Nd∶YAG激光治疗上消化道粘膜不典型增生的临床应用研究
作者：王玉梅 周传农 黄涛 贾建红 刘文凯 邓津生
单位：王玉梅 贾建红 河南省新乡市中心医院胃镜室453000；周传农 刘文凯 邓津生 中国医学科学院肿瘤研究所；黄涛 中国中医研究院针灸研究所
关键词：激光手术；食管；贲门；胃；不典型增生
中国激光医学杂志990203摘要：目的：探讨Nd∶YAG激光对上消化道粘膜重度不典型增生的治疗作用。
方法：经胃镜和活检证实为上消化道粘膜重度不典型增生患者30例，病变位于食管15例、贲门2例、胃13例；胃镜下观察病变呈糜烂型15例、充血型6例、微隆起型5例、浅溃疡型4例。激光治疗时，先在病灶周围注射生理盐水，使病灶局部膨隆，再用Nd∶YAG激光照射，功率30 W，准接触连续扫描照射病灶至凝固或汽化。激光治疗后1个月复查，胃镜检查见病灶消失、活检无不典型增生为近期痊愈。
, 百拇医药
结果：30例患者中，经1次治疗后近期痊愈26例，经2次治疗后近期痊愈4例，总近期痊愈率100%，未发生副作用或并发症。
结论：Nd∶YAG激光治疗上消化道粘膜重度不典型增生，效果确切，安全简便，痛苦少，费用低，可以门诊治疗，值得深入研究和推广应用。
Nd∶YAG Laser Ablation of Severe Dysplasia in the Upper Digestive Tract
WANG Yumei1, ZHOU Chuannong2, HUANG Tao3, JIA Jianhong1, LIU Wenkai2, DENG Jinsheng2
1.Central Hospital of Xinxiang City, Henan Province, Xinxiang 453000 2.Cancer Institute, Chinese Academy of
, 百拇医药
Medical Sciences, Beijing 3.Institute of Acupuncture, Chinese Academy of Traditional Chinese Medicine, Beijing
ABSTRACT Objective Severe dysplasia is considered as an important precancerous lesion in the upper digestive tract and there is lack of an effective and simple treatment for those lesions. The purpose of this study was to explore the possibilities and feasibility of Nd∶YAG laser ablation of severe dysplasia in the upper digestive tract and its significance in cancer prevention.
, http://www.100md.com
Methods Thirty patients with severe dysplasia of squamous epithelium of the esophagus and columnal epithelium of the gastric cardia or sto-
mach were included in this study. There were 20 males and 10 females, aged 30-68 years with an average of 45 years. All lesions were diagnosed during endoscopy and confirmed by histopathology of biopsies. The lesions were endoscopically classified as erosive type in 15, conjestive in 6, slightly protruding in 5 and shallow ulcerative in 4 cases. All patients gave informed concent prior to therapy and were treated in the outpatient department. 10 ml of physiological saline was injected, prior to the laser irradiation, into the submucosa to make the lesion swollen and protruded. It may very well prevent a possible perforation caused by serious photodamage to the deeper parts of the wall of the organs. The laser coagulation or vaporization was performed at a power of 30 W and the tip of optical fiber was kept at a distance of 0.5-1.0 cm from the lesions.
, http://www.100md.com
Results All patients were endoscopically examined at one month after the treatment. A normal appearance of the mucosa was restored and no dysplasia was revealed by histopathology. 26 cases (86.7%) with lesions smaller than 1.5 cm×1.5 cm were cured after one treatment and the 4 cases (13.3%) with lesions greater than 1.5 cm×1.5 cm were cured after the second treatment. The total cure rate was 100%. No ev-ident side effects or complications such as perforation, bleeding or stenosis occurred.
, http://www.100md.com
Conclusions Our results demonstrated that Nd∶YAG laser ablation may be an effective, safe, simple to operate, economic and minimally discomfortable treatment for severe dysplasia in the upper digestive tract.
Key words Laser surgery; Esophagus; Cardia; Stomach; Dysplasia
粘膜不典型增生与癌变关系密切，有报道7.4%的食管上皮重度不典型增生在1年内发展成癌[1]，约15%～20%的病例5～8年内发生癌变[2]。积极治疗上皮不典型增生对降低上消化道癌的发生有重要意义。为探讨激光治疗这种病变的效果和可行性，1994年以来，我们应用Nd∶YAG激光对30例上消化道粘膜重度不典型增生病人进行了治疗，现报道如下。
, 百拇医药
对象与方法
一、对象
本组30例患者系1994年4月至1998年12月期间就诊于新乡市中心医院门诊的病人。男性20例，女性10例；年龄30～68岁，平均45岁。临床有胸骨后烧灼感或疼痛、上腹部疼痛不适、嗳气、反酸、纳减等症状。胃镜检查见粘膜呈糜烂型、充血型、微隆起型或浅溃疡型病变，病变位于食管15例、贲门2例、胃13例(表1)。病变面积最小者为0.5 cm×0.5 cm,最大者为2.0 cm×2.0 cm。病变处粘膜活检证实为粘膜慢性炎伴重度不典型增生。
表1 30例上消化道粘膜重度不典型增生患者病变
的部位分布与内镜分型
Tab.1 Sites and endoscopic classification of severe dysplasia
, 百拇医药
of mucosa in the upper digestive tract in 30 cases 病变部位
Sites
内镜分型(例数) Endoscopic classification(cases)
糜烂型
Erosive
充血型
Congestive
微隆起型
Slightly
protruding
, http://www.100md.com
浅溃疡型
Shallow
ulcerative
合计
Total
食管 Esophagus
7
6
2
15
贲门 Cardia
2
2
, http://www.100md.com
胃 Stomach
胃体 Body
3
1
4
胃角 Angle
1
1
胃窦 Antrum
3
2
5
幽门 Pylorus
, http://www.100md.com
2
1
3
合计 Total
15
6
5
4
30
二、治疗方法
采用国产Nd∶YAG激光器，输出功率0～100 W可调，可选择脉冲或连续式输出，石英光纤传输。
治疗前30 min肌内注射安定10 mg、654-2 10 mg，以消除病人紧张情绪和减少胃蠕动与胃粘液分泌。常规胃镜检查，找准病灶后将其暴露在视野中央。通过活检孔插入注射专用针，对病灶四周注射生理盐水，使病灶局部肿胀隆起，拔出注射针，再插入石英光纤，光纤尖端超出镜端1.0～1.5 cm，以防烧毁胃镜。选用激光功率30 W、光距0.5～1.0 cm，以连续扫描方式由内向外照射病灶，范围大于病灶0.5 cm，使其凝固至灰白或汽化，然后退出光纤。激光治疗后禁食24 h，1周内进温凉全流饮食，避免剧烈活动。
, 百拇医药
三、疗效判断
激光治疗后1个月复查胃镜并在原病灶处取粘膜作病理检查。胃镜观察粘膜外观恢复正常、病理检查证实无不典型增生为近期痊愈。
结果
30例患者中，病灶面积小于1.5 cm×1.5 cm的26例经1次治疗获近期痊愈，占86.7%；对病灶面积等于或大于1.5 cm×1.5 cm的4例患者，因担心治疗时照射不均遗漏病灶，故间隔3～4周进行第2次补充照射，治疗后亦获近期痊愈。患者临床症状减轻或消失。未发生出血、穿孔、狭窄等并发症。有11例已随访1～2年，均未见异常。
讨论
由于上皮不典型增生与癌变关系密切，上消化道粘膜不典型增生的治疗引起国内外学者的关注。关于食管上皮的不典型增生，西方国家学者关注的热点集中于Barrett食管与食管腺癌的关系[3]，认为Barrett食管的上皮不典型增生是癌前病变[4]，发生癌变的机会比正常人群高出40倍[5]。Byrne等[6]应用氩凝法(argon beam plasma coagulation)治疗30例Barrett食管不典型增生获得成功。Overholt等[7]应用光敏剂sodium porfimer对Barrett食管进行光动力学治疗，45例中35例的重度不典型增生病变消失，但不少病人发生食管狭窄。Gossner等[8,9]以氨基酮戊酸(ALA)光动力学疗法治疗Barrett食管重度不典型增生9例和食管鳞状上皮重度不典型增生10例，全部获得成功。Bremner[10]综述1997年在法国举行的Barrett粘膜消融治疗国际会议的资料表明，药物或外科手术治疗Barrett食管上皮不典型增生的效果很不理想，而用物理或化学消融方法治疗的初步结果甚为喜人。关于如何治疗胃粘膜上皮不典型增生，文献报道很少。Modiaev等[11]曾以胃内He-Ne激光照射治疗37例慢性胃炎伴有不典型增生II～III级的病人，激光功率5～6 mW，每天照射30 min，5～7天为1个疗程，治疗后不典型增生病变完全缓解的占28%，由II～III级好转为I级的占37%，无变化的占35%，他们认为这一结果虽然不够理想，但对于预防癌变仍有积极意义。
, 百拇医药
我国的情况与西方国家明显不同，绝大多数的食管癌是鳞癌，食管的不典型增生也主要是鳞状上皮细胞增生，Barrett食管少见[12]。我国学者林培中等[13]研究食管重度不典型增生的阻断性治疗多年，对经食管拉网细胞学检查确诊为食管上皮重度不典型增生的患者，采用维甲类化合物维胺酯和由6味中药组成的抗癌乙片治疗，获得显著效果。服用维胺酯3年后，重度不典型增生的癌变率下降了37.3%；服用抗癌乙片3年和5年后，重度不典型增生的癌变率分别下降了52.2%和47.3%。本研究从另一角度出发，利用激光的热凝固原理对上消化道粘膜的不典型增生进行治疗。先在病变局部注射生理盐水，使病灶处肿胀隆起，这样便于照射时精确和彻底地凝固或汽化病变组织而不损伤周围正常组织，粘膜下层与肌层间的流体阻隔能有效地防止穿孔或出血。激光照射后，凝固坏死的病变组织并不立即被清除，而是形成结痂覆盖创面，创口在痂下愈合，结痂脱落后上皮恢复正常。30例患者经Nd∶YAG激光治疗后均获近期痊愈率。这一治疗只需通过内镜激光照射，操作简便快捷，痛苦少，术后反应轻，副作用少，见效快，效果好，可以门诊治疗，费用低廉，优点甚多，值得深入研究。如经长期随访肯定远期疗效，在食管癌和胃癌高发区推广应用，将能对预防癌变、降低癌的发病率发挥积极作用。本课题受卫生部科学研究基金资助(编号96-1-035)
, 百拇医药
参考文献
[1] 林培中, 陆士新, 张金生。食管癌前病变(食管上皮增生)的研究概况。中华肿瘤杂志, 1983, 5:391-395.
[2] The Coordinating Groups, Henan Province and Chinese Academy of Medical Sciences for the Research of Esophageal Carcinomas. Studies on relationship between epithelial dysplasia and carcinoma of the esophagus. Chin Med J 1975, 1:110-116.
[3] Morales TG. Adenocarcinoma of the gastric cardia. Dig Dis， 1997, 15:346-356.
, 百拇医药
[4] M de Almeida JC, Chaves P, Pereira AD, et al. Is Barrett's esophagus the precursor of most adenocarcinomas of the esophagus and cardia? A biochemical study. Ann Surg, 1997, 226:725-733.
[5] Wang KK. Barrett's esophagus: current and future management. Compr Ther 1994, 20:36-43.
[6] Byrne JP, Armstrong GR, Attwood SE. Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation. Am J Gastroenterol, 1998, 93:1810-1815.
, http://www.100md.com
[7] Overholt BF, Panjehpour M. Photodynamic therapy in Barrett's esophagus. J Clin Laser Med Surg, 1996, 14:245-249.
[8] Gossner L, Strolte M, Sroka R, et al. Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevlinic acid. Gastroenterology, 1998, 114:448-455.
[9] Gossner L, Strolte M, Sroka R, et al. Photodynamic therapy of early squamous epithelial carcinomas and severe squamous epithelial dysplasia of the esophagus with 5-aminolevlinic acid. Z Gastroenterol 1998, 36:19-26.
, http://www.100md.com
10 Bremner CG, Demeester TR. Proceeding from an international conference on ablation therapy for Barrett's mucosa. Brittany, France, 31 August-2 September 1997. Dis Esophagus 1998, 11(1):1-27.
[11] Modiaev VP, Karpov AB, Dikovich MF, et al. The potentials of low-intensity laser radiation in treating precancerous diseases of the stomach. Vopr Onkol, 1991, 37:731-734.
[12] 赵立群, 于国强, 主编。Barrett食管。郑州: 河南医科大学出版社，1998.
[13] 林培中, 高峰。食管癌的预防。见：刘复生, 林培中, 主编：食管癌的病理和预防。北京: 地质出版社，1994. 133-211.
收稿日期：1999-02-02, 百拇医药
单位：王玉梅 贾建红 河南省新乡市中心医院胃镜室453000；周传农 刘文凯 邓津生 中国医学科学院肿瘤研究所；黄涛 中国中医研究院针灸研究所
关键词：激光手术；食管；贲门；胃；不典型增生
中国激光医学杂志990203摘要：目的：探讨Nd∶YAG激光对上消化道粘膜重度不典型增生的治疗作用。
方法：经胃镜和活检证实为上消化道粘膜重度不典型增生患者30例，病变位于食管15例、贲门2例、胃13例；胃镜下观察病变呈糜烂型15例、充血型6例、微隆起型5例、浅溃疡型4例。激光治疗时，先在病灶周围注射生理盐水，使病灶局部膨隆，再用Nd∶YAG激光照射，功率30 W，准接触连续扫描照射病灶至凝固或汽化。激光治疗后1个月复查，胃镜检查见病灶消失、活检无不典型增生为近期痊愈。
, 百拇医药
结果：30例患者中，经1次治疗后近期痊愈26例，经2次治疗后近期痊愈4例，总近期痊愈率100%，未发生副作用或并发症。
结论：Nd∶YAG激光治疗上消化道粘膜重度不典型增生，效果确切，安全简便，痛苦少，费用低，可以门诊治疗，值得深入研究和推广应用。
Nd∶YAG Laser Ablation of Severe Dysplasia in the Upper Digestive Tract
WANG Yumei1, ZHOU Chuannong2, HUANG Tao3, JIA Jianhong1, LIU Wenkai2, DENG Jinsheng2
1.Central Hospital of Xinxiang City, Henan Province, Xinxiang 453000 2.Cancer Institute, Chinese Academy of
, 百拇医药
Medical Sciences, Beijing 3.Institute of Acupuncture, Chinese Academy of Traditional Chinese Medicine, Beijing
ABSTRACT Objective Severe dysplasia is considered as an important precancerous lesion in the upper digestive tract and there is lack of an effective and simple treatment for those lesions. The purpose of this study was to explore the possibilities and feasibility of Nd∶YAG laser ablation of severe dysplasia in the upper digestive tract and its significance in cancer prevention.
, http://www.100md.com
Methods Thirty patients with severe dysplasia of squamous epithelium of the esophagus and columnal epithelium of the gastric cardia or sto-
mach were included in this study. There were 20 males and 10 females, aged 30-68 years with an average of 45 years. All lesions were diagnosed during endoscopy and confirmed by histopathology of biopsies. The lesions were endoscopically classified as erosive type in 15, conjestive in 6, slightly protruding in 5 and shallow ulcerative in 4 cases. All patients gave informed concent prior to therapy and were treated in the outpatient department. 10 ml of physiological saline was injected, prior to the laser irradiation, into the submucosa to make the lesion swollen and protruded. It may very well prevent a possible perforation caused by serious photodamage to the deeper parts of the wall of the organs. The laser coagulation or vaporization was performed at a power of 30 W and the tip of optical fiber was kept at a distance of 0.5-1.0 cm from the lesions.
, http://www.100md.com
Results All patients were endoscopically examined at one month after the treatment. A normal appearance of the mucosa was restored and no dysplasia was revealed by histopathology. 26 cases (86.7%) with lesions smaller than 1.5 cm×1.5 cm were cured after one treatment and the 4 cases (13.3%) with lesions greater than 1.5 cm×1.5 cm were cured after the second treatment. The total cure rate was 100%. No ev-ident side effects or complications such as perforation, bleeding or stenosis occurred.
, http://www.100md.com
Conclusions Our results demonstrated that Nd∶YAG laser ablation may be an effective, safe, simple to operate, economic and minimally discomfortable treatment for severe dysplasia in the upper digestive tract.
Key words Laser surgery; Esophagus; Cardia; Stomach; Dysplasia
粘膜不典型增生与癌变关系密切，有报道7.4%的食管上皮重度不典型增生在1年内发展成癌[1]，约15%～20%的病例5～8年内发生癌变[2]。积极治疗上皮不典型增生对降低上消化道癌的发生有重要意义。为探讨激光治疗这种病变的效果和可行性，1994年以来，我们应用Nd∶YAG激光对30例上消化道粘膜重度不典型增生病人进行了治疗，现报道如下。
, 百拇医药
对象与方法
一、对象
本组30例患者系1994年4月至1998年12月期间就诊于新乡市中心医院门诊的病人。男性20例，女性10例；年龄30～68岁，平均45岁。临床有胸骨后烧灼感或疼痛、上腹部疼痛不适、嗳气、反酸、纳减等症状。胃镜检查见粘膜呈糜烂型、充血型、微隆起型或浅溃疡型病变，病变位于食管15例、贲门2例、胃13例(表1)。病变面积最小者为0.5 cm×0.5 cm,最大者为2.0 cm×2.0 cm。病变处粘膜活检证实为粘膜慢性炎伴重度不典型增生。
表1 30例上消化道粘膜重度不典型增生患者病变
的部位分布与内镜分型
Tab.1 Sites and endoscopic classification of severe dysplasia
, 百拇医药
of mucosa in the upper digestive tract in 30 cases 病变部位
Sites
内镜分型(例数) Endoscopic classification(cases)
糜烂型
Erosive
充血型
Congestive
微隆起型
Slightly
protruding
, http://www.100md.com
浅溃疡型
Shallow
ulcerative
合计
Total
食管 Esophagus
7
6
2
15
贲门 Cardia
2
2
, http://www.100md.com
胃 Stomach
胃体 Body
3
1
4
胃角 Angle
1
1
胃窦 Antrum
3
2
5
幽门 Pylorus
, http://www.100md.com
2
1
3
合计 Total
15
6
5
4
30
二、治疗方法
采用国产Nd∶YAG激光器，输出功率0～100 W可调，可选择脉冲或连续式输出，石英光纤传输。
治疗前30 min肌内注射安定10 mg、654-2 10 mg，以消除病人紧张情绪和减少胃蠕动与胃粘液分泌。常规胃镜检查，找准病灶后将其暴露在视野中央。通过活检孔插入注射专用针，对病灶四周注射生理盐水，使病灶局部肿胀隆起，拔出注射针，再插入石英光纤，光纤尖端超出镜端1.0～1.5 cm，以防烧毁胃镜。选用激光功率30 W、光距0.5～1.0 cm，以连续扫描方式由内向外照射病灶，范围大于病灶0.5 cm，使其凝固至灰白或汽化，然后退出光纤。激光治疗后禁食24 h，1周内进温凉全流饮食，避免剧烈活动。
, 百拇医药
三、疗效判断
激光治疗后1个月复查胃镜并在原病灶处取粘膜作病理检查。胃镜观察粘膜外观恢复正常、病理检查证实无不典型增生为近期痊愈。
结果
30例患者中，病灶面积小于1.5 cm×1.5 cm的26例经1次治疗获近期痊愈，占86.7%；对病灶面积等于或大于1.5 cm×1.5 cm的4例患者，因担心治疗时照射不均遗漏病灶，故间隔3～4周进行第2次补充照射，治疗后亦获近期痊愈。患者临床症状减轻或消失。未发生出血、穿孔、狭窄等并发症。有11例已随访1～2年，均未见异常。
讨论
由于上皮不典型增生与癌变关系密切，上消化道粘膜不典型增生的治疗引起国内外学者的关注。关于食管上皮的不典型增生，西方国家学者关注的热点集中于Barrett食管与食管腺癌的关系[3]，认为Barrett食管的上皮不典型增生是癌前病变[4]，发生癌变的机会比正常人群高出40倍[5]。Byrne等[6]应用氩凝法(argon beam plasma coagulation)治疗30例Barrett食管不典型增生获得成功。Overholt等[7]应用光敏剂sodium porfimer对Barrett食管进行光动力学治疗，45例中35例的重度不典型增生病变消失，但不少病人发生食管狭窄。Gossner等[8,9]以氨基酮戊酸(ALA)光动力学疗法治疗Barrett食管重度不典型增生9例和食管鳞状上皮重度不典型增生10例，全部获得成功。Bremner[10]综述1997年在法国举行的Barrett粘膜消融治疗国际会议的资料表明，药物或外科手术治疗Barrett食管上皮不典型增生的效果很不理想，而用物理或化学消融方法治疗的初步结果甚为喜人。关于如何治疗胃粘膜上皮不典型增生，文献报道很少。Modiaev等[11]曾以胃内He-Ne激光照射治疗37例慢性胃炎伴有不典型增生II～III级的病人，激光功率5～6 mW，每天照射30 min，5～7天为1个疗程，治疗后不典型增生病变完全缓解的占28%，由II～III级好转为I级的占37%，无变化的占35%，他们认为这一结果虽然不够理想，但对于预防癌变仍有积极意义。
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我国的情况与西方国家明显不同，绝大多数的食管癌是鳞癌，食管的不典型增生也主要是鳞状上皮细胞增生，Barrett食管少见[12]。我国学者林培中等[13]研究食管重度不典型增生的阻断性治疗多年，对经食管拉网细胞学检查确诊为食管上皮重度不典型增生的患者，采用维甲类化合物维胺酯和由6味中药组成的抗癌乙片治疗，获得显著效果。服用维胺酯3年后，重度不典型增生的癌变率下降了37.3%；服用抗癌乙片3年和5年后，重度不典型增生的癌变率分别下降了52.2%和47.3%。本研究从另一角度出发，利用激光的热凝固原理对上消化道粘膜的不典型增生进行治疗。先在病变局部注射生理盐水，使病灶处肿胀隆起，这样便于照射时精确和彻底地凝固或汽化病变组织而不损伤周围正常组织，粘膜下层与肌层间的流体阻隔能有效地防止穿孔或出血。激光照射后，凝固坏死的病变组织并不立即被清除，而是形成结痂覆盖创面，创口在痂下愈合，结痂脱落后上皮恢复正常。30例患者经Nd∶YAG激光治疗后均获近期痊愈率。这一治疗只需通过内镜激光照射，操作简便快捷，痛苦少，术后反应轻，副作用少，见效快，效果好，可以门诊治疗，费用低廉，优点甚多，值得深入研究。如经长期随访肯定远期疗效，在食管癌和胃癌高发区推广应用，将能对预防癌变、降低癌的发病率发挥积极作用。本课题受卫生部科学研究基金资助(编号96-1-035)
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收稿日期：1999-02-02, 百拇医药