冷冻疗法在口腔黏膜病治疗中的应用

doi:10.13591/j.cnki.kqyx.2023.09.013

摘要/Abstract

摘要：

冷冻疗法是一种利用低温冷冻技术来破坏病损组织的技术,具有安全、方便、不良反应少等优点,目前在各种皮肤疾病中被广泛应用。由于口腔黏膜结构与皮肤组织相似,许多发生于口腔黏膜的疾病如黏膜色素沉着、口腔溃疡、唾液腺囊肿、口腔扁平苔藓、口腔白斑病等,是冷冻疗法技术应用的理想场所。该文主要探讨冷冻疗法在口腔黏膜病的原理、方法及应用,因其对周围组织产生的损害小,治疗后无出血、无瘢痕、疼痛轻,继发感染发生率低,且操作简单,具有成为许多口腔黏膜疾病治疗的首选方法或替代方案的潜力。

关键词: 冷冻疗法, 组织冷冻, 口腔黏膜病

Abstract:

Cryotherapy is a surgical technique that employs freezing to destroy undesirable tissue. Major advantages of oral cryotherapy include safety, convenience and less side effects. It has been widely used in the treatment of many cutaneous diseases. Because oral mucosa is similar to skin, many diseases occurring in oral mucosa, such as vascular anomalies, mucosal pigmentation, oral ulcer, sialocele, oral lichen planus, oral leukoplakia, are appropriate for this technology. This article mainly discusses the principle, method and application of cryotherapy in the treatment of oral mucosal diseases. Due to its numerousadvantages, including small damage to surrounding tissues, no bleeding, no scar, light pain after treatment, low incidence of secondary infection and simple operation, cryotherapy has the potential to be the first choice or alternative in the treatment of many oral mucosal diseases.

Key words: cryotherapy, tissue freezing, oral mucosal disease

中图分类号:

R781.5

李正磊, 闫毓杰, 田欣, 曾昕, 王冏珂, 陈谦明. 冷冻疗法在口腔黏膜病治疗中的应用[J]. 口腔医学, 2023, 43(9): 837-843.

LI Zhenglei, YAN Yujie, TIAN Xin, ZENG Xin, WANG Jiongke, CHEN Qianming. Application of cryotherapy in the treatment of oral mucosal disease[J]. Stomatology, 2023, 43(9): 837-843.

图/表 2

参考文献 61

[1]	Arnott J. Practical illustrations of the remedial efficacy of a very low or anæsthetictemperature.—i. in cancer[J]. Lancet, 1850, 56(1409):257-259. doi: 10.1016/S0140-6736(02)89874-9
[2]	Pusey WA. The use of carbon dioxid snow in the treatment of nevi and other lesions of the skin.a preliminary report[J]. J Am Med Assoc, 1907, XLIX(16):1354.
[3]	Wolfe J, Bryant G. Freezing, drying, and/or vitrification of membrane- solute-water systems[J]. Cryobiology, 1999, 39(2):103-129. doi: 10.1006/cryo.1999.2195 pmid: 10529304
[4]	Rubinsky B. Cryosurgery[J]. Annu Rev Biomed Eng, 2000, 2:157-187. pmid: 11701510
[5]	Mahnken AH, König AM, Figiel JH. Current technique and application of percutaneous cryotherapy[J]. Rofo, 2018, 190(9):836-846. doi: 10.1055/a-0598-5134 pmid: 29665588
[6]	Toner M, Cravalho EG, Karel M. Thermodynamics and kinetics of intracellular ice formation during freezing of biological cells[J]. J Appl Phys, 1990, 67(3):1582-1593. doi: 10.1063/1.345670
[7]	Hoffmann NE, Bischof JC. The cryobiology of cryosurgical injury[J]. Urology, 2002, 60(2):40-49. doi: 10.1016/S0090-4295(02)01683-7
[8]	Kujan O, Azzeghaiby SN, Tarakji B, et al. Cryosurgery of the oral and peri-oral region:A literature review of the mechanism, tissue response, and clinical applications[J]. J Investig Clin Dent, 2013, 4(2):71-77. doi: 10.1111/jicd.2013.4.issue-2
[9]	Wen J, Duan Y, Zou Y, et al. Cryoablation induces necrosis and apoptosis in lung adenocarcinoma in mice[J]. Technol Cancer Res Treat, 2007, 6(6):635-640. doi: 10.1177/153303460700600607
[10]	Baust JG, Snyder KK, Santucci KL, et al. Cryoablation:Physical and molecular basis with putative immunological consequences[J]. Int J Hyperth, 2019, 36(sup1):10-16. doi: 10.1080/02656736.2019.1647355
[11]	Clarke DM, Baust JM, Van Buskirk RG, et al. Addition of anticancer agents enhances freezing-induced prostate cancer cell death:Implications of mitochondrial involvement[J]. Cryobiology, 2004, 49(1):45-61. doi: 10.1016/j.cryobiol.2004.05.003
[12]	Hanai A, Yang WL, Ravikumar TS. Induction of apoptosis in human colon carcinoma cells HT29 by sublethal cryo-injury:Mediation by cytochrome c release[J]. Int J Cancer, 2001, 93(4):526-533. doi: 10.1002/ijc.1359 pmid: 11477556
[13]	den Brok MHMGM, Sutmuller RPM, Nierkens S, et al. Synergy between in situ cryoablation and TLR9 stimulation results in a highly effective in vivo dendritic cell vaccine[J]. Cancer Res, 2006, 66(14):7285-7292. doi: 10.1158/0008-5472.CAN-06-0206
[14]	Mehta A, Oklu R, Sheth RA. Thermal ablative therapies and immune checkpoint modulation:Can locoregional approaches effect a systemic response?[J]. Gastroenterol Res Pract, 2016, 2016:9251375.
[15]	Erinjeri JP, Clark TWI. Cryoablation:Mechanism of action and devices[J]. J VascIntervRadiol, 2010, 21(8):S187-S191.
[16]	Baust JG, Gage AA. The molecular basis of cryosurgery[J]. BJU Int, 2005, 95(9):1187-1191. pmid: 15892798
[17]	Gage AA, Guest K, Montes M, et al. Effect of varying freezing and thawing rates in experimental cryosurgery[J]. Cryobiology, 1985, 22(2):175-182. pmid: 3979086
[18]	Clebak KT, Mendez-Miller M, Croad J. Cutaneous cryosurgery for common skin conditions[J]. Am Fam Physician, 2020, 101(7):399-406. pmid: 32227823
[19]	Farah CS, Savage NW. Cryotherapy for treatment of oral lesions[J]. Aust Dent J, 2006, 51(1):2-5. doi: 10.1111/j.1834-7819.2006.tb00392.x pmid: 16669469
[20]	Robati RM, Ghasemi-Pour M. Efficacy and safety of cryotherapyvs. electrosurgery in the treatment of cherry angioma[J]. J EurAcad Dermatol Venereol, 2018, 32(9):e361-e363.
[21]	Bassukas ID, Abuzahra F, Hundeiker M. Regression phase as therapeutic goal of cryosurgical treatment of growing capillary infantile hemangiomas. Treatment decision, treatment strategy and results of an open clinical study[J]. Hautarzt, 2000, 51(4):231-238. pmid: 10810657
[22]	Reischle S, Schuller-Petrovic S. Treatment of capillary hemangiomas of early childhood with a new method of cryosurgery[J]. J Am Acad Dermatol, 2000, 42(5):809-813. doi: 10.1067/mjd.2000.103985
[23]	García-Oreja S, Álvaro-Afonso FJ, García-Álvarez Y, et al. Topical treatment for plantar warts:A systematic review[J]. Dermatol Ther, 2021, 34(1):e14621.
[24]	Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars:Pathophysiology, classification, and treatment[J]. Dermatol Surg, 2017, 43(Suppl 1):S3-S18. doi: 10.1097/DSS.0000000000000819
[25]	Lanigan SW, Robinson TW. Cryotherapy for dermatofibromas[J]. Clin Exp Dermatol, 1987, 12(2):121-123. pmid: 3677469
[26]	Mirshams M, Daneshpazhooh M, Mirshekari A, et al. Cryotherapy in the treatment of pyogenic granuloma[J]. J EurAcad Dermatol Venereol, 2006, 20(7):788-790.
[27]	Blume-Peytavi U, Zouboulis CC, Jacobi H, et al. Successful outcome of cryosurgery in patients with granuloma annulare[J]. Br J Dermatol, 1994, 130(4):494-497. doi: 10.1111/bjd.1994.130.issue-4
[28]	Ataş H, Gönül M. Evaluation of the efficacy of cryosurgery in patients with sebaceous hyperplasia of the face[J]. J Cutan Med Surg, 2017, 21(3):202-206. doi: 10.1177/1203475416685076 pmid: 28300439
[29]	Antunes A, Rossel B, Adriaens E. Efficacy evaluation of the pixie^© skin tag cryogenic device on skin tags in a prospective, single-blinded, randomized, comparative clinical trial[J]. Dermatol Ther (Heidelb), 2021, 11(3):995-1007. doi: 10.1007/s13555-021-00532-w
[30]	Zouboulis CC, Rosenberger AD, Adler Y, et al. Treatment of solar lentigo with cryosurgery[J]. Acta Derm Venereol, 1999, 79(6):489-490. doi: 10.1080/000155599750010067
[31]	Zaresharifi S, Robati RM, Dadkhahfar S, et al. Efficacy and safety of cryotherapy, electrodesiccation, CO₂ laser, and Er:YAG laser in the treatment of seborrheic keratosis[J]. Dermatol Ther, 2021, 34(5):e15083.
[32]	Poulin Y, Lynde CW, Barber K, et al. Non-melanoma skin cancer in Canada chapter 3:Management of actinic keratoses[J]. J Cutan Med Surg, 2015, 19(3):227-238. doi: 10.1177/1203475415583414 pmid: 25926621
[33]	Zouboulis CC, Röhrs H. Cryosurgical treatment of actinic keratoses and evidence-based review[J]. Hautarzt, 2005, 56(4):353-358. pmid: 15580450
[34]	Kuflik EG. Cryosurgery for skin cancer:30-year experience and cure rates[J]. Dermatol Surg, 2004, 30(2 Pt 2):297-300.
[35]	Lansbury L, Bath-Hextall F, Perkins W, et al. Interventions for non-metastatic squamous cell carcinoma of the skin:Systematic review and pooled analysis of observational studies[J]. BMJ, 2013, 347:f6153. doi: 10.1136/bmj.f6153
[36]	Kuflik EG. Cryosurgery updated[J]. J Am Acad Dermatol, 1994, 31(6):925-944. pmid: 7962774
[37]	Kutlubay Z, Küçüktaş M, Yardımcı G, et al. Evaluation of effectiveness of cryotherapy on the treatment of cutaneous Kaposi's sarcoma[J]. Dermatol Surg, 2013, 39(10):1502-1506. doi: 10.1111/dsu.12285 pmid: 23879208
[38]	Gaitanis G, Bassukas ID. Immunocryosurgery-an effective combinational modality for Bowen's disease[J]. Dermatol Ther, 2016, 29(5):334-337. doi: 10.1111/dth.2016.29.issue-5
[39]	Arikan F, Gürkan A. Cryosurgical treatment of gingival melanin pigmentation with tetrafluoroethane[J]. Oral Surg Oral Med Oral Pathol Oral RadiolEndodontology, 2007, 103(4):452-457.
[40]	Farah CS, Koelmeyer N, Kaney A, et al. Nitrous oxide cryotherapy for the management of benign lesions of the oral cavity[J]. J Oral Pathol Med, 2019, 48(7):611-618. doi: 10.1111/jop.12912 pmid: 31192480
[41]	Garg A, Tripathi A, Chowdhry S, et al. Cryosurgery:Painless and fearless management of mucocele in young patient[J]. J Clin Diagn Res, 2014, 8(8):ZD04-ZD06.
[42]	何丹林, 颜昌云. 液氮冷冻治疗复发性口腔溃疡176例[J]. 中华理疗杂志, 1998(5):307-308.
[43]	Amanat D, Ebrahimi H, Zahedani MZ, et al. Comparing the effects of cryotherapy with nitrous oxide gas versus topical corticosteroids in the treatment of oral lichen planus[J]. Indian J Dent Res, 2014, 25(6):711-716. doi: 10.4103/0970-9290.152166 pmid: 25728101
[44]	Starzyńska A, Pawłowska A, Renkielska D, et al. Estimation of oral leukoplakia treatment records in the research of the Department of Maxillofacial and Oral Surgery, Medical University of Gdansk[J]. Postepy Dermatol Alergol, 2015, 32(2):114-122.
[45]	Shirazi AS, Moeintaghavi A, Khorakian F, et al. Treatment of gingival physiologic pigmentation in adolescents by liquid nitrogen cryosurgery:24-month follow-up[J]. Int J Periodontics Restorative Dent, 2012, 32(4):e142-e146.
[46]	Kamboj S, Salaria SK. Efficacy of liquid nitrogen and electrocautery assisted gingival depigmentation in term of patient's perception, histological wound healing-A randomized triple blind clinical trial[J]. J Indian Soc Periodontol, 2020, 24(2):135-144. doi: 10.4103/jisp.jisp_438_19
[47]	Eisen D, Carrozzo M, Bagan Sebastian JV, et al. Number V Oral lichen planus:Clinical features and management[J]. Oral Dis, 2005, 11(6):338-349. doi: 10.1111/j.1601-0825.2005.01142.x pmid: 16269024
[48]	Lodi G, Manfredi M, Mercadante V, et al. Interventions for treating oral lichen planus:Corticosteroid therapies[J]. Cochrane Database Syst Rev, 2020, 2(2):CD001168.
[49]	Thongprasom K, Dhanuthai K. Steriods in the treatment of lichen planus:A review[J]. J Oral Sci, 2008, 50(4):377-385. doi: 10.2334/josnusd.50.377 pmid: 19106464
[50]	Yu CH, Chen HM, Chang CC, et al. Cotton-swab cryotherapy for oral leukoplakia[J]. Head Neck, 2009, 31(8):983-988. doi: 10.1002/hed.v31:8
[51]	Yeh CJ. Treatment of verrucous hyperplasia and verrucous carcinoma by shave excision and simple cryosurgery[J]. Int J Oral Maxillofac Surg, 2003, 32(3):280-283. doi: 10.1054/ijom.2002.0331
[52]	Corrêa PH, Nunes LCC, Johann ACBR, et al. Prevalence of oral hemangioma, vascular malformation and varix in a Brazilian population[J]. Braz Oral Res, 2007, 21(1):40-45. pmid: 17384854
[53]	Nogueira PTBC, Remigio MMCJ, et al. Cryosurgery as an option for the treatment of vascular lesions of the oral cavity[J]. Case Rep Otolaryngol, 2017, 2017:8529016.
[54]	More CB, Bhavsar K, Varma S, et al. Oral mucocele:A clinical and histopathological study[J]. J Oral MaxillofacPathol, 2014, 18(Suppl 1):S72-S77.
[55]	Giraddi GB, Saifi AM. Micro-marsupialization versus surgical excision for the treatment of mucoceles[J]. Ann Maxillofac Surg, 2016, 6(2):204-209. doi: 10.4103/2231-0746.200324 pmid: 28299258
[56]	Prasad M, Kale TP, Halli R, et al. Liquid nitrogen cryotherapy in the management of oral lesions:A retrospective clinical study[J]. J Maxillofac Oral Surg, 2009, 8(1):40-42. doi: 10.1007/s12663-009-0010-2
[57]	Tsunoda N, Kawai T, Obara M, et al. Analysis of effects and indications of cryosurgery for oral mucoceles[J]. J Stomatol Oral Maxillofac Surg, 2021, 122(3):267-272. doi: 10.1016/j.jormas.2020.06.013 pmid: 32622002
[58]	Thai KE, Sinclair RD. Cryosurgery of benign skin lesions[J]. Australas J Dermatol, 1999, 40(4):175-184;quiz185-186. pmid: 10570551
[59]	Bacelieri R, Johnson SM. Cutaneous warts:An evidence-based approach to therapy[J]. Am Fam Physician, 2005, 72(4):647-652. pmid: 16127954
[60]	Sterling JC, Gibbs S, Haque Hussain SS, et al. British Association of Dermatologists' guidelines for the management of cutaneous warts 2014[J]. Br J Dermatol, 2014, 171(4):696-712. doi: 10.1111/bjd.13310 pmid: 25273231
[61]	Kawczyk-Krupka A, Waśkowska J, Raczkowska-Siostrzonek A, et al. Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia[J]. Photodiagnosis Photodyn Ther, 2012, 9(2):148-155. doi: 10.1016/j.pdpdt.2011.12.007 pmid: 22594985

冷冻疗法皮肤病适应证		有效率	复发率
皮肤良性病变	樱桃状血管瘤^[20?-22]	68%~100%	0%
	寻常疣^[23]	45.61%	-
	肥厚性瘢痕和瘢痕疙瘩^[24]	68%~81%	2%
	皮肤纤维瘤^[25]	91.4%	-
	化脓性肉芽肿^[26-27]	90%~100%	2%~9%
	皮脂腺增生^[28]	96.7%	0%
	皮赘^[29]	64.3%	-
	日光性黑子^[30]	100%	0%
	脂溢性角化病^[31]	68%	-
皮肤癌前病变	光化性角化病^[32-33]	57%~97%	2.1%~15.6%
皮肤恶性肿瘤	表浅型基底细胞癌^[34]	99%	1.2%
	鳞状细胞癌^[35]	97%	0.4%~0.8%
	恶性黑素瘤^[36]	-	10%
	卡波西肉瘤^[37]	63%	0%
	Bowen病^[38]	91.7%	14.2%

冷冻疗法口腔黏膜病适应证		有效率	复发率
发生于口腔黏膜的良性病变	牙龈色素沉着^[39]	100%	0%
	发生于口腔黏膜的脉管性疾病^[40]	100%	5%
	唾液腺囊肿^[41]	95.5%	0%
	复发性阿弗他溃疡^[42]	84.7%	-
口腔潜在恶性疾患	口腔扁平苔藓^[43]	76.7%	-
	口腔白斑病^[44]	77.78%	22.22%