Lerut Jan, Iesari Samuele
Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCL), Brussels, Belgium.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Transl Gastroenterol Hepatol. 2018 Sep 14;3:62. doi: 10.21037/tgh.2018.09.02. eCollection 2018.
Vascular tumours of the liver represent an underrated chapter of medical and surgical hepatology. These tumours cover a wide spectrum ranging from the frequent and most benign hepatic haemangioma (HH), via the rare and intermediately aggressive hepatic epithelioid haemangioendothelioma (HEHE) to the rare and most malignant hepatic haemangiosarcoma (HHS). In contrast to the treatment algorithms for hepatocellular and cholangiocellular cancer, the diagnostic and therapeutic approaches to HEHE and HHS are not well developed. The related uncertainty is explained by their rare occurrence and their protean clinical, morphological (imaging) and histopathological presentation and behaviour. This article gives an update about these particular tumours based on the analysis of the recent literature and of the studies on vascular tumours published by the European Liver Intestine Transplantation Association (ELITA)-European Liver Transplant Registry (ELTR). It focuses also on the place of liver transplantation (LT) in the respective therapeutic algorithms. The differential diagnosis between these vascular and other tumour types may be very difficult. Correct diagnosis is of utmost importance and is based on a high index of clinical suspicion and on the integration of clinical, radiological, histological [including immunohistochemistry (IHC) and molecular biology findings]. Surgery, be it partial or total hepatectomy (LT), should be proposed whenever possible, because it is the therapeutic mainstay. In HEHE, LT provides excellent results, with long-term disease-free survivals (DFS) reaching 75%. Good results can be obtained even in case of (frequent) extrahepatic spread. Based on the extensive ELITA-ELTR study a HEHE-LT prognostic score has been proposed in order to estimate the risk of recurrence after LT. In contrast, results of surgery and LT are extremely poor for HHS, for the almost invariably rapid recurrence (within 6 months) and related death within 2 years. LT remains a contraindication for HHS. Due to the still important recurrence rate after surgical resection (25% in HEHE and almost 100% in HHS), there is an urgent need to develop pharmacological treatments targeting angiogenic and non-VEGF angiogenic pathways. To date, some prospective pilot studies and case reports have shown some short-term stabilisation of the disease in small groups of patients. In order to make progress, combination of surgery, anti-angiogenic and immunotherapy seems worthwhile. To complete the panel of vascular liver tumours, infantile haemangioendothelioma, haemangiopericytoma, nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN) are also discussed.
肝脏血管肿瘤是医学和外科肝脏病学中一个被低估的领域。这些肿瘤涵盖范围广泛，从常见且最良性的肝血管瘤（HH），到罕见且侵袭性中等的肝上皮样血管内皮瘤（HEHE），再到罕见且最恶性的肝血管肉瘤（HHS）。与肝细胞癌和胆管细胞癌的治疗方案不同，针对HEHE和HHS的诊断和治疗方法尚未充分发展。其相关的不确定性源于它们的罕见性以及多样的临床、形态学（影像学）和组织病理学表现及行为。本文基于对近期文献以及欧洲肝脏肠移植协会（ELITA） - 欧洲肝脏移植登记处（ELTR）发表的关于血管肿瘤研究的分析，对这些特殊肿瘤进行了更新。它还重点关注了肝移植（LT）在各自治疗方案中的地位。这些血管肿瘤与其他肿瘤类型之间的鉴别诊断可能非常困难。正确诊断至关重要，其基于高度的临床怀疑指数以及临床、放射学、组织学[包括免疫组织化学（IHC）和分子生物学结果]的综合判断。只要有可能，就应建议进行手术，无论是部分肝切除术还是全肝切除术（LT），因为手术是主要的治疗手段。在HEHE中，肝移植效果极佳，长期无病生存率（DFS）可达75%。即使在（常见的）肝外扩散情况下也能取得良好效果。基于广泛的ELITA - ELTR研究，已提出了一个HEHE - LT预后评分，以评估肝移植后复发的风险。相比之下，HHS的手术和肝移植结果极差，几乎总是在6个月内迅速复发，并在2年内死亡。肝移植仍然是HHS的禁忌证。由于手术切除后仍有较高的复发率（HEHE中为25%，HHS中几乎为100%），迫切需要开发针对血管生成和非VEGF血管生成途径的药物治疗。迄今为止，一些前瞻性的试点研究和病例报告显示，在一小部分患者中疾病有短期稳定。为了取得进展，手术、抗血管生成和免疫治疗的联合似乎是值得的。为了完善肝脏血管肿瘤的范畴，还讨论了婴儿血管内皮瘤、血管外皮细胞瘤、结节性再生性增生（NRH）和肝脏小血管肿瘤（HSVN）。
