2004―2022年单中心高危胃肠道间质瘤的诊断与治疗（附568例报告）

蒋祈; 田红坤; 杜雨强; 吕剑波; 毛淦; 沈乾; 曾祥宇; 刘炜圳; 尹玉平; 陶凯雄; 张鹏

doi:10.3760/cma.j.cn115610-20240203-00065

2004―2022年单中心高危胃肠道间质瘤的诊断与治疗（附568例报告）

Diagnosis and treatment of high‑risk gastrointestinal stromal tumor from 2004 to 2022 in a single center: a report of 568 cases

摘要

摘要:
目的分析2004―2022年国内三甲医院单中心高危胃肠道间质瘤（GIST）的诊断与治疗。
方法采用回顾性队列研究方法。收集2004年1月至2022年12月华中科技大学同济医学院附属协和医院收治的568例高危GIST患者的临床病理资料；男334例,女234例；年龄为（55±12）岁。患者均行开放、腹腔镜或内镜手术治疗,并分为2004―2010年、2011―2014年、2015―2018年及2019―2022年4个时间段分析。观察指标：（1）2004―2022年高危GIST患者临床资料情况。（2）2004―2022年高危GIST患者术后病理学检查情况。（3）2004―2022年高危GIST患者生存情况。正态分布的计量资料以x±s表示,多组间比较采用单因素方差分析。偏态分布的计量资料以M（范围）表示。计数资料以绝对数或百分比表示,多组间比较采用χ²检验或Fisher确切概率法。两两比较采用Bonferroni校正。采用Kaplan⁃Meier法计算无复发生存率和总生存率并绘制生存曲线,Log‑Rank检验进行生存分析。
结果（1）2004―2022年高危GIST患者临床资料情况。568例高危GIST患者中,2004―2010年、2011―2014年、2015―2018年、2019―2022年分别为105、98、195、170例,分别占同期诊断GIST患者的33.55%（105/313）、24.14%（98/406）、27.46%（195/710）、20.21%（170/841）。2004―2010年、2011―2014年、2015―2018年、2019―2022年高危GIST患者首发症状、肿瘤部位、手术方式、术中出血量、术中输血、术后住院时间、辅助治疗比较,差异均有统计学意义（P<0.05）。进一步分析：①2011―2014年、2015―2018年、2019―2022年腹腔镜手术比例均高于2004―2010年（P<0.05）,2019―2022年腹腔镜手术比例高于2011―2014年和2015―2018年（P<0.05）。②2011―2014年、2015―2018年、2019―2022年术中出血量>500 mL比例和术中输血比例均低于2004―2010年（P<0.05）。③2015―2018年、2019―2022年术后住院时间均短于2004―2010年和2011―2014年（P<0.05）。④2011―2014年、2015―2018年、2019―2022年辅助治疗比例均高于2004―2010年（P<0.05）,2019―2022年辅助治疗比例高于2011―2014年（P<0.05）。（2）2004―2022年高危GIST患者术后病理学检查情况。2004―2010年、2011―2014年、2015―2018年、2019―2022年高危GIST患者肿瘤长径、核分裂象、DOG‑1、SDHB、Ki‑67、Ki‑67表达水平、基因检测比较,差异均有统计学意义（P<0.05）。进一步分析：①2011―2014年、2015―2018年、2019―2022年DOG‑1检测比例均高于2004―2010年（P<0.05）,2015―2018年、2019―2022年DOG‑1检测比例均高于2011―2014年（P<0.05）。②2015―2018年、2019―2022年SDHB检测比例均高于2004―2010年和2011―2014年（P<0.05）,2019―2022年SDHB检测比例高于2015―2018年（P<0.05）。③2011―2014年、2015―2018年、2019―2022年Ki‑67检测比例均高于2004―2010年（P<0.05）。④2011―2014年、2015―2018年、2019―2022年基因检测比例均高于2004―2010年（P<0.05）,2015―2018年、2019―2022年基因检测比例均高于2011―2014年（P<0.05）,2019―2022年基因检测比例高于2015―2018年（P<0.05）。（3）2004―2022年高危GIST患者生存情况。568例患者中,514例获得随访,随访时间为69（37~103）个月,3、5年无复发生存率分别为84.4%、73.9%,3、5年总生存率分别为90.1%、82.4%。2004―2010年、2011―2014年、2015―2018年、2019―2022年患者3年无复发生存率分别为85.7%、71.7%、86.7%、90.6%,3年总生存率分别为89.8%、87.1%、90.3%、92.6%,4者上述指标比较,差异均有统计学意义（P<0.05）。进一步分析：2015―2018年和2019―2022年患者无复发生存率均高于2004―2010年和2011―2014年（P<0.05）,2015―2018年患者总生存率高于2004―2010年和2011―2014年（P<0.05）。
结论 2004―2022年单中心高危GIST患者首发症状、肿瘤部位构成比例发生变化,腹腔镜手术比例提升,术中大出血（>500 mL）及输血比例下降,术后住院时间缩短,病理学检查逐渐规范,基因突变检测率及辅助治疗率均提高,但仍较低。

Abstract:
Objective To analyze the diagnosis and treatment of high‑risk gastrointestinal stromal tumor (GIST) in a single center of domestic grade A hospital from 2004 to 2022.
Methods The retrospective cohort study was conducted. The clinicopathological data of 568 patients with high-risk GIST who were admitted to Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2004 to December 2022 were collected. There were 334 males and 234 females, aged (55±12)years. All patients underwent open, laparoscopic or endoscopic surgery, and they were divided into four time periods (2004-2010, 2011-2014, 2015-2018 and 2019-2022) to be analyzed. Observation indicators: (1) clinical data of high‑risk GIST patients from 2004-2022; (2) postoperative pathologic examination of high‑risk GIST patients from 2004-2022; (3) survival of high‑risk GIST patients from 2004-2022. Measurement data with normal distribution were repre-sented as Mean±SD, and comparison between multiple groups was analyzed by one‑way ANOVA. Measurement data with skewed distribution were represented as M(range). Count data were expre-ssed as absolute numbers or percentages, and comparison between multiple groups was performed using the chi‑square test or Fisher exact probability. Bonferroni correction was used for pairwise comparisons. The Kaplan‑Meier method was used to calculate relapse‑free survival rates and overall survival rates and plot survival curves, and the Log‑Rank test was used for survival analysis.
Results (1) Clinical data of high‑risk GIST patients from 2004-2022. Of 568 high‑risk GIST pati-ents, there were 105, 98, 195 and 170 cases in 2004-2010, 2011-2014, 2015-2018 and 2019-2022, accoun-ting for 33.55%(105/313), 24.14%(98/406), 27.46%(195/710) and 20.21%(170/841) of all GIST cases diagnosed in the same period. There were significant differences in first symptoms, tumor location, surgical procedure, volume of intraoperative blood loss, intraoperative blood transfusion, duration of postoperative hospital stay, adjuvant therapy in patients with high‑risk GIST in the four time periods (P<0.05). In further analysis: ① the percentage of laparoscopic surgery was higher in 2011-2014, 2015-2018, and 2019-2022 than in 2004-2010 (P<0.05), and the percentage of laparoscopic surgery was higher in 2019-2022 than in 2011-2014 and 2015-2018 (P<0.05). ② The proportion of volume of intraoperative blood loss >500 mL and the proportion of intraoperative blood transfusions were lower in 2011-2014, 2015-2018, and 2019-2022 than in 2004-2010 (P<0.05). ③ The duration of postoperative hospital stay was shorter in 2015-2018 and 2019-2022 than in 2004-2010 and in 2011-2014 (P<0.05). ④ The proportion of adjuvant therapy was higher in 2011-2014, 2015-2018, and 2019-2022 than in 2004-2010 (P<0.05), and the proportion of adjuvant therapy was higher in 2019-2022 than in 2011-2014 (P<0.05). (2) Postoperative patho-logic examination of high‑risk GIST patients from 2004-2022. There were significant differences in tumor diameter, mitotic count, DOG‑1 test, SDHB test, Ki‑67 test, Ki‑67 expression, and genetic testing in patients with high‑risk GIST patients in the four time periods (P<0.05). In further analysis: ① the proportion of DOG‑1 test was higher in 2011-2014, 2015-2018, and 2019-2022 than in 2004-2010 (P<0.05), and higher in 2015-2018 and 2019-2022 than in 2011-2014 (P<0.05). ② The proportion of SDHB test was higher in 2015-2018 and 2019-2022 than in 2004-2010 and 2011-2014 (P<0.05), and also higher in 2019-2022 than in 2015-2018 (P<0.05). ③ The proportion of Ki‑67 test was higher in 2011-2014, 2015-2018, and 2019-2022 than in 2004-2010 (P<0.05). ④ The proportion of genetic testing was higher in 2011-2014, 2015-2018, and 2019-2022 than in 2004-2010 (P<0.05), and higher in 2015-2018 and 2019-2022 than in 2011-2014 (P<0.05), and also higher in 2019-2022 than in 2015-2018 (P<0.05). (3) Survival of high‑risk GIST patients from 2004-2022. Of 568 patients, 514 cases were followed up for 69(range, 37-103)months. The 3‑ and 5‑year progression‑free survival rates were 84.4% and 73.9%, and the 3‑ and 5‑year overall survival rates were 90.1% and 82.4%, respectively. The 3‑year progression-free survival rate was 85.7%, 71.7%, 86.7%, and 90.6%, and the 3‑year overall survival rate was 89.8%, 87.1%, 90.3%, and 92.6% in 2004-2010,2011-2014,2015-2018 and 2019-2022, respectively, showing significant differences (P<0.05). In further analysis, the progression‑free sur-vival rate was higher in 2015-2018 and 2019-2022 than in 2004-2010 and 2011-2014 (P<0.05), the overall survival rate was higher in 2015-2018 than in 2004-2010 and 2011-2014 (P<0.05).
Conclusions From 2004 to 2022, the first symptoms and tumor location of high-risk GIST patients have changed. The proportion of patients with laparoscopic surgery has increased, while the proportions of patients with intraoperative major bleeding (>500 mL) and blood transfusion have decreased. Duration of postoperative hospital stay has been shortened, pathological examinations have gradually standardized, in which gene mutation detection rates and adjuvant therapy rates have increased, but still relatively low.

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