Results of liver resection in combination with radiofrequency ablation for hepatic malignancies

Introduction

Liver tumors should be surgically treated whenever possible. In the case of bilobar disease or coexisting liver cirrhosis, surgical options are limited. Radiofrequency ablation (RFA) has been successfully used for irresectable liver tumors. The combination of hepatic resection and RFA extends the feasibility of open surgical procedures in patients with liver metastases and hepatocellular carcinoma (HCC).

Patients and methods

RFA was performed with two different monopolar devices using ultrasound guidance. Intraoperative use of RFA for the treatment of liver metastases or HCC was limited to otherwise irresectable tumors during open surgical procedures including hepatic resections. Irresectability was considered if bilobar disease was treated, the functional hepatic reserve was impaired or appraised marginal for allowing further resection.

Results

Ten patients with both liver metastases and HCC, and two patients with cholangiocellular carcinoma were treated. Complete initial tumor clearance was achieved in all patients. Two patients of the metastases group and five patients of the HCC group suffered from local recurrence after a median of 12 months (1–26) (local recurrence rate 32%). Five patients of the metastases group and six patients of the HCC group developed recurrent tumors in different areas of the ablation site after a median time of 4 months (2–18) (distant intrahepatic recurrence in 55%). Survival at 31 months was 36%.

Conclusion

RFA extends the scope of surgery in some candidates with intraoperatively found irresectability.     

Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

BackgroundThe benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI.MethodsThe PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors.Results12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors.ConclusionAdjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies.Lay summaryThe benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.     

Two-stages resection for advanced hepatocellular carcinoma

We performed two-stage resection for sixteen patients with advanced hepatocellular carcinoma from January, 1987 to July, 1991. All patients underwent various surgical therapies prior to resection which included gauze packing hemostasis in 1 case, hyperthermia plus radiotherapy in 1, hepatic arterial ligation in 2, operative hepatic arterial embolization in 3, and transcatheter embolization in 9. The median interval between the first therapy and tumour resection was 59 days with a range of 29--769 days, and the median diameter of tumours decreased from 10.5 cm to 7.5 cm. The majority of precedures on two-stage resection were irregular hepatectomy or Iobectomy under occlusion of porta hepatis. Regular hepatectomies were done in 4 cases. Pathalogical examination showed complete coagulation necrosis in 3 specimens. However, in the others were still found residual viable tumours. Survival periods of the patients who received two-stage resection were from 4 months to 4 years except 2 operative death. The significance, possibility as well as methods of two-stage resection were discussed.     

External validation of a simplified BCLC staging system for early hepatocellular carcinoma

Background and aims

The aim was to externally validate the capability of a simplified Barcelona Clinic Liver Cancer (s-BCLC) staging system in allocating patients to hepatic resection (HR) and the effect on survival: S-BCLC was defined by only 2 groups: AA included BCLC A1 + A2 classes with alpha-fetoprotein (AFP) ≤ 20 ng/ml and AB included A1 + A2 with AFP > 20 ng/ml plus A3 + A4 subgroups.

Methods

This study compared a training group (TG) with hepatocellular carcinoma (HCC) submitted to hepatic resection (HR) in Milan with another group of patients, the validation group (VG) in Creteil. All patients underwent ultrasound-guided anatomical resection (<3 segments).

Results

Overall survival got worse from A1 to A4 (p = 0.0271) in TG (n = 132), as well as in VG (n = 100) (p = 0.0044) with a more important overlapping of each curves. According s-BCLC classification, the survival curves of TG (p = 0.0001) and VG (p = 0.0250) showed a definitive separation in two different staging groups. The s-BCLC provided the best predictive accuracy and it also presented the highest separability index and C-statistics in both TG and VG. On the other hand, in the evaluation of discriminatory ability for death, measured by ROC curve areas, the s-BCLC system gave better results than the others.

Conclusion

This experience stressed the high value of BCLC system in staging of HCC, but the s-BCLC system seems to be more useful for therapeutic decision making.     

Therapeutic efficacy of multimodal combination therapy using transcatheter arterial infusion of epirubicin and cisplatin,systemic infusion of 5-fluorouracil,and additional percutaneous ethanol injection for unresectable hepatocellular carcinoma

Purpose Previous studies have shown that a treatment regimen using epirubicin, cisplatin, and 5-fluorouracil (5-FU) (ECF) has a survival benefit for gastric cancer patients. Based on these results and the hypothesis that a combination modality has a better therapeutic advantage over a single mode of therapy, the efficacy of multimodal combination therapy using a transarterial infusion of epirubicin and cisplatin, systemic infusion of 5-FU, and additional percutaneous ethanol injection (PEI) for unresectable hepatocellular carcinoma (HCC) was investigated in this study in comparison with conventional transarterial chemoembolization (TACE).Patients and methods From July 1997 to September 1998, a total of 52 patients with unresectable HCC who underwent at least two cycles of transarterial chemotherapy were enrolled in this study. Among the 52 patients, 30 (ECF group) received a multimodal combination therapy comprising transarterial infusion of epirubicin (50 mg/m²) and cisplatin (60 mg/m²), systemic infusion of 5-FU (200 mg/m²), and additional PEI every 4 weeks, and the remaining 22 (ADR group) received conventional TACE using Adriamycin (ADR, 50 mg) and Gelfoam every 8 weeks.Results During the follow-up period (mean 13.8±8.5 months), the objective tumor response of the ECF group was significantly higher than that of the ADR group (53.3 vs 22.7%, P=0.044). The median survival time was 13.5 months for the ECF group and 10.5 months for the ADR group (P=0.026). The cumulative survival rates at 6, 12, 18, and 24 months, respectively, were 90, 57, 27, and 17% for the ECF group and 73, 37, 7, and 0% for the ADR group. Univariate analysis showed five prognostic factors including tumor number, tumor morphology, portal vein thrombosis, Child-Pugh classification, and tumor response. With multivariate analysis, portal vein thrombosis and tumor response were identified as the two independent factors for survival. No serious adverse effect was observed in the ECF group, while there was a higher tendency for hepatic complications in the ADR group.Conclusions Combination therapy comprising transarterial infusion of epirubicin and cisplatin, systemic infusion of 5-FU, and additional PEI appears to be feasible and promising as a multimodal approach for unresectable HCC. Furthermore, it may provide a survival benefit for patients with more advanced disease.     

经皮肝穿刺注射无水乙醇配合肝动脉化疗栓塞术治疗原发性肝癌

目的 研究B超引导下经皮肝穿刺注射无水乙醇（percutaneous ethanol injection,PEI)配合肝动脉化疗栓塞术（transcatheter hepatic arterial chemoembolization,TACE)治疗原发性肝癌的疗效。方法 原发性肝癌87例,其中TACE组45例,TACE＋PEI组42例。结果 TACE组1,2,3年生存率分别为66．7％、41．2％和21．4％,组织学检查仅26．1％的病变完全坏死;TACE＋PEI组1,2,3年生存率分别为97．1％、85．7％和65．7％,组织学检查81．8％的病变完全坏死。两组间在生存率和肿瘤完全坏死率间差异均有显著性（P＜0．05）。结论 对于原发性肝癌,TACE＋PEI疗效优于单纯TACE,是一种较好的综合治疗方法。     

基于索拉非尼的联合治疗对晚期肝癌的疗效观察

目的　观察基于索拉非尼联合多种治疗手段综合治疗晚期肝癌的疗效。方法　２００８年１２月至２００９年１２月共８例患者应用索拉非尼联合其它３种以上的治疗方法,如ＴＡＣＥ、射频消融、放射性粒子植入、三维适形放疗和免疫治疗。按照ＲＥＣＩＳＴ标准对其疗效进行评价。结果　８例患者用４种治疗方法的４例,５种３例,６种１例。疗效评估获ＰＲ３例,ＳＤ４例,ＰＤ１例。所有患者的毒副反应均经对症处理后缓解,无严重不良反应发生。结论　基于索拉非尼的联合多种治疗手段的综合治疗模式可提高晚期肝癌的疗效     

肝动脉栓塞联合三维放射治疗肝癌的疗效评价

目的 评估经首次导管化疗栓塞(TACE)后,碘油栓塞不完全的中晚期肝细胞癌患者序贯适形外放射治疗的疗效及毒副作用。方法 2008年1月—2010年1月,纳入首次栓塞不完全的50例中晚期肝细胞癌患者,随机分两组,25例患者依据病情进行2~3次单纯TACE,25例序贯采用三维适型外放射补充治疗。测量肿瘤大小变化评价肿瘤的反应,评估治疗毒副作用。结果 单纯TACE组治疗前后平均肿瘤直径分别为(8.37±9.15)cm和(4.22±5.66)cm;TACE放疗组治疗前后平均肿瘤直径分别为(8.65±6.89)cm和(3.86±4.32)cm。两组治疗前后比较差异具有统计学意义,两组间比较无统计学意义。TACE放疗组总有效率为52%,完全反应16%,部分反应36%。两组患者12个月生存率分别为48%和64.0%,差异具有统计学意义(P＜0.05)。没有出现三级及更高级别的毒副作用。结论 对首次栓塞不完全的肝细胞癌患者,序贯采用三维适型外放射补充治疗能有效的提高患者的生存率,且毒副作用可以耐受。     

３５８例肝细胞癌综合治疗的预后分析

目的　探讨不同治疗方法对非手术肝细胞癌患者预后的影响。方法　回顾性分析我院肿瘤中心２００３年７月至２００７年１２月收治的３５８例肝癌患者,建立病例资料数据库,应用Ｋａｐｌａｎ-Ｍｅｉｅｒ方法计算生存期,对相关因素采用Ｌｏｇ-ｒａｎｋ检验进行生存率的单因素分析以及Ｃｏｘ风险比例模型进行多因素分析,筛选出独立预后因素。结果　３５８例患者中位总生存时间（ＯＳ）为１３个月。１、２、３年生存率分别为５５.７％、２３.９％和１１.０％。ＵＩＣＣ分期Ⅰ、Ⅱ、ⅢＡ、ⅢＢ和Ⅳ期患者中位ＯＳ分别为２６、２４、１３、９和１１个月。病灶数目、肿瘤大小、临床分期、Ｃｈｉｌｄ分级、ＡＦＰ水平、门脉癌栓和体质评分均为影响患者的预后因素,进一步多因素Ｃｏｘ风险比例模型分析显示,临床分期、Ｃｈｉｌｄ分级、肿瘤体积、门脉癌栓为独立的预后因素。２７例单独ＴＡＣＥ治疗患者的中位ＯＳ为１２个月,１８４例单独立体定向放疗患者的中位ＯＳ为１１个月,ＴＡＣＥ加立体定向放射治疗３７例患者的中位ＯＳ为１７个月,１８例重组人ｐ５３腺病毒注射液联合放化疗患者的中位ＯＳ为２２个月。结论　肝癌综合治疗的疗效显著高于单一治疗,可以根据临床分期、Ｃｈｉｌｄ分级、肿瘤体积和体质评分选择合适的治疗方法,尤其是多种治疗方法的序贯和同步联合治疗。     

Regorafenib联合TAS102新策略治疗肝细胞癌的研究

背景 与目的:瑞格菲尼(regorafenib,REG)和TAS102是治疗消化道肿瘤的新型药物.嘧啶类药物5-氟尿嘧啶(5-fluorouracil,5-FU)联合REG可抑制多药耐药转移性结肠癌的进展.肿瘤干细胞(cancer stem cell,CSC)决定肿瘤的自我更新,异质性及治疗耐受等,靶向CSC为治愈肿瘤...     

肝脏残留癌的动脉化疗栓塞及预后因素分析

目的 研究肝动脉化疗栓塞（transcather arterial chemoembolization,TACE)治疗原发性肝癌切除术后残癌的疗效,并分析影响疗效的因素。方法 原发性肝癌患者于术后2个月行B超和肝动脉造影检查,部分患者还行增强CT检查、证实残癌后行TACE。采用Kaplan-Meier方法分析TACE患者术后的生存期,以Cox比例风险模型分析影响TACE疗效的因素。结果 74例术后残癌患者经TACE术后,1,2,3年生存率分别为78．0％、57．6％和37．0％,中位生存期为33个月。单因素分析显示,原发癌体积＞5cm、有血管侵犯、TNM分期较晚为疗效差的影响因素;而合用其他局部治疗,如瘤内无水乙醇注射（PEI）或放射治疗则为疗效好的影响因素。但多因素分析显示,原发癌血管侵犯和合用其他局部治疗为独立的影响因素。结论 肝动脉化疗栓塞治疗术后残癌可取得较好疗效,如能合用PEI或放射治疗,还可进一步提高疗效。     

Continuous improvements in short and long-term outcomes after partial hepatectomy for hepatocellular carcinoma in the 21st century: Single institution experience with 1300 resections over 18 years

IntroductionTo investigate the changing trends in short- and long-term outcomes after partial hepatectomy(PH) for hepatocellular carcinoma(HCC) performed in the 21st century.MethodsA retrospective review was conducted on 1300 consecutive patients who underwent PH for HCC. The study cohort was divided into 3 time periods(P): P1(2000–2005), P2(2006–2011) and P3(20012-2017).ResultsComparison between the patients’ baseline demographic features across the 3 periods demonstrated that patients were significantly older, had decreasing frequency of hepatitis B, increasing non-alcoholic fatty liver disease, lower alpha-feto protein(AFP) level, lower creatinine levels, less likely to undergo emergency surgery, less likely to undergo major hepatectomy, more likely to undergo repeat resection and minimally-invasive surgery. There was also an increase in operation time, decrease in blood loss, increase frequency in the use of Pringles manoeuvre, decrease liver failure, decrease length of stay and decrease postoperative mortality. HCC resected were of smaller size, less likely to demonstrate microvascular invasion and less likely to have close margins. This was associated with significant improvement in overall survival and recurrence free interval over time. Period of resection was an independent predictor of 90-day mortality and OS on multivariate analysis.ConclusionWe observed a continuous improvement in postoperative outcomes including postoperative mortality and long-term survival after PH for HCC over the past 18 years.     

脾动脉部分栓塞联合肝动脉化疗栓塞治疗原发性肝细胞癌合并脾亢的临床研究

背景与目的：原发性肝细胞癌（primary hepatocellular carcinoma,PHC）患者70％-90%有肝硬化、脾功能亢进以致患者术前外周血象偏低或术后外周血象恢复缓慢常影响经肝动脉化疗栓塞（transcatheter hepatic arterial chemoembolization,TACE）的正常进行。本研究探讨脾动脉部分栓塞（partial splenic embolization,PSE）联合经TACE治疗合并脾功能亢进的PHC的方法和意义。方法：对26例PHC患者采用PSE联合TACE治疗的方法,26例PHC患者单用TACE治疗。结果：PSE联合TACE较单用TACE治疗明显改善PHC患者外周血象,PSE术后3天、1周、2周及4周外周血白细胞、红细胞、血小板较栓塞前明显提高。结论：PSE联合TACE是PHC合并脾亢的安全、有效治疗方法。     

高强度聚焦超声联合动脉栓塞化疗治疗晚期肝癌的初步临床研究

目的　探讨高强度聚焦超声 (HIFU)联合经动脉栓塞化疗 (TACE)治疗晚期肝癌的有效性。方法　 5 0例不能手术切除的晚期肝癌患者 (TNM分期Ⅳ期 )随机分为两组 :(1)单纯TACE组 2 6例 ;(2 )HIFU联合TACE组 2 4例 ,在TACE治疗后 2～ 3周 ,接受HIFU治疗。全部患者随访 3～ 2 4个月 ,平均 (8.16± 2 .79)个月。应用Kaplan Meier等统计学方法分别比较了两组患者的中位生存时间、6个月和 1年生存率、死亡患者平均生存时间。结果　HIFU联合TACE治疗组患者的中位生存时间为11.3个月 ,6个月和 1年生存率分别为 80 .4 %～ 85 .4 %和 4 2 .9% ;而TACE治疗组患者的中位生存时间为 4个月 ,6个月和 1年生存率分别为 13.2 %和 0 % ,两组比较 ,差异有显著性 (P <0 .0 1)。HIFU联合TACE治疗组死亡患者的平均生存时间为 (10 .2 1± 4 .12 )个月 ,而TACE组患者为 (4 .35± 2 .39)个月 ,两组比较 ,差异有显著性 (P <0 .0 1)。结论　HIFU联合TACE治疗晚期肝癌患者的疗效明显优于单纯TACE ,此联合治疗有望成为不能手术切除肝癌的一种有效手段。     

A preoperative model for predicting early recurrence in patients undergoing resection for single hepatocellular carcinoma

Background and aimThe updated Barcelona Clinic Liver Cancer guidelines recommend liver resection (LR) for patients with single hepatocellular carcinoma (HCC) of any size. This study developed a preoperative model for predicting early recurrence in patients undergoing LR for single HCC.Materials and methodsWe identified 773 patients undergoing LR for single HCC between 2011 and 2017 from the cancer registry database of our institution. Multivariate Cox regression analyses were performed to construct a preoperative model for predicting early recurrence, i.e., recurrence within 2 years of LR.ResultsEarly recurrence was identified in 219 patients (28.3%). The final model of early recurrence included four predictive factors—alpha-fetoprotein level of ≥20 ng/mL, tumor size of >30 mm, Model for End-Stage Liver Disease score of >8, and cirrhosis. Preoperative application of this model provided three risk strata for recurrence-free survival (RFS): low risk, with 2-year RFS of 79.8% (95% confidence interval [CI]: 75.7–84.2%); intermediate risk, with 2-year RFS of 66.6% (95% CI: 61.1–72.6%); and high risk, with 2-year RFS of 51.1% (95% CI: 43.0–60.8%).ConclusionWe developed a preoperative model for predicting early recurrence after LR for single HCC. This model provides useful information for clinical decision-making.     

经导管动脉化疗栓塞治疗肝细胞癌的疗效观察

目的研究经导管动脉化疗栓塞（TACE）治疗肝细胞癌（HCC）的疗效及对HCC预后的影响。方法经手术病理证实的HCC患者139例,其中TACE组81例,单纯手术组58例。用末端脱氧核苷转移酶介导的d—UTP毛地黄毒素缺口末端标记（TUNEL）法检测凋亡细胞,用免疫组化检测各标本bcl-2、bax、p53、增殖细胞核抗原（PCNA）和Ki-67蛋白表达,分析两组的肿瘤标志物改变、肿瘤坏死、包膜形成、体积、复发转移率及累计生存率。结果TACE可使肿瘤包膜形成、体积缩小,引起肿瘤坏死,诱导细胞凋亡,导致增殖转移潜能下降。TACE组患者的中位生存期为803．3d,1,2,3年生存率分别为84．0％、67．9％和40．7％;单纯手术组患者的中位生存期为742．5d,1,2,3年生存率分别为72．4％、55．2％和24．1％（P〈0．05）。结论TACE治疗HCC安全有效,可改善患者的生存率。     

大剂量碘油肝动脉栓塞化疗治疗巨块型肝癌

目的：探讨探讨大剂量碘油肝动塞化疗法巨块型原发性肝癌的方法和疗效。方法使用Seldinger方法,经股动脉做肝动塞化疗治疗肝癌,超液化碘油（lipiodol)的单次剂量为20－53ml,结果共3 163例患者接受大剂量碘油栓塞化疗,对ChildA级或吲哚靛青绿15min滞留率（ICG－R15）＜20％者,肝功能损害不大。术后CT碘油在瘤内的分布以完全型（Ⅰ型）和缺损型（Ⅱ型）多见。肝功能为ChildA级者,其1,2,3年生存率为79．8％、50．3％和38．5％,较常规剂量组高（P＝0．0136）。结论大剂量碘油肝动脉栓塞化疗治疗肝癌切实可行,疗效优于常南剂量的介入治疗,建议对肝功能分级为ChilA级或ICG－R15＜20％、肝右叶血管丰富的巨块型肝癌、采用20－40ml的大剂量碘油栓塞治疗,以使瘤床血管完全填塞,得到最佳栓塞效果。