进展期肝癌患者氩氦刀冷冻消融术前中性粒细胞/淋巴细胞比值与术后预后关系研究

目的探讨氩氦刀术前中性粒细胞/淋巴细胞比值(neutrophil/lymphocyte ratio,NLR)与进展期肝癌患者术后生存期的关系。方法回顾性分析2008—2009年在我院行氩氦刀冷冻消融治疗的150例进展期肝癌患者临床资料,根据术前NLR中位数(2.94)将患者分为2组(高NLR组和低NLR组),对2组进行生存分析和Cox回归分析。结果氩氦刀冷冻消融术前病理组织分化程度、NLR和肝硬化Child-Pugh分级是术后进展期肝癌患者生存期的影响因素。术前高NLR组患者生存期为5个月(95%CI 3.5~6.4),而低NLR组患者生存期为9个月(95%CI 6.9~11.0),2组生存期差异有统计学意义。结论 NLR2.94的进展期肝癌患者行氩氦刀冷冻消融治疗预后较差。     

氩氦冷冻消融治疗进展期肝细胞癌的临床疗效及其预测因素

目的 探讨氩氦冷冻消融治疗进展期肝细胞癌(HCC)的临床疗效,并分析影响其疗效的预测因素. 方法 对2005-2008年在我院治疗的190例乙型肝炎相关进展期HCC患者采用临床队列方法,分为氩氦冷冻消融治疗组(147例)和对照组(43例),比较两组中位生存期(OS)和肿瘤进展时间(TTP),评价年龄、性别、门静脉癌栓位置、HBeAg状态、肿瘤组织分化程度、Child-Pugh分级、终末期肝病模型(MELD)评分、进展期肝癌预测系统(ALCPS)评分及东部肿瘤协作组体能状态(ECOG PS)评分对冷冻消融疗效预测的影响.组间率的比较用x2检验;生存分析用Kaplan-Meier法,生存率的比较用Log-rank分析;多因素对生存期的影响用Cox回归模型进行分析. 结果 冷冻消融治疗组和对照组患者中位OS分别为7.5 (4.2～ 14.6)个月和3.2 (1.2 ～ 8.6)个月,中位TTP分别为3.5 (2.5 ～ 4.5)个月和1.5 (1.0 ～ 3.5)个月,差异均有统计学意义(P值均＜0.05).肿瘤细胞高分化、Child-pugh A级及MELD评分、ALCPS评分和ECOG PS评分好的进展期HCC患者中位OS和TTP明显长于肿瘤细胞低分化、Child-pugh B级及各系统评分差的患者(P值均＜ 0.05).对进展期HCC患者的OS具有独立预测作用的因素为ECOG PS(P＜0.05,95％可信区间为1.074 ～ 2.143)和ALCPS(P＜0.05,95％可信区间为1.005 ～ 2.121).结论 冷冻消融治疗进展期HCC能够延长患者中位OS和TTP; ECOG PS和ALCPS评分系统是进展期HCC患者OS的重要预测因素.     

经皮氩氦刀冷冻治疗肝细胞癌的安全性和疗效

肝细胞癌(hepatocellular carcinoma,HCC)居世界癌症死因第三位,在中国居第二位。手术切除率仅为20%～30%,因供体缺乏,肝移植术明显受限,因此多种局部消融术,如无水酒精、射频、激光、高强度聚集超声、微波和冷冻消融等在HCC治疗中发挥着重要作用。氩氦超导靶向手术系统(氩氦刀)冷冻治疗HCC是近年发展的一项局部消融术,尽管在中国经皮氩氦刀治疗HCC已有较多应用,但世界范围内对该技术尚存争议。与应用广泛的射频消融术及其他热消融技术相比,氩氦刀冷冻治疗有产生较大的毁损面积及更为清晰可辨的治疗区域等优势。本文对经皮氩氦刀冷冻治疗HCC的适应证、技术、患者管理、安全性及疗效进行评述。     

恩替卡韦治疗104例乙型肝炎肝硬化患者96周的疗效观察

目的 观察恩替卡韦治疗乙型肝炎肝硬化的临床疗效.方法 随机选择就诊于长春市中日联谊医院消化内科未经过抗病毒治疗的乙型肝炎肝硬化患者104例,给予恩替卡韦0.5 mg,每日1次口服,连续口服96周时总结临床疗效.观察患者治疗前、后血清HBV DNA水平、肝功能及HBV标志物,其中37例患者治疗前及治疗96周后行肝组织学检查.率的比较采用χ~2检验,相关性分析采用Pearson相关系数.结果 恩替卡韦治疗4周时,HBV DNA水平平均下降3.1 log_(10),至96周时平均下降幅度达到5.1 log_(10),HBV DNA不可测率达到98.1%,ALT复常率达到80.7%;72例HBeAg阳性患者96周时HBeAg/抗-Hbe血清转换率为13.9%.104例乙型肝炎肝硬化患者中,C基因型HBV感染者64例,占61.5%,B基因型28例,占26.9%.不同基因型HBV感染者患者接受恩替卡韦治疗后的HBV DNA不可测率、ALT复常率以及HBeAg血清转换率差异无统计学意义.Child-Pugh C级2例(2/21,9.5%),Child-Pugh B级1例(1/52,1.9%)出现疾病进展,Child-Pugh A级患者31例,未出现疾病进展.37例行肝组织学检查的乙型肝炎肝硬化患者治疗96周时,肝组织学改善者Child-Pugh A级17例(17/21,81.0%),B级6例(6/9,66.7%),C级3例(3/7,42.9%).治疗前HBV DNA水平越高,Knodell HAI评分越高,r=0.80.抗病毒治疗96周后血清HBV DNA下降水平与Knodell HAI评分下降水平仍呈正相关,r=0.93.结论 恩替卡韦抗病毒治疗乙型肝炎肝硬化患者疗效显著,可延缓及阻止肝硬化患者的疾病进展.     

局部治疗联合EGFR-TKIs在晚期耐药肺腺癌中的临床应用研究

目的探讨表皮细胞生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)使用后耐药进展的肺腺癌患者给予局部治疗(冷冻消融、支气管动脉栓塞)联合EGFR-TKIs的临床疗效。方法回顾性分析2012年3月至2018年10月应急总医院经病理证实并完成随访的原发性EGFR敏感突变型晚期肺腺癌患者,进展后再行EGFR基因检测为T790M阴性,继续应用EGFR-TKIs的同时联合局部治疗,分别统计PFS1(从使用EGFR-TKIs到疾病进展时间)、PFS2(从冷冻消融到疾病进展时间)、OS(总生存期)、OS1(冷冻消融后的生存期),及冷冻消融后的并发症情况。分析OS及PFS的统计学相关影响因素。结果32例符合入组标准的晚期肺腺癌患者,PFS1平均时间为(12.4±8.6)个月。其中14例患者冷冻消融前行支气管动脉栓塞治疗,共消融病灶38个。PFS2为(6.7±2.9)个月。OS为(31.5±13.5)个月,其中OS1为(15.5±7.6)个月。统计分析显示PFS1与PFS2与OS存在显著相关性(P<0.05),靶向治疗进展后至氩氦冷冻消融的时间与患者的OS及OS1存在相关性,支气管动脉栓塞联合氩氦消融治疗后并发症主要为气胸及肺内出血,对症处理后均可缓解。结论EGFR-TKIs耐药进展后晚期肺腺癌中,EGFR-TKIs继续使用并联合冷冻消融等局部治疗可延长患者生存,并发症少,取得临床获益。     

核苷(酸)类似物抗病毒治疗对乙型肝炎相关肝细胞癌患者预后的影响

目的探讨核苷(酸)类似物(NA)抗病毒治疗对于乙型肝炎相关性肝细胞癌(HCC)患者预后的影响。方法筛选2008年1月至2015年11月在上海瑞金医院确诊和治疗的HCC患者532例,收集入组患者的基线特征,记录入组的乙型肝炎相关性HCC患者NA治疗的信息。将乙型肝炎相关性HCC患者分为持续NA治疗组、HCC治疗后NA治疗组,NA未治组,对3组患者预后情况进行分析比较。结果 NA未治组患者的血清AFP水平为223.3 ng/mL,NA治疗组患者血清AFP水平为64.77 ng/mL(P0.01);NA未治组患者的血清ALT水平为44 U/L,血清AST水平为54 U/L,NA治疗组患者血清ALT水平为32 U/L,血清AST水平为35 U/L(P0.01);NA未治组患者的血清直接胆红素水平为5.4μmol/L,NA治疗组患者血清直接胆红素水平为4μmol/L(P0.05)。NA治疗组乙型肝炎相关性HCC患者的HCC分期处于A期和B期所占比例(72.03%)显著高于NA未治组患者(46.38%)。持续NA治疗能够显著延长乙型肝炎相关性HCC患者的生存时间(P0.01)。结论 NA治疗能够降低乙型肝炎相关性HCC患者的疾病严重程度,并有效延长患者的生存时间。     

氩氦刀靶向冷冻联合化疗治疗中晚期非小细胞肺癌

将30例不能手术切除的非小细胞肺癌(NSCLC)患者随机分为A组(单纯氩氦刀组)与B组(氩氦刀加化疗组)。根据肿瘤大小及方位选用不同的氩氦刀头靶向刺入NSCLC瘤体内进行同步冷冻消融。B组在氩氦刀治疗的基础上联合化疗。经氩氦刀冷冻消融治疗后,CT值较术前下降30 HU以上者占66.67%(20/30),术后1周肿瘤体积均增大。A、B两组术后1、3、6、12个月有效率(CR PR)分别为57.1%、56.3%,71.4%、75%,78.5%、81.3%,64.3%、81.3%,两组比较,P均>0.05。按Karnofsks行为状态评分(KPS):A组提高20分者占64.28%,B组占25%;两组比较,P<0.05。认为氩氦刀靶向冷冻消融法治疗中晚期NSCLC疗效确切,不良反应小;结合化疗疗效无明显提高,但不良反应增加。     

抗病毒联合经导管肝动脉化疗栓塞治疗乙型肝炎后肝硬化合并肝细胞癌患者的临床观察

目的探讨抗病毒联合经导管肝动脉化疗栓塞(TACE)治疗在乙型肝炎后肝硬化合并肝细胞癌(HCC)患者中的临床疗效。方法回顾性分析抗病毒联合TACE治疗78例乙型肝炎后肝硬化合并HCC患者的临床疗效,并与同期单独行TACE患者81例对比,观察比较两组患者1、2年生存率、肝功能Child-Pugh积分及HBV DNA定量的变化。两组基线临床资料(如性别、年龄、肿瘤的大小、实验室检查及Child-Pugh评分)比较差异无统计学意义(P均>0.05)。结果治疗1、2年后,治疗组HBV DNA阴转率均显著高于对照组(P均<0.0001),肝功能Child-Pugh积分治疗组明显低于对照组(P均<0.001),差异均有统计学意义。治疗组和对照组1、2年生存率分别为83.33%、66.67%和59.2%、36.67%(P均<0.001),差异均有统计学意义。结论应用核苷酸类似物联合TACE治疗乙型肝炎后肝硬化合并HCC的患者,可抑制HBV复制,保护患者肝功能,提高患者生存率。     

拉米夫定治疗乙型肝炎肝硬化的临床观察

目的观察拉米夫定治疗乙型肝炎肝硬化的临床疗效。方法选择Child-Pugh A、B级乙型肝炎肝硬化70例,36例接受拉米夫定治疗2~3年,另34例不规则口服护肝药物。结果治疗或随访至3年时,接受拉米夫定治疗的患者HBeAg阴转、HBeAg/抗HBe血清转换和HBV DNA阴转率分别为50%、44.4%和77.3%,显著高于对照组;Child-Pugh计分为7.5±1.1,而对照组为9.1±1.3(P<0.05);两组ALT复常率和发生肝衰竭和肝细胞癌情况无显著性相差。2例HBV相关性肾病患者病情恢复、稳定。结论拉米夫定治疗乙型肝炎肝硬化的临床效果肯定,可以延缓病情进展。     

氩氦刀联合肝动脉栓塞化疗与单纯氩氦刀治疗原发性肝癌比较研究

目的比较氩氦刀冷冻消融治疗联合肝动脉灌注化疗栓塞（TACE）与单纯氩氦刀治疗原发性肝癌的优劣。方法 86例原发性肝癌患者随机分为2组,A组43例行单纯氩氦刀冷冻消融治疗,B组43例行氩氦刀冷冻消融治疗联合TACE。分别在治疗前、治疗后8、15、30和50 d监测并记录各组甲胎蛋白（AFP）的动态变化。结果与A组比较,B组的AFP下降明显（P〈0.05）。结论氩氦刀冷冻消融联合TACE治疗原发性肝癌是一种微创、安全、有效的新方法,对于不适宜手术切除治疗的肝癌患者是一种有效的治疗方法。     

德氮吡格影响人肝癌细胞株QGY-7701亚细胞的蛋白质组学研究

目的 观察德氮吡格(TNBG)对人肝癌细胞QGY-7701亚细胞蛋白表达的影响,探讨其影响脂代谢的分子机制. 方法 分别提取TNBG处理前后人肝癌细胞QGY-7701的细胞质、细胞膜和细胞核蛋白进行双向电泳,PDQuest 7.4.0软件分析比对图像,采用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)鉴定差异蛋白质点. 结果 TNBG作用于人肝癌细胞QGY-770172h后,细胞质的差异表达蛋白质点有56个,细胞膜的差异表达蛋白质点有65个,细胞核的差异表达蛋白质点有34个,共计155个.利用MALDI-TOF-MS技术鉴定出其中33个差异表达蛋白质点,其中包括与脂质合成有关的10个蛋白质点和与脂质降解、转运有关的7个蛋白质点,如3-羟基-3甲基戊二酸单酰辅酶A还原酶、角鲨烯合成酶、低密度脂蛋白受体、三磷酸腺柠檬酸裂解酶、甘油醛-3-磷酸脱氢酶、甘油-3-磷酸酰基转移酶、长链酯 辅酶A脱氢酶等,这些都是固醇调节元件结合蛋白调控的靶基因.结论 TNBG可能通过固醇调节元件结合蛋白途径增加胆固醇和甘油三酯合成,导致肿瘤细胞内脂滴大量聚积.     

Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome

Background  Hepatocellular carcinoma (HCC) is uncommon in young adults. This study examined the clinical characteristics and survival outcome of young HCC patients compared with those in older patients. Methods  Data were prospectively collected from 638 patients diagnosed with HCC over a 9-year period. Patients aged ≤40 years at diagnosis of HCC were defined as young HCC patients. Their clinical characteristics and survival was compared with those aged >40 years. Results  The prevalence of young HCC was 8.6% (55/638). Young HCC patients had a significantly higher rate of hepatitis B-related disease (HBsAg positivity: 85.5% vs. 59.7%, P = 0.003), better Child-Pugh status (Child-Pugh class A: 69.1% vs. 43.9%, P = 0.002), and lower rates of cirrhosis (12.7% vs. 34.3%, P = 0.001) compared with the older group. They had more advanced disease at diagnosis, with higher α-fetoprotein levels (>12 000 μg/l: 45.4% vs. 30.5%, P = 0.026), a higher incidence of portal vein involvement (63.6% vs. 40%, P = 0.003), and a more advanced TNM stage (TNM IV: 83.6% vs. 66.4%, P = 0.018). More young patients were eligible for surgical resection (18.2% vs. 8.2%, P = 0.014). The overall survival between the two groups was similar, but when the patients were stratified for stage of disease, the median survival of young patients with early disease was superior to that of older patients (51.2 vs. 11.6 months, P = 0.025). Conclusions  HCC in young adults occurs mainly in hepatitis B carriers and is often diagnosed at an advanced stage. Their survival outcome is not different from that of older patients because the advanced disease at presentation offsets the advantages of better liver function and a higher resection rate. However, there is a distinct survival advantage for young patients diagnosed with early disease. These results support the importance of extending HCC surveillance to young hepatitis B carriers.     

Comparison of liver resection for hepatocellular carcinoma in hepatitis B and hepatitis C-related cirrhotic patients.

BACKGROUND/AIMS: The differences of liver resection for hepatocellular carcinoma (HCC) between hepatitis B and C-related cirrhotic liver remain unknown. This study compares the surgical results of HCC in hepatitis B and hepatitis C-related cirrhotic patients in an area endemic of hepatitis B. METHODOLOGY: A retrospective comparison of the clinicopathological features and early and long-term results of 110 cirrhotic patients with seropositive hepatitis B surface antigen only (group B) and 55 patients with seropositive anti-hepatitis C antibody only (group C) was carried out. RESULTS: Group C patients were older, had a lower serum alpha-fetoprotein level, greater indocyanine retention rate, and higher incidence of multicentric tumors. Tumor size was larger and there was a higher incidence of combined satellite nodules in group B patients. There were no significant differences in operative morbidity and mortality between the two groups. Group B patients had a slightly shorter disease-free interval (p = 0.07) but a better actuarial survival rate (p = 0.05) than group C patients. CONCLUSIONS: The hepatitis status did not affect the operative risks in cirrhotic livers. However, after resection of HCC, poorer liver functional reserve in hepatitis C-related cirrhotic patients caused poorer actuarial survival rate when compared with hepatitis B-related cirrhotic patients.     

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC ), and surveillance with ultrasound (US ) and alpha‐fetoprotein (AFP ) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR ) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona‐Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0‐3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY ), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI 95% 0.4‐1.5] in 2002‐2003 to 2.9/100 PY [2.4‐3.4] in 2012‐2013. One‐year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP  ≥ 20 ng mL^?1 was 17%. Twenty‐three (21%) patients were diagnosed with early‐stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early‐stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.     

Hepatocellular carcinoma and hepatitis C in Mexico

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has increased in many countries as a result of an increased frequency of hepatitis C virus (HCV) infection. In Mexico, the association of HCC to HCV infection has not been evaluated. This study aims to evaluate the epidemiological factors related to HCC in Mexican patients as well as the results of treatment. METHODOLOGY: A retrospective review of clinical files of patients with HCC diagnosed between May 1992 to July 2002 was performed. RESULTS: There were 63 males and 64 females with a median age of 57 years (range 17-82). Seventy-one patients were evaluated for hepatitis status. In 43 (60%) HCV was the etiological factor. Isolated HCV infection was present in 32 (45%), HCV infection and ethanol abuse was observed in 11 (15.5%). In six (8.4%) patients hepatitis B was the etiological factor. HCV and HBV infection were found in 9 (12.6%). HCV and HBV infection associated to ethanol abuse was present in one patient. Ethanol abuse alone was observed in six (8.4%) patients. The median size of the lesion was 8cm (range 3-20cm). Alpha-fetoprotein was measured in 113 patients and was higher than 500ng/dL in 60 (53%). Sixty-five patients received supportive measures. Sixty-two were treated. Eighteen were resected. Thirteen were treated with intraoperative large volume ethanol injection (ILVEI), 12 with chemotherapy and 19 with tamoxifen-talidomide. Patients without treatment had a median survival time of 11 months and patients who received treatment had a median survival time of 25.3 months. The median survival time in patients who received surgery was 26 months, the ILVEI group survival time was 18 months, the chemotherapy survival was 8.8 months, and the tamoxifen-talidomide survival time was 7 months. CONCLUSIONS: HCC is a rare neoplasm in Mexico and HCV infection is the main etiological factor. Surgical resection is the best form of treatment of HCC in our country. However, only 14% of the patients were candidates. For non-resectable lesions, ILVEI offers the best palliative results in our center.     

Outcomes of ultrasound-guided percutaneous argon-helium cryoablation of hepatocellular carcinoma

Purpose

To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous argon-helium cryoablation for hepatocellular carcinoma (HCC) and determine appropriate indications.

Methods

We reviewed outcomes of 300 HCC patients who underwent US-guided percutaneous cryoablation.

Results

Overall, 223 tumors (mean diameter 7.2?±?2.8?cm) in 165 patients were incompletely ablated, while 185 tumors (mean diameter 5.6?±?0.8?cm, P?=?0.0001 vs. incomplete ablation) in 135 patients were completely ablated. Nineteen patients (6.3%) developed serious complications while in hospital, including cryoshock syndrome in six patients, hepatic bleeding in five, stress-induced gastric bleeding in four, liver abscess in one and intestinal fistulas in one. Two patients died because of liver failure. The median follow-up was 36.7?months (range 6–63?months). The local tumor recurrence rate was 31%, and was related to tumor size (P?=?0.029) and tumor location (P?=?0.037). The mean survival duration of patients with early, intermediate and advanced HCC (Barcelona Clinic Liver Cancer staging system) was 45.7?±?3.8, 28.4?±?1.2 and 17.7?±?0.6?months, respectively.

Conclusions

US-guided percutaneous cryoablation is a relatively safe and effective therapy for selected HCC patients.     

Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: a population-based study

Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden.

Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017.

Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively.

Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.