氩氦冷冻消融治疗原发性肝癌临床研究

[目的]回顾性分析氩氦冷冻消融治疗肝细胞癌（HCC）的临床疗效。[方法]227例HCC患者,按巴塞罗那分期标准：早期26例、中期73例和进展期128例,行经皮穿刺氩氦刀冷冻消融治疗。[结果]氩氦冷冻消融治疗HCC后随访12—63个月,早期、中期及进展期HCC患者中位生存期分别为36、23和12个月。早期生存期为37．8±13．8个月,1、2、3、5年生存率分别为92.3％、84．6％、65．4％、11．5％;中期生存期为24．5±9．7个月,1、2、3年生存率分别为84．9％、56.2％、21．9％;进展期生存期为16．9±8．4个月,1、2、3年生存率分别为68．8％、22．7％、6．3％。AFP阳性HCC患者治疗后28．1％的患者转为阴性;55．6％的患者术后4周AFP明显降低：上消化道出血是HCC患者的主要死亡原因。[结论]氩氦冷冻消融并发症少、消融彻底;不同分期HCC的生存时间、生存中位数有显著差异,以早期最长;以延长进展期HCC生存期最明显,是一种较理想的消融治疗肝癌手段。     

肝动脉栓塞化疗联合氩氦刀冷冻消融治疗不能手术的中晚期肝癌的临床观察

目的观察肝动脉栓塞化疗联合氩氦刀冷冻消融治疗不能手术的中晚期肝癌的有效性和安全性。方法对35例原发性肝癌患者首先进行动脉栓塞化疗治疗,2～3周后进行氩氦刀冷冻消融治疗,氩氦刀冷冻消融治疗后1～2周再次进行动脉栓塞化疗,治疗结束后评价近期疗效,并随访生存情况。结果35例患者均可评价疗效,其中完全缓解7例,部分缓解21例,稳定4例,进展3例,临床有效率为80．00％（28／35）,疾病控制率为91．43％（32／35）。患者中位无进展生存（PFS）为8．9个月,中位总生存（OS）为16．3个月。结论肝动脉栓塞化疗联合氩氦刀冷冻消融治疗不能手术的原发性肝癌创伤小、恢复快、并发症少、疗效可靠。     

氩氦刀冷冻消融治疗原发性肝癌术后常见并发症及防治

目的探讨氩氦刀冷冻消融治疗肝硬化性、原发性肝癌并发症的防治。方法60例不宜手术切除的中晚期原发性肝癌患者,在超声引导下行氩氦刀冷冻消融治疗,观察术后并发症的发生并总结预防及治疗经验。结果肝硬化原发性肝癌氩氦刀冷冻消融治疗可出现多系统、多器官的并发症,经积极干预,并发症明显减少,部分可恢复。本组研究中胸腔积液比例明显高于文献,未出现致命性并发症。结论氩氦刀冷冻消融治疗肝硬化基础上的原发性肝癌是一种创伤小、疗效显著且安全的方法,其并发症是可防可控的。     

氩氦刀联合肝动脉化疗栓塞术治疗原发性肝癌的临床研究

目的：观察氩氦刀联合肝动脉化疗栓塞术治疗原发性肝癌的疗效。方法：40例原发性肝癌病人,根据病人情况选择TACE术和氩氦刀冷冻消融术治疗的先后顺序。1月后复查血清AFP、肝脏CT增强扫描及肝动脉造影（DSA）检查。随诊12个月。结果：治疗前AFP〉400ng/ml,治疗后下降〉50%者83.9%（26/31）;肝脏CT增强扫描及DSA造影提示：肿瘤完全坏死50.0%（20/40）;不完全坏死27.5%（11/40）;部分坏死22.5%（8/40）。6个月、12个月生存率分别为91.0%和76%。治疗中、 治疗后未发生严重并发症。结论：氩氦刀联合肝动脉化疗栓塞术治疗原发性肝癌疗效确切,不良作用少。     

B超引导氩氦民冷冻治疗肿瘤的价值

目的探讨B超引导氩氦刀冷冻治疗肿瘤的价值.方法无法手术切除的原发性肝癌、腹后腔血管内皮肉瘤、左肺鳞状细胞癌及右甲状腺髓样癌患者各一例在B超引导下进行氩氦刀冷冻治疗.结果4例患者三个月后B超及CT复查瘤体均缩小1/3,临床症状明显好转.结论B超引导氩氦刀冷冻治疗,定位准确,安全可靠,效果明显,具有重要的价值及临床意义.     

B超引导氩氦刀冷冻治疗肿瘤的价值

目的探讨B超引导氩氦刀冷冻治疗肿瘤的价值.方法无法手术切除的原发性肝癌、腹后腔血管内皮肉瘤、左肺鳞状细胞癌及右甲状腺髓样癌患者各一例在B超引导下进行氩氦刀冷冻治疗.结果4例患者三个月后B超及CT复查瘤体均缩小1/3,临床症状明显好转.结论B超引导氩氦刀冷冻治疗,定位准确,安全可靠,效果明显,具有重要的价值及临床意义.     

氩氦刀联合肝动脉化疗栓塞术治疗原发性肝癌的临床研究

目的:观察氩氦刀联合肝动脉化疗栓塞术治疗原发性肝癌的疗效.方法:40例原发性肝癌病人,根据病人情况选择TACE术和氩氦刀冷冻消融术治疗的先后顺序.1月后复查血清AFP、肝脏CT增强扫描及肝动脉造影(DSA)检查.随诊12个月.结果:治疗前AFP＞400ng/ml,治疗后下降>50%者83.9% (26/31);肝脏CT增强扫描及DSA造影提示:肿瘤完全坏死50.0% (20/40);不完全坏死27.5% (11/40);部分坏死22.5% (8/40).6个月、12个月生存率分别为91.0%和76%.治疗中、治疗后未发生严重并发症.结论:氩氦刀联合肝动脉化疗栓塞术治疗原发性肝癌疗效确切,不良作用少.     

氩氦刀靶向冷冻治疗肝癌的初步研究

目的初步建立氩氦刀靶向冷冻治疗肝癌的技术和探讨其原理、安全性及近期疗效.方法8例无法手术的原发和继发性肝癌,其中3例术前行肝动脉栓塞化疗,采用氩氦超导手术系统(简称氩氦刀),分别在CT、DSA定位或术中直视下对肿瘤病灶行冷冻治疗.结果8例患者冷冻治疗后无手术死亡、出血、胆瘘、皮肽冻伤、感染、穿刺道种植转移等严重并发症.术后CT影像能观察到病灶冷冻治疗的有效范围,3例术前接受肝动脉栓塞化疗者术后1～6个月瘤体有进一步不同程度的缩小.3例原发性肝癌术前AFP值增高的患者术后均有下降.治疗后随访2～11个月,仅1例死于全身转移,其余均存活.结论CT、DSA引导和术中直视氩氦刀冷冻治疗肝癌技术可靠,创伤小,安全性高,是治疗无手术机会肝癌的一种有效的新手段,其远期疗效和在肝癌综合治疗中的价值尚有待于进一步的前瞻性临床试验研究说明.     

肝癌氩氦刀冷冻和射频治疗的CT探讨

目的：分析氩氦刀冷冻和射频治疗肝脏恶性肿瘤的CT表现,探讨其与疗效的关系.方法：选择1999年11月～2002年10月用氩氦刀和射频治疗的肝癌共36例,其中原发性肝癌29例,转移性肝癌7例,分为氩氦刀组11例,射频治疗组25例.氩氦刀术后即刻CT扫描和两种方法术后1～2周开始复查CT.结果：氩氦刀冷冻治疗出现典型“冰球”CT表现者达70%以上,继续复查局部保持低密度、增强扫描无强化;射频治疗后近期复查近半数可见类圆形较低密度及周围环状更低密度区,无强化效应.结论：氩氦刀冷冻治疗出现大于原病灶区的典型“冰球”CT表现者,疗效较佳,原发性肝癌AFP下降率可达95%以上;射频治疗后出现类圆形较低密度区及周围大于原病灶的环状更低密度影,提示疗效好,其原发性肝癌AFP下降比例明显提高.以上两种疗法对直径小于5cm的肝癌均有较好的疗效,尤其对直径小于3cm的小肝癌疗效更佳.对原发性肝癌和转移性肝癌的疗效无明显差异.     

氩氦刀冷冻消融治疗原发性肝癌的临床研究

[目的]探讨氩氦刀冷冻消融综合治疗中晚期肝癌的疗效。[方法]96例中晚期原发性肝癌分3组观察。第一组用氩氦刀冷冻消融联合TACE治疗37例；第二组单纯用氩氦刀冷冻消融32例：第三组单纯用TACE27例。氩氦刀冷冻消融采用B超／或CT引导经皮穿刺肝肿瘤，共计对97个病灶使用203把氩氦刀二次循环冷冻。[结果]氩氦刀冷冻术后有94.2％（65/69）的患者精神状态得到改善，腹部疼痛症状减轻，恢复快。氩氦刀超低温冷冻联合TACE的近期疗效和12、24个月的生存率明显优于另外两组，中位生存期延长（P＜0．05）。[结论]氩氦刀联合TACE是治疗肝癌有效的方法之一，可望提高肝癌患者生存期和改善生命质量，为丧失手术机会的晚期肝肿瘤患者开辟了一条新的治疗途径。     

8cm以上肝癌术后残癌的肝动脉栓塞化疗预后因素分析

目的：了解肝动脉栓塞化疗对直径大于8cm肝癌术后残癌的疗效和影响预后的因素。方法：肝癌切除术后2个月内经超声和动脉造影证实有残癌的肝癌患者，行肝动脉栓塞化疗；采用COX模型研究影响疗效的因素。结果：治疗后1，2，3，4年生存率为74.9%，44.2%，36.8%，18.4%。肝癌切除术后残癌的TNM分期是影响疗效的独立因素（P=0.003)。而原发癌的肿瘤分期，手术方式（局部切除或肝叶切除），肝动脉栓塞化疗的次数，不是影响预后的独立因素。结论：肝癌术后行肝动脉栓塞化疗是可行的，术后残癌的分期是影响肝动脉栓塞化疗效果的主要因素，大体积肿瘤术后尽早行肝动脉栓塞化疗是必要的。     

Validation of The Hong Kong Liver Cancer Staging System in Patients with Hepatocellular Carcinoma after Curative Intent Treatment

Backgrounds: Recently Hong Kong Liver Cancer (HKLC) staging system has been proposed for staging of hepatocellular carcinoma (HCC), and has been shown to provide better prognostic ability than the Barcelona Clinic Liver Cancer (BCLC) system. However, the HKLC system lacks external validation, and its applicability remains uncertain. The present study was aimed to evaluate the prognostic performance of HKLC in HCC patients treated with curative intent. Methods: Medical records of HCC patients treated with either resection or radiofrequency ablation (RFA) from 2011 to 2016 were retrospectively reviewed. The overall survival and the prognostic ability of the HKLC and BCLC system were evaluated. Results: 79 HCC patients were included, of which 64.56% had Child A cirrhosis. Chronic viral hepatitis B infection was the leading cause of HCC, followed by chronic viral hepatitis C infection, alcohol and alcohol with HBV or HCV infection. According to the BCLC system, 82.28% were in stage 0-A, and according to the HKLC system, 93.67% were in stage I-IIb. RFA and liver resection were the primary treatment in 56.96% and 43.04%, respectively. The 5-year survival rate of patients in HKLC stage I, IIa and IIb were 81.64%, 61.66%, and 54.42%, respectively (P<0.001). Whereas, the 5-year survival rate of patients in BCLC stage 0, A and B were 60.00%, 75.90%, and 26.65%, respectively (P=0.053). The AUROC curve of the HKLC and BCLC for the entire cohort was 0.77 and 0.64, respectively (P=0.15). Subgroup analysis showed the AUROC curve of the HKLC and BCLC for the patients with viral-associated HCC was 0.79 and 0.68, respectively (P=0.02). Conclusions: Applying the HKLC staging system provides a good discriminative ability for survival prediction in HCC patients treated with curative intent. Comparing with the BCLC system, the HKLC system tends to yield better prognostic accuracy, particularly in viral-associated HCC.     

构建预测肝细胞肝癌术后CNLC III/IV期复发的网页计算器

目的:探讨肝细胞肝癌（hepatocellular carcinoma,HCC）术后出现CNLC III/IV期复发危险因素，并构建线上预测模型。方法:回顾性分析我院2011年1月至2017年12月接受肝癌切除术的289例HCC患者临床及病理资料，基于Logistic回归分析明确HCC患者术后出现CNLC III/IV期复发高危因素，并以多因素回归分析结果为基础构建线上预测模型，通过一致性指数（C指数）、校正曲线及临床决策曲线验证该模型预测能力及临床效能。结果:截止至随访日期，共有158例（54.7%）的HCC患者出现术后复发，其中56例（19.4%）为CNLC III/IV期复发。经过多因素Logistic回归分析得术前NLR≥1.56（OR:2.745,95%CI:1.041~7.240,P=0.041）、肿瘤直径≥5.75 cm（OR:3.664,95%CI:1.612~8.328,P=0.002）、肿瘤低分化（OR:4.197,95%CI:2.027~8.688,P＜0.001）、微卫星灶（OR:3.426,95%CI:1.241~9.460,P=0.017）及微血管侵犯（OR:3.127,95%CI:1.301~7.514,P=0.011）是术后出现CNLC III/IV复发的危险因素，以此为基础建立相应线上预测计算器，该预测模型时间依赖性受试者工作特征曲线下面积(AUC)为0.862，校正C指数为0.850。结论:HCC患者术后出现CNLC III/IV期复发与诸多因素相关，通过本研究所建立的网页计算器，临床医生可快速简便地识别高危人群并尽早予以干预措施，对临床工作具有指导意义。     

肝癌及癌旁组织中端酶检测的临床意义

目的 研究端粒酶作为原发性肝细胞癌（ＨＣＣ）肿瘤标志物的可能性。方法 采用ＴＲＡＰ方法检测了３３例原发性肝细胞癌及其３３例癌旁组织、４例肝转移癌及其４例癌旁组织、６例肝良性肿瘤和６例正常肝组织中的端粒酶活性。结果 ３３例原发性肝细胞癌组织中,有３０例端粒酶表达阳性,其阳性率为９０．９％。３３例癌旁组织中,有９例端粒酶表达阳性,其阳性率为２７．３％。４例肝转移癌端粒酶活性均阳性,４例癌旁组织中,２例     

Prospective study on the survival of HCC patients treated with transcatheter arterial lipiodol chemoembolization

Aim: Tanscatheter arterial embolization irrespective of with or without an anticancer agent and lipiodol has been controversial with regard to survival benefit. Therefore, we conducted a prospective study to analyze the effect of transcatheter arterial lipiodol chemoembolization (TACE) on the survival of HCC. Methods: A prospective study was conducted, and a total of 326 patients with primary liver cancer who were newly diagnosed were collected from January 2004 to January 2005 in Zhejiang Provincial People’s Hospital of China. A univariate Cox’s regression analysis was used to assess the survival of the HCC cases receiving TACE. Results: The duration of follow-up for the HCC patients treated with TACE ranged from 3 months to 60 months. For the overall patients, survival rate at 5 years was 42%. Both HBV Ag and HCV Ab positive patients showed significantly low survival rate at 5 years. The multivariate analysis revealed The IV TNM stage was related to an heavy increased risk of death of HCC patients, and Child C grade group showed a significant moderate increased risk. Conclusion: Our study showed TACE is associated with a better prognosis of HCC patients, and the HBV infection, TNM stage, Child-Pugh grade and number of TACE may influence the survival probability. Further TACE studies should be assess the quality of life of HCC patients, so as to provide more information for treatment of HCC.     

Diagnostic Performance of Circulating Tumor Cells for Predicting of Hepatocellular Carcinoma in Hepatitis C Virus-High Risk Patients: Role of Liquid Biopsy

Purpose: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of HCC. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), albumin, platelets count, and α-fetoprotein were assayed in HCC patients (42), liver cirrhosis patients (83) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-CTCs = AFP (U/L) × 0.08 - Albumin (g/dl) × 84 + CK 18 % × 2.9 + CK19 × 3.1- Platelets count (×109)/L× 0.75– 510. HCC-CTCs score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0. Conclusions: HCC-CTCs score could replace AFP during screening of HCV patients and early detection of HCC.     

Predictive Value of Serum Insulin-like Growth Factor-1 in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver inthe world. Insulin-like growth factor-1 (IGF-1) levels reflect hepatic function and are inversely correlated withthe severity of background chronic liver disease. Objective: This study evaluated whether basal serum IGF-1levels can predict prognosis of HCC patients according to different risks of disease progression. Materials andMethods: A total of 89 patients with hepatocellular carcinoma (HCC) were recruited in 3 groups: Group I, 30HCC patients receiving sorafinib; Group II, 30 HCC patients with best supportive care; and Group III include29 patients undergoing transcatheter arterial chemoembolization (TACE). All patients were investigated forserum levels of AST, ALP, Bb, Cr, BUN, AFP and IGF-I. Results: Patients with disease control had significantlyhigher baseline IGF-1 levels 210 (185-232.5) ng/mL (p value<0.01) than did patients without disease control.Low basal IGF-1 levels were associated with advanced HCC, such as multiple tumors and advanced stage, andlow IGF-1 levels predicted shorter TTP and overall survival in patients treated with TACE. Conclusions: Thelevels of serum IGF-1, expressed as continuous values, may be helpful for accurately assessing hepatic functionand the prognostic stratification of patients with HCC.     

2003～2013年某肿瘤专科医院肝细胞癌肿瘤分期及首次治疗方法调查分析

目的 分析广西某三级甲等肿瘤专科医院近10年肝细胞癌（hepatocellular carcinoma,HCC）肿瘤分期和首次治疗方法的构成比。方法 回顾性分析该院2003年1月至2013年10月收治首诊的HCC患者资料,参考巴塞罗那临床肝癌分期系统（Barcelona Clinical Liver Cancer,BCLC）,分析HCC各分期以及首次治疗方式所占比例。结果 共6 241例HCC患者纳入分析,其中BCLC-0/A期、B期、C期、D期HCC患者所占比例依次为28.9%、16.2%、53.6%、1.3%。所有患者中,接受肝切除术、介入治疗、放射治疗、消融治疗、全身系统化疗、中医中药治疗、靶向药物治疗和未治疗的患者依次占33.3%、36.7%、2.2%、0.9%、8.8%、4.2%、0.1%、13.8%。在BCLC-0/A期和B期HCC患者中,肝切除术是主要的治疗方式,而在BCLC-C期患者中,主要的治疗方式是介入治疗。结论 该院BCLC-B期和C期HCC患者比重大,肝切除术和介入治疗是主要的治疗方式。     

Decreased Expression of LKB1 Correlates with Poor Prognosisin Hepatocellular Carcinoma Patients Undergoing Hepatectomy

Aim: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases.Methods: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital ofWenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry.Patients were followed-up and prognostic factors were evaluated. Result: LKB1 expression was decreased in theHCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascularinvasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantlyshorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively).Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival(P = 0.033). Conclusion: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1expression is correlated with a lower survival rate.     

Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray

BACKGROUND: Amplifications of 1q21, c-myc at 8q24.1, and AIB1 at 20q12 are genetic alterations that are detected frequently in hepatocellular carcinoma (HCC). The authors evaluated the association of these amplifications with the prognosis of patients with HCC. METHODS: In the current study, amplification of 1q21, c-myc, and AIB1 was analyzed in 560 specimens from 400 patients with HCC and 20 patients with benign liver lesions using fluorescence in situ hybridization with high-throughput tissue microarray. Differences of amplification patterns were compared between small and large HCC, single nodular and multiple nodular HCC, primary and metastatic HCC, and primary and recurrent HCC. RESULTS: Significant differences between single nodular and multiple nodular HCC were detected in c-myc amplification (12% vs. 38%; P < 0.01) and AIB1 amplification (16% vs. 30%; P < 0.05). More frequent c-myc amplification was detected in metastatic HCC (45%) compared with primary HCC (29%) and in recurrent HCC (60%) compared with primary HCC (38%). Similarly, more frequent AIB1 amplification was observed in metastatic HCC (41%) compared with primary HCC (23%) and in recurrent HCC (60%) compared with primary HCC (29%). However, no significant differences in 1q21 amplification were observed. CONCLUSIONS: The current results strongly suggest that amplifications of the c-myc and AIB1 oncogenes are late genetic alterations in the progression of HCC and are correlated with a poor prognosis.