脾切除术对肝癌发生的影响

目的：探讨脾切除术对肝炎后肝硬化脾亢患者的肝癌发生发展的影响。方法：回顾性研究369名肝硬化脾亢伴或不伴肝癌患者,经倾向性得分匹配方法（PS法）均衡分为无脾切除组（246例）和脾切除组（123例）,分别比较脾切组中脾切除术对患者肝功能的影响和两组间肝癌发生率的差异。结果：脾切除术后患者AST、ALT在短期内有轻微升高,WBC和PLT记数明显增加,血清TBIL和PT也都降低。无脾切除组和脾切除组的肝癌发生率分别为33.33%和12.26%,卡方检验结果P〈0.05,有统计学意义。结论：脾切除术不但可以改善肝硬化肝癌患者的肝功能,还可以降低肝硬化脾亢患者肝癌发生的危险。     

门静脉高压脾功能亢进对大鼠肝癌发生率的影响

目的:通过对门静脉高压脾功能亢进大鼠药物诱导肝癌过程中进行脾脏切除,探讨门静脉高压脾功能亢进对大鼠肝癌发生率的影响。方法:将雌雄SD大鼠性别内分别分为对照组、脾亢组、脾亢切脾组,脾功能亢进大鼠模型采用门静脉缩窄术联合脾静脉结扎术进行制备,各组均予以DEN(二乙基亚硝胺)腹腔注射,按体重20mg/kg给药,每周3次,12周停药,14周处死。其中,脾亢脾切除组于给药第四周进行脾切除术,手术恢复期间持续给药。观察各组实验动物的肝脏大体变化及病理改变,计算成瘤率。结果:实际成瘤率显示脾亢组较对照组明显升高,而雄性脾亢切脾组的成瘤率较脾亢组有所降低。雌性脾亢切脾组成瘤率同脾亢组差异不明显。结论:门静脉高压脾功能亢进状态下进行脾切除,对于雄性能减低肝癌发生的风险,对于雌性的意义不大,给临床实际工作提供了新的思路。     

微波固化在肝硬化肝癌不规则性切除术中的应用

目的:探讨微波固化在肝硬化肝癌不规则性肝切除术中的应用价值。方法:回顾性分析第四军医大学唐都医院普外科2011年1月-2013年4月行不规则性肝切除肝硬化肝癌患者158例的临床资料,其中男性96例,女性62例,年龄32-65岁(47.7±9.4)。乙型肝炎后肝硬化58例,酒精性肝硬化21例。肝功能分级:Child-Pugh A级116例,B级42例。不规则性肝切除组(Ⅰ组)77例,微波固化+不规则性肝切除组(Ⅱ组)81例,两组在性别构成、年龄、肝炎病史、肝癌病史、门静脉高压症、AFP、PLT、Child-Pugh评分、肝功能(白蛋白、谷丙转氨酶、总胆红素、凝血酶原时间)等无显著差异(P0.05)。比较分析两组术中肝门阻断、出血量、输血量、手术时间、术后肝功能恢复及术后并发症的发生率情况。结果:微波固化+不规则性肝切除术组无肝门阻断,且在手术时间、出血量、补血量、补液量、住院时间、术后住院时间明显少于不规则性肝切除术组(P0.05)。而在淋巴结清扫数目、围手术期死亡率无显著差异(P0.05)。在术后1天、3天和7天时,两组在白蛋白、总胆红素、凝血时间无显著差异(P0.05),术后1天、3天谷丙转氨酶无显著差异(P0.05),术后7天时Ⅱ组较Ⅰ组恢复快(P0.05)。Ⅱ组术后并发症发生率明显少于Ⅰ组。结论:微波固化在不规则性肝切除术中无需行肝门阻断,具有出血少、输血少、手术时间短、术后住院时间短等优点。微波固化联合不规则性肝切除术在肝硬化肝癌中具有良好效果。     

不同肝血流阻断方式肝切除手术对原发性肝癌合并肝硬化患者肝功能及肠黏膜屏障的影响

目的:探讨肝切除手术运用Pringle法阻断、半肝血流阻断(HVC)后对原发性肝癌合并肝硬化患者肝功能及肠黏膜屏障的影响。方法:选取2016年4月～2019年9月期间我院收治的原发性肝癌合并肝硬化患者93例,根据随机数字表法将患者分为A组(n=46,Pringle法阻断)和B组(n=47,HVC),比较两组患者围术期指标、肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)以及总胆红素(TBIL)]、肠黏膜屏障指标[D-乳酸,内毒素]及并发症发生情况。结果:两组阻断时间、术中失血量、手术时间比较无差异(P0.05);B组住院时间短于A组(P0.05)。两组术前、术后3 d、术后7 d ALT、AST、TBIL呈升高后降低趋势,且B组低于A组(P0.05)。两组患者术后并发症发生率比较无差异(P0.05)。两组术前、术后3 d、术后7dD-乳酸、内毒素呈升高后降低趋势,且B组低于A组(P0.05)。结论:与Pringle法阻断相比,原发性肝癌合并肝硬化患者在肝切除手术中运用HVC,可有效缩短住院时间,减轻肝功能及肠黏膜屏障损害,且不增加并发症发生率,临床应用价值较高。     

部分脾栓塞术对肝硬化脾功能亢进的介入治疗

目的:探讨和评价部分脾栓塞术(PSE)治疗肝硬化脾功能亢进的临床应用价值。方法:采用Seldinger技术对28例乙肝后肝硬化伴脾功能亢进患者用高压消毒明胶海绵颗粒共进行31次PSE。结果:28例手术中27例获得成功,栓塞范围为30％-60％,25位患者术后1周以内、1-2周及2周以上WBC和PLT均有不同程度的上升(P<0.01),临床有效率为92.6％。手术前后肝功能变化不大。全部病例均未发生严重并发症。结论:部分脾栓塞术对治疗肝硬化脾亢有明显疗效,可替代脾切除术。对肝功能的改善,近期疗效不明显。     

脾切除对肝硬化门静脉高压症大鼠免疫功能的影响及意义

目的:对肝硬化门静脉高压症大鼠行脾切除手术,观察术后大鼠免疫系统功能的变化情况,探讨脾切除术对免疫系统的影响,为临床治疗提供理论基础。方法:选取SD大鼠45只建立PHT模型,随机分为PHT组、脾全切组及部分脾切除组,每组各15只。另选取10只健康大鼠为对照组。分别对四组大鼠行不同的脾切除方案,术后检测四组大鼠的血常规、免疫球蛋白含量、T淋巴细胞亚群的变化及组织病理学染色结果等,分析各指标的意义。结果:四组大鼠血常规检测结果显示,PHT组大鼠WBC高于对照组,PHTTS组高于PHT组,PHTSS组高于PHTTS组,差异显著且具有统计学意义(P0.05)。四组大鼠血浆中IgG含量差异显著(P0.05);IgA、IgM含量无显著性差异(P0.05)。四组大鼠CD4+、CD8+含量差异显著(P0.05);CD29+含量无显著性差异(P0.05)。结论:脾脏直接参于细胞介导免疫调节,脾切除可降低门脉压力,消除脾亢,有利于肝硬化门脉高压症的缓解。     

脾动脉结扎联合肝癌切除术治疗肝癌并门静脉高压症临床研究

目的:探讨脾动脉结扎联合肝癌切除术对肝癌并门静脉高压症的治疗效果和临床应用的价值。方法:对2008年10月至2013年10月期间我院收治的84例肝癌并门静脉高压症患者的资料进行回顾性分析,其中脾动脉结扎联合肝癌切除手术的患者50例为研究组,患者34例行肝癌切除及脾切断流术为对照组。比较两组治疗效果及患者术前、术后情况。结果:研究组术前白细胞计数、血小板计数、红细胞计数为(3.1±0.9)×109/L、(58.6±12.7)×109/L、(3.4±0.4)×109/L,术后2周白细胞计数、血小板计数、红细胞计数分别为(5.9±1.5)×109/L、(140.3±50.1)×109/L、(3.6±0.7)×109/L;对照组为术前白细胞计数、血小板计数、红细胞计数为(2.8±1.2)×109/L、(45.8±20.5)×109/L、(3.4±0.4)×109/L,术后2周白细胞计数、血小板计数、红细胞计数为(6.2±0.7)×109/L、(172.5±32.7)×109/L、(3.6±0.3)×109/L。研究组与对照组相比,术后2周白细胞计数、红细胞计数相比差异无统计学意义(P0.05),但术后2周血小板计数研究组低于对照组,差异有统计学意义(P0.05)。研究组术前与术后的白细胞计数、血小板计数、红细胞计数相比,差异均有统计学意义(P0.05)。研究组有17例患者出现术后并发症,占16.0%;对照组有20例患者出现术后并发症,占38.2%;两组对比差异有统计学意义(P0.05)。结论:根据病情合理选择使用脾动脉结扎联合肝癌切除术治疗肝癌并门静脉高压症,可以有效治疗肝癌和脾功能亢进,促进肝功能恢复,对延长原发性肝癌合并肝硬化脾功能亢进患者的生存时间,提高生活质量,具有重要意义。     

应用脾动脉结扎法行全腹腔镜巨脾切除术的临床研究

目的:探讨应用脾动脉结扎法行全腹腔镜巨脾切除术的安全性、可行性及手术技巧。方法:将2010年1月1日至2012年1月1日因肝硬化门脉高压脾机能亢进巨脾患者随机分为腹腔镜脾切除(Laparoscopic Splenectomy,LS)组及开腹脾切除(OpenSplenectomy,OS)组,比较两组的临床特征及围手术期差异。结果:LS组与OS组在性别组成、术前肝功能child分级、年龄组成及脾脏长径方面均无统计学意义。LS组手术时间比OS组略长,但无统计学意义,LS组术中出血量明显低于OS组(P<0.01),LS组术后进食、术后排气、引流管拔除及出院时间均明显早于OS组(P<0.01)。结论:腹腔镜脾切除术为治疗门脉高压巨脾的一种有效、安全、可行的手术方式。     

术前抗病毒治疗与否对乙肝相关性肝癌患者术后的影响

目的探讨术前抗病毒治疗与否对乙肝相关性肝癌患者术后肝功能及康复产生影响。方法回顾性分析广西柳州市人民医院2013年11月至2018年11月行肝癌切除术后的患者294例,其中术前抗病毒组202例,术前未抗病毒组92例。比较两组患者术后谷草转氨酶(ALT)、谷丙转氨酶(AST)及术后恢复时间。结果两组患者术后肝功能及患者康复时间比较,差异无统计学意义(P>0.05)。结论乙肝相关性肝癌患者术前抗病毒治疗与否对肝癌术后患者的肝功能及康复时间没有影响。     

肝动脉栓塞化疗术对原发性肝癌伴 有不同类型肝炎后肝硬化患者预后的影响

目的:探讨肝动脉栓塞化疗(TACE)对原发性肝癌伴有不同肝炎后肝硬化类型患者术后肝功能、凝血功能及其对远期预后的影响。方法:2007年8月至2009年8月,131例曾行TACE的伴有不同肝炎后肝硬化原发性肝癌患者,以肝炎后肝硬化类别(乙肝、丙肝)分类,乙肝后肝硬化组为组1,丙肝后肝硬化组为组2,随访观察术后一年肝功能、凝血功能、血小板等的变化以及预后。两组研究因素采用SPSS17.0进行卡方检验,随访预后采用Kaplan-Meier方法计算生存率,Log-rank法检验生存差异。以P<0.05为差异有统计学意义。结果:随访统计结果显示术后半年和一年AST、ALT、ALP、GGT、PT、PLT在两组间均无统计学差异,(P>0.05);组一半年、一年远处转移率同组二差异间无统计学意义;组一半年、一年生存率分别为70.1%,48.1%;组二半年、一年生存率分别为68.5%,58.9%,两组间同期生存率差异无统计学意义。(X2=0.039,P=0.884;X2=0.183,P=0.669)。结论:TACE治疗PHC安全可靠,对于伴有乙肝或丙肝后肝硬化患者术后肝功能、凝血功能、疗效及预后效果相当。     

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale,Multicentre Study

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.     

Phosphorylation of elongation factor-2 kinase differentially regulates the enzyme's stability under stress conditions

Chronic infection with hepatitis B virus (HBV) is associated with the majority of cases of hepatocellular carcinoma (HCC) in China. Despite this, there is no effective method for the early detection of HBV-induced liver cancer. Aberrant fucosylation is known to occur during the development of HCC. We, therefore, developed a method of applying matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze the relationship between aberrant fucosylation, tumor genesis and progression of HBV-associated HCC, and to establish proteomic profiling of serum for early diagnosis of HCC. The MALDI-TOF MS was based on Lens culinaris agglutinin (LCA) lectin magnetic beads and their affinity for separation. The method was applied initially to a 'training' cohort of 111 serum samples obtained from subjects in China with no liver disease (n=26), chronic hepatitis B without cirrhosis (n=21), HBV-infected cirrhosis (n=32), or HBV-infected HCC (n=32). In contrast to previous findings, the results of our profiling analysis demonstrated defucosylation on some of the glycoproteins involved in HCC. HCC was then diagnostically classified in a 'blind test' cohort (n=96). In this group we demonstrated that, HCC could be distinguished from all serum samples, HBV-associated chronic liver disease, and HBV-associated cirrhosis with a sensitivity/specificity of 70%/70%, 78%/74%, and 81%/82%, respectively. When combined with serum alpha-fetoprotein detection (AFP>20 ng/mL), the sensitivity/specificity improved to 78%/88%, 85%/88%, and 89%/91%, respectively. In conclusion, serum glycoprotein fucosylation abnormalities have diverse forms in patients with HCC. MALDI-TOF MS profiling of aberrant serum fucosylated glycoproteins distinguished HCC from controls with high accuracy.     

Development and Validation of a Clinical Scoring System for Predicting Risk of HCC in Asymptomatic Individuals Seropositive for Anti-HCV Antibodies

Background

The development of a risk assessment tool for long-term hepatocellular carcinoma risk would be helpful in identifying high-risk patients and providing information of clinical consultation.

Methods

The model derivation and validation cohorts consisted of 975 and 572 anti-HCV seropositives, respectively. The model included age, alanine aminotransferase (ALT), the ratio of aspirate aminotransferase to ALT, serum HCV RNA levels and cirrhosis status and HCV genotype. Two risk prediction models were developed: one was for all-anti-HCV seropositives, and the other was for anti-HCV seropositives with detectable HCV RNA. The Cox''s proportional hazards models were utilized to estimate regression coefficients of HCC risk predictors to derive risk scores. The cumulative HCC risks in the validation cohort were estimated by Kaplan-Meier methods. The area under receiver operating curve (AUROC) was used to evaluate the performance of the risk models.

Results

All predictors were significantly associated with HCC. The summary risk scores of two models derived from the derivation cohort had predictability of HCC risk in the validation cohort. The summary risk score of the two risk prediction models clearly divided the validation cohort into three groups (p<0.001). The AUROC for predicting 5-year HCC risk in the validation cohort was satisfactory for the two models, with 0.73 and 0.70, respectively.

Conclusion

Scoring systems for predicting HCC risk of HCV-infected patients had good validity and discrimination capability, which may triage patients for alternative management strategies.     

Cytohistologic correlation of cirrhosis and hepatocellular carcinoma. Pitfall in diagnosis?

OBJECTIVE: To compare the diagnostic criteria for cirrhosis and hepatocellular carcinoma (HCC) noted on liver fine needle aspirates (FNAs) and their corresponding liver needle core biopsies (NCBs). STUDY DESIGN: We reviewed FNA slides from 15 cases of cirrhosis and 6 cases of HCC and their corresponding NCBs. We compared a variety of specific nonarchitectural criteria, including small cell dysplasia (SCD) and large cell dysplasia (LCD), for distinguishing cirrhosis from HCC. RESULTS: FNA smears diagnostically correlated with NCBs. The cytologic criterion with the greatest correlation in predicting HCC on FNA was SCD. This was not noted in all the core biopsies, probably due to sampling error. LCD was seen more frequently in cirrhosis than HCC on both cytology and histology and therefore was not a criterion useful in establishing a diagnosis of malignancy. The remaining cytologic criteria had good correlations but did not aid in diagnosing HCC. CONCLUSION: FNA has good cytohistologic correlation with NCB for both cirrhosis and HCC. There is an association of SCD with HCC; however, LCD is not a reliable "precancerous" change as it is commonly seen in cirrhosis and HCC. Therefore, the presence of SCD on FNA should be reported and is an indication for close clinical follow-up to exclude HCC.     

Serum ficolin-2 concentrations are significantly changed in patients with hepatitis B virus infection and liver diseases

Human ficolin-2 is an important lectin complement pathway activator that is secreted from liver cells and has been implicated as an anti-infection innate immune molecule. However, the role of ficolin-2 protein and its dynamic changes over the course of and in the prognosis of chronic hepatitis B(CHB) and hepatocellular carcinoma(HCC) remain unclear. In this study, we analyzed ficolin-2 protein expression in a cohort of individuals with CHB infection, HCC and cirrhosis. A sandwich enzyme-linked immunosorbent assay(ELISA) method was used to measure serum ficolin-2 concentrations. Ficolin-2 expression in liver tissues was detected by immunohistochemical staining. Serum ficolin-2 concentrations in CHB patients were significantly higher than in healthy controls and HBV carriers. After 48 weeks of routine amelioration liver function treatment, serum ficolin-2 concentrations decreased and were positively correlated with favorable alanine aminotransferase(ALT), HBV DNA and HBe Ag-seroconversion outcomes. Interestingly, we observed much lower expression of serum and intrahepatic ficolin-2 in HCC and cirrhosis compared with healthy controls. Our findings suggest that serum and intrahepatic ficolin-2 levels may be considered one of the indicators for the response of chronic HBV infection, HCC and cirrhosis.     

Preoperative prediction of microvascular invasion in non-metastatic hepatocellular carcinoma based on nomogram analysis

PurposeThe presence of microvascular invasion (MVI) is an unfavorable prognostic factor for hepatocellular carcinoma (HCC). This study aimed to construct a nomogram-based preoperative prediction model of MVI, thereby assisting to preoperatively select proper surgical procedures.MethodsA total of 714 non-metastatic HCC patients undergoing radical hepatectomy were retrospectively selected from Zhongshan Hospital between 2010 and 2018, followed by random assignment into training (N = 520) and validation cohorts (N = 194). Nomogram-based prediction model for MVI risk was constructed by incorporating independent risk factors of MVI presence identified from multivariate backward logistic regression analysis in the training cohort. The performance of nomogram was evaluated by calibration curve and ROC curve. Finally, decision curve analysis (DCA) was used to determine the clinical utility of the nomogram.ResultsIn total, 503 (70.4%) patients presented MVI. Multivariate analysis in the training cohort revealed that age (OR: 0.98), alpha-fetoprotein (≥400 ng/mL) (OR: 2.34), tumor size (>5 cm) (OR: 3.15), cirrhosis (OR: 2.03) and γ-glutamyl transpeptidase (OR: 1.61) were significantly associated with MVI presence. The incorporation of five risk factors into a nomogram-based preoperative estimation of MVI risk demonstrated satisfactory discriminative capacity, with C-index of 0.702 and 0.690 in training and validation cohorts, respectively. Calibration curve showed good agreement between actual and predicted MVI risks. Finally, DCA revealed the clinical utility of the nomogram.ConclusionThe nomogram showed a satisfactory discriminative capacity of MVI risk in HCC patients, and could be used to preoperatively estimate MVI risk, thereby establishing more rational therapeutic strategies.     

Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignancy in the world with high morbidity and mortality rate. Identification of novel biomarkers in HCC remains impeded primarily because of the heterogeneity of the disease in clinical presentations as well as the pathophysiological variations derived from underlying conditions such as cirrhosis and steatohepatitis. The aim of this study is to search for potential metabolite biomarkers of human HCC using serum and urine metabolomics approach. Sera and urine samples were collected from patients with HCC (n = 82), benign liver tumor patients (n = 24), and healthy controls (n = 71). Metabolite profiling was performed by gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography-quadrupole time of flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Forty three serum metabolites and 31 urinary metabolites were identified in HCC patients involving several key metabolic pathways such as bile acids, free fatty acids, glycolysis, urea cycle, and methionine metabolism. Differentially expressed metabolites in HCC subjects, such as bile acids, histidine, and inosine are of great statistical significance and high fold changes, which warrant further validation as potential biomarkers for HCC. However, alterations of several bile acids seem to be affected by the condition of liver cirrhosis and hepatitis. Quantitative measurement and comparison of seven bile acids among benign liver tumor patients with liver cirrhosis and hepatitis, HCC patients with liver cirrhosis and hepatitis, HCC patients without liver cirrhosis and hepatitis, and healthy controls revealed that the abnormal levels of glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, and chenodeoxycholic acid are associated with liver cirrhosis and hepatitis. HCC patients with alpha fetoprotein values lower than 20 ng/ml was successfully differentiated from healthy controls with an accuracy of 100% using a panel of metabolite markers. Our work shows that metabolomic profiling approach is a promising screening tool for the diagnosis and stratification of HCC patients.