单中心肝内胆管癌外科治疗10年变迁与预后分析(附1 905例报告)

Ten‑year evolution of surgical treatment for intrahepatic cholangiocarcinoma and prognostic analysis (a single center study of 1 905 cases)

  • 摘要:
    目的 探讨单中心肝内胆管癌外科治疗10年变迁与预后改善情况。
    方法 采用回顾性队列及倾向评分匹配研究方法。收集2013年1月至2022年12月复旦大学附属中山医院收治的1 905例肝内胆管癌患者的临床病理资料;男1 161例,女744例;年龄为(61±10)岁。1 905例患者均行根治性肝癌切除术,根据收治时间分为2013—2017年738例,2018—2022年1 167例;根据手术方式分为开腹组1 639例,腹腔镜组266例。1 905例患者中,816例术后复发,早期复发656例,晚期复发160例。观察指标:(1)不同时期肝内胆管癌患者临床病理特征。(2)不同时期肝内胆管癌患者手术及预后情况。(3)肝内胆管癌患者手术情况分层分析。(4)不同时期肝内胆管癌患者辅助治疗及预后情况。正态分布的计量资料组间比较采用独立样本t检验。偏态分布的计量资料组间比较采用Wilcoxon秩和检验。计数资料组间比较采用χ²检验。采用Kaplan‑Meier法计算生存率并绘制生存曲线,Log‑rank检验进行生存分析。倾向评分匹配按1∶2最近邻匹配法匹配。
    结果 (1)不同时期肝内胆管癌患者临床病理特征:2013—2017年患者年龄,肝硬化(无、有),手术难度(中‑低、高),肿瘤长径(≤5 cm、>5 cm),肿瘤分化程度(高分化、中‑低分化),淋巴结清扫(是、否),辅助治疗(是、否)分别为(60±10)岁,628、110例,373、365例,376、362例,283、455例,308、430例,329、409例;2018—2022年患者上述指标分别为(62±10)岁,1 051、116例,526、641例,694、473例,632、535例,708、459例,780、387例;两者上述指标比较,差异均有统计学意义(P<0.05)。(2)不同时期肝内胆管癌患者手术及预后情况:2013—2017年患者手术时间、术中出血量、术中输血、术后并发症Clavien‑Dindo Ⅰ~Ⅲ级分别为245(180,320)min、200(100,300)mL、68例、178例;2018—2022年患者上述指标分别为210(180,300)min、100(100,300)mL、59例、231例;两者上述指标比较,差异均有统计学意义(P<0.05)。生存分析结果显示:2013—2017年和2018—2022年患者1、3、5年总生存率分别为76.0%、48.8%、38.5%和88.2%、61.5%、48.9%;两者比较,差异有统计学意义(χ²=33.784,P<0.05)。1 016例行淋巴清扫患者中,357例淋巴结镜检阳性和659例淋巴结镜检阴性患者1、3、5年总生存率分别为63.0%、26.0%、17.7%和89.0%、62.4%、49.8%,两者比较,差异有统计学意义(χ²=158.136,P<0.05);1、3、5年无复发生存率分别为64.4%、28.4%、21.8%和77.3%、51.1%、45.6%,两者比较,差异有统计学意义(χ²=37.397,P<0.05)。659例淋巴结镜检阴性和889例未行淋巴结清扫患者1、3、5年总生存率分别为89.0%、62.4%、49.8%和87.3%、63.3%、50.8%,两者比较,差异无统计学意义(χ²=0.261,P>0.05);1、3、5年无复发生存率分别为77.3%、51.1%、45.6%和77.1%、56.5%、49.7%,两者比较,差异无统计学意义(χ²=1.481,P>0.05)。(3)肝内胆管癌患者手术情况分层分析:1 905例患者中798例匹配成功,开腹组532例,腹腔镜组266例。开腹组患者术中出血量、术中输血、术后并发症Clavien‑Dindo Ⅰ~Ⅲ级分别为200(100,300)mL、21例、91例;腹腔镜组患者上述指标分别为100(50,100)mL、2例、9例;两组上述指标比较,差异均有统计学意义(P<0.05)。倾向评分匹配后,开腹组和腹腔镜组患者术后1、3、5年总生存率分别为89.8%、66.1%、50.6%和94.1%、74.5%、64.9%,两组比较,差异有统计学意义(χ²=8.113,P<0.05);无复发生存率分别为78.4%、53.7%、48.3%和85.7%、65.7%、61.4%,两组比较,差异有统计学意义(χ²=7.851,P<0.05)。(4)不同时期肝内胆管癌患者辅助治疗及预后情况:2013—2017年患者行辅助治疗方式比例最高为中医中药治疗,2018—2022年为系统治疗。2013—2017年至2018—2022年,系统治疗比例从30.09%(99/329)提升至69.23%(540/780),其中2013—2017年和2018—2022年行系统治疗方式比例最高均为化疗。656例早期复发患者行辅助治疗和未行辅助治疗1、3、5年总生存率分别为91.0%、44.3%、25.5%和80.8%、32.8%、19.7%,两者比较,差异有统计学意义(χ²=10.197,P<0.05)。
    结论 与2013—2017年比较,2018—2022年肝内胆管癌患者年龄更高,但肝硬化、肿瘤长径>5 cm及低分化比例均更低;高难度手术、淋巴结清扫及辅助治疗比例增加,手术时间、术中出血、术中输血及术后并发症均减少,总生存率提升。淋巴结转移患者预后差,但淋巴结阴性患者清扫未显获益。患者行腹腔镜手术较开腹手术围手术期指标更好,预后更佳。辅助治疗可改善早期复发患者的预后。

     

    Abstract:
    Objective To investigate the ten‑year evolution of surgical treatment for intra-hepatic cholangiocarcinoma (ICC) and improvement of prognosis in a single center.
    Methods The retrospective cohort and propensity score matching (PSM) study was conducted. The clinicopatholo-gical data of 1 905 patients with ICC who were admitted to Zhongshan Hospital of Fudan University from January 2013 to December 2022 were collected. There were 1 161 males and 744 females, aged (61±10) years. All 1 905 patients underwent radical resection of liver cancer. Based on the time of admission, there were 738 cases from 2013 to 2017, and 1 167 cases from 2018 to 2022. According to the surgical approach, there were 1 639 cases in the open surgery group and 266 cases in the laparoscopic surgery group. Of 1 905 patients, 816 cases had postoperative recurrence including 656 cases of early recurrence and 160 cases of late recurrence. Observation indicators: (1) clinico-pathological characteristics of patients with ICC in different periods; (2) surgical and prognostic conditions of patients with ICC in different periods; (3) stratified analysis of surgical conditions of patients with ICC; (4) adjuvant therapy and prognosis of patients with ICC in different periods. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon rank sum test. Comparison of count data between groups was conducted using the chi‑square test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log‑rank test was used for survival analysis. PSM was done by the 1∶2 nearest neighbor matching method.
    Results (1) Clinicopathological characteristics of patients with ICC in different periods: the age, cases without or with cirrhosis, cases with surgical difficulty as medium‑low difficulty or high difficulty, cases with tumor diameter ≤5 cm or >5 cm, cases with well differentiated tumor or medium‑low differentiated tumor, cases with or without lymph node dissection, cases with or without adjuvant therapy were (60±10) years, 628, 110, 373, 365, 376, 362, 283, 455, 308, 430, 329, 409 of patients who were admitted from 2013 to 2017, versus (62±10) years, 1 051, 116, 526, 641, 694, 473, 632, 535, 708, 459, 780, 387 of patients who were admitted from 2018 to 2022, respectively, showing significant differences in the above indicators between them (P<0.05). (2) Surgical and prognostic conditions of patients with ICC in different periods: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with grade Ⅰ‒Ⅲ complications of Clavien‑Dindo classification were 245 (180,320) minutes,200 (100,300) mL, 68, 178 of patients who were admitted from 2013 to 2017, versus 210 (180,300) minutes, 100 (100,300) mL, 59, 231 of patients who were admitted from 2018 to 2022, respectively, showing signifi-cant differences in the above indicators between them (P<0.05). Results of survival analysis showed that the 1‑, 3‑, 5‑year overall survival rates were 76.0%, 48.8%, 38.5% of patients who were admitted from 2013 to 2017, versus 88.2%, 61.5%, 48.9% of patients who were admitted from 2018 to 2022, respectively, showing a significant difference between them (χ²=33.784, P<0.05). Among 1 016 pati-ents with lymph node dissection, the 1‑, 3‑, 5‑year overall survival rates were 63.0%, 26.0%, 17.7% of 357 patients with positive lymph node microscopy, versus 89.0%, 62.4%, 49.8% of 659 patients with negative lymph node microscopy, respectively, showing a significant difference between them (χ²=158.136, P<0.05). The 1‑, 3‑, 5‑year recurrence‑free survival rates were 64.4%, 28.4%, 21.8% of 357 patients with positive lymph node microscopy, versus 77.3%, 51.1%, 45.6% of 659 patients with negative lymph node microscopy, respectively, showing a significant difference between them (χ²=37.397, P<0.05). The 1‑, 3‑, 5‑year overall survival rates were 89.0%, 62.4%, 49.8% of 659 patients with negative lymph node microscopy, versus 87.3%, 63.3%, 50.8% of 889 patients without lymph node dissection, respectively, showing no significant difference between them (χ²=0.261, P>0.05). The 1‑, 3‑, 5‑year recurrence‑free survival rates were 77.3%, 51.1%, 45.6% of 659 patients with negative lymph node microscopy, versus 77.1%, 56.5%, 49.7% of 889 patients without lymph node dissection, respectively, showing no significant difference between them (χ²=1.481, P>0.05). (3) Stratified analysis of surgical conditions of patients with ICC: of the 1 905 patients, 798 cases were successfully matched, including 532 cases in the open surgery group and 266 cases in the laparos-copic surgery group. The volume of intraoperative blood loss, cases with intraoperative blood trans-fusion, cases with grade Ⅰ‒Ⅲ complications of Clavien‑Dindo classification were 200 (100,300) mL, 21, 91 of patients in the open surgery group, versus 100 (50,100) mL, 2, 9 of patients in the laparos-copic surgery group, respectively, showing significant differences in the above indicators between them (P<0.05). After PSM, the 1‑, 3‑, 5‑year overall survival rates were 89.8%, 66.1%, 50.6% of patients in the open surgery group, versus 94.1%, 74.5%, 64.9% of patients in the laparoscopic surgery group, respectively, showing a significant difference between them (χ²=8.113, P<0.05). The 1‑, 3‑, 5‑year recurrence‑free survival rates were 78.4%, 53.7%, 48.3% of patients in the open surgery group, versus 85.7%, 65.7%, 61.4% of patients in the laparoscopic surgery group, respectively, showing a significant difference between them (χ²=7.851, P<0.05). (4) Adjuvant therapy and prognosis of patients with ICC in different periods: the method with the highest proportion of adjuvant therapy was traditional Chinese medicine for patients who were admitted from 2013 to 2017, and systemic therapy for patients who were admitted from 2018 to 2022. The proportion of patients receiving systemic therapy increased from 30.09%(99/629) in patients who were admitted during 2013‒2017 to 69.23%(540/780) in patients who were admitted during 2018-2022. Chemotherapy accounted for the highest proportion among systemic therapy for patients who were admitted during 2013‒2017 and 2018‒2022. For 656 early recurrence patients, the 1-, 3-, and 5-year overall survival rates were 91.0%, 44.3% and 25.5% of cases with adjuvant therapy, versus 80.8%, 32.8% and 19.7% of those without adjuvant therapy, respectively, showing a significant difference between them (χ²=10.197, P<0.05).
    Conclusions Compared to patients with ICC who were admitted from 2013 to 2017, patients with ICC who were admitted from 2018 to 2022 are older, but the proportions of patients with cirrhosis, tumor diameter >5 cm or low differentiated tumor are lower. The proportions of difficulty surgery, lymph node dissection and adjuvant therapy are increased, while the operation time, cases with perioperative bleeding, blood transfusion, and postoperative complications are decreased, resulting in an improved overall survival rate. Patients undergoing lymph node metas-tasis have a poor prognosis, but patients with negative lymph node do not benefit from lymph node dissection. Patients with laparoscopic surgery have better perioperative indicators and a better prognosis compared to cases undergoing open surgery. Adjuvant therapy can improve the prognosis of patients with early recurrence.

     

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