Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
JAMA Surg. 2022 Jul 1;157(7):590-596. doi: 10.1001/jamasurg.2022.1298.
Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation.
To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021.
Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test.
A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% [94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07).
This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.
肝内胆管细胞癌（iCCA）在初诊时常为多灶性（即卫星灶或肝内转移）。
比较多灶性 iCCA 患者接受肝动脉灌注泵（HAIP）氟尿嘧啶化疗与切除术的总生存期（OS）。
设计、地点和参与者：在这项队列研究中，符合组织学证实的多灶性 iCCA 患者有资格入组。HAIP 组由来自单一中心的连续患者组成，他们于 2001 年 1 月 1 日至 2018 年 12 月 31 日期间因不可切除的多灶性 iCCA 接受 HAIP 氟尿嘧啶化疗。切除术组由来自 12 个中心的连续患者组成，他们于 1990 年 1 月 1 日至 2017 年 12 月 31 日期间因多灶性 iCCA 接受根治性切除术。允许存在区域淋巴结转移性疾病和先前的系统治疗。排除远处转移性疾病（即 IV 期）患者、在开始 HAIP 氟尿嘧啶化疗之前接受切除术的患者和接受肝移植的患者。数据分析于 2021 年 9 月 1 日进行。
使用 Kaplan-Meier 方法和对数秩检验比较 2 个治疗组的总生存期。
共纳入 319 例多灶性 iCCA 患者：HAIP 组 141 例（中位[IQR]年龄，62[53-70]岁；79[56.0%]女性）和切除术组 178 例（中位[IQR]年龄，60[50-69]岁；91[51.1%]男性）。HAIP 组的特征为更高的双侧疾病发生率（88.0%[n=124] vs 34.3%[n=61]）、更大的肿瘤（中位数，8.4 cm vs 7.0 cm）和更多的患者存在 4 个或更多病灶（66.7%[94] vs 24.2%[43]）。HAIP 组术后 30 天死亡率为 0.8%（95%CI，0.0%-2.1%），切除术组为 6.2%（95%CI，2.3%-9.7%）（P=0.01）。HAIP 的中位 OS 为 20.3 个月，切除术为 18.9 个月（P=0.32）。2 个或 3 个病灶患者的 5 年 OS 分别为 HAIP 组 23.7%（95%CI，12.3%-45.7%）和切除术组 25.7%（95%CI，17.9%-37.0%）。4 个或更多病灶患者的 5 年 OS 分别为 HAIP 组 5.0%（95%CI，1.7%-14.3%）和切除术组 6.8%（95%CI，1.8%-25.3%）。在调整肿瘤直径、肿瘤数量和淋巴结转移后，HAIP 与切除术的风险比为 0.75（95%CI，0.55-1.03；P=0.07）。
这项队列研究发现，多灶性 iCCA 患者接受 HAIP 氟尿嘧啶化疗与切除术的 OS 相似。鉴于肝切除术的主要肝切除并发症发生率，需要仔细考虑多灶性肝内胆管细胞癌的切除术；HAIP 氟尿嘧啶化疗可能是一种有效的替代方案。
