Katsuhiko Iwakiri

Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease.

Background and Aims: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases. Methods: One hundred and fifty-one patients presenting with typical symptoms of FD (EPS, n = 36; PDS, n = 76) or NERD (n = 39), and 20 healthy volunteers were enrolled. Gastric motility was evaluated with the Tmax value as a marker of gastric emptying using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and SRQ-D scores to determine depression status. We measured both acylated and des-acylated ghrelin levels by ELISA methods. Results: The Tmax value in PDS patients was significantly higher than in healthy volunteers. Acylated ghrelin levels were significantly lower in NERD and PDS patients than in healthy volunteers. Interestingly, there was significant correlation between the acylated ghrelin levels and Tmax value in PDS patients but not in EPS or NERD patients. Conclusion: Our results suggest that acylated ghrelin might play an important role in the pathophysiology of PDS patients through its effect on gastric emptying.

Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia.

OBJECTIVES:Recent studies have shown that postinfectious functional dyspepsia (FD) symptoms may persist after elimination of gastrointestinal (GI) infection as well as postinfectious irritable bowel syndrome accompanying colonic inflammation. However, it is unclear whether intestinal chronic inflammation can contribute to clinical symptoms of certain FD patients such as postinfectious FD. To determine the relationship between local inflammation of the duodenum and clinical symptoms, we evaluated the infiltration of several phenotypes of duodenal inflammatory cells as well as gastric motility using 13C urea breath test in postinfectious FD patients.METHODS:We enrolled 136 consecutive patients diagnosed with FD according to Rome III criteria, and 20 healthy controls, after upper GI endoscopy. Gastric motility was evaluated by gastric emptying time (T-max) using the 13C-acetate breath test. Upper abdominal symptoms including epigastric pain, epigastric burning, postprandial fullness, abdominal distension, and early satiety were assessed by questionnaire scores. We obtained biopsy specimens from the stomach and duodenum during upper GI endoscopy. Histological gastritis and duodenitis were assessed as mild, moderate, or severe according to previously described criteria. Characteristics of inflammatory cells and neuroendocrine cells were determined immunohistochemically with antibodies to CD3, CD68, CCR2, Vdelta1 TCR, and serotonin.RESULTS:Endoscopic duodenitis was observed in only 5.7% of postinfectious FD patients. However, the rates of histological duodenitis in duodenal biopsies of postinfectious FD patients were 17% for mild, 26% for moderate, and 57% for severe grades of duodenitis. The degree of histological duodenitis of postinfectious FD patients was significantly greater than that of healthy volunteers. There was a significant correlation between epigastric burning and the degree of duodenitis in postinfectious FD patients. There was no significant difference in histological duodenitis and T-max value in the postinfectious FD patients with or without Helicobacter pylori infection. In addition, CD68-positive cell number in postinfectious FD patients was significantly increased compared with the numbers in subjects with epigastric pain syndrome or postprandial distress syndrome and in healthy volunteers. CCR2-/CD68-double positive cell number in postinfectious FD patients was significantly (P=0.009) increased compared with those in healthy volunteers.CONCLUSIONS:Migration of inflammatory cells, in particular, duodenal CCR2-positive macrophages, may have an important function in the pathophysiology of postinfectious FD patients.

Relationship between postprandial esophageal acid exposure and meal volume and fat content

The effect of meal volume and fat content on gastroesophageal reflux was investigated in 20 asymptomatic healthy subjects. In each subject, intraesophageal pH monitoring was performed during a 3-hr postprandial period (PP) in the same position (supine or upright) on two successive days. On day 1, 500-ml low- and high-fat meals were ingested and, on day 2, an 800-ml low-fat meal was ingested. The acid exposure time was assessed as the percentage of time with a pH<4.0. The acid exposure time in subjects in the upright position was significantly longer in the 800-ml group than in the 500-ml group for the entire PP (2.7 ± 1.5%; mean ±se, 0.7 ± 0.4%;P<0.05). Of subjects in the supine position, the high-fat group showed significantly longer acid exposure time than the low-fat group both for the entire PP (7.6 ± 3.0%, 0.7 ± 0.5%; p<0.05) and for the second hour (P<0.05). We have demonstrated that differences in the meal volume and fat content influence gastroesophageal reflux in healthy asymptomatic subjects and that this influence varies with the position.

Is there a set of histologic changes that are invariably reflux associated

Many histologic changes have been described in the esophageal squamous mucosa in patients with gastroesophageal reflux disease (GERD), including dilated intercellular spaces, balloon cells, intrapapillary vessel dilation, elongated papillae, basal cell hyperplasia, acanthosis, intraepithelial eosinophils, Langerhans cells, and p53 protein overexpression. To define a set of histologic changes that are invariably reflux associated, we examined the histologic changes in esophageal specimens from normal controls, patients with GERD, patients without GERD but with a suspicion of other pathology, and patients with esophageal carcinoma. We also examined biopsy specimens from sites with differing endoscopic features, including cloudy white and reddened mucosa. A definitive set of reflux-associated histologic changes could not be defined from the small number of biopsy specimens examined in the present study. Histologic changes indicative of GERD are likely to be found somewhere in the esophagus in all patients with GERD, but these changes are nonspecific. A set of histologic changes that are invariably reflux associated may exist, but these changes are nonspecific. To develop a set of characteristic reflux-associated features, endoscopists may perform targeted biopsies from several sites with various endoscopic features and at different stages of disease.

Randomised clinical trial: vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis

Vonoprazan is a novel potassium‐competitive acid blocker which may provide clinical benefit in acid‐related disorders.

Transient Lower Esophageal Sphincter Relaxations (TLESRs) Are the Major Mechanism of Gastroesophageal Reflux but Are Not the Cause of Reflux Disease

In healthy subjects, the rate of acid reflux during transient lower esophageal sphincter relaxations (TLESRs) is more frequent at the proximal margin of the LES. In this study, we investigated the hypothesis that the rate of acid reflux at the proximal margin of LES during TLESRs is similar in reflux disease to that in healthy subjects. Concurrent esophageal manometry and pH monitoring were performed in the sitting position for 3 hr after a standard meal in 10 patients with reflux disease and 10 age-matched healthy controls. The rate of TLESRs in patients with reflux disease (5.0/hr [3.3–6.7]; median [interquartile range]) was similar to that of controls (4.5/hr [3.7–5.7]). The incidence of acid reflux 7 cm above the LES during TLESRs in patients (48.1% [27.2–71.4%]) was significantly higher than that in controls (10.9% [0.0–18.8%]) but there was no difference 2 cm above the LES (75.0 [69.2–87.5] vs. 74.3 [55.5–90.0%]). The rate of TLESRs and the incidence of acid reflux during TLESRs are not increased in reflux disease. These findings, therefore, indicate that reflux disease is not a disorder of TLESRs and relates more to the proximal extent of the refluxate.

Randomised clinical trial: a dose‐ranging study of vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis

The potassium‐competitive acid blocker vonoprazan (VPZ) has potent acid‐inhibitory effects and may offer clinical advantages over conventional therapy for acid‐related disorders.

Randomised clinical trial: rabeprazole improves symptoms in patients with functional dyspepsia in Japan

The efficacy of proton pump inhibitors (PPIs) for treating functional dyspepsia (FD) is not well established.

Relationship between severity of reflux esophagitis according to the Los Angeles classification and esophageal motility

Purpose. We investigated the relationship between the severity of reflux esophagitis (RE) according to the Los Angeles (LA) classification and esophageal motility. Methods. We examined 28 healthy subjects (HS) and 48 RE patients (grade A of the LA classification, 16 patients; grade B, 16 patients; grade C or D, 16 patients). Esophageal manometry was performed by the intraluminal microtransducer method. Resting lower esophageal sphincter (LES) pressure was assessed by the rapid pull-through method. Esophageal contraction after ten repeated 5-ml water swallowings separated by 30-s intervals was measured at 3, 8, 13, and 18 cm above the LES. Results. The resting LES pressure and the amplitude of esophageal contraction 3 cm above the LES in the grades C + D group were significantly lower than those in the HS group. The amplitude of esophageal contraction 3 cm above the LES in the grade B group was significantly lower than those in the grade A group and the HS group. The frequency of failed peristalsis in the grades C + D group was significantly higher than that in the HS group and the grade A and grade B groups. Conclusions. The present findings suggested that the severity of RE according to the LA classification would be likely to mainly reflect esophageal volume clearance.

Structures of the normal esophagus and Barrett?s esophagus

This article reviews and discusses several topics, mainly relating to the histology of the normal esophagus and of Barrett’s esophagus, in order to facilitate the understanding of Barrett’s esophagus. The border between the esophagus and stomach is considered in Japan to be the lower limit of longitudinal vessels which are visible in the lower segment of the esophagus at endoscopy. This definition has been authorized by the Japanese Society for Esophageal Diseases. The longitudinal vessels are also visible through the metaplastic columnar epithelium of Barrett’s esophagus. Identification of the esophageal glands proper in biopsy specimens can assist in the histologic diagnosis of Barrett’s esophagus. The histologic diagnosis of Barrett’s esophagus in biopsy specimens, in relation to the presence of esophageal glands proper, is discussed. Ciliated pseudostratified epithelium is discussed in detail, including the fact that it is thought to be an intermediate stage between squamous and columnar epithelium at the esophagogastric junction and at ectopic gastric mucosa in the upper esophagus. The differences in the histopathologic criteria for a diagnosis of Barrett’s adenocarcinoma between Western countries and Japan are also discussed. The four editions of the Comprehensive Registry of Esophageal Cancer in Japan, and the Long Term Results of Esophagectomy in Japan (1988–2000), published by the Japanese Society for Esophageal Diseases and available on its website (http://jsed.umin.ac.jp), are introduced. These editions give detailed information on the pathology, endoscopic features, radiation treatment, and surgery of esophageal cancer in Japan.