Andel Daan, van den Bent Lotte, Ernest Hendrik Lam Marnix Gerard, Johannes Smits Maarten Leonard, Molenaar Isaac Quintus, de Bruijne Joep, Laclé Miangela Marie, Kranenburg Onno, Max Borel Rinkes Inne Hildbrand, Hagendoorn Jeroen
Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands.
Laboratory for Translational Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands.
JHEP Rep. 2023 Dec 5;6(2):100981. doi: 10.1016/j.jhepr.2023.100981. eCollection 2024 Feb.
BACKGROUND & AIMS: High-dose unilobar radioembolization, or 'radiation lobectomy' (RL), is an induction therapy that achieves contralateral future liver remnant hypertrophy while simultaneously irradiating the tumor. As such, it may prevent further growth, but it is unknown whether RL affects intrahepatic lymphatics, a major route via which liver tumors disseminate.
This was a case-control study conducted at University Medical Center Utrecht. The study compared lymph vessels in livers that had undergone RL (cases) with those in livers that had not undergone RL (controls). Histological samples were acquired from patients diagnosed with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) between 2017 and 2022. Lymph vessel morphology was analyzed by two researchers using podoplanin, a protein that is expressed in lymphatic endothelium. liver lymph drainage of radioembolized livers was assessed using intraoperative liver lymphangiography (ILL): during liver surgery, patent blue dye was injected into the liver parenchyma, followed by inspection for staining of perihepatic lymph structures. ILL results were compared to a previously published cohort.
Immunohistochemical analysis on post-RL tumor tissues from ten patients with CRLM and nine patients with HCC revealed aberrant morphology of irradiated liver lymphatics when compared to controls (n = 3 per group). Irradiated lymphatics were tortuous ( <0.05), thickened ( <0.05) and discontinuous ( <0.05). Moreover, post-RL lymphatics had larger lumens (1.5-1.7x, <0.0001), indicating lymph stasis. ILL revealed diminished lymphatic drainage to perihepatic lymph nodes and vessels in irradiated livers when compared to non-radioembolized controls ( = 1.0x10).
Radioembolization impairs peritumoral lymph vessel function. Further research is needed to evaluate if radioembolization impairs tumor dissemination via this route.
Unilobar radioembolization can serve as an alternative to portal venous embolization for patients who are considered unresectable due to an insufficient future liver remnant. This research suggests that radioembolization impairs the function of peritumoral liver lymph vessels, potentially hindering dissemination via this route. These findings provide support for considering unilobar radioembolization over standard portal venous embolization.
高剂量单叶放射性栓塞术，即“放射性肝叶切除术”（RL），是一种诱导治疗方法，可使对侧未来肝残余组织肥大，同时对肿瘤进行照射。因此，它可能会阻止肿瘤进一步生长，但尚不清楚RL是否会影响肝内淋巴管，而肝内淋巴管是肝肿瘤扩散的主要途径。
这是一项在乌得勒支大学医学中心进行的病例对照研究。该研究比较了接受RL治疗的肝脏（病例组）和未接受RL治疗的肝脏（对照组）中的淋巴管。从2017年至2022年间被诊断为肝细胞癌（HCC）或结直肠癌肝转移（CRLM）的患者获取组织学样本。两名研究人员使用在淋巴管内皮中表达的一种蛋白质——血小板内皮细胞黏附分子（podoplanin）对淋巴管形态进行分析。使用术中肝淋巴管造影术（ILL）评估放射性栓塞肝脏的肝淋巴引流：在肝脏手术期间，将专利蓝染料注入肝实质，随后检查肝周淋巴结构的染色情况。将ILL结果与先前发表的队列进行比较。
对10例CRLM患者和9例HCC患者的RL术后肿瘤组织进行免疫组织化学分析发现，与对照组（每组n = 3）相比，照射后的肝淋巴管形态异常。照射后的淋巴管迂曲（P<0.05）、增粗（P<0.05）且不连续（P<0.05）。此外，RL术后淋巴管的管腔更大（1.5 - 1.7倍，P<0.0001），表明存在淋巴淤滞。与未进行放射性栓塞的对照组相比，ILL显示照射后肝脏向肝周淋巴结和血管的淋巴引流减少（P = 1.0×10）。
放射性栓塞会损害肿瘤周围淋巴管的功能。需要进一步研究以评估放射性栓塞是否会通过该途径损害肿瘤扩散。
对于因未来肝残余组织不足而被认为无法切除的患者，单叶放射性栓塞术可作为门静脉栓塞术的替代方法。这项研究表明，放射性栓塞会损害肿瘤周围肝淋巴管的功能，可能会阻碍通过该途径的扩散。这些发现为考虑采用单叶放射性栓塞术而非标准门静脉栓塞术提供了支持。
