修回日期: 2015-10-20
接受日期: 2016-03-13
在线出版日期: 2016-04-18
目的: 本研究通过高分辨率食管测压(high resolution esophageal manometry, HRM)方法分析食管裂孔疝患者食管动力变化的特点, 为胃食管反流病的机制提供新的依据.
方法: 回顾性分析从2014-06/2015-04在中国人民解放军总医院消化动力中心行HRM且3 mo内经胃镜诊断为食管裂孔疝的患者66例, 其中, 单纯食管裂孔疝患者35例, 合并反流性食管炎者31例, 另选取资料库中健康志愿者数据28例作为对照组, 比较3组之间的临床资料和HRM数据.
结果: 35例单纯食管裂孔疝患者中, 16例以反酸烧心为主诉前来就诊, 12例以胸痛为主诉前来就诊, 其余以吞咽困难、嗳气等症状前来就诊. 行HRM后经2014新版芝加哥分型诊断, 其中21例食管动力正常, 4例有食管胃流出道梗阻, 1例为重度食管动力障碍, 9例为轻度食管动力障碍. 31例合并反流性食管炎患者中, 20例以反酸烧心为主诉前来就诊, 6例以胸痛为主诉前来就诊, 其余以吞咽困难、嗳气等症状前来就诊. 行HRM后经2014新版芝加哥分型诊断, 其中19例食管动力正常, 2例有食管胃流出道梗阻, 3例为重度食管动力障碍, 10例为轻度食管动力障碍. 以上结果在两组间的分布均无统计学差异(P>0.05). 食管裂孔疝组下食管括约肌(lower esophageal sphincter, LES)静息压平均值显著低于健康对照组(P = 0.016), 尤其是合并反流性食管炎组LES静息压显著低于健康对照组(13.43 mmHg±8.75 mmHg vs 21.66 mmHg±7.19 mmHg, P = 0.004). 上食管括约肌(upper esophageal sphincter, UES)压力3组间数据并无统计学差异(P = 0.854). 然而, 食管裂孔疝组患者UES静息压异常的发生率, 尤其是UES低压的发生率显著高于健康对照组(25.7% vs 3.6%, P = 0.041).
结论: 40%以上的食管裂孔疝患者存在食管体部动力障碍. 相比健康人群, 食管裂孔疝导致患者LES静息压显著降低, UES低压的发生率显著增高. 异常的食管体部动力和降低的上下食管括约肌压力, 可能是食管裂孔疝患者发生胃食管反流相关症状, 甚至出现食管黏膜损伤的关键因素. 高分辨率食管测压可以提供有关食管裂孔疝食管动力学的准确全面的数据, 对研究其病理机制、进一步诊断和评估治疗预后起指导作用.
核心提示: 食管裂孔疝患者下食管括约肌(lower esophageal sphincter, LES)静息压显著低于健康人群, 上食管括约肌(upper esophageal sphincter, UES)低压的发生率显著高于健康人群. 食管裂孔疝与反流性食管炎患者间LES和UES压力无显著差异.
引文著录: 马欣, 彭丽华, 王潇潇, 艾洁, 郭志远, 杨云生. 食管裂孔疝患者高分辨率食管测压的特点. 世界华人消化杂志 2016; 24(11): 1718-1724
Revised: October 20, 2015
Accepted: March 13, 2016
Published online: April 18, 2016
AIM: To investigate the functional change of esophageal motility in hiatal hernia (HH) patients using high resolution esophageal manometry (HRM), in order to determine the possible pathogenesis of HH and provide more evidence for detection and treatment of HH.
METHODS: We performed a retrospective study of 66 patients with hiatal hernia who underwent HRM from June 2014 to April 2015 as well as upper endoscopy and/or barium esophagogram within 3 mo at our hospital. Among them, 31 patients were diagnosed with reflux esophagitis (RE) by endoscopy. Besides, we selected 28 healthy volunteers as controls to compare clinical characteristics and HRM data between the three groups.
RESULTS: In total there were 35 patients with HH alone (Group A), of whom 16 had typical symptoms including acid reflux and heartburn, 12 suffered main symptoms resembling retrosternal pain, and the remainder had typical symptoms including dysphagia and belching. After HRM, 4 of them were diagnosed with esophagogastric junction (EGJ) outflow obstruction, 1 with severe esophageal motility disorder, and 9 with mild esophageal motility disorder. In total there were 31 patients with RE (Group B), of whom 20 had typical symptoms including acid reflux and heartburn, 6 suffered main symptoms resembling retrosternal pain, and the remainder had typical symptoms including dysphagia and belching. After HRM, 2 of them were diagnosed with esophagogastric junction (EGJ) outflow obstruction, 3 with severe esophageal motility disorder, and 10 with mild esophageal motility disorder. There was no significant difference in the above findings between groups A and B (P > 0.05). Lower esophageal sphincter (LES) pressure in groups A and B was significantly lower than that in the control group (P = 0.016), especially group A (13.43 mmHg ± 8.75 mmHg vs 21.66 mmHg ± 7.19 mmHg, P = 0.004). Upper esophageal sphincter (UES) pressure had no significant difference among the three groups (P = 0.854). However, the morbidity of UES hypotensive pressure was significantly higher in group A than the control group (25.7% vs 3.6%, P = 0.041).
CONCLUSION: About 40% of HH patients have esophageal motility disorders. HH patients have significantly lower LES and UES pressure than the health group. The reduced LES and UES pressure and esophageal motility disorder may play a crucial role in reflux events and even result in esophageal mucosal injury. HRM can provide accurate and exhaustive data to guide diagnosis and evaluate prognosis.
- Citation: Ma X, Peng LH, Wang XX, Ai J, Guo ZY, Yang YS. Characteristics of esophageal motility measured by high resolution esophageal manometry in hiatal hernia patients. Shijie Huaren Xiaohua Zazhi 2016; 24(11): 1718-1724
- URL: https://www.wjgnet.com/1009-3079/full/v24/i11/1718.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v24.i11.1718
食管裂孔疝是指腹腔内容物(主要是胃)通过食管裂孔疝入胸腔, 是膈疝的最常见的一种, 他可通过多种机制破坏食管下括约肌功能, 导致食管胃连接处抗反流屏障破坏, 降低了食管酸清除能力, 导致了胃食管反流症状的发生[1,2]. 临床上, 部分食管裂孔疝患者仅表现为反酸烧心等反流症状, 但部分严重者, 在产生胃食管反流症状时, 进一步发生了食管黏膜损伤, 而这其中的病理生理机制, 尤其是食管体部动力及食管上下括约肌的压力改变并不十分清楚[3,4]. 以往, 食管裂孔疝可通过内镜、钡餐进行检测, 随着高分辨率食管测压(high resolution manometry, HRM)的出现, 为食管裂孔疝提供了更全面直接的临床检测及分析, 他通过软件转换形成彩色三维时空图像, 更直观显示食管上段括约肌(upper esophageal sphincter, UES)、食管下段括约肌(lower esophageal sphincter, LES)及食管体部各段运动过程的细节特征[5,6]. 本研究通过对66例来中国人民解放军总医院就诊的经胃镜诊断为食管裂孔疝合并或未合并反流性食管炎的患者行HRM方法评价其食管动力变化的特点, 旨在为此类患者的病理机制研究提供新的信息.
回顾性分析2014-06/2015-04来中国人民解放军总医院就诊的近3 mo内经胃镜发现食管裂孔疝患者, 在中国人民解放军总医院消化动力中心行高分辨率食管测压, 数据不全或有食管动力障碍相关治疗史的患者排除, 共66例, 其中合并反流性食管炎者31例. 选取资料库中健康志愿者数据28例作为对照, 并对3组患者的临床资料和HRM数据进行分析.
1.2.1 高分辨率食管测压方法: 采用36通道高分辨率固态食管测压系统, 包括: ManoScan™ESO高分辨率测压仪, ManoScan360 Acquisition™采集软件, ManoView ESO 3.0™分析软件, 36通道电极导管(导管直径4.2 mm). 检查前3 d禁用任何可能影响胃食管功能的药物, 前1 d禁烟、酒、咖啡, 已行胃镜检查的应间隔1 d再行测压检查, 检查前禁食6 h以上, 登记个人基本信息并问询病史、临床症状及体征.
1.2.2 观察指标: 上食管括约肌静息压(upper esophageal sphincter resting pressure, UESP)、上食管括约肌残余压(upper esophageal sphincter relaxation pressure, UESRP)、下食管括约肌静息压(lower esophageal sphincter resting pressure, LESP)、下食管括约肌综合松弛压(integrated relaxation pressure, IRP). 指标定义: (1)UES异常包括: UES高压、UES低压及UES松弛障碍. UESP正常值范围是34-104 mmHg(1 mmHg = 0.133 kPa), UES低压为<34 mmHg, UES高压为>104 mmHg, UESRP正常值范围是<12 mmHg, UES松弛障碍为UESRP>12 mmHg; (2)LESP的正常值范围是13-43 mmHg, LESP低压为<13 mmHg, LESP高压为>43 mmHg. IRP正常值为<15 mmHg, LES综合松弛压异常为IRP>15 mmHg. HREM诊断标准: 参照2014年芝加哥分型v3.0分型.
统计学处理 应用SPSS17.0统计软件. 计量资料以mean±SD表示, 组间比较采用t检验, 多组间比较采用方差分析及单因素ANOVA检验; 计数资料用百分率表示, 组间比较采用卡方检验或Fisher确切概率法. P<0.05为差异有统计学意义.
94例资料中, 男性共44例. 35例单纯食管裂孔疝患者中, 16例以反酸烧心为主诉前来就诊, 12例以胸痛(非心源性)为主诉前来就诊, 其余以吞咽困难、嗳气等症状前来就诊. 行HRM后经2014新版芝加哥分型诊断, 其中21例食管动力正常, 4例有食管胃流出道梗阻, 1例为重度食管动力障碍, 9例为轻度食管动力障碍. 31例合并反流性食管炎患者中, 20例以反酸烧心为主诉前来就诊, 6例以胸痛为主诉前来就诊, 其余以吞咽困难、嗳气等症状前来就诊. 行HRM后经2014新版芝加哥分型诊断, 其中19例食管动力正常, 2例有食管胃流出道梗阻, 3例为重度食管动力障碍, 10例为轻度食管动力障碍, 两组间的分布无统计学差异(P>0.05)(表1).
| 项目 | 单纯食管裂孔疝组 | 食管裂孔疝合并反流性食管炎组 | 健康对照组 |
| 性别(男) | 14(40.0) | 16(51.6) | 14(50.0) |
| 主要症状 | |||
| 反酸烧心 | 16(45.7) | 20(64.5) | 0(0.0) |
| 胸痛 | 12(34.3) | 6(19.4) | 0(0.0) |
| 吞咽困难 | 2(5.7) | 2(6.5) | 0(0.0) |
| HRM诊断 | |||
| 正常 | 21(60.0) | 17(54.8) | 28(100.0) |
| 食管胃流出道梗阻 | 4(11.4) | 1(3.2) | 0(0.0) |
| 重度食管动力障碍 | 1(2.9) | 3(9.7) | 0(0.0) |
| 轻度食管动力障碍 | 9(25.7) | 10(32.3) | 0(0.0) |
3组间LESP值有显著差异(P = 0.016), 尤其, 食管裂孔疝合并反流性食管炎组更显著低于健康对照组(13.43 mmHg±8.75 mmHg vs 21.66 mmHg±7.19 mmHg, P = 0.004), 合并反流性食管炎组IRP略低于单纯食管裂孔疝组和健康对照组, 但并无统计学差异(P = 0.209). 此外, 3组间LESP异常的发生率有显著差异(P<0.0001), 单纯食管裂孔疝组和合并反流性食管炎组分别与对照组相比, LESP异常的发病率均有显著差异(P<0.0001), 而IRP异常的发生率3组之间差异并无统计学意义(表2).
单纯食管裂孔疝组的UESP值略小于合并反流性食管炎组, 且小于健康对照组, 但3组间UESP值无显著差异(P = 0.854); 单纯食管裂孔疝组UESRP低于合并反流性食管炎组和健康对照组, 但并无统计学差异(P = 0.861). 此外, 3组间UESP低压的发病率有显著差异(P = 0.034), 单纯食管裂孔疝组UESP低压的发生率显著高于健康对照组(P = 0.041)(表3).
| 指标 | 单纯食管裂孔疝组 | 食管裂孔疝合并反流性食管炎组 | 健康对照组 | P值 |
| UESP(mmHg) | 60.97±33.87 | 62.83±31.24 | 65.24±22.54 | 0.854 |
| UESRP(mmHg) | 5.93±4.96 | 6.50±4.92 | 6.49±4.78 | 0.861 |
| UESP异常[n(%)] | 10(28.6) | 6(19.4) | 2(7.1) | 0.100 |
| UESP高压 | 1(2.9) | 2(6.5) | 1(3.6) | 0.763 |
| UESP低压 | 9(25.7)a | 4(12.9) | 1(3.6) | 0.034 |
| UESRP异常[n(%)] | 4(11.4) | 5(16.1) | 4(14.3) | 0.856 |
通过内镜或者影像学检查的相关研究发现, 约一半以上的胃食管反流性疾病都合并了食管裂孔疝, 而在其他疾病中却没有这么高的并发率[7,8]. 本研究表明, 绝大部分食管裂孔疝患者均以反酸、烧心、胸痛等胃食管反流相关症状为主诉前来就诊, 说明食管裂孔疝患者确实更易发生反流症状.
食管裂孔疝由于胃食管连接处的抗反流机制损坏, 食管接受酸暴露增加, 清除酸的时间延长, 进而产生了胃食管反流相关症状[9-11]. 有研究[12]证明, 大型食管裂孔疝与小型食管裂孔疝相比, 具有的反流症状更明显, 同时, 反流造成的酸暴露也可能会进一步导致食管黏膜的损伤, 发生反流性食管炎. 尽管人们发现了这些现象, 但其中的病理生理机制尚未完全确定, 尤其是对于食管动力和上下括约肌的研究, 并不全面. 内镜或影像学检查仅能为我们提供通过肉眼观察得到的食管胃等形态上、动力上的相关临床证据, 而食管测压检查能为我们提供更直接的参数, 且伴随着高分辨率食管测压的产生和广泛应用, 其快速, 高效, 敏感性和特异性高的优势, 为食管裂孔疝提供了更为敏感精确的检测手段, 能为我们提供更细致的食管动力的相关数据, 尤其是食管上下括约肌的相关参数[13]. 在我们的研究中, 约40%的单纯食管裂孔疝患者经2014新版芝加哥标准分型诊断具有食管动力障碍类疾病, 其中大部分是轻度食管动力障碍, 合并反流性食管炎组具有食管动力障碍类疾病的比例较单纯食管裂孔疝组稍高, 具有食管动力障碍的患者比例约50%, 重度食管动力障碍发生率高于单纯食管裂孔疝组. 曾有研究[14]发现, 经内镜证实有食管炎或Barret食管的患者, 行HRM后约60%的患者诊断有食管动力障碍. 这也提示我们, 食管裂孔疝患者易发生食管体部障碍, 这可能是发生胃食管反流的机制之一[15].
通过测压法已证明, 食管裂孔疝患者LES压力降低、一过性LES松弛是此类患者产生反流的主要机制[16-19]. 有研究发现重度侵袭性反流性食管炎和Barret食管患者的抗反流屏障明显弱于轻度侵袭性反流病和非侵袭性反流病, 主要表现在LES压力降低和食管裂孔疝[20]. 我们的研究证实了这一点: 食管裂孔疝患者LES压力显著降低, 且LESP低压的发病率显著高于健康对照组, 尤其是食管裂孔疝合并反流性食管炎组, 其LES压力下降的更加明显, 说明LES压力异常可能是食管裂孔疝患者发生胃食管反流症状的关键因素, 尤其是对合并反流性食管炎患者的发病起着重要作用, LES静息压压力降低越大, 从非侵袭性食管炎转变为黏膜损伤的反流性食管炎的几率越大.
另一方面, HRM所提供的有效信息并没有被充分利用, 比如UES的相关测量信息, 其与临床诊断的关系尚未建立, 以至于UES压力变化在食管动力障碍的病理生理过程和临床表现中的临床意义至今仍不甚清楚[21]. 胃食管反流引起的咽部不适等症状, 与UES异常有着密不可分的关系. 有报道[22]称, UES异常经常出现于食管动力障碍的患者中, 特别是贲门失弛缓症和硬皮病, 鲜有研究发现其在食管裂孔疝等反流疾病的意义, 我们的研究发现, 3组患者的UES压力虽无显著差异, 但食管裂孔疝患者UES低压的发病率高于健康对照组, 尤其是单纯食管裂孔疝组UESP低压的发病率显著高于健康对照组, 这说明食管裂孔疝不单引起LES压力降低、食管蠕动功能障碍, 还使得UES发生功能异常, 引发咽部不适等症状, 但合并反流性食管炎组的UES低压发生率与健康对照组却无显著差异, 这一现象提示我们, UES异常可能是食管裂孔疝LES低压的继发机制, 但当出现严重的胃食管反流病后, 机体通过一种不自主的吞咽动作使UES长久处于不松弛的状态, 对食管加压, 从而迫使反流物顺利进入胃部, 出现了相对性的UES静息压升高. 类似的, 曾有研究[23]发现, 胃食管反流病导致的咳嗽症状会引起UES和食管动力的变化, 这种变化是由于食团清除功能受损导致的, 而这其中的机制尚待进一步证实.
总之, 食管裂孔疝对患者的食管生理功能有显著的影响, 40%以上的食管裂孔疝患者存在食管体部动力障碍. 相比健康对照组, 食管裂孔疝患者LES静息压显著降低, UES低压的发生率显著增高. 食管裂孔疝与反流性食管炎组LES和UES压力无显著差异. 异常的食管体部动力和降低的上下食管括约肌压力, 可能是食管裂孔疝患者发生胃食管反流相关症状, 甚至出现食管黏膜损伤的关键因素. 高分辨率食管测压可以提供有关食管裂孔疝食管动力学的准确全面的数据, 对研究其病理机制、进一步诊断和评估治疗预后起指导作用.
食管裂孔疝常与胃食管反流病并存, 约一半以上的胃食管反流性疾病都合并了食管裂孔疝. 临床上, 部分食管裂孔疝患者仅表现为反酸烧心等反流症状, 部分严重者, 在产生胃食管反流症状时会进一步发生食管黏膜损伤.
潘秀珍, 教授, 主任医师, 福建省立医院消化科
食管裂孔疝患者会发生抗反流屏障异常、食管下括约肌功能障碍, 利用高分辨率食管测压, 可以精确地提供食管上下括约肌以及食管动力的数据, 为研究者进一步探究该病合并胃食管反流的病理生理机制, 提供更多证据.
食管裂孔疝患者产生反流的主要机制是下食管括约肌(lower esophageal sphincter, LES)压力降低和一过性LES松弛, 同时有研究发现, 上食管括约肌(upper esophageal sphincter, UES)异常与胃食管反流引起的咽部不适等症状紧密相关.
本文研究发现, 食管裂孔疝患者UES低压的发病率显著高于健康人群, 这说明食管裂孔疝不单引起LES压力降低、食管蠕动功能障碍, 还使得UES发生功能异常, 引发咽部不适等症状.
异常的食管体部动力和降低的上下食管括约肌压力, 可能是食管裂孔疝患者发生胃食管反流相关症状, 甚至出现食管黏膜损伤的关键因素. 高分辨率食管测压可以提供有关食管裂孔疝食管动力学的准确全面的数据, 对研究其病理机制、进一步诊断和评估治疗预后起指导作用.
食管裂孔疝: 是指腹腔内容物(主要是胃)通过食管裂孔疝入胸腔, 是膈疝的最常见的一种, 他可通过多种机制破坏食管下括约肌功能, 导致食管胃连接处抗反流屏障破坏, 降低了食管酸清除能力, 导致了胃食管反流症状的发生.
本文作者认为, 不少食管裂孔疝患者存在食管体部动力障碍, LES静息压显著降低, UES低压的发生率显著增高. 类似研究不多, 选择病例规范, 检测方法较先进, 统计正确, 结果可信, 观点明确, 研究结果对食管裂孔疝诊治有参考意义.
编辑:于明茜 电编:都珍珍
| 1. | Kahrilas PJ, Lin S, Chen J, Manka M. The effect of hiatus hernia on gastro-oesophageal junction pressure. Gut. 1999;44:476-482. [PubMed] [DOI] |
| 2. | Gryglewski A, Pena IZ, Tomaszewski KA, Walocha JA. Unsolved questions regarding the role of esophageal hiatus anatomy in the development of esophageal hiatal hernias. Adv Clin Exp Med. 2014;23:639-644. [PubMed] [DOI] |
| 3. | van Herwaarden MA, Samsom M, Smout AJ. Excess gastroesophageal reflux in patients with hiatus hernia is caused by mechanisms other than transient LES relaxations. Gastroenterology. 2000;119:1439-1446. [PubMed] |
| 4. | Prasad KK, Chaudhary RK. Post Esophagectomy Hiatal Hernia; Expect the Unexpected. J Clin Diagn Res. 2015;9:XL01. [PubMed] [DOI] |
| 5. | Weijenborg PW, van Hoeij FB, Smout AJ, Bredenoord AJ. Accuracy of hiatal hernia detection with esophageal high-resolution manometry. Neurogastroenterol Motil. 2015;27:293-299. [PubMed] [DOI] |
| 6. | Ciriza-de-los-Ríos C, Canga-Rodríguez-Valcárcel F, Castel-de-Lucas I, Lora-Pablos D, de-la-Cruz-Bértolo J, Castellano-Tortajada G. How useful is esophageal high resolution manometry in diagnosing gastroesophageal junction disruption: causes affecting this disruption and its relationship with manometric alterations and gastroesophageal reflux. Rev Esp Enferm Dig. 2014;106:22-29. [PubMed] [DOI] |
| 7. | Ott DJ, Gelfand DW, Chen YM, Wu WC, Munitz HA. Predictive relationship of hiatal hernia to reflux esophagitis. Gastrointest Radiol. 1985;10:317-320. [PubMed] [DOI] |
| 8. | Borobio E, Fernández-Urién I, Elizalde I, Jiménez Pérez FJ. Hiatal hernia and lesions of gastroesophageal reflux disease diagnosed by capsule endoscopy. Rev Esp Enferm Dig. 2009;101:355-356. [PubMed] |
| 9. | Jones MP, Sloan SS, Jovanovic B, Kahrilas PJ. Impaired egress rather than increased access: an important independent predictor of erosive oesophagitis. Neurogastroenterol Motil. 2002;14:625-631. [PubMed] |
| 10. | Andrici J, Tio M, Cox MR, Eslick GD. Hiatal hernia and the risk of Barrett's esophagus. J Gastroenterol Hepatol. 2013;28:415-431. [PubMed] [DOI] |
| 11. | Weber C, Davis CS, Shankaran V, Fisichella PM. Hiatal hernias: a review of the pathophysiologic theories and implication for research. Surg Endosc. 2011;25:3149-3153. [PubMed] [DOI] |
| 12. | Franzén T, Tibbling L. Is the severity of gastroesophageal reflux dependent on hiatus hernia size? World J Gastroenterol. 2014;20:1582-1584. [PubMed] [DOI] |
| 13. | Kahrilas PJ, Kim HC, Pandolfino JE. Approaches to the diagnosis and grading of hiatal hernia. Best Pract Res Clin Gastroenterol. 2008;22:601-616. [PubMed] [DOI] |
| 14. | Ravi K, Friesen L, Issaka R, Kahrilas PJ, Pandolfino JE. Long-term Outcomes of Patients With Normal or Minor Motor Function Abnormalities Detected by High-resolution Esophageal Manometry. Clin Gastroenterol Hepatol. 2015;13:1416-1423. [PubMed] [DOI] |
| 15. | Conrado LM, Gurski RR, da Rosa AR, Simic AP, Callegari-Jacques SM. Is there an association between hiatal hernia and ineffective esophageal motility in patients with gastroesophageal reflux disease? J Gastrointest Surg. 2011;15:1756-1761. [PubMed] [DOI] |
| 16. | Savas N, Dagli U, Sahin B. The effect of hiatal hernia on gastroesophageal reflux disease and influence on proximal and distal esophageal reflux. Dig Dis Sci. 2008;53:2380-2386. [PubMed] [DOI] |
| 17. | Shi G, Pandolfino JE, Joehl RJ, Brasseur JG, Kahrilas PJ. Distinct patterns of oesophageal shortening during primary peristalsis, secondary peristalsis and transient lower oesophageal sphincter relaxation. Neurogastroenterol Motil. 2002;14:505-512. [PubMed] [DOI] |
| 18. | Scheffer RC, Bredenoord AJ, Hebbard GS, Smout AJ, Samsom M. Effect of proximal gastric volume on hiatal hernia. Neurogastroenterol Motil. 2010;22:552-56, e120. [PubMed] [DOI] |
| 19. | Kahrilas PJ, Shi G, Manka M, Joehl RJ. Increased frequency of transient lower esophageal sphincter relaxation induced by gastric distention in reflux patients with hiatal hernia. Gastroenterology. 2000;118:688-695. [PubMed] [DOI] |
| 20. | Lord RV, DeMeester SR, Peters JH, Hagen JA, Elyssnia D, Sheth CT, DeMeester TR. Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease. J Gastrointest Surg. 2009;13:602-610. [PubMed] [DOI] |
| 21. | Kahrilas PJ, Sifrim D. High-resolution manometry and impedance-pH/manometry: valuable tools in clinical and investigational esophagology. Gastroenterology. 2008;135:756-769. [PubMed] [DOI] |
| 22. | Chavez YH, Ciarleglio MM, Clarke JO, Nandwani M, Stein E, Roland BC. Upper esophageal sphincter abnormalities: frequent finding on high-resolution esophageal manometry and associated with poorer treatment response in achalasia. J Clin Gastroenterol. 2015;49:17-23. [PubMed] [DOI] |
| 23. | Vardar R, Sweis R, Anggiansah A, Wong T, Fox MR. Upper esophageal sphincter and esophageal motility in patients with chronic cough and reflux: assessment by high-resolution manometry. Dis Esophagus. 2013;26:219-225. [PubMed] [DOI] |