根治性手术后肝门部胆管癌早期复发的定义：来自美国肝外胆管恶性肿瘤联盟的多机构研究
Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium.
作者信息
Zhang Xu-Feng, Beal Eliza W, Chakedis Jeffery, Chen Qinyu, Lv Yi, Ethun Cecilia G, Salem Ahmed, Weber Sharon M, Tran Thuy, Poultsides George, Son Andre Y, Hatzaras Ioannis, Jin Linda, Fields Ryan C, Buettner Stefan, Scoggins Charles, Martin Robert C G, Isom Chelsea A, Idrees Kamron, Mogal Harveshp D, Shen Perry, Maithel Shishir K, Schmidt Carl R, Pawlik Timothy M
机构信息
Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
出版信息
World J Surg. 2018 Sep;42(9):2919-2929. doi: 10.1007/s00268-018-4530-0.
BACKGROUND
Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection.
METHODS
A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late.
RESULTS
With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence.
CONCLUSIONS
Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.
背景
肿瘤复发时间可能与肝胆癌切除术后的预后相关。本研究的目的是调查根治性切除术后肝门部胆管癌（HCCA）早期与晚期复发患者的危险因素及预后情况。
方法
从美国10个学术中心共纳入225例行根治性切除的HCCA患者。分析其临床病理特征、术前、术中和术后细节以及总生存期（OS）。采用线性回归确定的曲线斜率将复发分为早期和晚期。
结果
中位随访时间为18.0个月，99例（44.0%）患者出现肿瘤复发。根据线性回归确定的曲线斜率，两条直线的函数分别为y = -0.465x + 16.99和y = -0.12x + 7.16。两条直线的截距值为28.5个月，因此将30个月（2.5年）定义为区分早期与晚期复发的临界值。在99例复发患者中，大多数（n = 80，80.8%）在2.5年内复发（早期复发），而19.2%的复发发生在2.5年之后（晚期复发）。早期复发更可能表现为远处转移（75.1%对31.6%，p = 0.001），且与较差的总生存期相关（中位总生存期，早期为21.5个月，晚期为50.4个月，p < 0.001）。多变量分析显示，肿瘤低分化（HR 10.3，p = 0.021）、微血管侵犯（HR 3.3，p = 0.037）、神经周围侵犯（HR 3.9，p = 0.029）、淋巴结转移（HR 5.0，p = 0.004）和显微镜下切缘阳性（HR 3.5，p = 0.046）是与早期复发相关的独立危险因素。
结论
根治性切除术后HCCA早期复发很常见（约35.6%）。早期复发与侵袭性肿瘤特征、远处转移复发风险增加及较差的长期生存密切相关。
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