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。     

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。     

肝炎后肝硬化患者肝癌发生的保护因素与危险因素研究

目的:通过回顾性病例对照研究,探讨多种因素在病毒性肝炎后肝化门静脉高压症患者HCC发生过程中的作用以及脾切除是否抑制了肝癌的发生进程。方法:收集第四军医大学西京医院病案统计室检索2002年1月～2008年12月之间出院诊断为病毒性肝炎后(HBV/HCV)肝硬化门脉高压的病例2300余例,收集所有病例的一般资料,临床及实验室检查数据,影象学检查结果,以及在治疗过程中的脾切除手术史。采用病例对照,按年龄、性别两个指标进行1:1配对,根据研究对象是否合并HCC将其分为合并HCC组(组1),未合并HCC组(组2),采用SPSS17.0进行单因素分析及多因素logistic回归分析。结果:描述性统计结果显示,两组的ALB、AST、TP、ALP、GGT等差异有统计学意义(P<0.05),而PLT、ALT、TBIL等在两组间差异无统计学意义(P>0.05)。将单因素分析有意义的研究因素纳入多因素logistic回归方程得知,AST、ALP、GGT异常升高增加了肝癌发生的危险性,而行脾切除和门奇断流术明显降低了肝癌发生的危险性,仅为无手术患者肝癌发生危险性的57.1%(OR:0.571,95%CI:0.394～0.825)。...     

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。     

脾切断流术对肝硬化门静脉高压症患者肝功能的影响

目的:观察脾切断流术对肝硬化门静脉高压症患者肝功能的影响.方法:回顾性分析2010年4月-2011年12月在我科住院的肝硬化门静脉高压症患者行脾切除术前后肝功能的变化.应用超声多普勒分别检测手术前后门静脉血流量(portal venous flow,PVF)、肝动脉血流量(hepatic arterial flow,HAF),术中采用水柱法测量自由门静脉压力(free portal pressure,FPP).结果:肝硬化门静脉高压症患者共480例,行脾切除加贲门周围血管离断术450例,单纯脾切除30例.PVF由术前的(1368± 402) ml/min减少至术后的(986±295)ml/min(P＜0.01);HAF由术前的(412± 68)ml/min增加至术后的(526±132)ml/min(P＜0.01);FPP由术前的(30±6)cm H2O降至术后的(26±5)cm H2O(P＜0.01).R15 ICG由术前的(18±8)％降至术后的(16±7)％(P＞0.05).肝功能Child分级A级患者比例由术前的85％增加至术后的95％(P＜0.01).其他肝功能指标如TBIL素、凝血酶原延长时间及腹水消失率都明显好转.结论:脾切断流术后PVF虽然减少,但是HAF增加及术后门体分流减少均有利于肝功能的恢复.     

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。     

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。     

ET-1、IL-6对肝炎后肝硬化患者预后的评价

目的:探讨肝炎后肝硬化患者血浆活性物质ET-1、IL-6的表达及其对患者预后判断的意义。方法:对70例肝炎后肝硬化患者按照Child-Pugh分级标准分为A级(23例)、B级(22例)和C级(25例)三组,并采用30例健康志愿者作为对照。采用放射免疫(RIA)方法检测ET-1和IL-6水平,对获得的数据进行统计学处理。结果:肝炎后肝硬化组ET-1和IL-6水平较健康组明显升高(P<0.01),且A、B、C三组中的ET-1和IL-6水平比较具有统计学意义。结论:ET-1和IL-6水平可反映肝炎后肝硬化肝脏损害程度,可作为预后判断的重要指标。     

高龄肝癌患者肝癌切除术后并发症及预后分析

目的:探讨高龄原发性肝癌患者肝癌根治性切除术的疗效及安全性。方法:回顾性分析63例(高龄组≥70岁)与98例(对照组70岁)行肝部分切除术的原发性肝癌患者的一般资料及其围手术期情况,对其术后并发症及预后进行探讨。结果:高龄组术后并发症发生率为36.5%,对照组31.6%(P0.05),高龄组7(11.1%)例肝衰竭,2(3.17%)例术后有出血现象,3(4.8%)例切口感染,3(4.8%)例胸腔积液,1(1.5%)例伴有隔下感染,1(1.5%)例有严重肺部感染,由于下肢深静脉血栓脱落,死于急性肺动脉栓塞。组织病理类型高龄组以结节型多见,Edmondson Ⅰ-Ⅱ级33例,Ⅲ-Ⅳ级18例,胆管细胞癌8例,混合细胞型4例。BCLC-0、A、B、C期分别占2、9、35、17例。高龄组与对照组1、2、3年生存率分别为82.5%VS85.7%、34.9%VS46.3%、15.9%VS36.8%。结论:高龄对肝部分切除术后并发症的发生并无明显影响,并不是原发性肝癌根治性手术切除术的禁忌症,高龄患者2、3年生存率较对照组低。     

肝炎肝硬化和酒精性肝硬化的B超表现比较

目的比较肝炎肝硬化和酒精性肝硬化的B超表现,为临床工作提供参考。方法收集2007年1月1日至2008年12月31日入住温州医学院附属第三医院肝硬化患者的B超资料,回顾性分析比较其B超表现特点。结果酒精性肝硬化患者肝脏肿大的比例高于肝炎肝硬化患者,差异有统计学意义(P0.001),但二者肝脏缩小比例差异无统计学意义。酒精性肝硬化患者肝脏表面光滑的比例较高而呈锯齿状的比例较低,与肝炎肝硬化患者比较差异均有统计学意义(P=0.015和P=0.027)。酒精性肝硬化患者肝内明显可见结节的比例低于肝炎肝硬化患者,二者差异有统计学意义(P=0.009)。门静脉宽度比较2组均数差异无统计学意义(P=0.581)。结论与肝炎肝硬化患者比较,酒精性肝硬化患者肝右叶斜径增大的比例较高,表面较光滑而较少出现锯齿状,发现粗大不规则结节的比例较低,而门静脉内径二者无差异。     

The Survival Benefit of Liver Transplantation for Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection and Cirrhosis

Background

A precise predictive survival model of liver transplantation (LT) with antiviral prophylaxis for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and cirrhosis has not been established. The aim of our study was to identify predictors of outcome after LT in these patients based on tumor staging systems, antitumor therapy pre-LT, and antiviral prophylaxis in patients considered to be unfit by Milan or UCSF criteria.

Methods

From 2002 to 2008, 917 LTs with antiviral prophylaxis were performed on patients with HBV-cirrhosis, and 313 had concurrent HCC.

Results

Stratified univariate and multivariate analyses demonstrated that independent predictors for poor survival were tumor size >7.5 cm (P = 0.001), tumor number >1 (P = 0.005), vascular invasion (P = 0.001), pre-LT serum alpha-fetoprotein (AFP) level ≥1000 ng/ml (P = 0.009), and pre-LT aspartate aminotransferase (AST) level ≥120 IU/L (P = 0.044). Pre-LT therapy for HCC was an independent predictor of better survival (P = 0.028). Based on CLIP and TNM tumor staging systems, HCC patients with HBV-cirrhosis who met the following criteria: solitary tumor ≤7.5 cm, or ≤4 multifocal nodules, the largest lesion ≤5 cm and total tumor diameter ≤10 cm, or more nodules with the largest lesion ≤3 cm, and pre-LT serum AFP level <1000 µg/L and AST level <120 IU/L without vascular invasion and lymph node metastasis who were unfit for UCSF, had survival rates of 89% at 5 years. There was a 47% 5-year survival rate for patients with HCC exceeding the revised criteria.

Conclusions

The current criteria for LT based on tumor size, number and levels of AFP and AST may be modestly expanded while still preserving excellent survival after LT. The expanded criteria combined with antiviral prophylaxis and pre-LT adjuvant therapy for HCC may be a rational strategy to prolong survival after LT for HCC patients with HBV-associated cirrhosis.     

Plasma Protein Biomarkers of Hepatocellular Carcinoma in HCV-Infected Alcoholic Patients with Cirrhosis

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV) infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP), complement component 4a (C4a), fibrinogen-alpha (FGA), immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1). Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029), being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015), with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81). In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic patients.     

丹红注射液对肝硬化的肝功能、肝纤维化指标、血流变的影响

目的:观察丹红注射液对肝硬化病人在保护肝细胞、肝纤维化及血流变的影响。方法:治疗组40例,在对照组基础上予丹红注射液40ml加入250ml葡萄糖注射液中稀释后缓慢滴注,每天一次;对照组38例,以甘利欣、Vitc、肌苷静脉滴注,每天一次,同时口服水飞蓟素,两组疗程均为4周。结果:治疗组与对照组比较,总有效率有显著差异(P0.05);胆红素和转氨酶复常方面,治疗组亦优于对照级,有显著差异(P0.05);两组治疗前后肝纤维化指标检测结果,治疗组与对照组治疗后比较有显著差异(P0.05);两组治疗前后血流变检测结果,治疗组与对照组治疗后比较部分项目有显著差异(P0.05、P0.01)。结论:丹红注射液对肝功能、肝纤维化及部分血流变项目有改善。     

Association of Serum Level of Growth Differentiation Factor 15 with Liver Cirrhosis and Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.     

思连康对肝硬化血浆内毒素影响的研究

目的：探讨益生菌制剂思连康治疗肝硬化内毒素血症的作用机制.方法：采用大鼠肝硬化模型,其中治疗组予以思连康液灌胃治疗,共8周,检测治疗组及对照组血浆内毒素指标;并选取70例肝硬化ChildPugh分级为B级的患者,其中治疗组口服思连康（每次两粒,每日三次）3周,观察治疗前后血浆内毒素变化.结果：思连康治疗组的肝硬化大鼠及患者血浆内毒素均明显低于对照组（p〈0.05）.结论：思连康能明显降低肝硬化患者血浆内毒素水平,可作为肝硬化患者的辅助用药.     

思连康对肝硬化血浆内毒素影响的研究

目的:探讨益生菌制剂思连康治疗肝硬化内毒素血症的作用机制。方法:采用大鼠肝硬化模型,其中治疗组予以思连康液灌胃治疗,共8周,检测治疗组及对照组血浆内毒素指标;并选取70例肝硬化ChildPugh分级为B级的患者,其中治疗组口服思连康(每次两粒,每日三次)3周,观察治疗前后血浆内毒素变化。结果:思连康治疗组的肝硬化大鼠及患者血浆内毒素均明显低于对照组(p<0.05)。结论:思连康能明显降低肝硬化患者血浆内毒素水平,可作为肝硬化患者的辅助用药。     

Smo 蛋白在肝癌和肝硬化中的表达及临床意义

目的:研究Smoothened(SMO)在肝癌和肝硬化中的表达及临床意义。方法:选取组织标本后,运用石蜡包埋,切片后,HE染色,构建组织芯片,免疫组织化学和原位杂交方法检测Smo蛋白在肝癌和肝硬化中的表达。结果:Smo蛋白在肝癌细胞浆、良性肝肿瘤组织细胞浆、肝硬化组织中强染色,在正常组织中无染色。并且在典型肝硬化中强染色,在中度肝硬化中弱阳性。结论:Smo蛋白表达与肝癌的发生有关,Smo基因的高表达可能激活某种机制而参与诱导肝癌的发生。可能是通过异常激活Sonic hedgchog信号通路,从而诱导肝癌的发生与发展。     

不同临床分期肝癌患者抗AFPTh1和Tc1应答反应研究

目的:研究CD4(Th1)和CD8(Tc1)T细胞对肝癌患者的AFP的应答反应及其与临床特征的相关性,为其早期诊断与预防提供新策略。方法:研究对象为62例HCC患者,30例肝硬化患者及30例健康志愿者;重点分析CD4 T细胞和CD8 T细胞对HCC患者的AFP-衍生肽的反应;用胞内细胞因子检测法对IFN-γ进行检测。结果:抗AFP的Tc1反应检测阳性结果在对照组为28.5%,在OkudaⅠ期的肝癌患者中为25.0%,在Ⅱ或Ⅲ期的HCC患者中为31.6%。抗AFP Th1阳性反应仅在HCC患者中检测到。抗AFP Th1阳性反应在44.4%的Child-Pugh A级的HCC患者中检测到,但是在Child-Pugh B或C级中仅15.4%。Tc1型反应在Child-Pugh A级肝功的患者中为16.7%,在Child-Pugh B或C级患者中为46.2%。结论:抗AFP Th1应答更多出现在早期肝硬化的HCC的患者中,而抗AFP Tc1应答更可能出现在晚期肝硬化患者中,这些结论为抗肝癌疫苗药物设计提供了理论基础。