转移酶、天冬氨酸转氨酶及总胆红素,并能显著提高MI和PCNA(P＜0.05,＜0.01).[结论]大黄具有改善FHF大鼠肝功能和促进肝细胞增殖及再生的作用.     

Influence of resection margin on survival in hepatic resections for colorectal liver metastases

Background:

Traditionally a 1-cm margin has been accepted as the gold standard for resection of colorectal liver metastases. Evidence is emerging that a lesser margin may provide equally acceptable outcomes, but a critical margin, below which recurrence is higher and survival poorer, has not been universally agreed. In a recent publication, we reported peri-operative morbidity and clear margin as the two independent prognostic factors. The aim of the current study was to further analyse the effect of the width of the surgical margin on patient survival to determine whether a margin of 1 mm is adequate.

Methods:

Two hundred and sixty-one consecutive primary liver resections for colorectal metastases were analysed from 1992 to 2007. The resection margins were assessed by microscopic examination of paraffin sections. The initial analysis was performed on five groups according to the resection margins: involved margin, 0–1 mm, >1–<4 mm, 4–<10 mm and ≥ 10 mm. Subsequent analysis was based on two groups: margin <1 mm and >1 mm.

Results:

With a median follow-up of 4.7 years, the overall 5-year patient and disease-free survival were 38% and 22%, respectively. There was no significant difference in patient- or disease-free survival between the three groups with resection margins >1 mm. When a comparison was made between patients with resection margins ≤1 mm and patients with resection margins >1 mm, there was a significant 5-year patient survival difference of 25% versus 43% (P < 0.04). However, the disease-free survival difference did not reach statistical significance (P= 0.14).

Conclusions:

In this cohort of patients, we have demonstrated that a resection margin of greater than 1 mm is associated with significantly improved 5-year overall survival, compared with involved margins or margins less than or equal to 1 mm. The possible beneficial effect of greater margins beyond 1 mm could not be demonstrated.     

Vascular endothelial growth factor does not improve liver regeneration and survival after 90% subtotal liver resection

Aim: Vascular endothelial growth factor (VEGF) has been shown to stimulate liver regeneration after 70% partial hepatectomy (PH). It is unclear, however, whether exogenous administration of VEGF can also be used to improve liver regeneration and survival after 90% subtotal liver resection. The aim of this study was to determine the effect of exogenous and endogenous VEGF after 90% subtotal hepatectomy (SH). Methods: Rats were subjected to 90% SH and treated with VEGF, anti-VEGF or NaCl. Postoperatively (3 h - 5 days) liver body weight ratio (LBR), hepatocyte proliferation and biochemical markers were assessed. ELISA was performed to measure protein levels for VEGF. Gene expression was determined by customized cDNA arrays and quantitative RT-PCR. Results: Administration of VEGF did not enhance LBR or hepatic proliferation, or reduce the serum parameters. VEGF levels were the highest in VEGF-treated animals. The overall survival after 90% SH reached 78% in VEGF-treated animals, but did not differ significantly from that of anti-VEGF or NaCl-treated animals (74% and 75%, respectively). Gene expression analysis showed a modulation of anti-apoptotic and cell cycle control genes that was independent of VEGF. Conclusions: In contrast to PH, liver regeneration and survival after SH cannot be modulated by VEGF. This indicates that the relevant mechanisms that stimulate liver regeneration after hepatectomy at least partially depend upon the extent of liver resection.     

白藜芦醇促进肝部分切除术后肝再生的实验研究

目的研究白藜芦醇对小鼠70%肝切除后残余肝的再生是否有促进作用。方法实验动物为雄性C57BL/6小鼠。将100只小鼠随机分为实验组(白藜芦醇预处理组)和对照组(生理盐水预处理组)。采用肝大部分切除术建立肝再生模型,术前连续5 d分别给予小鼠腹腔内注射白藜芦醇12 g/kg(实验组)和生理盐水(对照组),第5天注射完白藜芦醇和生理盐水2 h后给两组小鼠分别进行70%的肝切除手术(pH)。用肝重/体重比,实时定量聚合酶链式反应及免疫组化等方法来评估白藜芦醇对小鼠肝再生的促进作用。结果 pH术后36 h、48 h实验组与对照组相比,肝重/体重比增高(4.56±0.07对3.93±0.07;5.36±0.07对4.6±0.09)。肝脏ki-67术后36 h表达最为活跃,48 h后下降,实验组与对照组相比ki-67表达明显增高。实验组中组织肝细胞生长因子(HGF)及肿瘤坏死因子(TNF-α)水平明显比对照组增强。结论白藜芦醇能明显促进小鼠部分肝切除后的肝再生。     

Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy

Abstract: Aims/Background: Hepatic stimulator substance (HSS) is a liver‐specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats. Methods: Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA. Results: Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA‐intoxicated and HSS‐treated rats compared to TAA‐intoxicated and saline‐treated ones. Furthermore, HSS ameliorated liver regenerative indices – DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity – in a statistically significant manner. Conclusions: Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.     

Liver failure after major hepatic resection

Introduction

The consequence of excessive liver resection is the inexorable development of progressive liver failure characterised by the typical stigmata associated with this condition, including worsening coagulopathy, hyperbilirubinaemia and encephalopathy. The focus of this review will be to investigate factors contributing to hepatocyte loss and impaired regeneration.

Methods

A literature search was undertaken of Pubmed and related search engines, examining for articles relating to hepatic failure following major hepatectomy.

Results

In spite of improvements in adjuvant chemotherapy and increasing surgical confidence and expertise, the parameters determining how much liver can be resected have remained largely unchanged. A number of preoperative, intraoperative and post-operative factors all contribute to the likelihood of liver failure after surgery.

Conclusions

Given the magnitude of the surgery, mortality and morbidity rates are extremely good. Careful patient selection and preservation of an obligate volume of remnant liver is essential. Modifiable causes of hepatic failure include avoidance of sepsis, drainage of cholestasis with restoration of enteric bile salts and judicious use of portal triad inflow occlusion intra-operatively. Avoidance of post-operative sepsis is most likely to be achieved by patient selection, meticulous intra-operative technique and post-operative care. Modulation of portal vein pressures post-operatively may further help reduce the risk of liver failure.     

Beneficial effects of Kampo medicine Inchin-ko-to on liver function and regeneration after hepatectomy in rats.

Aim: Inchin-ko-to (ICKT), Kampo medicine, is known to inhibit hepatocyte apoptosis as well as promote the secretion and excretion of bile. The aim of this study is to clarify the effects of ICKT on liver function and hepatic regeneration after massive hepatectomy in rats. Methods: Male Wistar rats received 2 g/kg ICKT from 3 days preoperatively and underwent 90% hepatectomy. Liver sections were stained using immunohistochemistry (hemeoxygenase-1 [HO-1], alpha-smooth muscle actin [SMA], and proliferating cell nuclear antigen [PCNA]). Results: The survival period was significantly prolonged, and the remnant liver/body weight ratio was significantly increased postoperatively in the ICKT group. The values of transaminase, total bile acid, and total bilirubin were significantly improved in the ICKT group. In the ICKT group, PCNA and HO-1 were strongly expressed early postoperatively, but the expression of alpha-SMA was weak. Conclusion: The preoperative administration of ICKT has been suggested to provide beneficial effects in promoting hepatic regeneration and preventing postoperative hepatic failure. The reduced activation of stellate cells may be involved in their mechanisms.     

Clinical experience of hepatic hemangioma undergoing hepatic resection

The indications for surgery on cavernous hemangiomas, the most common benign tumors of the liver, remain unclear. This study reviewed 43 patients with cavernous hemangioma of the liver who underwent hepatic resection from 1984 to 2000. Patients were divided into three groups based on the reasons for surgery. Group I comprised 13 patients whose lesions presented symptoms and dimensions that were the main indications for operation. Group II consisted of 28 patients diagnosed with malignant tumors or who displayed malignant growth that could not be ruled out preoperatively. Group III comprised 2 patients with tumors found incidentally at laparotomy for other malignancies. No surgical mortality related to hepatectomy was noted. Postoperative bile leak was found in 2 (morbidity rate: 4.7%). Patients were followed up from 6 months to 12 years. Thirteen residual tumors progressed in size. The clinical status or symptoms changed only slightly in 10 patients with recurrence. The results suggest that resection therapy is an effective indicator for patients with symptoms and a questionable diagnosis. Hepatic resection may and should be carried out with no mortality and minimal morbidity risks since the lesion is benign.     

Intraoperative echography for hepatic resection

Basic intraoperative ultrasonographic techniques for safe and accurate hepatic resection are described, with particular reference to understanding the locational relationships between tumors and intrahepatic vascular structures, echo guidance for needle puncture, portal area staining, orientation of the transected hepatic plane, evaluation of all tumors to be removed in the resected specimen, and assessment of blood flow and patency of reconstructed vessels. The use of this approach and the consequent selection of the most appropriate surgical techniques for the removal of multiple metastatic liver tumors are then described in three case reports.     

Measurement of serum hyaluronic acid level during the perioperative period of liver resection for evaluation of functional liver reserve

BACKGROUND AND AIM: The serum hyaluronic acid (HA) concentrations reflect the degree of hepatic fibrosis and sinusoidal endothelial cell damage. The HA concentrations were examined to evaluate liver damage during the perioperative period of hepatectomy. METHODS: The HA level of serum samples from 79 patients who underwent a hepatectomy was measured, and the results were compared to conventional liver function tests, the degree of fibrosis, liver regeneration and complications. RESULTS: Hyaluronic acid concentrations correlated with the severe fibrosis or histological activity index, and also correlated with liver function tests including transaminase level, platelet counts, prothrombin time activity, indocyanine green retention rate at 15 min (ICG R15), liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy (LHL 15), and portal pressure. The HA level postoperatively correlated with liver function, especially with total bilirubin. Hyaluronic acid levels at day 28 postoperatively correlated with ICG R15 and LHL 15. The hyaluronic acid level before surgery and at day 28 postoperatively correlated with the regeneration of remnant liver in major hepatectomy. The HA levels were significantly higher in patients with hepatic failure or prolonged ascites. CONCLUSION: Our results indicate that the measurement of the HA level is useful for monitoring liver damage or predicting complications associated with liver surgery.     

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.     

Liver regeneration after liver resection: Clinical aspects and correlation with infective complications

AIM:To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications.METHODS:A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010.Regeneration was evaluated by multidetector computed tomographyat a mean follow-up of 43.85 d.The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation,and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data.Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration.RESULTS:Ten of the 27 patients(37%)underwent chemotherapy prior to surgery,with a statistically significant prevalence of patients with metastasis(P=0.007).Eight patients(30%)underwent embolization,3 with primary tumors,and 5 with secondary tumors.Twenty patients(74%)experienced complications,with 12(60%)experiencing Clavien-Dindo Grade 3a to 5 complications.Regeneration≥100%occurred in 10(37%)patients.The predictors were smaller future remnant liver volume(-0.002;P<0.001),and a greater spleen volume/future remnant liver volume ratio(0.499;P=0.01).Patients with a resection of≥5 Couinaud segments experienced greater early regeneration(P=0.04).Nine patients experienced surgical site infections,and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected(P=0.016).There were no significant differences between patients with primary or secondary tumors,and either onset or infections or severity of surgical complications.CONCLUSION:Regardless of the onset of infective complications,future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.