肝动脉化疗栓塞联合射频消融和免疫靶向治疗术后复发的肝细胞癌患者近远期疗效研究*

目的 探讨采用肝动脉化疗栓塞(TACE)联合射频消融(RFA)和免疫靶向治疗术后复发的肝细胞癌(HCC)患者的疗效。方法 2014年8月～2018年4月我院诊治的术后复发性HCC患者150例,采用随机数字表法将患者分为对照组75例和观察组75例,分别给予TACE联合RFA治疗或在此基础上给予抗程序性细胞死亡蛋白-1(PD-1)抗体和阿帕替尼治疗,采用实体瘤mRESIST标准评估临床疗效,使用流式细胞仪测定外周血T细胞亚群,采用Kaplan-Meier法比较生存率。结果 在治疗后3 m,观察组有效率为81.3%,显著高于对照组的53.3%(P<0.05);观察组外周血CD3⁺、CD4⁺细胞百分比和CD4⁺/CD8⁺细胞比值分别为(68.2±6.8)%、(45.9±4.7)%和(1.8±0.3),显著高于对照组【分别为(56.5±6.1)%、(33.3±4.5)%和(1.3±0.2),P<0.05】,而CD8⁺细胞百分比为(22.5±1.8)%,显著低于对照组【(28.3±1.4)%,P<0.05】;观察组I/II级不良反应发生率为73.3%,显著高于对照组的32.0%(P<0.05);观察组1 a生存率为49.3%,显著高于对照组的30.7%(P<0.05)。结论 采用TACE联合RFA和免疫靶向治疗能够有效提高复发性HCC患者的近期临床疗效,可能与提高了机体免疫功能,抑制了肿瘤血管生成有关。     

肝动脉栓塞化疗及射频消融治疗肝细胞癌的疗效及肝储备功能观察

目的探讨肝动脉栓塞化疗(TACE)与射频消融(RFA)对肝细胞癌患者疗效及肝储备功能的影响。方法选取我院2013年10月—2016年10月收治的肝细胞癌患者124例,根据随机数字表法分成对照组、观察组各62例。对照组单纯给予RFA治疗,观察组采用TACE联合RFA治疗,两组于治疗后6个月评估疗效。比较两组治疗效果,分别于治疗前、治疗后6个月采血检测血清谷丙转氨酶(ALT)、总胆红素(TBil)、天冬氨酸氨基转移酶(AST)、前白蛋白(PA)、白蛋白(Alb)水平,并检测患者的肝脏硬度与吲哚菁绿试验15 min留滞率(ICGR-15)。术后电话随访24个月,记录中期生存率。结果观察组(69.35%)总缓解率显著高于对照组(51.61%)(P0.05)。在治疗后,观察组ALT、TBil、AST显著低于对照组,PA、Alb显著高于对照组(P0.05)。观察组治疗后的肝脏硬度、ICGR-15显著低于对照组(P0.05)。观察组随访24个月的生存率显著高于对照组(P0.05)。结论与单纯RFA治疗相比,采用TACE联合RFA治疗,能提高临床疗效,进一步改善患者的肝功能、肝储备功能,提高中期生存率。     

射频消融在肝细胞癌治疗中的研究进展

近年来,肝细胞癌(HCC)发病率居高不下,而射频消融(RFA)自临床开展以来对HCC的治疗取得了令人瞩目的成绩。此文就RFA治疗HCC的进展作一综述。     

射频消融治疗快速心律失常复发原因分析

目的　分析射频消融治疗快速心律失常复发的原因。方法　射频消融治疗快速心律失常 30 0例 ,包括房室结折返性心动过速 (AVNRT)、房室折返性过速 (AVRT)、特发性室性心动过速 (IVT)、心房扑动 (AF) ,快心室率心房纤颤房室结改良。结果　其中 10例复发 ,复发率 3 4%。复发病例包括 :AVNRT 2例、AVRT 5例、IVT 2例、AF 1例。结论　分析复发因素可归纳为 :AVNRT :①以双径路现象消失为最佳终点 ;②电生理检查中 ,最长A2 H2 间期 >32 0ms ,复发率增高。AVRT :①选择最佳靶点除强调AV或VA融合外 ,更强调V或A提前 ;②温控消融电极和Swartz鞘的应用可降低复发率 ;③正确识别和处理某些特殊病例。AF :对峡部的消融要达到峡部传导全部阻断。IVT :①选择最佳靶点 ;②导管与组织的密切接触或采用温控消融电极。     

射频消融与无水酒精注射治疗术后复发肝细胞癌患者的疗效比较

目的对比肝细胞癌（HCC）术后复发肿瘤病灶经射频消融（RFA）与无水酒精（PEI）注射治疗的疗效,以期为临床治疗HCC肿瘤复发提供参考。方法回顾性分析2007年8月至2010年1月HCC术后单一病灶复发患者175例,分为PEI治疗101例与RFA治疗74例。所有病例治疗前后均行常规彩超和超声造影/增强CT检查,观察比较治疗次数、病灶完全灭活率及治疗并发症发生率,记录患者治疗后1、2、3年生存率。计量资料采用t检验,计数资料采用χ2检验。结果 HCC术后复发病灶,平均每例的PEI治疗次数多于RFA（P〈0.05）,PEI和RFA治疗并发症的发生率比较差异无统计学意义（P〉0.05）;肿瘤直径〈2.0 cm的HCC术后复发病灶组中,PEI和RFA治疗病灶完全灭活率比较差异无统计学意义（P〉0.05）,而2.0～5.0 cm HCC术后复发病灶组,PEI治疗病灶完全灭活率低于RFA,差异均有统计学意义（P〈0.05）。HCC术后复发病灶直径〈2.0 cm组中,PEI和RFA治疗术后1、2、3年生存率分别为89.1%和90.2%、69.1%和70.7%、49.1%和53.7%,两种治疗方式术后生存率比较差异无统计学意义（P〉0.05）。而2.0～5.0cm组中,PEI和RFA治疗术后1、2、3年生存率分别为63.0%和84.8%、43.5%和66.7%、21.7%和45.5%,两种治疗方式术后生存率比较差异均有统计学意义（P〈0.05）。结论肿瘤直径小于2.0 cm HCC术后复发病灶的RFA和PEI局部消融治疗,患者术后的生存率无明显差异,而肿瘤直径2.0～5.0 cm时,RFA治疗后生存期优于PEI。     

射频消融治疗肝细胞癌的预后因素及研究新进展

随着医学诊疗水平的提高,射频消融在治疗原发性肝癌的临床应用和基础研究方面都取得飞速进展,发挥着越来越重要的作用:(1)射频消融治疗原发性肝癌的10年总生存率为27.3%-46.1%,对于肿瘤单发且最大径≤3 cm的HCC患者, 10年总生存率可达74%,生存结果与手术切除相似;(2)射频消融联合其他治疗等可以扩大消融治疗的适应证,使患者生存获益;(3)建立预测射频消融治疗原发性肝癌的预后模型,可指导制定治疗和随访策略,为临床个体化诊疗提供重要依据.     

载瘤动脉栓塞阻断血流对射频消融治疗原发性肝癌效果的影响

目的探讨肝动脉化疗栓塞术（TACE）阻断载瘤动脉血流提高经皮射频消融（RFA）治疗原发性肝癌的效果。方法选择原发性肝癌100例,随机分为两组各50例,一组采用TACE＋RFA治疗,另一组单纯采用RFA治疗,评价两组肿瘤坏死率及生存率的差异。结果TACE＋RFA组的肿瘤坏死率、12个月生存率明显高于RFA组,局部复发率明显低于RFA组,差异均有统计学意义（P均〈0.05）。TACE＋RFA组无严重并发症出现,RFA组出现包膜下出血2例,均为CT明显强化病例,经内科止血治疗后好转。结论TACE阻断载瘤动脉血流可明显提高RFA治疗原发性肝癌的效果。     

肝动脉插管化疗栓塞联合射频消融对大肝癌疗效评价

目的 探讨经导管肝动脉化疗栓塞(TACE)联合射频消融(RFA)治疗大肝癌的临床应用价值.方法 收集我院2006年4月～2008年7月肝细胞癌患者66例,并将其分为经导管肝动脉化疗栓塞+射频消融组(19例)、经导管肝动脉化疗栓塞组(24例)和射频消融组(23例),并将其疗效进行比较.结果 经导管肝动脉化疗栓塞+射频消融组的肿瘤坏死率达73.68％,明显高于单纯经导管肝动脉化疗栓塞组及单纯射频消融组(分别为50.00％和52.17％,P＜0.01或P＜0.05).局部复发率分别为26.32％、37.50％和30.43％,3组比较差异无统计学意义(P＞0.05).经导管肝动脉化疗栓塞+射频消融组的平均生存期为28.3个月,高于经导管肝动脉化疗栓塞组与单纯射频消融组(分别为13.6个月、21.7个月,P＜0.01或P＜0.05).结论 经导管肝动脉化疗栓塞联合射频消融治疗大肝癌与单纯经导管肝动脉化疗栓塞和单纯射频消融治疗效果相比,可提高肿瘤坏死率,延长患者生存期.     

肝细胞癌的综合介入治疗

肝细胞癌（HCC）是世界范围内第五大常见肿瘤,每年新增病例超过50万。由于HCC早期症状隐匿,大多数患者在确诊时已是中晚期,失去了接受治愈性治疗的机会。而中晚期HCC患者由于肝功能损伤及肿瘤进展致预后很差,目前,以肝动脉栓塞化疗术（TACE）为主的综合介入治疗已成为中晚期HCC的主要治疗方式。本文就HCC的综合介入治疗的最新进展综述如下。     

动态三维超声造影评估原发性肝细胞癌射频消融后的近期疗效

背景射频消融(radiofrequency ablation, RFA)在非手术治疗肝细胞癌(hepatocellular carcinoma, HCC)方面发挥着重要作用,而准确评估术后HCC残留状态对于临床制定下一步治疗方案有着重要指导意义.临床上常常采用各种影像学方法评估RFA疗效.超声因其具有无创、便捷、可重复等优点,在RFA疗效评估方面日益受到临床重视.其中动态三维超声造影(dynamic three-dimensionalcontrast-enhancedultrasound,3DCEUS)能动态显示肿瘤组织在三维立体空间下的血流灌注状态,有望为RFA疗效评估提供一种全新的影像学方法.目的运用3DCEUS评估原发性HCCRFA后的近期疗效,并探讨其临床价值.方法回顾性分析2016-03/2018-11期间,在嘉兴市第二医院接受超声引导下RFA的93例原发性HCC患者,共117个肿瘤.术后1 mo均接受3DCEUS检查,同期行增强磁共振成像(enhanced magnetic resonance imaging,CEMRI)检查.以CEMRI作为疗效评估"金标准",分析3DCEUS在评估RFA疗效中的效能.结果 CEMRI判定82.05%(96/117)的肿瘤完全消融,17.95%(21/117)的肿瘤消融不全;3DCEUS判定82.91%(97/117)的肿瘤完全消融,17.09%(20/117)的肿瘤消融不全.3DCEUS评估RFA后肿瘤残留的敏感度为90.48%(19/21)、特异度为98.96%(95/96)、准确率为97.44%(114/117)分别与CEMRI比较,差异均无统计学意义(P0.05).结论 3DCEUS能准确评估原发性HCCRFA后的近期疗效,具有较高临床应用价值.     

肝细胞肝癌射频术后肝内复发情况及其影响因素分析

目的探讨肝细胞肝癌射频灭活后肝内复发情况及其影响因素。方法2001年3月至2006年8月共47例患者55个肿瘤接受射频治疗。患者肝功能Child—Pugh分级为A或B级，肿瘤直径小于5cm，病灶数目不超过3个。随访肿瘤多发情况，时间6～71个月，射频后的肝内复发分为肿瘤局部复发与肝内远处转移。分析因素包括患者全身情况（有无肝炎肝硬化、肝功能Chilcl-Pugh分级、血清甲胎蛋白水平）、肿瘤局部情况（大小、位置、数目）与治疗方法。采用Kaplan-Meier模型计算无瘤生存期，Log—rank检验进行单因素分析，Cox比例风险模型进行多因素分析。结果全组共25例患者出现肝内复发，其中8例肿瘤局部复发，14例肝内远处转移，3例同时合并局部及远处转移。射频术后1、2、3年肝内累计无瘤生存率分别为57．3％、40，3％、35．3％。单因素Log—rank检验显示肝内复发与肿瘤大小、位置与肝功能Child-Pugh分级相关。Cox比例风险模型显示肿瘤大小和肝功能Child—Pugh分级是影响肿瘤局部复发的危险因素，肿瘤数目是影响肝内远处转移的危险因素。结论选择肝功能Child-PughA级，直径≤3cm的单发肿瘤患者进行射频治疗，有助于提高疗效，降低术后肝内复发的风险。     

Diffuse intrahepatic recurrence after percutaneous radiofrequency ablation for solitary and small hepatocellular carcinoma

Two patients developed segmental, diffuse intrahepatic recurrence after percutaneous radiofrequency ablation (RFA) to treat a primary, solitary, and small (2.5 cm) hepatocellular carcinoma (HCC). Despite the size of the HCC, levels of the tumor markers (α-fetoprotein, α-fetoprotein-L3%, and des-γ-carboxyprothrombin) were all elevated before RFA, and tumors in both patients were contiguous with a major branch of the portal vein. Tumor biopsies of both patients revealed moderately differentiated HCC but diagnostic imaging showed an area of reduced tumor blood flow, suggesting a poorly differentiated component. Since early detection of post-RFA malignancies by standard ultrasonography and contrast-enhanced computed tomography was difficult, the most sensitive indicator of recurrence in these two patients was the elevated tumor markers. The diffuse intrahepatic recurrence was thought to be caused by increased intratumoral pressure during RFA, resulting in the dissemination of cancer cells through the contiguous portal vein. The clinical course of these tumors indicate that the choice of RFA should be carefully considered when treating specific subtype of HCC that is adjacent to main portal vein branch and involves a possible poorly differentiated component and that surgical resection or combinations of RFA with other treatment modalities such as transcatheter arterial chemoembolization should be considered as alternative treatment strategies.     

Risk factors for the recurrence of hepatocellular carcinoma after radiofrequency ablation of hepatocellular carcinoma in patients with hepatitis C

AIM: To analyze the risk factors of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation (RFA) treatment with HCV-associated hepatitis. METHODS: Twenty-six patients with HCV-associated HCC who were followed-up for more than 12 mo were selected for this study. Risk factors for distant intrahepatic recurrences of HCC were evaluated for patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule.Twelve clinical and tumoral factors were examined: Age, gender, nodule diameter, number of primary HCC nodule, Child-Pugh classification, serum platelet, serum albumin, serum AST, post RFA AST, serum ALT, post RFA ALT, post RFA treatment. RESULTS: Distant recurrences of HCC in remnant liver after RFA were observed in 14 cases and in the number of primary HCC nodules (P = 0.047), and the serum platelets (P = 0.030), the clear difference came out by the recurrence group and the non-recurrence group. The cumulative recurrence rates after 1 and 2 years were 30.8% and 86.8%, respectively for primary multinodular HCC, and 15.4% and 29.5% respectively, for primary uninodular HCC. In addition the 1-year recurrence rates for patients with serum albumin more than 3.4 g/dL and less than 3.4 g/dL were 23.1% for both, but the 2-years recurrence rates were 89.0% and 23.1%, respectively. The number of primary HCC nodules (relative risk, 6.970; P = 0.016) were found to be a statistically significant predictor for poor distant intrahepatic recurrence by univariate analysis. CONCLUSION: Patients who have multiple HCC nodules, low serum platelets and low serum albumin accompanied by HCV infection, should be carefully followed because of the high incidence of new HCC lesions in the remnant liver, even if coagulation RFA is complete.     

Scattered and rapid intrahepatic recurrences after radio frequency ablation for hepatocellular carcinoma

AIM: To evaluate a series of patients with hepatocellular carcinoma (HCC) treated with several different protocols and devices. METHODS: We treated 138 patients [chronic hepatitis/ liver cirrhosis (Child-Pugh A/B/C), 3/135 (107/25/3)] with two different devices and protocols: cool-tip needle [initial ablation at 60 W (standard method) (n = 37) or at 40 W (modified method) (n = 28)] or; ablation with a LeVeen needle using a standard single-step, full expansion (single-step) method (n = 39) or a multi-step, incremental expansion (multi-step) method. RESULTS: Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol (60 W) (9/37 = 24%) and the other two by the LeVeen single-step method (2/39 = 5%). The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one lobule or both lobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method (40 W) or the LeVeen multi-step method. CONCLUSION: There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool-tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.     

Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency.     

Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival

AIM: To evaluate outcomes of radiofrequency ablation(RFA) therapy for early hepatocellular carcinoma(HCC) and identify survival- and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography(CT) or magnetic resonance imaging(MRI)(single nodule of ≤ 5 cm, or multi-(up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Cancer do Estado de S o Paulo, Brazil were enrolled in the study. RFA of the liver tumors(with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response(absence of enhancing tissue at the tumor site) or incomplete response(enhancing tissue remaining at the tumor site). Overall survival and diseasefree survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients(age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo(range, 1-33). The study population showed predominance of male sex(76%), less severe liver disease(Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor(65%). The maximum tumor diameters ranged from 10 to 50 mm(median, 26 mm). The initial(immediately post-procedure) rate of RFAinduced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule(vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema(resolved with intervention) and intestinal perforation(led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis(HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1-and 2-year cumulative disease-free survival rates were 65% and 36%, respectively. CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.     

Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: Risk factors and patterns

Background. The pathogenesis of frequent intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection or local ablation therapy remains uncertain. Risks and patterns of intrahepatic distant recurrence (IDR) of a single, primary HCC lesion after radiofrequency (RF) ablation were examined. Methods. Ninety patients with a single primary HCC lesion of less than 3 cm who had complete RF ablation were enrolled in the study. Risk factors for IDR and the patterns of IDR after RF ablation were analyzed. Results. The median follow-up was 37.4 months. IDR was observed in 44 (48.9%) patients. The cumulative rate of IDR was 10.4%, 52.5%, and 77.0% at 1, 3, and 5 years, respectively. Univariate analysis revealed that a pretreatment serum α-fetoprotein (AFP) level of ≥50 ng/ml (P = 0.0324), a des-γ-carboxy prothrombin (DCP) level of ≥40 mAu/ml (P = 0.006), an ablative margin of <5 mm of the ablation zone (P = 0.0306), and a prothrombin time of <70% (P = 0.0188) were related to IDR. A multivariate stepwise Cox proportional hazards regression model revealed that pretreatment serum AFP and DCP level and the ablative margin were independent risk factors for IDR pretreatment. Serum DCP level ≥ 40 mAu/ml (P = 0.025), local tumor progression (P = 0.011), and ablative margin < 5 mm (P = 0.024) were related to multiple IDR. Conclusions. HCC patients with high serum AFP or DCP before RF ablation should be carefully followed up to monitor any IDR. A suffi cient ablative margin in RF ablation for HCC is required to prevent IDR.     

Risk factors of intrahepatic recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: Although the risk factors for the development of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) have been widely studied, little attention has been given to the prognostic factors affecting such patients. METHODOLOGY: Intrahepatic recurrence occurred in 105 (56%) of 188 patients who underwent curative hepatic resection of HCC and were discharged from the hospital. Among them, 17 (16%) also had simultaneous extrahepatic recurrence. Independent prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that presence of extrahepatic recurrence, hepatitis B, and non-surgical treatments for recurrence were independent predictors of poor overall survival after initial hepatic resection or after recurrence. Risk factors of extrahepatic recurrence were young age, solitary and large HCC, high hepatitis activity, and large amount of intraoperative blood loss and blood transfusion. CONCLUSIONS: Survival of patients with intrahepatic recurrent HCC after resection should be stratified by the type of recurrence, type of hepatitis, and type of treatment for recurrence.