Assessing recent recurrence after hepatectomy for hepatitis Brelated hepatocellular carcinoma by a predictive model based on sarcopenia

BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Metabolomics Analysis of the Responses to Partial Hepatectomy in Hepatocellular Carcinoma Patients

In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and 3 to 5 months after partial hepatectomy. To investigate the changes in metabolic phenotypes after the hepatic resection, principal components analysis (PCA) and support vector machine (SVM) were performed for the data grouping and classification. Based on the obtained SVM model, mass spectrometry spectra, database searching as well as the confirmation from authentic standards, several differentiating metabolites were tentatively identified. To improve visualization, z-score plot and heat map display were performed, which exhibited the changes in concentration of the metabolites. As a result, depletion of circulating carnitine, reduced amino acid biosynthesis and increased rate of lipid peroxidation were observed. Meanwhile, up-regulation of hypoxanthine indicated that purine metabolism might serve as the salvage pathway. Collectively, the results reflected metabolic responses to surgical operation in HCC patients, suggesting perturbation of energy metabolism may occur in 3 to 5 months after the partial hepatectomy.

Research Progress in Animal Models of Hepatocellular Carcinoma

[Objective] To establish good animal models of hepatocellular carcinoma （HCC） and serve treatment of HCC in humans. [Method] Several common animal models of HCC were introduced briefly. [Result] The commonly used animal models include C57BL/6J mouse model of or- thotopic HCC induced with Hepa1-6 cells, nude mouse model of HCC constructed with Hep_G2 cell lines, rat HCC model constructed through direct transplantation or direct injection, HU-PBL-SCID mice modal, and other transplanted HCC models or genetic HCC models. [ Conclusion] Animal model is an important means and platform for experimental studies. To establish animal models of HCC is of important significance for studies on pathogenesis, diagnosis and treatment of HCC.

End-stage liver disease score and future liver remnant volume predict post-hepatectomy liver failure in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the world’s sixth most common malignant tumor and the third cause of cancer death.Although great progress has been made in hepatectomy,it is still associated with a certain degree of risk of posthepatectomy liver failure(PHLF),which extends the length of hospital stay and remains the leading cause of postoperative death.Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF.AIM To assess the value of model for end-stage liver disease(MELD)score combined with standardized future liver remnant(sFLR)volume in predicting PHLF in patients undergoing hepatectomy for HCC.METHODS This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018.Discrimination of sFLR volume,MELD score,and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve.RESULTS The patients were divided into two groups according to whether PHLF occurred after hepatectomy.The incidence of PHLF was 8.4%in our research.The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score.Both sFLR volume and MELD score were considered independent predictive factors for PHLF.Moreover,the cut-off value of the sFLR/MELD score to predict PHLF was 0.078(P<0.001).This suggests that an sFLR/MELD≥0.078 indicates a higher incidence of PHLF than an sFLR/MELD<0.078.CONCLUSION MELD combined with sFLR is a reliable and effective PHLF predictor,which is superior to MELD score or sFLR volume alone.

Three-dimensional morphometric analysis for hepatectomy of centrally located hepatocellular carcinoma:A pilot study

AIM: To describe a three-dimensional model(3DM) to accurately reconstruct anatomic relationships of centrally located hepatocellular carcinomas(HCCs).METHODS: From March 2013 to July 2014, reconstructions and visual simulations of centrally located HCCs were performed in 39 patients using a 3D subject-based computed tomography(CT) model with customdeveloped software. CT images were used for the 3D reconstruction of Couinaud's pedicles and hepatic veins, and the calculation of corresponding tumor territories and hepatic segments was performed using Yorktal DMIT software. The respective volume, surgical margin, and simulated virtual resection of tumors were also estimated by this model preoperatively. All patients were treated surgically and the results were retrospectively assessed. Clinical characteristics, imaging data, procedure variables, pathologic features, and postoperative data were recorded and compared to determine the reliability of the model.RESULTS: 3D reconstruction allowed stereoscopic identification of the spatial relationships between physiologic and pathologic structures, and offered quantifiable liver resection proposals based on individualized liver anatomy. The predicted values were consistent with the actual values for tumor mass volume(82.4 ± 109.1 m L vs 84.1 ± 108.9 m L, P = 0.910), surgical margin(10.1 ± 6.2 mm vs 9.1 ± 5.9 mm, P = 0.488), and maximum tumor diameter(4.61 ± 2.16 cm vs 4.53 ± 2.14 cm, P = 0.871). In addition,the number and extent of portal venous ramifications, as well as their relation to hepatic veins, were visualized. Preoperative planning based on simulated resection facilitated complete resection of large tumors located in the confluence of major vessels. And most of the predicted data were correlated with intraoperative findings.CONCLUSION: This 3DM provides quantitative morphometry of tumor masses and a stereo-relationship with adjacent structures, thus providing a promising technique for the management of centrally located HCCs.

Establishment of NOD/SCID mouse models of human hepatocellular carcinoma via subcutaneous transplantation of histologically intact tumor tissue

Hepatocellular carcinoma （HCC） is one of the most deadly human cancers, but it is very difficult to establish an animal model by using surgical specimens. In the present experiment, histologically intact fresh surgical specimens of HCC were subcutaneously transplanted in non-obese diabetic/severe combined immunodeficienccy （NOD/SCID） mice. The biological characteristics of the original and the corresponding transplanted tumors and cell lines were investigated. The results showed that 5 new animal models and 2 primary cell lines were successfully established f^om surgical specimens. Hematoxylin-eosin staining showed that xenografts retained major histological features of the original surgical specimens. The two new cell lines had been cultivated for 3 years and successively passaged for more than 100 passages in vitro. The morphological characteristics and biologic features of the two cell lines were genetically similar to the original tumor. The subcutaneous transplant animal models with histologically intact tumor tissue and primary cell lines could be useful for in vivo and in vitro testing of anti-cancer drugs and be ideal models to study various biologic features of HCC.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Patterns of cancer recurrence in localized resected hepatocellular carcinoma

BACKGROUND： Tumor resection in non-metastatic hepato- cellular carcinoma （HCC） patients with adequate liver reserve offers a potential cure, but has a high 5-year recurrence rate. We analyzed the patterns of cancer relapse after partial hepa- tectomy to guide post-operative management.

Detection and characterization of hepatocellular carcinoma in rats with liver cirrhosis:diagnostic value of combined use of MR positive and negative contrast agents

BACKGROUND: Gadolinium-enhanced multi-phase dynamic imaging has improved the accuracy of the diagnosis of hypervascular hepatocellular carcinoma (HCC), but using gadolinium-enhanced dynamic imaging alone is problematic in evaluating hypovascular HCC. This work aimed at evaluating the combined use of superparamagnetic iron oxide (SPIO)-enhanced and gadolinium set in distinguishing HCCs from regenerative nodules (RNs) in a rat model induced by diethylnitrosamine (DEN). METHODS: DEN-induced HCC model rats (n=40) and control rats (n=10) were studied. From weeks 16 to 19 after DEN administration, 4 animals were scanned every week. The hepatic changes were tested with a 1.5 Tesla magnet, and MR images of SPIO-enhanced and gadolinium set were obtained. According to the pathologic changes, the tumorigenesis was divided into HCC and RN (diameter of nodules >= 3 mm). Diagnostic accuracy of the combined SPIO-enhanced and gadolinium set and the gadolinium set alone was evaluated using receiver-operating characteristic curves. Sensitivity and specificity of the combined SPIO-enhanced and gadolinium set and the gadolinium set alone were calculated. RESULTS: The listed tests were completed in 29 rats (21 treated and 8 controls). One hundred and six nodules (82 HCCs, 24 RNs) were analyzed. The Az value and sensitivity with the combined SPIO-enhanced and gadolinium set (Az 0.94, sensitivity 0.96) were higher than those with the gadolinium set alone (Az 0.92, sensitivity 0.89). Using the combined SPIO-enhanced and gadolinium set led to detection of 6 nodules which were negative in the gadolinium set alone and 3 nodules were correctly characterized. CONCLUSION: Using the combined SPIO-enhanced and gadolinium set improved the detectability of HCCs and the SPIO-enhanced imaging compensated for the gadolinium set in differentiating HCCs from RNs in a rat model.

Complete response to sorafenib in a patient with recurrent hepatocellular carcinoma

Partial hepatectomy is still the treatment of choice aiming at a cure for patients with hepatocellular carcinoma(HCC), provided that the patient can tolerate the treatment. For patients with multiple recurrent HCC after partial hepatectomy which cannot be treated by re-hepatectomy or local ablative therapy, the prognosis is extremely poor. sorafenib is a molecular-targeted agent which has been demonstrated in two global phase III randomized controlled trials to show survival benefit for advanced HCC. Here, we present a 56-yearold patient with HCC who showed complete clinical response after sorafenib was used for tumor recurrence which developed 3 mo after partial hepatectomy. There was no evidence of progression of disease for 60 mo till now after continuous treatment with sorafenib.

Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma

AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.

Magnetic resonance imaging of hepatocellular carcinoma induced by diethylnitrosamine in Sprague-Dawley rats

Diethylnitrosamine (DENA) is able to induce various benign and malignant liver lesions in rats with a high success rate and a low mortality rate. It provides a more appropriate model that better simulates the various lesions occurring in humans than the usual model of tumor implantations. The aim of the present study was to evaluate MRI liver examination in Sprague-Dawley(SD) rats as a routine method to detect hepatocellular carcinoma (HCC) nodules induced by DENA and to follow up their growth. METHODS:Hepatic carcinogenesis was induced in 80 male SD rats using oral DENA solution. All animals were imaged for liver tumor detection with a 1.5 Tesla magnet (Siemens Sonata,Erlangen, Germany) using correspondence scan parameters and a radio-frequency knee coil. Macroscopic examinations were performed along the axial MRI sections to evaluate magnetic resonance imaging (MRI) findings, and histopathological assessment was also performed. RESULTS:No false negative results were obtained on MR images. Hepatic tumors in 72 rats were confirmed macro-scopically and 68 rats were detected by MRI till the 20th week. The smallest and the largest nodules detected by MRI were 2 mm and 37 mm in diameter respectively. The agreement rate of MRI with macroscopic observation was 39. 1% and 97. 4% respectively for 2 mm to 5 mm and more than 5 mm nodules. CONCLUSIONS:The hepatic tumor induced by DENA provides a more representative range of tumors for imaging diagnosis and interventional treatment. MRI is the best approach for scrutinizing pathological changes of rat livers in the period of observation.

Enhancement of leukocyte adhesion after percutaneous irradiation in rats with hepatocellular carcinoma

AIM: To evaluate the effects of percutaneous radiation on leukocyte-endothelium interaction (LEI) in experimental hepatocellular carcinoma (HCC).METHODS: Twelve ACI rats underwent HCC-inoculation,six of which on day 12 received low-dose external radiation and six did not. After 12 h intravital microscopy was performed.RESULTS: LEI was significantly reduced in tumor tissue.However, irradiation of liver sinusoids and tumor tissue with 6 Gy led to a significant activation of leukocyte adhesion in the tumor with a marked increase of the proinfiammatory cytokine TNF-α.CONCLUSION: The findings indicate that the immunological tumor-endothelial barrier can be overcome by external irradiation.

肝癌病人肝切除术后难治性胸腔积液风险预测模型的构建

目的:分析原发性肝癌病人行肝切除术后发生难治性胸腔积液的危险因素,建立肝切除术后难治性胸腔积液的早期风险预测模型。方法:回顾性分析2018年1月—2019年7月在广西医科大学第一附属医院肝胆外科行肝切除术的原发性肝细胞癌病人的临床资料,采取Logistic回归分析筛选术后难治性胸腔积液的独立影响因素并建立风险预测模型,通过Hosmer-Lemeshowχ^(2)检验和受试者工作特征(ROC)曲线下面积评价模型的预测效能。结果:617例肝切除术病人中,54例(8.8%)病人发生术后难治性胸腔积液。多因素分析显示,肝硬化[OR=1.985,95%CI(1.071,3.681)]、手术时间≥234 min[OR=1.986,95%CI(1.031,3.828)]、开腹手术[OR=7.927,95%CI(1.876,33.494)]、术中出血量≥300 mL[OR=2.934,95%CI(1.488,5.785)]是术后难治性胸腔积液的独立危险因素;据此构建的预测模型的Hosmer-Lemeshow检验显示,χ^(2)=5.953,P=0.652;ROC曲线下面积为0.775[0.719,0.832]。结论:构建的预测模型具有较好的预测效能,可为医务人员术后早期筛查高危病人并采取相应预防措施以减少术后难治性胸腔积液的发生提供参考。

离体低温储存瘤块构建VX2肝癌模型效果研究

目的比较观察新鲜瘤块及不同时间低温冻存VX2肝癌瘤块经复苏后构建兔肝癌模型的效果。方法选取鱼肉状新鲜VX2瘤块,剔除周边坏死组织和肌肉后,-80℃下冰冻3、5和7个月。20只新西兰大白兔随机分为4组,A组予新鲜瘤块肝脏原位种植法构建VX2兔肝癌模型;B、C、D组分别给予-80℃冰冻3、5和7个月的瘤块,复苏后采用肝脏原位种植法构建兔肝癌模型。14 d后观察各组瘤兔肝脏的成瘤效果。通过免疫荧光观察肿瘤的增殖、凋亡及新生血管。结果A、B、C、D 4组的成瘤率为100%,但随着冻存时间的延长,5个月以后的瘤块活性差异性变大,肝脏肿瘤中心坏死面积增加。组织学检查发现,A、B两组模型TUNEL、Ki67、HIF1-α、VEGF、CD31表达无明显差异,而A、B组与C、D组相比,TUNEL、Ki67、HIF1-α、VEGF、CD31表达差异显著。结论-80℃下离体低温储存瘤块构建的兔VX2肝癌模型7个月内均可成瘤,5个月后瘤块间活性差异性变大,但整体来看可较好地保存瘤株活性,节省人力物力。

EVALUATION ON FACTORS INFLUENCING LIVER CANCER METASTASIS AFTER LIVER SURGERY BY A MOUSE MODEL

Objective: To evaluate the influence of surgical trauma on liver cancer metastasis. Methods: A mouse model of experimental liver cancer metastasis was established by subcapsule injecting hepatoma ascites tumor cells (H22) into spleen of NIH mice. Simple intrasplenic inoculation, with sham operation, partial hepatectomy, total occlusion of hepatic blood inflow and blood loss and re-perfusion were performed and metastatic effects were observed. Results: There were significant higher metastasis-augmenting effects in sham operation and partial hepatectomy groups. Compared with no-blood transfusion, blood transfusion group was found to be potent to increase intrahepatic metastases. But, neither inhibition nor enhancement with total occlusion of hepatic blood inflow for 20 and 30 minutes was seen. Conclusions: Surgical trauma, especially partial hepatectomy and blood transfusion, are involved in enhancing metastasis, but total occlusion of hepatic blood inflow is not responsible for enhanced liver metastasis in the experimental metastasis model.

Suitability of the woodchuck HCC as a preclinical model for evaluation of intra-arterial therapies

The most commonly used preclinical models of hepatocellular carcinoma(HCC)are limited for use in testing of intra-arterial therapies such as transarterial chemoembolization and radioembolization.Issues encountered with the more commonly used animal models include dissimilarity in their disease development compared with humans and the size of the vasculature which can make intra-arterial therapy testing difficult or impossible.Here we describe the suitability of the woodchuck HCC model for testing of intra-arterial therapies.We describe the techniques for pre-embolization imaging assessment using CT and MRI,technical tips on performing angiography and embolization,and pathological assessment of treated liver.

Animal models for hepatocellular carcinoma arising from alcoholic and metabolic liver diseases

Hepatocellular carcinoma (HCC) is a major and increasing cause of clinical and economic burden worldwide. Now that there are effective therapies to control or eradicate viral aetiologies, the landscape of HCC is changing with alcoholic and metabolic liver diseases becoming major catalysts. The pathogenesis of HCC is complex and incompletely understood, hampering improvements in therapy. Animal models are essential tools for advancing study on the cellular and molecular processes in HCC and for screening potential novel therapies. Many models of hepatocarcinogenesis have been established using various methods including genetic engineering, chemotoxic agents and dietary manipulation to direct implantation of tumour cells. However, none of these can accurately replicate all features found in human diseases. In this review, we provide an overview of different mouse models of HCC with a particular focus on cancer arising from alcoholic liver disease, non-alcoholic fatty liver disease and hereditary haemochromatosis. We also highlight their strengths and limitations and provide perspectives for future study.

基于数字减影血管造影的VX2肝癌兔靶向药物治疗模型的建立

目的探讨基于数字减影血管造影(DSA)的VX2兔肝癌模型建立以及影响建模成功的相关因素。方法2019年11月至2022年6月,44只健康新西兰大白兔使用随机数字表法等分成A、B两组,各22只。均实施开腹穿刺接种法移植肝癌,A组行常规经导管动脉化疗栓塞术(TACE)手术治疗(阿霉素+碘化油),B组在传统TACE治疗的基础上联合使用靶向药物贝伐单抗。根据手术后生存时间分为死亡组(存活时间<14 d)和存活组(存活时间≥14 d),将可能影响存活的因素分别行单因素及logistic多因素回归分析,使用受试者操作特征曲线(ROC曲线)分析相关因素的诊断预测效能。结果死亡组为10只,存活组为34只。多因素分析显示体质量[OR=0.20,95%CI:(0.07,0.59)]、总胆红素[OR=6.02,95%CI:(2.55,14.16)]是VX2肝癌兔术后短期死亡的独立影响因素。ROC曲线分析显示当肝癌兔体质量≤2.44 kg、总胆红素≥4.84µmol/L时预测术后短期死亡的效能最高,此时曲线下面积(AUC)分别为0.90和0.89。结论基于DSA的VX2肝癌兔靶向药物治疗模型的建立成功率较为可靠,但较低的体质量和较高的术后血清总胆红素是肝癌兔术后短期内死亡的独立危险因素。