清热利胆颗粒预防腹腔镜联合胆道镜术后胆总管结石复发的效果分析

李积强; 齐清会; 张桂信

doi:10.3969/j.issn.1001-5256.2023.10.020

清热利胆颗粒预防腹腔镜联合胆道镜术后胆总管结石复发的效果分析

DOI: 10.3969/j.issn.1001-5256.2023.10.020

李积强^{1, 2},
齐清会¹,
张桂信^{1, 2, , ,}

1.
大连医科大学附属第一医院普外三科，辽宁大连 116011
2.
大连医科大学中西医结合研究院，辽宁大连 116000

基金项目:

国家自然科学基金 (82174136);

辽宁省卫健委中医药临床重点专科能力建设项目 (LiaoNing Health Office 2019（169）)

伦理学声明：本研究方案于2021年12月24日经由大连医科大学附属第一医院伦理委员会审核批准，批号：PJ－KS－KY－2021－282。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：李积强负责临床数据收集、随访、分析及撰写论文；齐清会负责论文的审核及修改；张桂信负责拟定写作思路，指导撰写文章并最终定稿。

详细信息

通信作者:
‍张桂信， zgx@126.com （ORCID： 0000－0002－6171－394X）

计量
- 文章访问数: 174
- HTML全文浏览量: 69
- PDF下载量: 27
- 被引次数: 0
出版历程
- 收稿日期: 2023-02-06
- 出版日期: 2023-10-30

Clinical effect of Qingre Lidan granules in preventing the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy

Jiqiang LI^{1, 2},
Qinghui QI¹,
Guixin ZHANG^{1, 2
, ,
,}

1.
Third Department of General Surgery，The First Affiliated Hospital of Dalian Medical University，Dalian，Liaoning 116011，China
2.
School of Integrated Traditional Chinese and Western Medicine，Dalian Medical University，Dalian，Liaoning 116000，China

Research funding:

National Natural Science Foundation of China (82174136);

Key Clinical Specialty Capacity Building Project of TCM of LiaoNing Provincial Health Commission (LiaoNing Health Office 2019（169）)

More Information

Corresponding author: ZHANG Guixin， zgx@126.com （ORCID： 0000－0002－6171－394X）

摘要

摘要: 目的通过回顾性队列研究分析中药清热利胆颗粒对于腹腔镜联合胆道镜术后胆总管结石复发的预防作用。方法纳入大连医科大学附属第一医院2010年1月1日—2020年12月31日行腹腔镜联合胆道镜取石术治疗的胆总管结石（含合并胆囊结石）住院患者共337例。收集患者相关临床资料，并依据随访结果将患者分为暴露组（常规治疗+清热利胆颗粒组）225例与非暴露组（常规治疗组）112例，详细记录两组患者结石复发的相关情况以及中药清热利胆颗粒的服用情况。观察两组患者胆总管结石的复发率及结石复发的时间，并分析胆总管结石复发的危险因素。计量资料符合正态分布时两组间比较采用成组t检验，不符合正态分布时两组间比较采用Mann－Whithey U检验；计数资料两组间比较采用χ²检验或Fisher确切概率法。使用Kaplan－Meier曲线估计两组患者胆总管结石复发的累积概率，两组间比较采用Log－rank检验。结果腹腔镜联合胆道镜术后胆总管结石复发26例，其中暴露组12例（5.33%），非暴露组14例（12.5%），暴露组复发率较非暴露组明显降低（χ²=5.394，P=0.020）。暴露组患者结石复发的平均时间为（40.1±26.7）个月，较非暴露组患者的结石复发平均时间（19.2±13.5）个月明显延长（t=2.383，P=0.017）。Kplan－Meier曲线分析显示非暴露组患者不同时间段的累积复发率均高于暴露组（P<0.05）。多因素Logistic回归分析显示胆总管直径≥14 mm（OR=2.935，P=0.031）与多发结石（OR=2.911，P=0.029）是腹腔镜联合胆道镜取石术后胆总管结石复发的独立危险因素。结论清热利胆颗粒可以有效降低腹腔镜联合胆道镜术后胆总管结石的复发率，并延长结石复发的时间，具有一定的预防术后结石复发的作用。
- 胆总管结石病 /
- 腹腔镜检查 /
- 清热利胆颗粒 /
- 复发
Abstract: Objective To investigate the effect of Qingre Lidan granules in preventing the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy through a retrospective cohort study. Methods A total of 337 inpatients with choledocholithiasis （including those with cholecystolithiasis at the same time） who underwent laparoscopy combined with choledochoscopic lithotomy in The First Affiliated Hospital of Dalian Medical University from January 1， 2010 to December 31， 2020 were enrolled， and related clinical data were collected. According to the follow－up results， the patients were divided into exposure group （conventional treatment+Qingre Lidan granules） with 225 patients and non－exposure group （conventional treatment） with 112 patients. The recurrence of choledocholithiasis and the administration of Qingre Lidan granules were recorded in detail for both groups. The recurrence rate of choledocholithiasis and the time to recurrence were observed for both groups， and the risk factors for the recurrence of choledocholithiasis were analyzed. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann－Whitney U test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan－Meier curve was used to estimate the cumulative probability of choledocholithiasis recurrence in the two groups， and the Log－rank test was used for comparison between two groups. Results A total of 26 patients experienced the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy， with 12 patients （5.33%） in the exposure group and 14 （12.5%） in the non－exposure group， and the exposure group had a significantly lower recurrence rate than the non－exposure group （χ²=5.394， P=0.020）. The exposure group had a significantly longer mean time to the recurrence of choledocholithiasis than the non－exposure group （40.1±26.7 months vs 19.2±13.5 months， t=2.383， P=0.017）. The Kaplan－Meier curve analysis showed that the non－exposure group had a significantly higher cumulative recurrence rate than the exposure group in different periods of time （P<0.05）. The multivariate logistic regression analysis showed that common bile duct diameter ≥14 mm （odds ratio 〔OR〕=2.935， P=0.031） and multiple calculi （OR=2.911， P=0.029） were independent risk factors for the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopic lithotomy. Conclusion Qingre Lidan granules can effectively reduce the recurrence rate of choledocholithiasis and prolong the time to the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy and has a certain clinical effect in preventing the recurrence of choledocholithiasis after surgery.
- Choledocholithiasis /
- Laparoscopy /
- QingreliDan Granule /
- Recurrence

HTML全文

图 1 暴露组与非暴露组累积复发率曲线图

Figure 1. Kaplan－Meier chart of cumulative recurrence rates in exposed and non－exposed groups

下载: 全尺寸图片幻灯片

表 1 暴露组与非暴露组患者基线资料比较

Table 1. Comparison of baseline data between exposed group and non－exposed group

基线资料	暴露组（n=225）	非暴露组（n=112）	统计值	P值
男［例（%）］	114（50.7）	60（53.6）	χ ²=0.253	0.615
年龄（岁）	64.3 ± 14.2	61.3 ± 13.4	t=1.870	0.062
既往疾病史［例（%）］
高血压	72（32.0）	32（28.6）	χ ²=0.412	0.521
糖尿病	40（17.8）	15（13.4）	χ ²=1.053	0.305
冠心病	18（8.0）	6（5.4）	χ ²=0.790	0.374
肝硬化	2（0.9）	1（0.9）	χ ²=0.001	>0.05
慢性肾衰竭	3（1.3）	1（0.9）	χ ²=0.002	>0.05
急性胆管炎	68（30.2）	35（31.3）	χ ²=0.073	0.847
胆道手术史［例（%）］
经皮肝胆囊穿刺引流术（PTGD）	21（9.3）	7（6.3）	χ ²=0.933	0.334
经皮肝胆管穿刺引流术（PTCD）	4（1.8）	3（2.7）	χ ²=0.020	0.888
住院时间（天）	13.7 ± 6.2	15.5 ± 5.9	t=－2.552	0.011
随访时间（月）	55.43 ± 22.16	80.73 ± 31.61	t=－7.593	<0.001
胆总管闭合方式［例（%）］
一期缝合	64（28.4）	22（19.6）	χ ²=3.048	0.081
T管引流	161（71.6）	90（80.4）	χ ²=3.048	0.081
取石方式［例（%）］
经胆囊管切开取石	33（14.7）	10（8.9）	χ ²=2.212	0.137
经胆总管切开取石	192（85.3）	102（91.1）	χ ²=2.212	0.137
胆总管最大直径（cm）	12.6 ± 3.9	13.6 ± 5.2	t=－1.460	0.144
结石最大直径（cm）	10.2 ± 5.6	10.5 ± 5.8	t=－0.506	0.613
结石数量［例（%）］
单发	109（48.4）	45（40.2）	χ ²=2.059	0.151
多发（≥2枚）	116（23.2）	67（59.8）	χ ²=2.059	0.151
T管拔除时间（天）	74.8 ± 18.2	78.7 ± 15.2	t=－1.727	0.085
入院实验室检查
WBC（×10⁹/L）	7.84 ± 4.16	9.31 ± 5.77	t=－0.448	0.669
ALT（U/L）	134（42～281）	143（58～309）	Z=－1.110	0.267
AST（U/L）	76（32～178）	86（41～171）	Z=－0.537	0.594
ALP（U/L）	211.2 ± 137.1	194.5 ± 141.0	t=－2.355	0.559
GGT（U/L）	271（96～526）	409（207～621）	Z=－3.069	0.002
DBil（μmol/L）	15.3（7.4～38.5）	18.4（9.1～45.6）	Z=－1.700	0.089
TBil（μmol/L）	29.0（16.8～70.1）	34.6（22.2～77.4）	Z=－1.877	0.058

下载: 导出CSV

表 2 暴露组与非暴露组患者复发情况比较

Table 2. Comparison of recurrence rate between exposed group and non－exposed group

项目	暴露组（n=225）	非暴露组（n=112）	统计值	P值
复发率［例（%）］	12（5.33）	14（12.5）	χ ²=5.394	0.020
复发时间（月）	40.1 ± 26.7	19.2 ± 13.5	t=2.383	0.017

下载: 导出CSV

表 3 LCBDE术后胆总管结石复发的影响因素分析

Table 3. Analysis of influencing factors of choledocholithiasis recurrence after laparoscopy combined with choledochoscopy

影响因素	单因素Logistic分析		多因素Logistic分析
影响因素	P值	OR（95%CI）	P值	OR（95%CI）
性别（男）	0.814	1.101（0.494～2.465）
年龄（>65岁）	0.153	1.829（0.791～4.228）
糖尿病史	0.128	2.019（0.805～5.063）
高血压病史	0.935	0.981（0.412～2.333）
急性胆管炎病史	0.388	0.662（0.258～1.700）
胆总管最大直径（≥14 mm）	0.000	4.230（1.821～9.829）	0.031	2.935（1.101～7.829）
结石数量（≥2枚）	0.019	2.949（1.153～7.544）	0.029	2.911（1.118～7.584）
结石最大直径（≥15 mm）	0.002	3.513（1.547～7.978）	0.142	2.060（0.784～5.411）
T管引流	0.048	2.791（1.010～7.273）
PTGD手术史	0.893	0.702（0.159～3.105）
经胆总管切开取石	0.085	0.084（0.817～9.540）

下载: 导出CSV

参考文献(30)

[1]	CIANCI P, RESTINI E. Management of cholelithiasis with choledocholithiasis: Endoscopic and surgical approaches[J]. World J Gastroenterol, 2021, 27( 28): 4536－ 4554. DOI: 10.3748/wjg.v27.i28.4536.
[2]	HORI T. Comprehensive and innovative techniques for laparoscopic choledocholithotomy: A surgical guide to successfully accomplish this advanced manipulation[J]. World J Gastroenterol, 2019, 25( 13): 1531－ 1549. DOI: 10.3748/wjg.v25.i13.1531.
[3]	YAN Y, SHA Y, YUAN W, et al. One－stage versus two－stage management for acute cholecystitis associated with common bile duct stones: a retrospective cohort study[J]. Surg Endosc, 2022, 36( 2): 920－ 929. DOI: 10.1007/s00464－021－08349－6.
[4]	RICCI C, PAGANO N, TAFFURELLI G. et al. Comparison of efficacy and safety of 4 combinations of laparoscopic and intraoperative techniques for management of gallstone disease with biliary duct calculi: A systematic review and network Meta－analysis[J]. JAMA Surg, 2018, 153( 7): e181167. DOI: 10.1001/jamasurg.2018.1167.
[5]	LI ZQ, SUN JX, LI B, et al. Meta－analysis of single－stage versus two－staged management for concomitant gallstones and common bile duct stones[J]. J Minim Access Surg, 2020, 16( 3): 206－ 214. DOI: 10.4103/jmas.JMAS_146_18.
[6]	VAKAYIL V, KLINKER ST, SULCINER ML, et al. Single－stage management of choledocholithiasis: intraoperative ERCP versus laparoscopic common bile duct exploration[J]. Surg Endosc, 2020, 34( 10): 4616－ 4625. DOI: 10.1007/s00464－019－07215－w.
[7]	CAHYADI O, TEHAMI N, DE－MADARIA E, et al. Post－ERCP pancreatitis: Prevention, diagnosis and management[J]. Medicina(Kaunas), 2022, 58( 9): 1261. DOI: 10.3390/medicina58091261.
[8]	ZHU J, WANG G, XIE B, et al. Minimally invasive management of concomitant gallstones and common bile duct stones: an updated network meta－analysis of randomized controlled trials[J]. Surg Endosc, 2023, 37( 3): 1683－ 1693. DOI: 10.1007/s00464－022－09723－8.
[9]	MANSOUR S, KLUGER Y, KHURI S. Primary recurrent common bile duct stones: Timing of surgical intervention[J]. J Clin Med Res, 2022, 14( 11): 441－ 447. DOI: 10.14740/jocmr4826.
[10]	CHEN XP, WANG JP. Surgery[M]. Eighth Edition. Beijing: People’s Medical Publishing House, 2018: 440－ 441. 陈孝平, 汪建平. 外科学[M]. 8版. 北京: 人民卫生出版社, 2018: 440－ 441.
[11]	YOO ES, YOO BM, KIM JH, et al. Evaluation of risk factors for recurrent primary common bile duct stone in patients with cholecystectomy[J]. Scand J Gastroenterol, 2018, 53( 4): 466－ 470. DOI: 10.1080/00365521.2018.1438507.
[12]	WANG YF, XU B, WANG J, et al. Clinical effect of laparoscopy,choledochoscopy,and duodenoscopy combined with T－tube－free drainage in treat－ment of gallstones with common bile duct stones[J]. J Clin Hepatol, 2021, 37( 4): 872－ 876. DOI: 10.3969/j.issn.1001－5256.2021.04.029. 王云峰, 徐斌, 王杰, 等. 腹腔镜、胆道镜及十二指肠镜联合免T管引流对胆囊结石合并胆总管结石的治疗效果分析[J]. 临床肝胆病杂志, 2021, 37( 4): 872－ 876. DOI: 10.3969/j.issn.1001－5256.2021.04.029.
[13]	LEE SJ, CHOI IS, MOON JI, et al. Optimal treatment for concomitant gallbladder stones with common bile duct stones and predictors for recurrence of common bile duct stones[J]. Surg Endosc, 2022, 36( 7): 4748－ 4756. DOI: 10.1007/s00464－021－08815－1.
[14]	ZENG SM, LIU XR, LI SF, et al. Research progress of traditional Chinese medicine in the treatment of cholelithiasis[J]. J Chin Med Pharm, 2020, 48( 9): 72－ 76. DOI: 10.19664/j.cnki.1002－2392.200166. 曾思敏, 刘熙荣, 李生发, 等. 中医药治疗胆石症的研究进展[J]. 中医药学报, 2020, 48( 9): 72－ 76. DOI: 10.19664/j.cnki.1002－2392.200166.
[15]	ZHANG Y, ZHENG L. Experience of zheng liang in the treatment of cholelithiasis[J/CD]. Cardiov Dis Electronic J Integr Tradit Chin Western Med, 2019, 7( 31): 167－ 168. 张怿, 郑亮. 郑亮治疗胆石症临证经验[J/CD]. 中西医结合心血管病电子杂志, 2019, 7( 31): 167－ 168.
[16]	HU SW, ZHANG W, DING QY, et al. Econstruction of Chinese Materia Medica－Herba Lysimachiae[J]. J Changchun Univ Chin Med, 2023, 39( 5): 476－ 479. DOI: 10.13463/j.cnki.cczyy.2023.05.002. 胡诗宛, 张伟, 丁齐又, 等. 重构本草——金钱草[J]. 长春中医药大学学报, 2023, 39( 5): 476－ 479. DOI: 10.13463/j.cnki.cczyy.2023.05.002.
[17]	NIJIATIJIANG ABBL, ALIMUJIANG ABLMT, ALIDAN AKE, et al. Efficacy of LC combinedwith LCHTD in treatment of choledocholithiasis complicated with cholecystolithiasis and the related factors of postoperative recurrence of choledocholithiasis[J]. J Hepatopancreatobiliary Surg, 2021, 33( 7): 419－ 422. DOI: 10.11952/j.issn.1007－1954.2021.07.007. 尼加提江·艾比不拉, 阿力木江·阿布力米提, 阿里旦·艾尔肯, 等. LC联合LCHTD治疗胆总管结石合并胆囊结石的效果及术后胆总管结石复发的相关因素分析[J]. 肝胆胰外科杂志, 2021, 33( 7): 419－ 422. DOI: 10.11952/j.issn.1007－1954.2021.07.007.
[18]	LYU YH, ZHANG HC, SONG CY, et al. Logistic regression analysis of related factors of stone recurrence after laparoscopic cholecystectomy combined with choledocholithotomy and T－tube drainage[J]. Chongqing Med J, 2016, 45( 9): 1262－ 1264. DOI: 10.3969/j.issn.1671－8348.2016.09.033. 吕运海, 张焕常, 宋朝阳, 等. 腹腔镜胆囊切除联合胆总管切开取石T管引流术后结石复发相关因素的Logistic回归分析[J]. 重庆医学, 2016, 45( 9): 1262－ 1264. DOI: 10.3969/j.issn.1671－8348.2016.09.033.
[19]	PENG LJ, CHENG XN, ZHANG L. Risk factors of stone recurrence after endoscopic retrograde cholangiopancreatography for common bile duct stones[J]. Medicine(Baltimore), 2020, 99( 27): e20412. DOI: 10.1097/MD.0000000000020412.
[20]	MENG H. Risk factors for recurrent choledocholithiasis after ERCP lithotomy[J]. Hebei Med, 2016, 38( 5): 716－ 718. DOI: 10.3969/j.issn.1002－7386.2016.05.025. 孟环. ERCP取石后胆总管结石复发的相关危险因素研究[J]. 河北医药, 2016, 38( 5): 716－ 718. DOI: 10.3969/j.issn.1002－7386.2016.05.025.
[21]	PARK SY, HONG TH, LEE SK, et al. Recurrence of common bile duct stones following laparoscopic common bile duct exploration: a multicenter study[J]. J Hepatobiliary Pancreat Sci, 2019, 26( 12): 578－ 582. DOI: 10.1002/jhbp.675.
[22]	HUANG P, KE H, QIU Y, et al. Systematically characterizing chemical profile and potential mechanisms of qingre lidan decoction acting on cholelithiasis by integrating UHPLC－QTOF－MS and network target analysis[J]. Evid Based Complement Alternat Med, 2019, 2019: 2675287. DOI: 10.1155/2019/2675287.
[23]	FANG BJ, SHEN JY, ZHANG H, et al. Effect of emodin on mobility signal transduction system of gallbladder smooth muscle in Guinea pig with cholelithiasis[J]. Asian Pac J Trop Med, 2016, 9( 10): 1013－ 1018. DOI: 10.1016/j.apjtm.2016.07.021.
[24]	CAO LP, JIN HL, HONG Y, et al. Effect of kaempferol solid dispersion on cholestatic liver injury induced by α－naphthalene isothiocyanate in rats[J]. J Chin Med Materls, 2022, 45( 7): 1740－ 1743. DOI: 10.13863/ j.ssn1001－4454. 曹丽萍, 金红柳, 洪晔, 等. 山柰酚固体分散体对α－萘异硫氰酸诱导大鼠胆汁淤积性肝损伤的影响[J]. 中药材, 2022, 45( 7): 1740－ 1743. DOI: 10.13863/j.issn1001－4454.
[25]	WANG Y, ZHANG C, FENG JG. Effect of emodin on cholesterol stone formation[J]. Shaanxi Med J, 2016, 45( 6): 656－ 658. DOI: 10.3969/j.issn.1000－7377.2016.06.005. 王羊, 张成, 冯金鸽. 大黄素影响胆固醇结石形成的实验研究[J]. 陕西医学杂志, 2016, 45( 6): 656－ 658. DOI: 10.3969/j.issn.1000－7377.2016.06.005.
[26]	DING Y, XIONG XL, ZHOU LS, et al. Preliminary study on Emodin alleviating alpha－naphthylisothiocyanate－induced intrahepatic cholestasis by regulation of liver farnesoid X receptor pathway[J]. Int J Immunopathol Pharmacol, 2016, 29( 4): 805－ 811. DOI: 10.1177/0394632016672218.
[27]	TU JX, HUANG WR, HE CJ, et al. Protective effect of quercetin on cholestasis induced by 17α－acetylidiol[J]. Zhejiang Med J, 2020, 42( 17): 1802－ 1808. DOI: 10.12056/j.issn.1006－2785.2020.42.17.2019－3898. 涂君雪, 黄婉然, 何储君, 等. 槲皮素对17α－乙炔雌二醇诱导胆汁淤积的肝保护作用研究[J]. 浙江医学, 2020, 42( 17): 1802－ 1808. DOI: 10.12056/j.issn.1006－2785.2020.42.17.2019－3898.
[28]	ZHANG M, XIE Z, GAO W, et al. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol－to－bile acid conversion and cholesterol efflux in rats[J]. Nutr Res, 2016, 36( 3): 271－ 279. DOI: 10.1016/j.nutres.2015.11.019.
[29]	VOVKUN T, YANCHUK P, SHTANOVA L, et al. Water－soluble quercetin modulates the choleresis and bile lipid ratio in rats[J]. Gen Physiol Biophys, 2018, 37( 1): 111－ 120. DOI: 10.4149/gpb_2017015.
[30]	KLINE L. The flavone luteolin, an endocrine disruptor, relaxed male guinea pig gallbladder strips[J]. Gastroenterology Res, 2019, 12( 2): 53－ 59. DOI: 10.14740/gr1142.