Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion

Background

Microvascular invasion (MVI) has recently been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). This study compared the outcomes of adjuvant transarterial chemoembolization (A-TACE) after hepatic resection (HR) in patients with HCC involving MVI.

Anatomic versus non-anatomic resection of hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan–Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72–1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45–0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50–0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65–0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47–0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.     

合并微血管侵犯的肝癌肝移植受者的预后评价

目的  探讨合并微血管侵犯（MVI）的肝细胞癌（肝癌）肝移植受者的预后情况。方法  通过美国国立癌症研究所的监测、流行病学和最终结果（SEER）数据库提取行肝移植术的3 447例肝癌受者的临床资料。根据受者有否MVI分为MVI组（376例）和无MVI组（3 071例）。分析比较两组肝移植受者的预后情况,包括术后1、3、5年总生存率（OS）及肝癌特异生存率（LCSS）。纳入两组受者的相关临床资料,包括年龄、性别、人种、病理分化、肿瘤大小、淋巴结转移、远处转移、肿瘤-淋巴结-转移（TNM）分期、MVI,采用多因素Cox模型分析肝癌肝移植受者预后的独立危险因素。绘制预测受者预后的列线图,通过一致性指数评价模型准确度。结果  无MVI组受者术后1、3、5年OS和LCSS分别为93.5%、82.1%、75.3%和98.3%、93.8%、90.7%,明显高于MVI组的88.8%、72.1%、68.4%和95.3%、83.1%、80.4%（均为P < 0.05）。多因素回归分析显示病理分化、肿瘤大小、淋巴结转移、远处转移、TNM分期以及MVI均是影响肝癌肝移植受者OS与LCSS的独立危险因素（均为P < 0.05）。列线图一致性指数为0.624（0.602~0.648）。结论  MVI是肝癌肝移植受者预后的独立危险因素,与受者预后不良显著相关,以此为基础构建的列线图可预测患者预后情况。     

肝癌侵犯右膈肌的外科处理

目的 探讨肝癌合并右膈肌部分切除的适应证、手术方法、术中应注意的问题,总结肝癌侵犯右膈肌的外科处理经验.方法 对广东省东莞市人民医院1998年9月至2008年9月收治的27例肝癌合并右膈肌部分切除患者的临床资料进行回顾性分析.结果 全部病例手术均获得成功.切除肿瘤直径5.0～15.0(平均8.5)cm,合并切除右膈肌面积9.0～50(平均28.5)cm2,手术时间110～250(平均165)min,失血量450～2600(平均870)ml.术后病理证实膈肌侵犯者9例(33.3％).术后全部病例均见少量右胸积液.其他并发症包括慢性肝功能不全4例及术后早期出血、上消化道出血、胆汁瘘、膈下感染各1例.所有患者经相应处理后均康复出院,无围手术期死亡病例.术后19例接受综合治疗,6例拒治,2例失访.术后6个月、1年、2年、3年生存率分别为92.6％、81.5％、51.9％、33.3％.结论 右膈肌侵犯不是肝癌切除禁忌证.合并右膈肌部分切除安全可行,而且远期疗效比较满意.     

Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation

Microvascular invasion affects survival after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). We sought to identify preoperative predictors of microvascular invasion in patients with HCC who were candidates for OLT. A cohort of 245 patients who underwent resection for HCC and fulfilled the criteria for OLT (i.e., single tumors ≤5 cm or no more than three tumors S3 cm) were identified from a multi-institutional database. Thirty-three percent of the patients had pathologic evidence of microvascular invasion. Thirty percent of patients with single tumors and 47% with multiple tumors had microvascular invasion (P = 0.04). Only 25% of patients with tumors smaller than ≤2 cm had microvascular invasion, compared to 31% and 50% with tumors greater than 2 to 4 cm or larger than 4 cm, respectively (P = 0.01). Tumor grade was highly correlated with microvascular invasion: 12% of patients with well-differentiated tumors had microvascular invasion, compared to 29% and 50% with moderately or poorly differentiated tumors, respectively (P < 0.001). The independent predictors of microvascular invasion were tumor size greater than 4 cm (odds ratio [OR], 3.0, 95% confidence interval [CI], 1.2 to 7.1), and high tumor grade (OR, 6.3; 95% CI, 2.0 to 19.9). Tumor size and grade are strong predictors of microvascular invasion. A tumor biopsy with pathologic grading at the time of pretransplantation ablative therapy could improve selection of patients with HCC for OLT. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001. Supported by a T-32 Surgical Oncology Training Grant from the National Institutes of Health (N.F.E).     

基于肝细胞癌磁共振成像强化模式的术前微血管侵犯预测研究

目的:探讨肝细胞癌(HCC)患者术前肿瘤MRI影像学特征与强化模式在预测微血管侵犯(MVI)中的价值。方法:收集2017年1月至2019年6月在宁夏医科大学总医院行MRI检查并在肝胆外科行手术切除的孤立性HCC患者临床资料,按照术后病理诊断分为MVI(＋)与MVI(-)两组,分析MVI与HCC的扩散加权成像(DWI)信...     

早期肝癌的手术治疗:肝切除与肝移植比较

肝切除及肝移植被认为是可能治愈肝癌的主要方法.以往认为肝切除适合肝功能代偿良好的病人,而肝移植则适用肝功能不佳及肿瘤无法切除的病人.对于符合米兰标准的早期肝癌,哪种方式更适合?近年来,一些研究显示:肝移植病人在无瘤生存方面具有优势.但是由于肝移植相关并发症的存在,例如移植物排斥及免疫抑制等,在长期生存方面,肝移植并无明显优势.目前由于肝源紧张,肝癌病人在等待移植时,可能因肿瘤进展而失去移植机会.肝切除后补救性肝移植对于肝癌治疗同样是一个很好的策略.因此建议肝功能良好病人行肝切除治疗,必要时行补救性肝移植.如果等待肝源时间较短,可以选择肝移植而获得较好的无瘤生存.     

切缘宽度对原发性肝癌合并微血管侵犯患者并发症及预后的影响

目的探讨解剖性肝切除术不同切缘宽度对原发性肝癌合并微血管侵犯（MVI）患者术后并发症及预后的影响。 方法回顾性选取2016年10月至2018年12月于快速康复外科下行解剖性肝切除术的96例原发性肝癌合并MVI患者病例资料。根据手术切缘宽度分组为宽切缘组（切缘≥10 mm,n=39例）和窄切缘组（切缘<10 mm,n=57例）。观察两组患者术后并发症发生率及并发症分级;Kaplan-Meier生存曲线分析术后无复发生存（RFS）和总生存（OS）情况;COX回归模型分析不同切缘宽度对原发性肝癌合并MVI患者预后生存的影响。 结果宽切缘组患者术后并发症发生率为25.6%,窄切缘组患者并发症发生率为29.8%,两组并发症发生率及并发症Clavien-Dindo分级比较,差异均无统计学意义（P>0.05）。宽切缘组患者术后5年累积RFS为33.3%,累积OS为41.0%;窄切缘组患者术后5年累积RFS为24.6%,累积OS为36.8%。宽切缘组累积RFS高于窄切缘组（Log-Rank χ²=4.029,P=0.045）,两组累积OS差异无统计学意义（Log-Rank χ²=0.837,P=0.402）。肿瘤直径、临床分期Ⅲ-Ⅳ期、肿瘤数目、淋巴结转移、包膜完整性及切缘<10 mm是影响患者术后无复发生存的独立危险因素（P<0.05）;肿瘤直径>5 cm、肿瘤多发灶、淋巴结转移是影响患者总生存的独立危险因素（P<0.05）,术后辅助治疗是保护因素。 结论快速康复外科下解剖性肝切除术中宽切缘对原发性肝癌合并MVI患者术后并发症的发生没有影响,增加切缘宽度能够提高患者术后无复发生存率,但不改善总生存率。     

原发性细胞癌伴微血管侵犯的危险因素分析

目的探讨原发性肝细胞癌（hepatocellular carcinoma，HCC）伴微血管侵犯的危险因素。方法回顾性复习134例HCC切除术病人的临床资料，分析微血管侵犯与HCC病人临床理资料的相关性。结果134例HCC中46例（34．3％）有微血管侵犯。单因素分析显示肿瘤体积〉3cm、包膜缺失、组织分化恶性程度高、血清AFP阳性（〉20ng／ml）与微血管侵犯显著相关（P〈0．05），而病人年龄、性别、肝炎病毒感染、是否合并肝硬化、组织学类型与微血管侵犯之间无明显相关性。微血管侵犯与HCC大体卫星结节的形成成显著相关（P=0．001）。结论微血管侵犯是HCC的常见恶性事件，肿瘤体积〉3cm、包膜缺失、组织分化恶性程度高、血清AFP阳性是微血管侵犯的危险因素。     

中晚期肝癌的转化手术切除

原发性肝癌是我国常见恶性肿瘤之一,手术治疗是肝癌根治性治疗方式。对于评估为不可切除的部分中晚期肝癌病人,可以通过一些治疗手段将肿瘤转化为可切除,使这些病人得到手术治疗,获得更好的疗效。     

肝细胞癌伴MVI的危险因素分析

目的探讨肝细胞癌(HCC)发生微血管侵犯(MVI)的危险因素。方法回顾分析2018-06—2019-07间郑州大学第一附属医院行肝癌根治术的182例HCC患者的临床资料,其术后病理提示65例患者存在MVI、117例患者无MVI。对相关临床指标进行统计学分析,利用受试者工作特征曲线,取约登指数最大值确定各指标的临界值。应用χ2检验进行单因素分析和多因素Logistic回归模型分析得出,HCC患者伴MVI的危险因素,比值比(0R)和95%可信区间(95%CI)评价相关性。结果单因素分析结果显示HCC患者术前肿瘤直径>5 cm、AF P>20μg/L、AST>40 U/L、FAR>0.065、PLR>104.741、NLR>1.627、TBil>25μmol/L、肿瘤数目>1、Alb≤35 g/L、INR>1.025,以及术后Edmondson-Steiner病理分级与MVI的发生有关;多因素Logistic回归分析显示:术前肿瘤直径>5 cm(OR=3.549、95%CI:1.628~7.373,P=0.001)、NLR>1.627(OR=3.620、95%CI:1.338~9.798,P=0.011)、肿瘤多发(OR=3.723,95%CI:1.342~10.325,P=0.012)、INR>1.025(OR=3.094,95%CI:1.446~6.617,P=0.004),以及AF P>20μg/L(OR=3.313、95%CI:1.471~7.464,P=0.004)是HCC发生MⅥ的独立危险因素。结论术前肿瘤直径、NLR>1.627、肿瘤多发、INR以及AFP水平是HCC患者伴MVI的独立危险因素。     

Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation

BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular invasion appears to be a significant risk factor for tumor recurrence. Therefore, it was the aim of this study to investigate tumor differentiation and microvascular invasion in relation to tumor number and size and their impact on survival after transplantation. PATIENTS AND METHODS: In 97 adult HCC patients who underwent OLT between June 1985 and December 2005 the incidence of microvascular invasion, tumor differentiation, and the number and size of tumor lesions were analyzed retrospectively. Their impact on survival was studied by multivariate analysis. RESULTS: Microvascular invasion was the only independent negative predictor of survival after OLT for HCC (p = 0.025). Tumor size > 5 cm was predictive for microvascular invasion (p = 0.007). In contrast, tumor number did not affect the incidence of microvascular invasion or cumulative survival. CONCLUSION: The size of the largest HCC lesion, but not the number of tumors, determined microvascular invasion, a predictor of the outcome following OLT for HCC. Thus, the number of HCC lesions should not be applied to patient selection prior to OLT. These data support the extension of the Milan criteria for the selection of HCC patients for OLT with regard to tumor number, but not tumor size.     

Current status of surgery and transplantation in the management of hepatocellular carcinoma: an overview

Despite many therapeutic advances in the field of hepatocellular carcinoma over the past two decades, this disease continues to be a major cause of cancer-related mortality worldwide. This review focuses on the recent advances in surgical technique, perioperative management, and transplantation of cirrhotic and noncirrhotic patients with hepatocellular carcinoma. Liver resection continues to be the mainstay of curative treatment in noncirrhotic patients and selected cirrhotic patients with small tumors and preserved liver function. Transplantation should be advocated for patients with poor liver function and localized lesions or for patients with large fibrolamellar carcinomas that are otherwise unresectable. Surgery has a definite role in the management of hepatic recurrences in the absence of systemic dissemination. Newer advances in the therapeutic armamentarium, such as cryotherapy, radiofrequency ablation, microwave coagulation, and ethanol injections are discussed, and their overall efficacy assessed. Received: December 25, 2000 / Accepted: April 16, 2001     

A review of the prognostic factors in patients with recurrence after liver resection for hepatocellular carcinoma

BACKGROUND: Liver transplantation achieves better results when hepatocellular carcinoma fits the Milan criteria. This study investigated predictors of recurrent hepatocellular carcinoma exceeding the Milan criteria. METHODS: Among 285 patients with hepatocellular carcinoma fitting the Milan criteria who underwent curative resection, 143 patients suffered initial recurrence (92 had tumors fitting the criteria) and 71 patients suffered a second recurrence (40 conforming tumors). RESULTS: Survival after hepatectomy was significantly worse when initial recurrence was nonconforming. Similarly, survival after initial recurrence was significantly worse when the second recurrence was nonconforming. A preoperative increase of protein induced by vitamin K absence/antagonist II, a tumor diameter of 3 cm or greater, age of 65 years or younger, and intraoperative blood transfusion increased the risk of nonconforming initial recurrence. CONCLUSIONS: Liver transplantation should be considered initially for younger patients with hepatocellular carcinoma fitting the Milan criteria, larger tumors, and an increase of protein induced by vitamin K absence/antagonist II.     

符合杭州标准肝癌肝移植受者术前接受经导管动脉化疗栓塞术治疗对术后疗效影响临床分析

目的分析符合杭州标准肝癌肝移植受者术前接受经导管动脉化疗栓塞术(TACE)治疗对术后肿瘤复发和受者生存情况的影响。 方法回顾性分析2008年1月至2018年12月在中国人民解放军联勤保障部队第九〇〇医院收治的92例符合杭州标准并行肝移植治疗的肝移植受者临床资料,所有受者均经术后病理检查证实为肝细胞癌。根据受者肝移植术前是否接受TACE治疗将其分为TACE治疗组(n＝58)和直接移植组(n＝34)。符合正态分布计量资料采用成组t检验比较,不符合正态分布计量资料采用Mann-Whitney U检验比较,计数资料采用卡方检验或Fisher确切概率法比较。采用Kaplan-Meier法进行生存分析,并采用log-rank检验进行比较。P<0.05为差异有统计学意义。 结果随访截至2021年12月31日,92例受者术后平均随访时间为(77±48)个月,随访期间共32例受者肿瘤复发。92例受者中9例术前合并门静脉癌栓(PVTT),术前影像学检查均未发现有门静脉侵犯,术后病理提示存在微静脉癌栓,均属于PVTT Ⅰ₀型,9例受者中6例移植术后肿瘤复发,平均无瘤生存时间为(51±48)个月,7例死亡,平均生存时间为(62±43)个月。TACE治疗组受者术后1、3和5年生存率分别为96.6%、84.5%和82.8%,直接移植组分别为91.2%、67.6%和61.8%,两组受者术后1、3年生存率差异均无统计学意义(χ²＝1.205和3.571,P均>0.05);两组受者术后5年生存率差异有统计学意义(χ²＝5.039,P<0.05)。TACE治疗组受者术后1、3和5年无瘤生存率分别为87.9%、77.6%和75.9%,直接移植组分别为76.5%、58.8%和52.9%,两组受者术后1、3年无瘤生存率差异均无统计学意义(χ²＝2.063和3.639,P均>0.05);两组受者术后5年无瘤生存率差异有统计学意义(χ²＝5.124,P<0.05)。两组受者术后生存率及术后无瘤生存率差异均有统计学意义(χ²＝5.013和5.406,P<0.05)。 结论对于符合杭州标准的肝癌肝移植受者,术前接受TACE治疗可能改善移植术后长期疗效。     

Liver transplantation for hepatocellular carcinoma: prognostic factors associated long-term survival

Abstract  Between December 1985 and February 1995, 260 orthotopic liver transplantations (OLTX) were performed on 238 patients at Niguarda Hospital. Sixty-three patients had hepatocellular carcinoma (HCC); in 13 of the patients HCC was incidental. All patients had negative lymph nodes. According to the Child classification, 13 patients were Child A, 30 Child B, and 18 Child C. According to the TNM classification, 11 patients were stage I, 22 stage II, 15 stage III, and 15 stage IVa. Pre-OLTX chemoem-bolization was performed on 25 patients. The perioperative mortality rate was 27 % (17 patients). Overall survival and disease-free actuarial survival rates at 1, 3, and 5 years were 94 %, 76 %, 76 %, and 83 %, 75 %, 75 %, respectively. Survival curves were compared for 16 different variables. No difference was observed for all parameters analyzed except tumor site, TNM stage, pre-OLTX AFP levels and vascular infiltration. These results seem to demonstrate that the OLTX for un-resectable HCC can be considered in specifically selected cases as the treatment of choice. An adequate tumor staging is also necessary for a better patient selection in order to increase survival.     

影响肝癌肝移植预后的主要因素和抗肿瘤治疗

目的：总结肝细胞癌（hepatocellular carcinoma，HCC）肝移植的临床经验，探讨影响HCC肝移植预后的主要因素和综合抗肿瘤措施。方法：回顾分析我院1999年2月至2004年12月施行的98例HCC肝移植的临床资料和随访结果。分别按是否有门静脉主干或分支癌栓（portal vein tumor thrombi，PVTT）和原发肿瘤是否＞6．5cm为标准将病例分为4组，用Kaplan—Meier方法计算全组和各组的累积生存率，用Log—Rank检验比较组间生存率的差异。结果：随访时间1～78个月，中位时间37．6个月，全组1、3和5年累计生存率分别为84．9％、49.3％和33．2％。1、3和5年无瘤生存率分别为71.2％、42．4％和29．1％。原发肿瘤＜6．5cm和无PVTT组与另外两组的生存率有显著性差异。结论：原发肿瘤大小和PV’丌是影响HCC肝移植预后的主要因素，综合抗肿瘤措施有助于提高HCC肝移植的整体疗效。     

肝细胞癌微血管侵犯的危险因素及其对预后的影响分析

背景与目的 肝细胞癌（HCC）在我国属于较常见的恶性肿瘤,根治性切除是其首选治疗方式,但是术后复发仍然严重影响患者的预后。在众多影响因素中,微血管侵犯（MVI）被认为是HCC患者术后复发风险的重要预测指标。因此,本研究探讨HCC患者MVI的危险因素及MVI对根治术术后预后的影响,以期为临床治疗提供更多的参考指标。方法 回顾性收集2017年2月—2020年2月中国人民解放军联勤保障部队第九〇四医院肝胆外科收治的150例行HCC根治术患者的临床病理资料。病理检查证实42例有MVI,108例无MVI,通过两组患者的临床数据分析MVI的影响因素,通过随访数据分析两组患者术后的生存情况。结果 单变量分析结果显示,肿瘤最大直径、术前甲胎蛋白（AFP）、术前血小板（PLT）与HCC患者MVI发生有关（均P<0.05）。多变量分析结果显示,肿瘤最大直径（>5 cm）、术前AFP（≥400 μg/L）、术前PLT（>200×10⁹/L）也是HCC患者MVI发生的独立危险因素（均P<0.05）。150例患者均获得随访,随访时间范围12~48个月,中位时间为26个月。与无MVI患者比较,有MVI患者术后1、2年总体生存率明显降低（76.19% vs. 91.67%,P<0.05;47.20% vs. 78.70%,P<0.05）,中位生存时间明显缩短（23个月 vs. 34个月,P<0.05）。结论 肿瘤较大、术前AFP与PLT水平较高的HCC患者发生MVI的风险升高,对于此类患者应进行严格的术后随访,以便一旦出现复发征象及时进行后续治疗,改善患者生存。