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

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.

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.

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.

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)

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)

Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders

( Shino Shimura ),( Norihisa Ishimura ),( Hironobu Mikami ),( Eiko Okimoto ),( Goichi Uno ),( Yuji Tamagawa ),( Masahito Aimi ),( Naoki Oshima ),( Shuichi Sato ),( Shunji Ishihara ),( Yoshikazu Kinosh 대한소화기기능성질환·운동학회 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.1

Background/Aims Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. Methods We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value ≥ 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. Results A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. Conclusions Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care. (J Neurogastroenterol Motil 2016;22:60-68)

Distinction between Chronic Enteropathy Associated with the SLCO2A1 Gene and Crohn’s Disease

Shunichi Yanai,Satoko Yamaguchi,Shotaro Nakamura,Keisuke Kawasaki,Yosuke Toya,Noriyuki Yamada,Makoto Eizuka,Noriyuki Uesugi,Junji Umeno,Motohiro Esaki,Eiko Okimoto,Shunji Ishihara,Tamotsu Sugai,Takayu 거트앤리버 소화기연관학회협의회 2019 Gut and Liver Vol.13 No.1

Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1 ) as causative variants of chronic nonspecific multiple ulcers of the small intestine (chronic enteropathy associated with SLCO2A1, CEAS). The aim of this study was to investigate the gastroduodenal expression of the SLCO2A1 protein in patients with CEAS and Crohn’s disease (CD). Methods: Immunohistochemical staining for SLCO2A1 was performed with a polyclonal antibody, HPA013742, on gastroduodenal tissues obtained by endoscopic biopsy from four patients with CEAS and 29 patients with CD. Results: The expression of SLCO2A1 was observed in one of four patients (25%) with CEAS and in all 29 patients (100%) with CD (p<0.001). The three patients with CEAS without SLCO2A1 expression had a homozygous splice-site mutation in SLCO2A1, c.1461+1G>C (exon 7) or c.940+1G>A (exon 10). The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous c.664G>A and c.1807C>T mutations. Conclusions: Immunohistochemical staining for SLCO2A1 in gastroduodenal tissues obtained by endoscopic biopsy is considered useful for the distinction of CEAS from CD.