胃食管反流病284例分析

目的：探讨胃食管反流病（GERD）临床表现与食管酸反流程度、食管炎症之间的关系。方法：回顾性分析284例GERD患者经胃镜或24 h食管pH监测的胃食管反流病的临床症状与食管炎症和反流程度之间的关系。结果：反流性食管炎（RE）组和非糜烂性反流病（NERD）组在年龄、性别上无显著差异（P〉0.05）,且在酸反流严重程度上及食管症状无显著差异（P〉0.05）。结论：GERD患者的临床症状表现与食管酸反流程度、食管炎症之间无显著差异。     

非糜烂性反流病研究概况

胃食管反流病（GERD）是由于下段食管括约肌功能障碍引起胃内容物反流导致的一系列慢性症状和食管黏膜损害。其疾病谱广泛，包括反流性食管炎（RE）、非糜烂性反流病（NERD）及Barrett食管（BE），是临床上的常见病、多发病，该病症状多，既有消化道症状，又有消化道外症状。NERD是指具有典型的反流症状但内镜检查食管黏膜正常者，亦称内镜阴性反流病或称症状性GERD。     

圣阳安中片联合奥美拉唑治疗非糜烂性反流病的临床观察

胃食管反流病（GERD）是消化系统常见病，定义为胃、十二指肠内容物反流入食管引起烧心、反酸等症状，并可导致食管炎和咽、喉、气道等食管以外的组织损害。约30％患者在内镜下可见食管粘膜任何长度的破损，包括糜烂、溃疡、狭窄等病变，称反流性食管炎（RE）及Barrett’s食管；70％左右的患者内镜下可无食管沾膜损坏的表现，称为内镜阴性的GERD或非糜烂性反流病（NERD）。目前治疗NERD以抑酸及促胃肠动力为主，但抑酸药只对大约一半的NERD有效，当抑酸药无效时应考虑其他综合治疗。作者以圣阳安中片联合奥美拉唑治疗NERD取得较好疗效，现报告如下。     

反流性食管炎和非糜烂性反流病患者食管压力与酸暴露的结果分析

目的 比较反流性食管炎(RE)与非糜烂性反流病(NERD)患者食管酸暴露特点、食管下括约肌压力以及食管体部压力,为临床治疗提供科学依据.方法 具有典型反酸、烧心等症状的患者78例,经胃镜等系统检查确诊RE 48例,NERD 30例.便携式pH监测仪行食管24 h pH监测,De-Meester积分≥14.72分为存在病理性酸反流;对两组患者分别进行食管下括约肌(LES)、食管体部(即LES上方3 cm、8 cm、13 cm、18 cm)和食管上括约肌(UES)的压力指标.结果 78例患者中,24 hpH监测阳性在RE组和NERD组分别为33例(68.75%)和17例(56.67%),差异无统计学意义(P>0.05);两组DeMeester积分值差异亦无统计学意义(51.42±62.05 vs.40.37±62.60,P>0.05);RE组长反流次数显著高于NERD组(8.08±10.17 vs.3.87±6.15,P<0.05),RE组酸暴露与食管炎严重程度有一定关系:两组LES压力及食管体部压力比较差异无统计学意义(P>0.05):RE组UES压力明显低于NERD组(P<0.05).结论 RE患者食管炎严重程度与酸暴露呈正相关.胃酸与食管黏膜接触时间的长短可能是导致食管黏膜炎症改变的重要因素.     

胃食管反流病研究进展

胃食管反流病(GERD)是指胃十二指肠内容物反流入食管,引起不适症状和(或)并发症的一种疾病,包括非糜烂性反流病(NERD)、反流性食管炎(RE)和巴雷特食管(BE)。1934年,美国胃肠病学家Winkelstein首先将烧心和反流导致的食管炎联系起来,建立了GERD概念。典型表现为烧心和反流。     

胃食管反流病新分类与非糜烂性反流病

胃内容物 (包括十二指肠液 )反流入食管产生症状或并发症时 ,称胃食管反流病 (GERD) ,酸 (碱 )反流导致的食管黏膜破损称为反流性食管炎 (refluxesophagitis,RE)。GERD广义地包括了食管黏膜破损或无破损以及食管溃疡、出血、狭窄、Barrett食管和食管腺癌等并发症。内镜检查阴性GERD ,即内镜下未观察到食管黏膜糜烂性或更严重的病变 ,称为非糜烂性反流病 (nonerosiverefluxdisease,NERD)。近年GERD一直被视为一种疾病谱 (spectrum) ,是一种从轻型症状群 (NERD)到糜烂食管炎 (erosiveesophagitis,EE)及其并发症递进性的疾病谱。G…     

非糜烂性反流病24小时PH值监测及分析

非糜烂性反流病（NERD），也称作内镜阴性反流病（ENRD）或症状性胃食管反流病，占胃食管反流病（GERD）的50％～70％。我国北京、上海的一项调查报告显示，NERD约占GERD的67％，其发病机制与酸有明显的相关性。作者通过监测70例NERD患者24hPH值并与RE患者、正常对照组比较，分析NERD患者酸暴露特点及其对临床诊治的意义。     

非糜烂性反流病24小时PH值监测及分村

非糜烂性反流病(NERD),也称作内镜阴性反流病(ENRD)或症状性胃食管反流病,占胃食管反流病(GERD)的50%～70%[1].我国北京、上海的一项调查报告显示,NERD约占GERD的67%[2],其发病机制与酸有明显的相关性.作者通过监测70例NERD患者24 h PH值并与RE患者、正常对照组比较,分析NERD患者酸暴露特点及其对临床诊治的意义.     

非糜烂性反流病诊断研究中的几个热点问题

胃食管反流病（gastroesophageal reflux disease,GERD）是指胃内容物反流入食管引起不适症状和（或）并发症的一种疾病[1].2006年蒙特利尔共识意见对GERD进行了重新定义和分类.GERD分为食管综合征和食管外综合征.前者包括症状综合征（典型反流症状和反流相关胸痛）和食管损伤综合征[反流性食管炎,食管狭窄,Barrett＇s食管（Barrett＇s esophagous,BE）及食管腺癌];后者包括一些已肯定与反流相关的综合征如反流性咳嗽、反流性喉炎、反流性哮喘及反流性牙侵蚀,同时还包括了一些与反流可能相关的综合征如咽炎、鼻窦炎、特发性肺纤维化及复发性中耳炎.根据内镜所见,一般还可将GERD分为非糜烂性反流病（non-erosive reflux diseases,NERD）、糜烂性食管炎（erosive esophagitis,EE）及BE三种类型[2].     

非糜烂性反流病研究概况

非糜烂性反流病(NERD)是指有典型胃食管反流症状而无内镜下食管黏膜损害表现的疾病,约占胃食管反流病(GERD)的60%~70%,其发病机制复杂,既与GERD有相似之处,又有其特殊性,主要包括酸反流与非酸反流、内脏高敏感、应激和精神因素等多种原因。其发病机制的多样性和复杂性是导致患者对抑酸治疗总体效果不佳的主要原因,强力抑酸治疗改善症状的疗效明显低于伴食管炎患者。现就NERD研究概况进行综述。     

胃食管反流病不同亚型食管酸暴露及发病机制的差异

目的比较反流性食管炎（reflux esophagitis,RE）和非糜烂性反流病（nonerosive reflux disease,NERD）不同亚型食管酸暴露情况,探计其发病机制的差异。方法115例具有典型反流症状的患者进行胃镜及24小时食管pH监测。结果①115例中26例（22．6％）为RE,89例（77．4o．4）为NERD,RE中pH监测阳性率高于NERD92．3％（24／26）VS74．2％（66／89）（P〈0．05）,包括DeMeester积分[64．55（128．28）VS26．60（59．11）]在内的全部pH监测指标均高于NERD（P〈0．05或〈0．01）。②REPH监测阳性组（RE＋）与NERDpH监测阳性组（NERD＋）的24小时pH〈4时间百分比[17．6％（38．8％）VS9．0％（20．3％）],卧位pH〈4时间百分比[18．3％（49．3％）VS6．5％（18．4％）],pH〈4长于5分钟的次数[15．00（19．00）次VS5．00（8．25）次]及DeMeester积分[69．70（120;47）分VS35．58（64．97）分],（P〈0．05或〈0．01）。③中重度RE包括DeMeester积分[151．70（124．24）分VS49．93（57．92）分]在内的多项pH监测指标均高于轻度RE（Pd0．05或〈0．01）。轻度RE多项pH值监测指标的中位数比NERD＋高。④NERDpH监测阴性组（NERD-）症状的发生与病理性酸反流无关。结论病理性酸反流是导致RE黏膜损害的主要因素,食管酸暴露程度越重,食管炎症越重。NERD＋症状发生与病理性酸反流相关。NERD＋和RE可能为同一疾病谱中程度递增的病变。在NERD-组中,内脏高敏感是症状指数（symptomindex,SI）阳性组症状发生的主要机帝】_,而SI阴性组症状的发生与酸无关。     

组织学改变对胃食管反流病的诊断价值

目的对非糜烂性反流病（NERD）和糜烂性食管炎（RE）患者以及正常人的食管远端黏膜病理组织学进行比较分析,探讨其症状产生的机制。方法 104例受试者分为正常对照组20例、NERD组30例和RE组54例;在齿状线上2~3 cm取活检行光镜检查,观察其组织学改变,包括：①黏膜上皮细胞间隙增宽;②上皮细胞气球样膨胀;③乳头内毛细血管扩张、充血、乳头延长;④嗜酸性粒细胞、中性粒细胞浸润;⑤基底层过度增生,并对其进行统计学分析。结果反流相关病理组织学特征指标的总体检出情况：在组织学第①~⑤项中NERD与正常组的检出率差异有统计学意义（P〈0.05）,而NERD与RE组的检出率差异无统计学意义（P〉0.05）。结论 NERD患者与正常组远端食管组织通过光镜观察时病理改变明显,且差异有统计学意义,但与RE组比较差异无统计学意义。     

Pathophysiology of gastroesophageal reflux disease: motility factors

Reflux esophagitis (RE) is characterized by excessive esophageal acid exposure. The number of acid reflux episodes, the way acid comes up after reflux and the delay of acid bolus clearance cause excessive esophageal acid exposure. Transient lower esophageal sphincter relaxation(TLESR) is the major mechanism of acid reflux in both healthy subjects (HS) and in patients with acid reflux disease, but there is no difference in the rate of TLESRs or in the rate of acid reflux during TLESRs above the LES between HS and patients with severe RE. In patients with severe RE, refluxed acid above the LES rises more easily to the proximal esophagus but it does not clear easily from the esophagus when compared with HS. The pathophysiology of non-erosive reflux disease (NERD) is poorly understood, however with regard to esophageal motility in patients with NERD, the LES pressure, the pressure wave amplitude and the rates of successful primary peristalsis were similar to that of HS but the triggering of secondary peristalsis was defective. This may lead to prolonged contact time between refluxed gastric acid and esophageal mucosa thereby leading to symptoms.     

胆汁反流与食管下端括约肌组织中一氧化氮及血管活性肠肽的关系

目的探讨胆汁反流与食管下端括约肌组织中一氧化氮及血管活性肠肽的关系。方法对20名健康志愿者及86例反流性食管炎患者,进行食管压力测定、24h食管内pH、食管胆汁监测及食管下端括约肌组织中一氧化氮及血管活性肠肽含量检测;比较健康志愿者、酸反流者、胆汁反流者及混合反流者食管下端括约肌压力、一氧化氮及血管活性肠肽含量的变化。结果酸反流组、胆汁反流组及混合反流组一氧化氮及血管活性肠肽含量较健康志愿者组增多,而混合反流组较酸反流组、胆汁反流组增高(P<0.01);反流性食管炎患者食管下端括约肌压力与食管下端括约肌组织内的一氧化氮及血管活性肠肽呈负相关(r=-88.5,P<0.05和r=-89.9,P<0.05)。结论胆汁反流可导致食管粘膜炎症,食管下端括约肌局部组织中一氧化氮及血管活性肠肽明显增高,食管下端括约肌压力下降,胆汁与胃酸反流具有协同作用,加重食管粘膜损伤。     

Management of gastroesophageal reflux disease (GERD) with refractory to standard dose of proton pump inhibitor

Approximately 10% of Japanese patients with reflux esophagitis (RE) are refractory to a standard dose of proton pump inhibitor(PPI) and most refractory patients have severe RE. Lack of response may be due to inadequate gastric acid suppression in conjunction with CYP2C19 genotype status and nocturnal acid reflux. Twice-daily dosing of PPI for inadequate gastric acid suppression and the administration of H2-receptor antagonist before bedtime for nocturnal acid reflux, is effective in most cases. The response to a standard dose of PPI in patients with non-erosive reflux disease (NERD) is approximately 50%. The reasons for a lower response rate, compared with RE patients, are not clear but may relate to an acid-hypersensitive esophagus, inadequate gastric acid suppression, non -acid reflux and emotional or psychological abnormality. High dose PPI therapy, endoscopic or surgical anti-reflux therapy, or/and pain modulators may be effective in some patients.     

Pro-inflammatory chemokine IL-8 in gastroesophageal reflux disease

Recent reports have demonstrated significantly higher expression levels of interleukin-8 (IL-8) in patients with gastroesophageal reflux disease (GERD) including non-erosive reflux disease (NERD). The levels of IL-8 mRNA expression were significantly decreased after proton pump inhibitor. The esophageal expression of CINCs, rat IL-8-like chemokines, was markedly enhanced in the models of acute or chronic esophagitis in rats. The production of IL-8 from esophageal mucosal cells was enhanced by the exposure to bile acid. These results suggest that IL-8 chemokine may play a major role in the pathogenesis of esophageal inflammation in GERD.     

Gastroesophageal reflux disease: presentation and assessment of a common, challenging disorder

Although gastroesophageal reflux disease (GERD) is frequently referred to as a continuous spectrum, it is more useful to consider GERD as 2 discrete entities with several subsets that differ in pathophysiology, clinical presentation, natural history, and therapy. One entity is classic severe acid reflux with erosive esophagitis and its complications. Barrett's esophagus is an important subset of this group, with markedly increased acid exposure and an increased risk of adenocarcinoma. The second entity is nonerosive reflux disease (NERD) with minimal or no esophagitis. Patients with NERD do not develop local mucosa complications, like stricture or Barrett's esophagus, but their symptom severity can equal that of erosive esophagitis. Acid is involved in the symptoms of many but not all NERD patients. This acid dependence is evident either as an increase in esophageal acid reflux or a hypersensitivity to acid, and both generally respond well to proton pump inhibitor (PPI) therapy. NERD patients who are not acid-dependent have what is called functional heartburn; GERD-like symptoms are present, but there is no obvious involvement of refluxed acid. An important subset of GERD is refractory GERD, which consists of patients who fail aggressive PPI therapy. Parallel findings with other refractory syndromes can be anticipated; however, there are indications that psychosocial factors play a major role in refractory GERD, and these patients may benefit more from an integrated biopsychosocial approach. Diagnosis of GERD is usually made on clinical grounds, often supplemented by a therapeutic trial with antisecretory agents. Endoscopy is reserved for patients with alarm symptoms, such as dysphagia, anemia, or weight loss, or to detect Barrett's esophagus. Endoscopy is not useful to exclude the diagnosis of GERD because it will be negative in 70% of cases in primary care. Ambulatory 24-hour esophageal pH monitoring is necessary only when the diagnosis is in doubt, the patient fails medical management, or surgery is contemplated.     

Esophageal pH monitoring

According to westernization of dairy life-style and aging, gastroesophageal reflux disease (GERD) with its physical symptoms such as heartburn is increasing in Japan. Although typical GERD has reflux esophagitis, GERD patients without abnormal endoscopic findings called non-erosive GERD (NERD) have been paid great attention. And more, the association between GERD and chronic respiratory diseases or laryngeal disease has been reported. To catch the more information about clinical questionnaire of GERD cases, esophageal pH monitoring is a useful method because of evaluating the direct condition of acid exposure of esophagus. Recently the new wireless pH monitoring system have been developed, this system is less stress than conventional method and has performance of pH recording for continuous 48 hours time. The widespread usage of pH monitoring system is expected to give us the new knowledge of GERD, NERD and GERD associated diseases.     

难治性胃食管反流病的反流危险因素调查

目的：收集胃食管反流病（gastroesophageaf reflux disease,GERD）患者的临床信息、胃镜表现以及24 h食管pH-阻抗监测结果,比较难治性GERD和非难治性GERD的反流特点,探讨难治性GERD的预测因素,为临床处理提供依据.方法：入选2008年10月-2012年12月因反酸、烧心、非心源性胸痛、咽痛等症状在复旦大学附属中山医院消化科疑诊为GERD的74例患者.记录患者的年龄、性别、身高、体质量、胃镜结果等.监测患者的食管下段pH和食管阻抗变化.难治性GERD诊断：符合GERD诊断标准,同时经过质子泵抑制剂（PPI）治疗4周（每天至少1次）无效或者deMeester评分下降少于50％;非难治性GERD诊断：符合GERD诊断标准,同时经过PPI治疗4周（每天至少1次）症状改善明显;非GERD诊断：内镜检查未见食管黏膜损害,且24 h食管pH-阻抗监测反流次数和deMeester评分不足以诊断GERD.计数资料正态分布者用r±s表示,菲正态分布者用中位数和百分位数（25th,75th）表示.采用SPSS 17.0软件进行统计学处理.按是否为GERD、是否为难治性GERD分组,比较患者的一般资料和反流特征性因素.结果：（1）难治性GERD患者与非难治性GERD患者的酸反流次数、总反流次数差异无统计学意义;难治性GERD患者的deMeester评分较非难活性GERD患者高,长酸反流次数较非难治GERD患者多（P=0.032,P=0.008）;（2）经Logistic多因素分析发现,难治性GERD与长酸反流次数、非糜烂性胃食管反流病（NERD）呈正相关（P值分别为0.01和0.045）.长酸反流次数增加1次,发生难治性GERD的危险增加36％;NERD患者发生难治性GERD的危险是反流性食管炎患者的4.54倍;（3）不同类型GERD的反流特征：NERD患者的近端反流次数大于反流性食管炎和Barrett食管患者,而近端反流百分比显著大于反流性食管炎患者和Barrett食管患者（P=0.006）.结论：（1）长酸反流次数多和NERD是难治性GERD的独立危险因素;（2）NERD患者比糜烂食管炎患者更容易发展为难治性GERD.NERD患者的近端反流百分比的升高可能与其对PPI的反应差有关.     

The daily response for proton pump inhibitor treatment in Japanese reflux esophagitis and non-erosive reflux disease

We investigated comparison according to reflux esophagitis and non-erosive reflux disease about “daily” symptom improvement for proton pump inhibitor treatment. We enrolled 57 reflux esophagitis and 90 non-erosive reflux disease patients. They took rabeprazole 10 mg/day for 28 days and completed “daily” in the Frequency Scale for the Symptoms of GERD from baseline until day 14, and after 28 days of treatment. The efficacy endpoint was the improvement rates in Frequency Scale for the Symptoms of GERD, based on baseline. Frequency Scale for the Symptoms of GERD was decreased in reflux esophagitis and non-erosive reflux disease (p<0.001) and was significantly lower in reflux esophagitis than in non-erosive reflux disease from the first day of treatment (p<0.05). Symptomatic improvement rates were also significantly higher in reflux esophagitis (50.3 ± 44.9%) than in non-erosive reflux disease (31.7 ± 43.2%) from the first day of treatment (p<0.0001). The symptomatic improvement rates in reflux esophagitis were significant increased from the second day of treatment until after 28 days of treatment (p = 0.0006), however, these in non-erosive reflux disease were significant increased from third days until after 28 days of treatment (p = 0.0002). In non-erosive reflux disease, the improvement of dysmotility symptom was particularly gradual as well as of reflux symptom, too. As for results of prediction of proton pump inhibitor response (completed symptom resolution) form early symptom improvement within 1 week, it was able to predict proton pump inhibitor response from the symptom improvement rate on 3 days in reflux esophagitis and on day 7 in non-erosive reflux disease. In conclusion, the prediction of the proton pump inhibitor response in non-erosive reflux disease was slow in comparison with reflux esophagitis. The cause was gradual improvement of dysmotility symptom.