Prostaglandin D2 receptor d‐type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus

Eosinophilic esophagitis is characterized by eosinophil‐predominant inflammation in the esophagus. How eosinophils migrate and infiltrate into the esophagus, however, is less clear. Our previous study demonstrated that mast cell activation led to eosinophil infiltration in the esophagus. Prostaglandin D2 (PGD2) is an important mediator released from activated mast cells. The present study aims to determine whether PGD2 induces eosinophil infiltration into the esophagus via a d ‐type prostanoid receptor 2 (DP2) receptor‐dependent mechanism. Using an in vivo guinea pig model, PGD2, d ‐type prostanoid receptor 1 (DP1) agonist, or DP2 agonist were injected into the esophagus. Esophageal tissues were removed 2 hours after injections and proceeded to either hematoxylin–eosin (HE) staining or immunofluorescent staining of eosinophil major basic protein (MBP) to compare each treatment‐induced eosinophil infiltration in the esophagus. In a separate study, ovalbumin (OVA)‐sensitized guinea pigs were pretreated with either DP2 or DP1 antagonists, followed by inhalation of OVA to induce mast cell activation. Esophageal tissues were then processed for immunofluorescent staining of MBP. PGD2 injection in the esophagus led to an increase of eosinophil infiltration in esophageal epithelium at the injection site as revealed by HE staining. Increased infiltration of eosinophils was further confirmed by the increased presence of MBP‐labeled immunopositive (MBP‐LI) cells in esophageal epithelium. Injection with DP2 agonist 15(R)‐PGD2, but not DP1 agonist BW 245C, mimicked the PGD2‐induced response. In OVA‐sensitized animals, antigen inhalation increased MBP‐LI cells in esophageal epithelium. Pretreatment with DP2 antagonist BAY‐u3405, but not DP1 antagonist BW 868C, inhibited the antigen inhalation‐induced increase of MBP‐LI cells in esophageal epithelium. These data support the hypothesis that PGD2 induces eosinophil trafficking into the esophageal epithelium via a DP2‐mediated pathway, suggesting a role of DP2 antagonist in the prevention of eosinophilic esophagitis.     

Differences in the risk factors of reflux esophagitis according to age in Korea

The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.     

Gluten-free diet does not appear to induce endoscopic remission of eosinophilic esophagitis in children with coexistent celiac disease

BACKGROUND:

Celiac disease and eosinophilic esophagitis are usually considered to be separate gastrointestinal diseases; however, it appears that they may coexist more often than would be expected. It is unknown whether eosinophilic esophagitis in patients with celiac disease responds to a gluten-free diet.

OBJEVTIVES:

To examine the clinical, endoscopic and histological features of children with both conditions to evaluate whether eosinophilic esophagitis responds to a gluten-free diet.

METHODS:

From January 1, 2009, to June 30, 2011, the medical records of children <18 years of age diagnosed with eosinophilic esophagitis and/or celiac disease were reviewed. Patients with clinical, endoscopic and histological diagnoses of both diseases were identified and included. These findings were analyzed, as were laboratory results, treatment and follow-up.

RESULTS:

During the study period, there were 206 celiac disease patients, 86 eosinophilic esophagitis patients and nine (4.4% of total celiac) patients with both diagnoses. Gluten-free diet was the primary treatment for both conditions in seven of nine (78%) cases. In six of these seven (86%) patients, no endoscopic or histological improvement of eosinophilic esophagitis was observed, while in one patient, histological remission of esophageal eosinophilia occurred while on a gluten-free diet.

CONCLUSION:

The prevalence of eosinophilic esophagitis in patients with celiac disease was 4.4%, confirming a higher than expected prevalence of eosinophilic esophagitis compared with the general population. In patients with celiac disease, a gluten-free diet did not appear to induce remission of coexistent endoscopic and histological features of eosinophilic esophagitis.     

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009

AIM: To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy (EGD) over the past decade.METHODS: EGDs with the indication of dysphagia at an urban, university medical center in 1999, 2004 and 2009 were retrospectively identified from the electronic medical record. The entire patient chart, including EGD, pathology, manometry, radiographic and clinician reports, was reviewed for demographic and clinical data and to determine the etiology of dysphagia. The number of EGDs in which an esophageal biopsy was performed was also noted. Gastroesophageal reflux disease (GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition (PPI). Cases of eosinophilic esophagitis (EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field. PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008. Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999, 2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect.RESULTS: A total of 1371 cases (mean age 54 years, 43% male) met pre-specified inclusion criteria with 191, 504 and 675 cases in 1999, 2004 and 2009, respectively. Patients were older in 2004 compared to 2009 (mean ± SD, 54.0 ± 15.7 years vs 52.3 ± 16.8 years, P = 0.02) and there were more males in 1999 compared to 2004 (57.5% vs 40.8%, P = 0.005). Overall, GERD (27.6%) and EoE (7.7%) were the most common identifiable causes of dysphagia. An unspecified diagnosis accounted for 21% of overall cases. There were no significant differences in the relative prevalence of achalasia or other motility disorders, peptic stricture, Schatzki’s ring, esophageal cancer or unspecified diagnoses over the 10-year time period. There was, however, a decrease in the relative prevalence of GERD (39.3% vs 24.1%, P < 0.001) and increases in the relative prevalence of EoE (1.6% vs 11.2%, P < 0.001) and oropharyngeal disorders (1.6% vs 4.2%, P = 0.02) from 1999 to 2009. Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009 (5.4% vs 11.6%, P < 0.001), but not between 1999 and 2004 (1.6% P 5.4%, P = 0.21). On the other hand, the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004 (39.3% vs 27.7%, P = 0.006), but not between 2004 and 2009 (27.7% vs 24.1%, P = 0.36). There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009 (36.7% vs 68.7%, P < 0.001) as well as between 2004 and 2009 (37.5% vs 68.7%, P < 0.001). While total EGD volume did increase over the 10-year time period, the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE.CONCLUSION: EoE has emerged as a dominant cause of dysphagia in adults. Whether this was due to a rise in disease incidence or increased recognition is unclear.     

近端胃癌患者根治性切除术后三种消化道重建方式的对比研究

目的比较胃底贲门癌患者根治性胃切除术后不同消化道重建术式的反流性食管炎发生情况及生活质量。方法前瞻性人组2010年2月至2011年8月间河南省肿瘤医院收治的、拟行根治性胃切除的123例胃底贲门癌患者,按照随机数字表法分为3组,每组41例,在根治性胃切除术后分别行空肠间置吻合术、食管残胃后壁吻合术及食管空肠Roux-en-Y吻合术。分别于术前和术后1月行胃排空试验和食管下段pH值测定以评估患者食管反流情况．追踪肝肾功能及血常规变化情况：于术前和术后12月评估患者肝肾功能及生活质量。结果3组患者手术前、后血常规和肝肾功能指标的变化均无统计学意义（均P〉0．05）。术后空肠间置吻合组、食管残胃后壁吻合组和食管空肠Roux—en—Y吻合组分别有1例（2．4％）、10例（24．4％）和7例（17．1％）患者出现反流性食管炎症状,差异具有统计学意义（P=0．017）;分别有1例（2．4％）、7例（17．1％）和8例（19．5％）患者于上消化道钡餐造影检查时发现钡剂反流入食管,差异有统计学意义（P=0．046）;食管下段pH值分别为6．9±0．2、6.8±0．1和6．9±0．1,差异无统计学意义（P=0．196）。术后1年,3组患者在整体健康状况、躯体功能、情绪功能、疲劳、恶心呕吐、疼痛症状、便秘及腹泻方面的生活质量评分明显优于术前（均P〈0．05）;空肠间置吻合组患者在整体健康状况、情绪功能、恶心呕吐、便秘及腹泻方面的生活质量评分显著优于其他两组（均P〈0．05）。结论近端胃癌患者根治性胃切除术后采用空肠间置吻合术、食管残胃后壁吻合术及食管空肠Roux—en—Y吻合术均能够满足消化道重建的需要,能够有效地改善患者的生活质量;其中空肠间置吻合重建术在减少反流性食管炎的发生和提高患者生活质量方面的效果更为显著,是比较理想的近端胃癌根治术后消化道重建术式。     

蒲元和胃胶囊联合莫沙必利和泮托拉唑治疗反流性食管炎的疗效观察

目的探讨蒲元和胃胶囊联合莫沙必利和泮托拉唑治疗反流性食管炎的临床疗效。方法选取安阳市人民医院2013年10月—2016年10月收治的102例反流性食管炎患者,随机分为对照组和治疗组,每组各51例。对照组患者饭前口服枸橼酸莫沙必利片,1片/次,3次/d;同时早晨空腹口服泮托拉唑钠肠溶片,1片/次,1次/d。治疗组患者在对照组的基础上于饭后1 h口服蒲元和胃胶囊,4粒/次,3次/d。两组患者均连续治疗6周。评价两组患者临床疗效,比较治疗前后两组患者生活质量和临床症状评分。结果治疗后,对照组的总有效率为84.31%,显著低于治疗组的96.08%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者各项生活质量评分均较治疗前明显升高,临床症状评分均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患者生活质量和临床症状评分改善程度显著优于对照组,两组比较差异有统计学意义(P0.05)。结论蒲元和胃胶囊联合莫沙必利和泮托拉唑治疗反流性食管炎疗效显著,安全性较高,具有一定的临床推广应用价值。     

舒肝顺气丸对胃溃疡、反流性食管炎模型鼠的保护作用

目的:研究舒肝顺气丸对胃溃疡、反流性食管炎模型鼠的保护作用。方法:通过对利血平、无水乙醇、幽门结扎、水应激复制鼠胃溃疡模型;对贲门切开联合半结扎幽门复制大鼠反流性食管炎模型。5个实验均分为正常对照组、模型组、舒肝健胃丸组、化学药对照(西咪替丁/西沙比利)组与舒肝顺气丸高、中、低剂量组。检查胃溃疡模型鼠胃溃疡病变程度,计算溃疡指数或溃疡发生率;测定反流性食管炎模型大鼠血管活性肠肽、血浆胃动素和血清胃泌素含量。结果:与胃溃疡模型组(利血平/无水乙醇导致/水应激)比较,舒肝顺气丸高、中剂量组鼠溃疡指数降低,差异有统计学意义(P<0.01或P<0.05);与胃溃疡模型组(幽门结扎)比较,舒肝顺气丸高、中剂量组大鼠溃疡发生率降低,差异有统计学意义(P<0.01或P<0.05);与反流性食管炎模型组比较,舒肝顺气丸高、中剂量组大鼠血管活性肠肽含量减少,血浆胃动素和血清胃泌素含量增加,差异有统计学意义(P<0.01或P<0.05)。结论:舒肝顺气丸具有较强的改善功能性消化不良症状、治疗胃溃疡的作用。该研究为舒肝顺气丸的再评价及临床应用提供了药理学依据。