Eosinophilic Esophagitis and Eosinophilic Gastroenteritis: Similarities and Differences

Yoshikazu Kinoshita,Norihisa Ishimura,Shunji Ishihara Korean Society of Gastrointestinal Cancer 2018 Journal of digestive cancer reports Vol.6 No.1

Eosinophilic gastrointestinal disease (EGID), a chronic allergic condition characterized by dense infiltration of eosinophils in the digestive tract, is classified into two types, eosinophilic esophagitis (EoE), which features dense infiltration of eosinophils in the esophageal epithelial layer, and eosinophilic gastroenteritis (EGE), in which the entire digestive tract including the esophagus may be involved. Patients with EoE only have esophageal symptoms, since the other parts of the digestive tract are not involved. On the other hand, 80% of EGE patients have lesions in the small intestine. The esophageal epithelial layer in healthy individuals has no or negligible infiltration by eosinophils, while the small intestinal mucosal layer, especially the distal small intestinal mucosa, can show dense eosinophil infiltration even in the absence of disease. Therefore, histological changes observed in cases of EGE are not qualitative but rather quantitative, as compared to EoE, which has qualitative histopathological changes, indicating important pathogenetic differences between the types. Comparisons of clinical, laboratory, and morphological characteristics between EoE and EGE have revealed several interesting differences. Both EoE and EGE patients are frequently affected by atopic diseases, such as bronchial asthma and allergic rhinitis, and elevated plasma levels of Th2 type cytokines and chemokines are also similarly seen in both. On the other hand, age at diagnosis differs, as the former is generally found in individuals from 30 to 50 years old, while the latter appears in all age groups. Additionally, 80% of patients with EoE are male as compared to only 50% of those with EGE. Furthermore, approximately 60% of patients with EoE respond favorably to proton pump inhibitor (PPI) administration, whereas EGE patients rarely show a response to PPIs. Nevertheless, both diseases show a similarly favorable response to a six foods elimination diet and glucocorticoid administration. These similarities and differences of EoE and EGE provide important clues for understanding the pathogenesis of these EGID types.

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

Yoshikazu Kinoshita,Norihisa Ishimura,Shunji Ishihara 대한소화기 기능성질환∙운동학회 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.2

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.

Original Articvle : Observations of Acid Reflux and Motor Function in Distal Esophagus Using Simultaneous Measurements of Intra-esophageal pH and Pressure in 8 Directions With Novel Sensor Catheter - A Feasibility Study

( Masahito Aimi ),( Kenji Furuta ),( Yoshiya Morito ),( Kousuke Fukazawa ),( Kyoichi Adachi ),( Yoshikazu Kinoshita ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.1

Background/Aims Esophagogastric junctional lesions, such as mucosal breaks with Los Angeles grade A or B reflux esophagitis, lacerations in Mallory Weiss syndrome, and short segment Barrett`s esophagus, are mainly found in the right anterior wall of the distal esophagus. Asymmetrical lower esophageal sphincter pressure and resting radial asymmetrical acid reflux may be causes of this asymmetrical distribution of reflux esophagitis and short segment Barrett`s esophagus. We developed a novel pH and pressure catheter to investigate the asymmetrical distributions of pH and intra-esophageal pressure in the distal esophagus. Methods One healthy male volunteer was enrolled in this study. Acid reflux and motor function in distal esophagus was investigated using simultaneous measurements of intra-esophageal pH and pressure in 8 directions with novel sensor catheter. Results Thirty-six acid and weak acid reflux events were observed, of which 22 were circumferential refluxes with pH drops in all channels and 14 were partial refluxes with pH drops in some channels. Increase in transient circumferential intraesophageal pressure was observed just after 72.7% of the circumferential reflux and 42.9% of the partial reflux events. Conclusions Using a novel sensor catheter, 2 different types of acid reflux events were identified in the present study. (J Neurogastroenterol Motil 2013; 19:42-46).

Evaluations of Gastric Acid Pocket Using Novel Vertical 8-Channel pH Monitoring System and Effects of Acid Secretion Inhibitors

( Shohei Sumi ),( Norihisa Ishimura ),( Hironobu Mikami ),( Eiko Okimoto ),( Yuji Tamagawa ),( Tsuyoshi Mishiro ),( Yoshikazu Kinoshita ),( Shunji Ishihara ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.3

Background/Aims The gastric acid pocket has an important role in gastroesophageal reflux disease development. In this study, we utilized a novel 8-channel pH monitoring system with sensor intervals of 1 cm on the vertical axis for evaluation of postprandial gastric acid pocket in healthy Japanese adults, as well as the effects of vonoprazan and rabeprazole. Methods Twelve healthy volunteers without Helicobacter pylori infection were enrolled. A catheter was inserted transnasally and positioned under X-ray guidance, then postprandial acid pocket formation was monitored over time in a sitting position. Thereafter, acid pocket changes were assessed following administration of vonoprazan (20 mg) or rabeprazole (20 mg). Results The gastric acid pocket was successfully measured by use of the present system in 10 cases, while failure occurred in 2 because of inappropriate catheter positioning. Observed acid pockets were visualized with a mean length of 2.2 ± 0.4 channels on the top layer of food contents approximately 20 minutes after finishing a meal. There were some variations for lasting time of the acid pocket. Complete elimination within 3 hours after administration of vonoprazan was noted in all cases. Likewise, following administration of rabeprazole, the acid pocket was eliminated in 7 cases, while acidity was reduced though the pocket remained observable in 3. Conclusions Gastric acid pocket observations were possible using our novel vertical 8-channel sensor catheter. The present findings showed that vonoprazan strongly suppressed acid secretion within a short period, suggesting its effectiveness for gastroesophageal reflux disease treatment. (J Neurogastroenterol Motil 2021;27:370-376)

Irritable bowel syndrome-like symptoms associated with endoscopic activity predict ulcerative colitis relapse in patients with clinical remission

( Nobuhiko Fukuba ),( Shunji Ishihara ),( Kousaku Kawashima ),( Yoshiyuki Mishima ),( Naoki Oshima ),( Yoshikazu Kinoshita ) 대한장연구학회 2017 Intestinal Research Vol.15 No.4

Generation of Gastroesophageal Reflux Disease Symptoms During Esophageal Acid Infusion With Concomitant Esophageal pH Monitoring in Healthy Adults

( Shunji Ohara ),( Kenji Furuta ),( Kyoichi Adachi ),( Kousuke Fukazawa ),( Masahito Aimi ),( Masaharu Miki ),( Yoshikazu Kinoshita ) 대한소화기기능성질환·운동학회 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.4

Background/Aims The sensitivity of the upper and lower esophageal mucosa to acid is considered to differ. We investigated the relationship between pH changes in different sites of the esophagus and generation of gastroesophageal reflux symptoms during an acid infusion test. Methods An acid infusion catheter was placed at 5 or 15 cm above the lower esophageal sphincter (LES) in 18 healthy volunteers, while a 2-channel pH sensor catheter was also placed in each with the sensors set at 5 and 15 cm above the LES. Solutions containing water and hydrochloric acid at different concentrations were infused through the infusion catheter. Results Acid infusion in the upper esophagus caused a pH drop in both upper and lower esophageal sites, whereas that in the lower esophagus resulted in a significant pH drop only in the lower without a corresponding pH decline in the upper esophagus. Stronger heartburn, chest pain, and chest oppression symptoms were noted when acid was infused in the upper as compared to the lower esophagus, while increased intra-esophageal acidity strengthened each symptom. Regurgitations caused by upper and lower esophageal acid infusions were similar, and not worsened by a larger drop in intra-esophageal pH. Chest pain was caused only by lowered intra-esophageal pH, while heartburn, chest oppression, and regurgitation were induced by a less acidic solution. Conclusions Higher intra-esophageal acidity caused stronger heartburn, chest pain, and chest oppression symptoms. However, regurgitation was not significantly influenced by intra-esophageal acidity. The upper esophagus showed higher acid sensitivity than the lower esophagus. (J Neurogastroenterol Motil 2013;19:503-508)

Acotiamide Has No Effects on Esophageal Motor Activity or Esophagogastric Junction Compliance

Hironobu Mikami,Norihisa Ishimura,Mayumi Okada,Daisuke Izumi,Eiko Okimoto,Shunji Ishihara,Yoshikazu Kinoshita 대한소화기 기능성질환∙운동학회 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.2

Background/Aims The novel prokinetic drug acotiamide is used for treatment of functional dyspepsia. It is still unclear how acotiamide has effects on esophageal motor function. Esophageal peristalsis and esophagogastric junction (EGJ) compliance has an important role for prevention of esophageal mucosal damage caused by gastroesophageal reflux, however, few studies have analyzed the effects of acotiamide on those former activities and none have investigated its effects on EGJ compliance. The aim of our research was to examine the effects of acotiamide on esophageal motility and EGJ compliance. Methods We enrolled 3 gastroesophageal reflux disease (GERD) patients as well as 9 healthy volunteers. Using high-resolution manometry, we examined esophageal motor activity parameters, including esophageal body contractions and lower esophageal sphincter (LES) pressure. While, EGJ compliance was evaluated using a functional lumen imaging probe. Following determination of baseline values for esophageal motor activities and EGJ compliance, acotiamide at a standard dose of 300 mg/day was administered for 3 days. All measurements were performed again 2 hours after the last acotiamide administration. Results In the healthy volunteers, as compared with the baseline values, acotiamide administration did not significantly change esophageal body contractions and LES pressure. And EGJ distensibility was not significantly changed (distensibility index in 40-mL distension: 3.5 ± 0.4 vs 3.3 ± 0.5 mm2/mmHg). Similarly in the GERD patients, there were no differences in either esophageal motility or EGJ compliance between before and after acotiamide administration (distensibility index in 40-mL distension: 6.2 ± 0.5 vs 6.5 ± 1.1 mm2/mmHg). Conclusion In both healthy individuals and GERD patients, standard dose acotiamide dose does not have significant effects on esophageal motor activities or EGJ compliance.

Effects of Rikkunshito (TJ-43) on Esophageal Motor Function and Gastroesophageal Reflux

( Terumi Morita ),( Kenji Furuta ),( Kyoichi Adachi ),( Shunji Ohara ),( Takashi Tanimura ),( Kenji Koshino ),( Tomochika Uemura ),( Kohji Naora ),( Yoshikazu Kinoshita ) 대한소화기기능성질환·운동학회 (구 대한소화관운동학회) 2012 Journal of Neurogastroenterology and Motility (JNM Vol.18 No.2

Background/Aims Rikkunshito (TJ-43), an herbal medicine, has been demonstrated to relieve gastroesophageal reflux symptoms. However, the effects of TJ-43 on esophageal motor functions have not been fully determined. This double-blind crossover study was performed to investigate the effects of TJ-43 on esophageal motor functions and gastroesophageal reflux. Methods The subjects were 10 normal male volunteers. Lower esophageal sphincter pressure and esophageal body peristaltic contractions with and without 1-week administration of TJ-43 were examined in a crossover fashion. Post-prandial gastroesophageal reflux was also determined using a multi-channel impedance pH dual monitor. Results TJ-43 at a standard dose of 7.5 g/day did not significantly augment esophageal peristaltic contraction pressure measured in the proximal, middle and distal segments of the esophagus, whereas increment of resting lower esophageal sphincter pressure was observed in a supine position. In addition, TJ-43 administration did not decrease post-prandial gastroesophageal acid, non-acid reflux events or accelerate esophageal clearance time. Conclusions TJ-43 at a standard dose did not have a significant effect on esophageal motor activity or gastroesophageal reflux in healthy adults.

Influence of Full-body Water Immersion on Esophageal Motor Function and Intragastric Pressure

( Masahito Aimi ),( Kenji Furuta ),( Tsukasa Saito ),( Shino Shimura ),( Kousuke Fukazawa ),( Shunji Ohara ),( Goichi Uno ),( Hiroshi Tobita ),( Kyoichi Adachi ),( Yoshikazu Kinoshita ) 대한소화기기능성질환·운동학회 (구 대한소화관운동학회) 2012 Journal of Neurogastroenterology and Motility (JNM Vol.18 No.2

Background/Aims In Japan, it is customary to take a daily bath during which the body is immersed in water to the neck. During full-body im - mersion, hydrostatic pressure is thought to compress the chest and abdomen, which might influence esophageal motor function and intragastric pressure. However, whether water immersion has a significant influence on esophageal motor function or intragastric pressure has not been shown. The aim of this study was to clarify the influence of full-body water immersion on esophageal motor function and intragastric pressure. Methods Nine healthy male volunteers (mean age 40.1 ± 2.8 years) were enrolled in this study. Esophageal motor function and intragastric pressure were investigated using a high-resolution 36-channel manometry device. Results All subjects completed the study protocol. Intragastric pressure increased significantly from 4.2 ± 1.1 to 20.6 ± 1.4 mmHg with full-body water immersion, while the lower esophageal high pressure zone (LEHPZ) value also increased from 20.5 ± 2.2 to 40.4 ± 3.6 mmHg, with the latter being observed regardless of dietary condition. In addition, peak esophageal peristaltic pressure was higher when immersed as compared to standing out of water. Conclusions Esophageal motor function and intragastric pressure were altered by full-body water immersion. Furthermore, the pressure gradient between LEHPZ and intragastric pressures was maintained at a high level, and esophageal peristaltic pressure was elevated with immersion.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers

( Hironobu Mikami ),( Norihisa Ishimura ),( Kousuke Fukazawa ),( Mayumi Okada ),( Daisuke Izumi ),( Shino Shimura ),( Eiko Okimoto ),( Masahito Aimi ),( Shunji Ishihara ),( Yoshikazu Kinoshita ) 대한소화기기능성질환·운동학회 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.1

Background/Aims Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Methods Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumenimaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Results Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm2/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Conclusions Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults. (J Neurogastroenterol Motil 2016;22:112-117)