This editorial contains comments on the article "Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature" in the recent issue of World Journal of Gastrointestinal Surgery. It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation (ELRAT) and systemic therapy, underlying molecular mechanisms for targeted therapy in perihilar cholangiocarcinoma (pCCA) management. pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis. The only curative option is radical surgery. Surgical excision and reconstruction become extremely complicated and not always could be performed even in localized disease. On the other hand, ELRAT takes its place among surgical options for carefully selected pCCA patients. In advanced disease, systemic therapy becomes a viable option to prolong survival. This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with kinase inhibitors and immunotherapy in both palliative and adjuvant settings. Fibroblast grow factor and fibroblast grow factor receptor, human epidermal growth factor receptor 2, isocitrate dehydrogenase, and protein kinase cAMP activated catalytic subunit alpha (PRKACA) and beta (PRKACB) pathways have been actively investigated in CCA in last years. Several agents were introduced and approved by the Food and Drug Administration. They all demonstrated meaningful activity in CCA patients with no global change in outcomes. That is why every successfully treated patient counts, especially those with advanced disease. In conclusion, pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options. ELRAT also brings some hope, but it could be performed in very carefully selected patients. Advanced disease requires systemic anticancer treatment, which is supposed to be individualized according to the genetic and molecular features of cancer cells. Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

中文翻译：

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离体肝切除和自体移植以及肝门周围胆管癌治疗的特殊全身治疗。

本社论包含对最近一期《世界胃肠外科杂志》上的文章“离体肝切除和自体移植的系统序贯治疗：病例报告和文献综述”的评论。它指出了本文的现实性和重要性，并主要关注离体肝切除和自体移植（ELRAT）和全身治疗的作用和地位，以及肝门周围胆管癌（pCCA）治疗中靶向治疗的潜在分子机制。 pCCA 是一种棘手的恶性肿瘤，诊断时晚期疾病的比例很高。唯一的治疗选择是根治性手术。手术切除和重建变得极其复杂，即使是局部病变也并不总是能够进行。另一方面，ELRAT 在精心挑选的 pCCA 患者的手术选择中占有一席之地。在晚期疾病中，全身治疗成为延长生存的可行选择。这篇社论描述了目前化疗的可能性，并揭示了姑息和辅助环境中激酶抑制剂靶向治疗和免疫治疗的潜在机制和预测。近年来，成纤维细胞生长因子和成纤维细胞生长因子受体、人表皮生长因子受体 2、异柠檬酸脱氢酶和蛋白激酶 cAMP 激活催化亚基 α (PRKACA) 和 β (PRKACB) 途径在 CCA 中得到了积极研究。推出多种制剂并获得食品药品监督管理局批准。它们都在 CCA 患者中表现出有意义的活性，且结果没有总体变化。这就是为什么每一位成功治疗的患者都很重要，尤其是那些患有晚期疾病的患者。总之，由于诊断较晚且手术选择极其复杂，pCCA 仍然很难治疗。 ELRAT 也带来了一些希望，但它可以在非常仔细挑选的患者中进行。晚期疾病需要全身抗癌治疗，应根据癌细胞的遗传和分子特征进行个体化治疗。靶向治疗与化学免疫疗法相结合对易感患者可能有效。