Super minimally invasive surgery for gallstones:peroral transpapillary ultrasonic lithotripsy and litholysis with D-limonene in vitro

doi:10.3877/cma.j.issn.2095-7157.2025.02.005

Abstract

Abstract:

Objective

To assess the feasibility and efficacy of peroral transpapillary ultrasonic lithotripsy and litholysis with D-limonene for gallbladder-preserving gallstone removal in vitro experiment.

Methods

Between October 15,2024,and April 1,2025,72 fresh gallstones (24 cholesterol,24 pigment,24 mixed) were collected after cholecystectomy at the First Medical Center of Chinese PLA General Hospital and classified by infrared spectroscopy. Each stone type was randomly divided into D-limonene dissolution alone group (D-limonene group) or the other group combined with D-limonene dissolution and ultrasonic lithotripsy (hybrid group). There was no significant difference in the weight and size of the stones between the two groups. The D-limonene group received 20 mL of D-limonene at 37℃ with 60 rpm stirring for 8 hours, while the hybrid group received additional 1 MHz ultrasonic intervention. Dissolution time andefficiency were compared between the two groups. For stone types that could achieve complete dissolution, dissolution time was compared; for those that could not, dissolution rate was compared.Dissolution rate was defined as: (pre-procedure gallstone weight -post-procedure gallstone weight)/preprocedure gallstone weight.

Results

For cholesterol stones and mixed stones, the complete dissolution time in hybrid group were much shorter than those in D-limonene group (36. 42 ± 18. 05 vs. 130. 83 ±51.60 min,93.75 ±26.38 vs. 353.33 ±120.70 min, respectively, all P <0.001). For pigment stones,5 stones (41. 6%) in hybrid group achieved complete dissolution within 8 hours, while no stones in D-limonene group did. Based on the weight of residual stones, the median dissolution rate in hybrid group was much higher (72.46% vs. 16.70%, P <0.001).

Conclusion

Our in vitro experiment preliminarily showed that peroral transpapillary ultrasnonic lithotripsy and litholysis with D-limonene is feasible, and more efficient compared with D-limonene dissolution alone. With the spread of super minimally invasive surgery,it may provide a viable and promising therapeutic alternative for gallstone for gallbladder-preserving gallstone removal.

Key words: Gallstones, Super-Minimally invasive surgery, Ultrasonic lithotripsy, Contact dissolution, In vitro experiment

Yaqi Zhai, Dexin Chen, Wentao Wu, Zhiyuan Yao, Mingyang Li, Enqiang Linghu. Super minimally invasive surgery for gallstones:peroral transpapillary ultrasonic lithotripsy and litholysis with D-limonene in vitro[J]. Chinese Journal of Gastrointestinal Endoscopy(Electronic Edition), 2025, 12(02): 90-95.

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References 30

[1]	中华消化杂志编辑委员会,中华医学会消化病学分会肝胆疾病协作组. 中国慢性胆囊炎、胆囊结石内科诊疗共识意见(2018 年) [J].临床肝胆病杂志,2019,35(6):1231-1236.
[2]	Song Y,Ma Y,Xie FC,et al.Age,gender,geographic and clinical differences for gallstones in China:a nationwide study[J]. Ann Transl Med,2022,10(13):735-735.
[3]	Jaunoo SS, Mohandas S, Almond LM. Postcholecystectomy syndrome (PCS)[J].Int J Surg,2010,8(1):15-17.
[4]	Fujita N,Yasuda I,Endo I,et al.Evidence-based clinical practice guidelines for cholelithiasis 2021[J]. J Gastroenterol,2023,58(9):801-833.
[5]	Walker JE. THE REMOVAL OF GALL-STONES BY ETHER SOLUTION [J].Lancet,1891,137:874-875.
[6]	Plaisier PW,Vergunst H,Terpstra OT. Dissolution of gallstones[J]. Dig Dis,1993,11(3):181-188.
[7]	Janowitz P,Schumacher KA,Swobodnik W,et al. Transhepatic topical dissolution of gallbladder stones with MTBE and EDTA.Results, side effects,and correlation with CT imaging[J]. Dig Dis Sci,1993,38(11):2121-2129.
[8]	Hellstern A,Leuschner U,Benjaminov A,et al. Dissolution of gallbladder stones with methyl tert-butyl ether and stone recurrence:a European survey[J].Dig Dis Sci,1998,43(5):911-920.
[9]	Wang BS,Xu GR,He LQ,et al. Extracorporeal shock wave lithotripsy. Experience in treating 245 patients with gallbladder stones[J].Chin Med J (Engl),1990,103(6):443-446.
[10]	Sackmann M, Delius M, Sauerbruch T, et al. Shock-wave lithotripsy of gallbladder stones.The first 175 patients[J].N Engl J Med,1988,318(7):393-397.
[11]	Hao Y, Yang Z, Yang H, et al. Gallbladder-preserving cholecystolithotomy[J].Expert Rev Gastroenterol Hepatol,2022,16(3):265-272.
[12]	中华医学会外科学分会胆道外科学组,中国医师协会外科医师分会胆道外科医师委员会.胆囊良性疾病外科治疗的专家共识(2021 版)[J].中华外科杂志,2022,60(1):4-9.
[13]	赵健楠,刘洋,王向,等.胆囊结石处理的临床决策:从适应证到术式选择的再探索[J].中国普通外科杂志,2025,34(2):245-252.
[14]	王晓虹,袁海鹏,张亚利,等.内镜下经胃入路保胆取石术短期临床疗效及安全性分析[J].中国实用内科杂志,2025,45(2):127-130.
[15]	何朝晖,赵秋灵,周微薇,等. 中国经口胰胆管镜超级微创诊疗技术共识意见(2023 年,北京)解读[J/OL].中华胃肠内镜电子杂志,2024,11(2):75-80.
[16]	张波,姚怡,张文刚,等.胆道镜直视系统在胆胰系统中的诊疗价值[J/OL].中华胃肠内镜电子杂志,2023,10(4):264-266.
[17]	Zhang WG,Chai NL,Zhang B,et al. Cholangioscopy-assisted extraction through novel papillary support for small-calibre and sediment-like common bile duct stones [ J ]. World J Gastroenterol,2023,29(16):2495-2501.
[18]	董浩,张文刚,刘圣圳,等.胆道镜直视下胆总管结石取出术的初步探索[J/OL].中华胃肠内镜电子杂志,2023,10(2):92-96.
[19]	令狐恩强.手术发展史的新阶段—超级微创技术[J/OL]. 中华胃肠内镜电子杂志,2016,3(3):97-98.
[20]	韩旭,苏鑫,陈哲,等. 不同胆结石接触式溶石剂效果比较[J].实用老年医学,2023,37(4):411-415.
[21]	Hirakawa N,Yamamoto K,Sofuni A,et al. Factors predicting technical failure of endoscopic transpapillary gallbladder drainage for acute cholecystitis[J].DEN Open,2024,4(1): e308.
[22]	Yoshida M,Naitoh I,Hayashi K,et al.Four-Step Classification of Endoscopic Transpapillary Gallbladder Drainage and the Practical Efficacy of Cholangioscopic Assistance[J]. Gut Liver,2021,15(3):476-485.
[23]	张文刚,柴宁莉,令狐恩强.经口胆道镜超级微创诊断术中不明原因胆道狭窄(IBS)病变性质鉴别新标准[J/OL].中华胃肠内镜电子杂志,2023,10(1):11-13.
[24]	Zhang W,Chai N,Zhai Y,et al.Cholangioscopy-assisted extraction of choledocholithiasis and partial sediment-like gallstones through papillary support:A pilot exploration for super minimally invasive surgery [J].Endoscopy,2023,55(S 01):E274-E275.
[25]	陈伟民,胡海,张圣道,等.胆囊结石甲基叔丁醚溶石联合超声助溶的研究[J].中华实验外科杂志,1996,(4):193-194,257.
[26]	林书玉.超声技术的基石—超声换能器的原理及设计[J].物理,2009,38(3):141-148.
[27]	Bailey MR,Maxwell AD,Cao S,et al. Improving Burst Wave Lithotripsy Effectiveness for Small Stones and Fragments by Increasing Frequency:Theoretical Modeling and Ex Vivo Study[J].J Endourol,2022,36(7):996-1003.
[28]	Chapman WC, Stephens WH, Williams LF Jr. Principles of biliary extracorporeal lithotripsy. Technical considerations and clinical implications[J].Am J Surg,1989,158(3):179-183.
[29]	Igimi H,Hisatsugu T,Nishimura M. The use of d-limonene preparation as a dissolving agent of gallstones[J].Am J Dig Dis,1976,21(11):926-939.
[30]	Lee YT,Li DS,Pozzo LD.Kinetic Analysis of Ultrasound-Induced Oil Exchange in Oil-in-Water Emulsions through Contrast Variation Time-Resolved Small-Angle Neutron Scattering[J].Langmuir,2019,35(47):15204-15213.

项目	结石总数（n = 72）	超声波联合溶石组（n = 36）	单纯溶石组（n = 36）	t 值	P 值
重量[mg,（x̄ ± s）]	665.65 ± 316.81	683.01 ± 318.73	648.28 ± 318.41	0.46	0.645
胆固醇结石	631.45 ± 251.34	684.97 ± 223.21	627.93 ± 289.29	0.54	0.594
混合性结石	667.70 ± 361.25	645.08 ± 432.27	690.33 ± 291.34	-0.30	0.766
胆色素结石	672.78 ± 338.34	719.00 ± 289.11	626.57 ± 388.72	0.66	0.516
大小[cm,（x̄ ± s）]	1.07 ± 0.29	1.03 ± 0.27	1.11 ± 0.31	-1.22	0.224
胆固醇结石	1.04 ± 0.31	0.97 ± 0.29	1.11 ± 0.32	-1.13	0.645
混合性结石	1.01 ± 0.26	1.00 ± 0.30	1.01 ± 0.21	-0.08	0.938
胆色素结石	1.18 ± 0.30	1.12 ± 0.21	1.25 ± 0.37	-0.84	0.410

项目	结石总数（n = 72）	超声波联合溶石组（n = 36）	单纯溶石组（n = 36）	t 值	P 值
重量[mg,（x̄ ± s）]	665.65 ± 316.81	683.01 ± 318.73	648.28 ± 318.41	0.46	0.645
胆固醇结石	631.45 ± 251.34	684.97 ± 223.21	627.93 ± 289.29	0.54	0.594
混合性结石	667.70 ± 361.25	645.08 ± 432.27	690.33 ± 291.34	-0.30	0.766
胆色素结石	672.78 ± 338.34	719.00 ± 289.11	626.57 ± 388.72	0.66	0.516
大小[cm,（x̄ ± s）]	1.07 ± 0.29	1.03 ± 0.27	1.11 ± 0.31	-1.22	0.224
胆固醇结石	1.04 ± 0.31	0.97 ± 0.29	1.11 ± 0.32	-1.13	0.645
混合性结石	1.01 ± 0.26	1.00 ± 0.30	1.01 ± 0.21	-0.08	0.938
胆色素结石	1.18 ± 0.30	1.12 ± 0.21	1.25 ± 0.37	-0.84	0.410

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