Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.     

The effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis

BackgroundA comprehensive re-evaluation on the role of trans-arterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma.MethodsA thorough database searching was performed in PubMed, EMBASE, and the Cochrane Library. Eligible studies were restricted to comparative studies between TACE and non-TACE cohorts. RevMan5.3 software and Stata 13.0 software were used for statistical analyses. The primary endpoint of our study was long-term survival.ResultsA total of 11 studies with 2036 patients were finally identified. Pooled results revealed that patients receiving TACE had a significantly better overall survival (OS) versus those without TACE (P < 0.05). Subgroup analyses were performed according to different types of TACE. Prophylactic post-surgical TACE (PPTACE) was associated with a significantly better OS versus those without PPTACE (P < 0.05). Palliative TACE (PTACE) also achieved a significantly better OS compared with those with supportive treatment (ST) only (P < 0.00001). However, TACE had no impact on disease-free survival (P = 0.87) and was less effective than surgical resection (P = 0.003).ConclusionPPTACE has a remarkable impact on OS versus those with surgical resections only and should be regularly performed. Regarding patients with unresectable disease, apart from conventional ST, adjuvant PTACE is also recommended. Upcoming prospective randomized controlled trials are warranted for further validation.     

Top advances of the year: Hepatobiliary cancers

This commentary reviews top advances in hepatobiliary cancer research in 2021–2022, focusing on leveraging immunotherapeutics in combination with other therapies earlier in the disease course and targeted to patient's individualized biomarkers that may predict response or resistance to checkpoint inhibitors.     

A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

肝内胆管癌多学科综合治疗优化选择

肝内胆管癌（ICC）作为第二常见的肝脏恶性肿瘤，虽然R0根治性切除是首选的可治愈方法，但ICC诊断时仅12%～40%病人可获得手术根治的机会，手术后5年存活率也仅为25%～40%。通过辅助化疗和区域治疗降期后可使部分晚期ICC病人获得行根治性手术或肝移植的机会。靶向药物和免疫治疗作为有益的补充，对于有基因突变作用靶点的选择性病人可能会延长生存期。以肝胆外科为主，包含影像科、病理科、肿瘤化疗科、放疗科和介入科的多学科诊疗团队，通过多学科讨论模式，结合病人具体病情，采取个体化、综合化的治疗手段，才能使ICC病人获得最优化的治疗选择。     

肝内胆管癌术前评估要点

肝内胆管癌（ICC）是发病率仅次于肝细胞癌的原发性肝癌，其恶性程度高，预后差。近年来，ICC的发病率逐步上升。根治性手术切除是目前可能使病人获得长期生存最有效的治疗方式，但根治性切除率低、术后复发率高仍是外科医生和ICC病人共同面临的巨大阻碍。然而由于ICC发病隐匿和恶性程度高的特性使很多病人初诊时便丧失了手术治疗的机会。因此，早期筛查、准确临床诊断、充分术前评估及完备精准的手术方案是手术赖以顺利实施的保障。癌胚抗原（CEA）和CA19-9对ICC的诊断具有一定价值。影像学检查是诊断ICC的最重要手段。腹部超声是临床第一线的早期筛查手段；CT和MRI是临床上用于ICC最常用的影像学检查。三维重建技术为术前残肝体积预估，手术方案制定提供更直接更精准的信息。建立能准确预测ICC预后的分期系统非常重要。术前减黄是否需要尚存争议。残肝体积和肿瘤是否转移是判断手术可切除性的两个要点。腹腔镜探查、腹腔镜超声检查及术中快速冷冻活检是判断是否可实施根治性切除的重要手段。     

基于TCGA数据初步探查肝内胆管癌预后相关基因

目的 分析tCGA数据库中肝内胆管癌（ICC）高通量测序数据，寻找其预后相关基因，构建风险模型，并研究其在ICC组织中表达及作用通路。方法 下载tCGA数据库中33例ICC组织和8例癌旁组织中的RNA-seq表达矩阵数据和患者临床资料信息，利用edgeR软件包进行基因差异表达分析，通过单因素Cox回归分析筛选出预后相关差异基因，对差异基因绘制生存曲线，筛选出具有临床意义的基因，经多因素Cox回归分析并构建风险模型，通过京都基因与基因组百科全书（KEGG）通路富集分析了解预后相关基因的作用通路。结果 通过edgeR分析后得到6 617个差异基因（筛选标准为|log2 Fold Change|＞1，P＜0.05），其中高表达组4 094个，低表达组2 523个。通过功能富集发现，这些基因主要集中在化学物致癌作用、药物代谢-细胞色素P450系统、细胞色素P450对异生物质的代谢影响以及视黄醇代谢通路。经单因素Cox回归、R软件“survival”包生存曲线分析显示，UCN2、CST1、PROS1、SLC35E4、PEMT五个基因对ICC患者预后存在显著性影响。通过多因素Cox回归分析，CST1、PEMT、PROS1构建的风险模型对ICC患者预后具有判断作用。结论 UCN2、CST1、PROS1、SLC35E4、PEMT基因可能成为ICC预后判断指标，为后续临床试验提供数据支持。     

Is laparoscopic liver resection safe for intrahepatic cholangiocarcinoma? A meta-analysis

BackgroundThe use of laparoscopic liver resection for curative surgery of intrahepatic cholangiocarcinoma (ICC) is not well established. Herein, we perform a meta-analysis to compare the differences between laparoscopic liver resection (LLR) and open liver resection (OLR) for ICC.MethodsMultiple electronic databases were searched and 8 relevant studies containing 552 patients treated by LLR and 2320 treated by OLR were identified. The fixed effects and a random-effects model were used to perform a meta-analysis.ResultsCompared with OLR, LLR for ICC was associated with less blood transfusion (7.14% versus 17.11%; OR: 0.32; 95% CI 0.15 to 0.71; P < 0.05), higher R0 resection (85.63% versus 74.69%; OR: 1.48; 95% CI 1.13 to 1.95; P < 0.05), shorter length of stay (LOS) (SMD: −0.40; 95% CI -0.80 to 0.00; P = 0.05), less overall morbidities (20% versus 32.69%; OR: 0.50; 95% CI 0.33 to 0.78; P < 0.05), and less death due to tumor recurrence (22.39% versus 35.48%; OR: 0.50; 95% CI 0.29 to 0.86; P <0.05); but LLR was associated with smaller ICC, fewer major hepatectomies, less lymph node (LN) dissection rate, and inferior 5-year overall survival (OS) (P < 0.05). Duration of operation, blood loss, average LN retrieved, LN metastasis, major morbidities, mortality, tumor recurrence, 3-year OS and disease free survival (DFS), and 5-year DFS were comparable (P >0.05).ConclusionLLR for ICC is in the initial phase of exploration. More evidence is necessary to validate LLR for ICC.     

腹腔镜根治性切除治疗肝门部胆管癌15例分析

目的 探讨腹腔镜根治性切除治疗肝门部胆管癌的可行性及安全性。方法 回顾性分析2013年5月至2018年5月在川北医学院附属医院行根治性手术治疗并经病理学检查证实的15例肝门部胆管癌病人的临床资料，分析术中及术后情况，并随访观察。结果 15例肝门部胆管癌病人中13例行完全腹腔镜手术，2例病人中转开放手术。手术时间为（404.3±62.8）min，术中出血（502.0±133.8）mL，术后住院时间为（9.6±2.7）d，术后首次排气时间为（3.2±0.8）d。术后淋巴结检出数目为（9.5±2.6）枚，1例发现N2淋巴结转移。术后发生胆漏1例，大量腹腔积液1例，切口脂肪液化1例，均经保守治疗后好转出院。所有病人均获得随访，截至2018年5月，随访时间为6～60个月，死亡4例。结论 通过术前充分评估及术中探查制定相应手术策略，并且在严格掌握手术适应证的前提下，由具备丰富腹腔镜手术经验的医生主持操作，腹腔镜技术应用于肝门部胆管癌病人相对安全、可行。