第八章、混合型肝細胞-膽管癌之治療

8.1 混合型肝細胞-膽管癌之流行病學與診斷

混合型 HCC-CCA 是一種罕見 (佔原發性肝癌 1-10%) 且侵襲性高的腫瘤，同時具有肝細胞癌與膽管癌的特徵。⁽¹⁾

• 組織形態：

  • 離散型：部分病例在腫瘤的不同區域分別含有獨立的 HCC 和 CCA 組織病灶。

  • 雙表型：同一細胞同時表現獨立與HCC和CCA相關的免疫組化標記。

• 基因學：混合型HCC-CCA的次世代定序顯示，基因變異的流行率與HCC較為接近 (例如常見TP53和TERT啟動子突變)，這在伴隨HCV感染的患者中尤為明顯，但受限於樣本數較少，相關結果仍需謹慎解讀。

• 診斷困境：影像學可能同時呈現HCC的「快進快出」與CCA的「延遲強化」，導致誤診。病理確診是黃金標準。

8.2 混合型肝細胞-膽管癌之早期治療

• 肝切除術。可切除混合型HCC-CCA的標準治療。⁽¹⁾

• 局部導向治療：雖然缺乏前瞻性數據，但對於病灶範圍有限且無法手術切除的肝病，肝臟導向局部治療 (如燒灼術或栓塞術) 可能是合適的選擇，其管理流程可參考HCC與肝內膽管癌 (iCCA) 的指引。

8.3 混合型肝細胞-膽管癌之復發或晚期治療

• 復發與轉移：建議再次切片。若患者在手術或局部治療後出現轉移或局部進展，建議考慮進行再次切片，以確認復發病灶中的優勢組織學組成。⁽¹⁾

• 組織特異性治療：若切片顯示為單一的HCC或CCA成分，指引建議選用適合該組織成分的全身性治療方案 。分子檢測：所有晚期混合型 HCC-CCA 患者均應考慮進行腫瘤分子分析 ，以識別可能與 CCA 相關的潛在可標靶基因變異。

8.3.1 晚期首選療法：免疫合併化學療法

• 試驗設計。Gemcitabine + Cisplatin聯合Durvalumab或Pembrolizumab。
  歐洲多中心回顧性研究納入101名混合型HCC-CCA患者，並比較化療合併免疫療法 (如 Gemcitabine/Cisplatin加上Durvalumab或Pembrolizumab) 相對於非化療 (如 Sorafenib) 的治療效果。⁽⁶⁸⁾

• 關鍵結果：化療組的OS中位數有延長趨勢 (15.5 個月 vs 5.3 個月; p=0.052)，但未達統計上顯著差異，可能是樣本數不足導致之結果。

• 建議：基於此數據及Gemcitabine/Cisplatin在膽管癌的療效，NCCN指引建議 Gemcitabine + Cisplatin聯合免疫檢查點抑制劑 (如 Durvalumab或 Pembrolizumab) 作為第一線全身性治療選擇。

8.3.2 晚期二線療法

• 分子標靶治療。若腫瘤帶有可標靶變異，應優先考慮。

• 缺乏可標靶變異之後線治療：Nivolumab + Ipilimumab 或 Regorafenib為在HCC和CCA中皆證實有效的方案。

總結 (Summary)

• 篩檢的必要性：上海大型對照試驗確立了超音波合併AFP篩檢能降低37%死亡率的黃金標準，強調了對高危族群進行監測的倫理義務。

• 客觀肝功能評估：ALBI 分級的引入修正了 Child Pugh class 系統的主觀誤差，為臨床醫師提供了更精準的工具來預測患者對治療的耐受性。

• 早期疾病：首選手術切除與移植仍是首選根治手段，但需結合FLR計算與門靜脈高壓評估進行嚴格篩選。對於小腫瘤，消融療法亦可視為根治性治療。

• 肝臟移植需遵循Milan或UNOS標準，降期治療成功後的移植預後與初始符合標準者相當，是重要的挽救策略。

• 中期疾病：動脈導向治療 (TACE/TARE) 為主，SBRT提供了另一種局部控制手段。

• 晚期疾病：免疫聯合療法 (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab) 已徹底改變了以往Sorafenib的一線治療標準，顯著延長了存活期。後線治療則有 TKI (Cabozantinib, Regorafenib) 與其他免疫藥物等選擇。

作者：傅彥崴 藥師 2026.01.01

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