Wang Ji,Li Zhi.Recent advances of non-surgical treatment of Hirschsprung’s disease[J].Journal of Clinical Pediatric Surgery,2022,21(02):186-190.[doi:10.3760/cma.j.cn.101785-202104064-016]
先天性巨结肠非手术治疗研究进展
- Title:
- Recent advances of non-surgical treatment of Hirschsprung’s disease
- 关键词:
- Hirschsprung病/治疗; Hirschsprung病/外科学; 扩肛; 灌肠; 方剂; 肉毒素; 生物反馈; 干细胞治疗
- Keywords:
- Hirschsprung Disease/TH; Hirschsprung Disease/SU; Anal Dilatation; Enema; Chinese Medical Formula; Botulinum Toxin; Biofeedback Therapy; Stem-cell Therapy
- 摘要:
- 先天性巨结肠（Hirschsprung’s disease，HSCR）是一种常见的先天性消化道发育畸形，以病变肠管神经节细胞缺乏为特征，发病率约1/5 000，男女比例约4：1。HSCR的治疗主要包括手术治疗和非手术治疗，目前通过手术切除无神经节细胞肠段及移行段仍为HSCR的主要治疗方式。近年来，国内外学者对HSCR非手术治疗进行了深入研究，非手术治疗在HSCR患儿手术前、手术后解决排便问题方面起到了重要作用。本文从扩肛和灌肠、中医药治疗、肉毒素注射治疗、生物反馈治疗以及干细胞治疗等方面对HSCR非手术治疗研究进展进行综述。
- Abstract:
- As a congenital bowel disorder, Hirschsprung’s disease (HSCR) is characterized by the absence of intestinal ganglion cells with a prevalence of 1/5000 and a male-to-female ratio of 4:1.Its treatment options include surgery and non-surgical measures.The major treatment remains surgical resection by removing ganglion-free intestine and transitional segments.Domestic and foreign scholars actively exploring non-surgical option have concluded that it plays an important role in resolving defecation problems before and after operation.This review summarized non-surgical option of HSCR from the aspects of anal dilation and enema, traditional Chinese medicine, botulinum toxin injection, biofeedback and stem-cell therapies.
参考文献/References:
[1] Heuckeroth RO.Hirschsprung disease-integrating basic science and clinical medicine to improve outcomes[J].Nat Rev Gastroenterol Hepatol,2018,15(3):152-167.DOI:10.1038/nrgastro.2017.149.
[2] Hartman EE,Oort FJ,Aronson DC,et al.Quality of life and disease-specific functioning of patients with anorectal malformations or Hirschsprung’s disease:a review[J].Arch Dis Child,2011,96(4):398-406.DOI:10.1136/adc.2007.118133.
[3] 曾纪晓.先天性巨结肠非计划性再手术的相关问题[J].临床小儿外科杂志,2018,17(2):94-98.DOI:10.3969/j.issn.1671-6353.2018.02.004. Zeng JX.Related issues of unscheduled re-operation for Hirs-chsprung’s disease[J].J Clin Ped Sur,2018,17(2):94-98.DOI:10.3969/j.issn.1671-6353.2018.02.004.
[4] Tam PKH,Chung PHY,St Peter SD,et al.Advances in paediatric gastroenterology[J].The Lancet,2017,390(10099):1072-1082.DOI:10.1016/S0140-6736(17)32284-5.
[5] Frykman PK,Short SS.Hirschsprung-associated enterocolitis:prevention and therapy[J].Semin Pediatr Surg,2012,21(4):328-335.DOI:10.1053/j.sempedsurg.2012.07.007.
[6] Pontarelli EM,Ford HR,Gayer CP.Recent developments in Hirschsprung’s-associated enterocolitis[J].Curr Gastroenterol Rep,2013,15(8):340.DOI:10.1007/s11894-013-0340-6.
[7] 李智,袁宏耀,郭先娥,等.扩肛治疗在婴幼儿便秘及巨结肠根治术后的应用研究[J].临床小儿外科杂志,2017,16(2):151-154.DOI:10.3969/j.issn.1671-6353.2017.02.011. Li Z,Yuan HY,Guo XE,et al.Application of anal dilation in infants with constipation and after radical surgery for Hischsprung’s disease[J].J Clin Ped Sur,2017,16(2):151-154.DOI:10.3969/j.issn.1671-6353.2017.02.011.
[8] 郭先娥,徐蓉,胡露红,等.巨结肠患者术后家庭康复护理指导的实施及效果评价[J].中国康复,2006,21(5):349-350.DOI:10.3870/j.issn.1001-2001.2006.05.041. Guo XE,Xu R,Hu LH,et al.Practice and effect evaluation of home rehabilitation and introduction in children with Hirschsprung disease after operation[J].Chinese Journal of Rehabilitation,2006,21(5):349-350.DOI:10.3870/j.issn.1001-2001.2006.05.041.
[9] Temple SJ,Shawyer A,Langer JC.Is daily dilatation by parents necessary after surgery for Hirschsprung disease and anorectal malformations?[J].J Pediatr Surg,2012,47(1):209-212.DOI:10.1016/j.jpedsurg.2011.10.048.
[10] Lin Z,Lin Y,Bai J,et al.Outcomes of preoperative anal dilatation for hirschsprung disease[J].J Pediatr Surg,2021,56(3):483-486.DOI:10.1016/j.jpedsurg.2020.05.008.
[11] Malone PS,Ransley PG,Kiely EM.Preliminary report:the antegrade continence enema[J].The Lancet,1990,336(8725):1217-1218.DOI:10.1016/0140-6736(90)92834-5.
[12] Granstr?m AL,Husberg B,Nordenskj?ld A,et al.Laparoscopic-assisted pull-through for Hirschsprung’s disease,a prospective repeated evaluation of functional outcome[J].J Pediatr Surg,2013,48(12):2536-2539.DOI:10.1016/j.jpedsurg.2013.07.017.
[13] Chong C,Featherstone N,Sharif S,et al.5 years after an ACE:what happens then?[J].Pediatr Surg Int,2016,32(4):397-401.DOI:10.1007/s00383-016-3857-6.
[14] Lu C,Xie H,Li H,et al.Feasibility and efficacy of home rectal irrigation in neonates and early infancy with Hirschsprung disease[J].Pediatr Surg Int,2019,35(11):1245-1253.DOI:10.1007/s00383-019-04552-8.
[15] 谷春山,江明性,童尔昌.人参等药物对先天性巨结肠症病变肠段运动的影响[J].武汉医学院学报,1980,(3):7-10. Gu CS,Jiang MX,Tong EC.Influence of radix ginseng and other drugs on intestinal movements in infant with congenital megacolon[J].Acta Medicinae Universitatis Scientiae et Technologiae Huazhong,1980,(3):7-10.
[16] Shia C,Juang S,Tsai S,et al.Metabolism and pharmacokinetics of anthraquinones in rheum palmatum in rats and ex vivo antioxidant activity[J].Planta Med,2009,75(13):1386-1392.DOI:10.1055/s-0029-1185725.
[17] Wang S,Liu Y,Fan Y,et al.Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons[J].World J Gastroenterol,2015,21(31):9358.DOI:10.3748/wjg.v21.i31.9358.
[18] Gao L,Wang J,Li F,et al.Literature-based analysis on relationship of symptoms,drugs and therapies in treatment of intestinal diseases[J].J Tradit Chin Med,2014,34(1):106-114.DOI:10.1016/S0254-6272(14)60063-7.
[19] Li J,Zhang X,Ji J,et al.Three inulin-type fructans from codonopsis pilosula (franch.) nannf.roots and their prebiotic activity on bifidobacterium longum[J].Molecules,2018,23(12):3123.DOI:10.3390/molecules23123123.
[20] Yu J,Guo J,Tao W,et al.Gancao-Gansui combination impacts gut microbiota diversity and related metabolic functions[J].J Ethnopharmacol,2018,214:71-82.DOI:10.1016/j.jep.2017.11.031.
[21] Wang G,Zhang SH,Lin HJ,et al.Nonoperative treatment of Hirschsprung’s disease:a new approach[J].J Pediatr Surg,1987,22(5):439-442.DOI:10.1016/S0022-3468(87)80265-8.
[22] 朱妤,姚敏华,王翔.加味四君子汤对巨结肠患者肠屏障功能影响的临床观察[J].中国中西医结合杂志,2012,32(2):199-202.DOI:10.1016/S0022-3468(87)80265-8. Zhu Y,Tao MH,Wang X.Clinical observation of effects of modified Sijunzi Decoction on intestinal mucosal barrier of megacolon children[J].Chinese Journal of Integrated Traditional and Western Medicine,2012,32(2):199-202.DOI:10.1016/S0022-3468(87)80265-8.
[23] 姚敏华,王翔,王金湖.加味四君子汤治疗先天性巨结肠术后并发症的临床观察[J].中国中西医结合儿科学,2010,2(3):246-247.DOI:10.3969/j.issn.1674-3865.2010.03.023. Yao MH,Wang X,Wang JH.Clinical observation on modified Sijunzi Decoction for postoperative complications of congenital megacolon[J].Chinese Pediatrics of Integrated Traditional and Western Medicine,2010,2(3):246-247.DOI:10.3969/j.issn.1674-3865.2010.03.023.
[24] Balint B,Mencacci NE,Valente EM,et al.Dystonia[J].Nat Rev Dis Primers,2018,4(1):1-23.DOI:10.1038/s41572-018-0023-6.
[25] Roorda D,Abeln ZA,Oosterlaan J,et al.Botulinum toxin injections after surgery for Hirschsprung disease:Systematic review and meta-analysis[J].World J Gastroenterol,2019,25(25):3268.DOI:10.3748/wjg.v25.i25.3268.
[26] Youn JK,Han J,Oh C,et al.Botulinum toxin injection for internal anal sphincter achalasia after pull-through surgery in Hirschsprung disease[J].Medicine (Abingdon),2019,98(45):e17855.DOI:10.1097/MD.0000000000017855.
[27] Cariati M,Chiarello MM,Cannistra’ M,et al.Gastrointestinal uses of botulinum toxin[J].Handb Exp Pharmacol,2021,263:185-226.DOI:10.1007/164_2019_326.
[28] Langer JC,Birnbaum E.Preliminary experience with intrasphincteric botulinum toxin for persistent constipation after pull-through for Hirschsprung’s disease[J].J Pediatr Surg,1997,32(7):1059-1061.DOI:10.1016/S0022-3468(97)90399-7.
[29] Minkes RK,Langer JC.A prospective study of botulinum toxin for internal anal sphincter hypertonicity in children with Hirschsprung’s disease[J].J Pediatr Surg,2000,35(12):1733-1736.DOI:10.1053/jpsu.2000.19234.
[30] Halleran DR,Lu PL,Ahmad H,et al.Anal sphincter botulinum toxin injection in children with functional anorectal and colonic disorders:A large institutional study and review of the literature focusing on complications[J].J Pediatr Surg,2019,54(11):2305-2310.DOI:10.1016/j.jpedsurg.2019.03.020.
[31] Church JT,Gadepalli SK,Talishinsky T,et al.Ultrasound-guided intrasphincteric botulinum toxin injection relieves obstructive defecation due to Hirschsprung’s disease and internal anal sphincter achalasia[J].J Pediatr Surg,2017,52(1):74-78.DOI:10.1016/j.jpedsurg.2016.10.023.
[32] Louis-Borrione C,Faure A,Garnier S,et al.Neurostimulation-guided anal intrasphincteric botulinum toxin injection in children with Hirschsprung disease[J].J Pediatr Gastroenterol Nutr,2019,68(4):527-532.DOI:10.1097/MPG.0000000000002204.
[33] Keshtgar AS,Ward HC,Clayden GS.Transcutaneous needle-free injection of botulinum toxin:a novel treatment of childhood constipation and anal fissure[J].J Pediatr Surg,2009,44(9):1791-1798.DOI:10.1016/j.jpedsurg.2009.02.056.
[34] Naumann M,Carruthers A,Carruthers J,et al.Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX?) across multiple indications[J].Mov Disord,2010,25(13):2211-2218.DOI:10.1002/mds.23254.
[35] Han-Geurts IJ,Hendrix VC,de Blaauw I,et al.Outcome after anal intrasphincteric botox injection in children with surgically treated hirschsprung disease[J].J Pediatr Gastroenterol Nutr,2014,59(5):604-607.DOI:10.1097/MPG.0000000000000483.
[36] Tantiphlachiva K,Rao S.Biofeedback therapy for bowel problems in adults after surgical treatment for childhood Hirschsprung’s disease[J].Dev Neurorehabil,2009,12(6):442-449.DOI:10.3109/17518420903046745.
[37] Engel BT,Nikoomanesh P,Schuster MM.Operant conditioning of rectosphincteric responses in the treatment of fecal incontinence[J].N Engl J Med,1974,290(12):646-649.DOI:10.1056/NEJM197403212901202.
[38] Wiesel PH,Norton C,Roy AJ,et al.Gut focused behavioural treatment (biofeedback) for constipation and faecal incontinence in multiple sclerosis[J].J Neurol Neurosurg Psychiatry,2000,69(2):240-243.DOI:10.1136/jnnp.69.2.240.
[39] Sun X,Wang R,Zhang L,et al.Efficacy of pelvic floor muscle training for the treatment of fecal incontinence after soave procedure for Hirschsprung disease[J].Eur J Pediatr Surg,2012,22(4):300-304.DOI:10.1055/s-0032-1313351.
[40] 李殿国,罗娟,孙小兵,等.生物反馈辅助盆底肌训练治疗儿童肌源性大便失禁89例[J].中国现代普通外科进展,2014,17(2):156-158.DOI:10.3969/j.issn.1009-9905.2014.02.024. Li DG,Luo J,Sun XB,et al.Biofeedback assisted pelvic floor muscle training for children with myogenic fecal incontinence:a report of 89 cases[J].Chin J Curr Adv in Gen Surg,2014,17(2):156-158.DOI:10.3969/j.issn.1009-9905.2014.02.024.
[41] 谢承,刘昇,郭碧霞,等.肌电刺激生物反馈治疗巨结肠患者术后肛门失禁的效果观察[J].中外医学研究,2018,16(1):1-3.DOI:10.14033/j.cnki.cfmr.2018.1.001. Xie C,Liu S,Guo BX,et al.Therapeutic effect of electrical stimulation biofeedback for postoperative anal incontinence of children with colonic colon[J].Chin and Foreign Med Res,2018,16(1):1-3.DOI:10.14033/j.cnki.cfmr.2018.1.001.
[42] 宋翠萍,张海洋,饶旺,等.电刺激生物反馈治疗先天性巨结肠术后大便失禁的疗效分析[J].临床小儿外科杂志,2016,15(1):53-55.DOI:10.3969/j.issn.1671-6353.2016.01.015. Song CP,Zhang HY,Rao W,et al.Clinical observation of electrical stimulation biofeedback therapy for fecal incontinence after Soave procedure for Hirschsprung’s disease in children[J].J Clin Ped Sur,2016,15(1):53-55.DOI:10.3969/j.issn.1671-6353.2016.01.015.
[43] Zhao Y,Ge X,Yu H,et al.Inhibition of ROCK signaling pathway accelerates enteric neural crest cell-based therapy after transplantation in a rat hypoganglionic model[J].Neurogastroenterology & Motility,2020,32(9):e13895.DOI:10.1111/nmo.13895.
[44] Burns AJ,Goldstein AM,Newgreen DF,et al.White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies[J].Dev Biol,2016,417(2):229-251.DOI:10.1016/j.ydbio.2016.04.001.
[45] McCann CJ,Cooper JE,Natarajan D,et al.Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon[J].Nat Commun,2017,8(1):1-11.DOI:10.1038/ncomms15937.
[46] Workman MJ,Mahe MM,Trisno S,et al.Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system[J].Nat Med,2017,23(1):49-59.DOI:10.1038/nm.4233.
[47] Fattahi F,Steinbeck JA,Kriks S,et al.Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease[J].Nature,2016,531(7592):105-109.DOI:10.1038/nature16951.
[48] 谢华,唐维兵.规范、统一先天性巨结肠分型的建议[J].临床小儿外科杂志,2021,20(3):212-216.DOI:10.12260/lcxewkzz.2021.03.003. Xie H,Tang WB.Unifying the classification of Hirschsprung’s disease[J].J Clin Ped Sur,2021,20(3):212-216.DOI:10.12260/lcxewkzz.2021.03.003.
[49] 曾纪晓,徐晓钢.先天性巨结肠诊疗规范化的再思考[J].临床小儿外科杂志,2021,20(3):201-207.DOI:10.12260/lcxewkzz.2021.03.001. Zeng JX,Xu XG.Some focal issues of standardizing the diagnosis and treatment of Hirschsprung’s disease[J].J Clin Ped Sur,2021,20(3):201-207.DOI:10.12260/lcxewkzz.2021.03.001.
相似文献/References:
[1]苏义林,王忠荣,徐兵,等.经肛门Soave巨结肠根治术后肛门功能与直肠肛管测压的研究[J].临床小儿外科杂志,2008,7(01):11.
[2]吴鸿根,邓洪强,周明,等.经肛门Soave Ⅰ期拖出根治术治疗婴儿先天性巨结肠[J].临床小儿外科杂志,2008,7(01):36.
[3]黄华,陈琦,曹振杰,等.SOX10 mRNA在先天性巨结肠肠壁中的表达[J].临床小儿外科杂志,2008,7(03):11.
[4]严志龙,吴晔明,陈其民,等.先天性巨结肠微创化手术治疗研究[J].临床小儿外科杂志,2008,7(04):0.
[5]叶祥东,户佐珍,骆敏,等.经肛门Soave拖出术治疗婴幼儿先天性巨结肠[J].临床小儿外科杂志,2008,7(04):0.
[6]罗喜荣,包国强,詹江华,等.先天性巨结肠的微创手术治疗[J].临床小儿外科杂志,2007,6(03):13.
[7]毛永忠,汤绍涛,阮庆兰,等.结肠次全切除术治疗巨结肠同源病23例[J].临床小儿外科杂志,2007,6(04):9.
[8]黄河 戚士芹 高群 陈晨 卢贤映 未德成. 腹腔镜辅助改良Soave术根治小儿先天性巨结肠[J].临床小儿外科杂志,2012,11(02):112.
[9]钟微 余家康 夏慧敏 孙静.回肠拖出Soave术治疗全结肠型巨结肠的中远期疗效评估[J].临床小儿外科杂志,2012,11(05):340.
[J].Journal of Clinical Pediatric Surgery,2012,11(02):340.
[10]徐兵 孙传成 孙华.经肛门改良Swenson和Soave术治疗先天性巨结肠比较[J].临床小儿外科杂志,2012,11(06):415.
[J].Journal of Clinical Pediatric Surgery,2012,11(02):415.
备注/Memo
收稿日期:2021-04-06。
基金项目:国家自然科学基金项目（81400579）
通讯作者:李智,Email:lizhimdphd@163.com