Choitsu Sakamoto

Systematic review with meta‐analysis: post‐infectious functional dyspepsia

The prevalence of functional dyspepsia (FD) following infectious gastroenteritis has not been systematically reviewed.

Efficacy and Safety of the Selective Cyclooxygenase-2 Inhibitor Celecoxib in the Treatment of Rheumatoid Arthritis and Osteoarthritis in Japan

Background/Aims: Gastrointestinal (GI) disorders are common adverse reactions of nonsteroidal anti-inflammatory drugs (NSAIDs). Loxoprofen is a representative NSAID widely used in East Asia. A selective cyclooxygenase-2 inhibitor, celecoxib, was introduced in Japan in 2007. In this study, we aimed to compare the efficacy and safety of celecoxib with those of loxoprofen in Japanese patients. Methods: We analyzed the data from 12 clinical studies conducted in Japan. These data of Japanese patients were compared with those of the patients in the West that had been published after 2000. Results: The efficacy of celecoxib as an analgesic was comparable to that of loxoprofen, whereas serious GI events, including symptomatic ulcers, were significantly less frequent with celecoxib than with loxoprofen in Japanese patients with rheumatoid arthritis (RA) and osteoarthritis (OA) (p = 0.039). These results were consistent with the findings of the studies conducted in the West. The incidence of serious cardiovascular events was 0.1% in 2,398 subjects on celecoxib, which was not statistically different from the incidence in subjects on loxoprofen (0.3%; p = 0.3404) and those on placebo (0.2%); this result was also consistent with the data of the studies conducted in the West. Conclusion: The analgesic activity of celecoxib, which was used for the treatment of RA, OA, and low back pain, was comparable to that of loxoprofen, and celecoxib was safer in terms of GI injury often caused by other nonselective NSAIDs.

Nizatidine improves clinical symptoms and gastric emptying in patients with functional dyspepsia accompanied by impaired gastric emptying.

Background/Aims: In this crossover study, we investigated whether nizatidine, a H2-receptor antagonist, can alleviate clinical symptoms and gastric emptying in patients with Rome III-based functional dyspepsia (FD) with or without impaired gastric emptying. Methods: We enrolled 30 patients presenting with FD symptoms (epigastric pain syndrome, n = 6; postprandial distress syndrome, n = 24). Rome III-based FD patients were treated with nizatidine (300 mg/day) or placebo for 4 weeks in a crossover trial. Gastric motility was mainly evaluated with the Tmax value using the 13C-acetate breath test. Meal-related symptoms were defined as postprandial fullness and early satiation. Gastroesophageal symptom was defined as a burning feeling rising from the stomach or lower chest up toward the neck. Acylated- and desacylated ghrelin levels were evaluated by the ELISA method. Clinical symptoms, gastric emptying and ghrelin levels were evaluated at three different points during the study (pretreatment, after 4 weeks former treatment and after 4 weeks later treatment). The primary end point of this study was to determine whether nizatidine would improve clinical symptoms and gastric emptying in FD patients with or without impaired gastric emptying via affecting ghrelin levels. Results: Meal-related symptoms of the patients treated with nizatidine improved significantly (21/30; 70%) compared to those treated with placebo (3/30; 10%). In addition, nizatidine treatment also significantly improved gastroesophageal symptoms (16/30; 53%) compared to those treated with placebo (0/30; 0%). Nizatidine treatment in patients with FD accompanied by impaired gastric emptying significantly improved clinical symptoms and Tmax value as a marker of gastric emptying (10/11, 91%; 9/11, 82%) compared to placebo therapy, respectively. There were no significant differences in ghrelin levels between nizatidine treatment and placebo therapy. Conclusion: Nizatidine administration significantly improved both gastric emptying and clinical symptoms in FD patients with impaired gastric emptying.

Impact of sleep disorders in Japanese patients with functional dyspepsia (FD): Nizatidine improves clinical symptoms, gastric emptying and sleep disorders in FD patients

The association between functional dyspepsia (FD) and sleep disorders has yet to be studied in detail. The aim of this study is to evaluate the risk factors associated with sleep disorders and the clinical response to nizatidine therapy for sleep disorders in Rome III‐based FD patients.

Impact of Sleep Disorders, Quality of Life and Gastric Emptying in Distinct Subtypes of Functional Dyspepsia in Japan

Background/Aims The association between clinical symptoms, gastric emptying, quality of life and sleep disorders in distinct functional dyspepsia (FD) patients has not been studied yet in detail. Methods We enrolled 79 FD patients (postprandial distress syndrome [PDS], n = 65; epigastric pain syndrome [EPS], n = 47; EPS-PDS overlap, n = 33) and 44 healthy volunteers. Gastric motility was evaluated. We used Rome III criteria to evaluate clinical symptoms and State-Trait Anxiety Inventory (STAI) scores to determine anxiety status. Sleep disorder was evaluated using the Pittsburgh Sleep Quality Index scores. Results There were no significant differences in age, sex and Helicobacter pylori positivity between FD subtypes and healthy volunteers. The scores of Glasgow dyspepsia severity scores (GDSS), SF-8 and Pittsburgh Sleep Quality Index (PSQI) in distinct subtypes of FD patients were significantly different from those in healthy volunteers. However, there were not significant differences in these scores, Tmax and T1/2 among 3 subtypes of FD patients. PSQI score was significantly (P = 0.027, P = 0.002 and P = 0.039, respectively) associated with GDSS among EPS, PDS and EPS-PDS overlap patients. In addition, 8-item short form health survey (SF-8; Physical Component Score and Mental Component Score) was significantly associated with global PSQI score in PDS and EPS-PDS overlap patients. In contrast, SF-8 (Mental Component Score) only was significantly linked to global PSQI score in EPS patients. Conclusions Prevalences for sleep disorders, gastric motility and quality of life in 3 subtypes of FD patients were similar levels. In PDS and EPS-PDS overlap patients, SF-8 was significantly associated with global PSQI score.

Apurinic/apyrimidinic endonuclease-1 is associated with angiogenesis and VEGF production via upregulation of COX-2 expression in esophageal cancer tissues.

Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA base excision repair and is also a multifunctional protein such as redox effector for several transcriptional factors. Our study was designed to investigate APE-1 expression and to study its interaction with cyclooxygenase (COX)-2 expression and VEGF production in the esophageal cancer. The expression of APE-1, COX-2, monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF were evaluated by immunohistochemistry in 65 human esophageal squamous cell carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of APE-1 and p-signal transducer and activator of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE 220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in the regulation of COX-2 expression, VEGF production, and antiapoptotic effect against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was observed in 92.3% (60/65) of all tissues. There was a significant relationship (P = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1 stimulation significantly increased mRNA and protein expression of APE-1. Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1 significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded that APE-1 is overexpressed and associated with COX-2 expression and VEGF production in esophageal cancer tissues.

Impact of Eating Attitude and Impairment of Physical Quality of Life Between Tertiary Clinic and Primary Clinic Functional Dyspepsia Outpatients in Japan

Background/Aims There is no available data on factors associated with healthcare-seeking behavior for functional dyspepsia (FD) symptoms at either tertiary or primary clinics in Japan. Therefore, we aimed to compare clinical symptoms and life styles such as sleep disorders and eating attitude in FD patients visiting general practitioners at primary clinics with those consulting gastroenterologists at tertiary clinics to clarify healthcare-seeking patterns in Japanese patients. Methods Fifty-one FD outpatients in a tertiary clinic (college hospital), 50 FD outpatients visiting primary clinics and 50 healthy volunteers were enrolled. Clinical symptoms, quality of life, sleep disorders, eating attitude and anxiety were estimated using the Gastrointestinal Symptom Rating Scale (GSRS), Social Functioning-8 (SF-8) test, Pittsburg Sleep Quality Index (PSQI) test and State-Trait Anxiety Inventory (STAI) for FD outpatients and healthy volunteers. Results FD outpatients exhibited higher mean scores of GSRS than healthy volunteers. The SF-8 physical component summary scores in the tertiary clinic group were significantly lower than those in the primary clinic group. GSRS scores were significantly (P < 0.001, P = 0.002) associated with global PSQI scores in FD outpatients as well as with STAI-trait scores (P = 0.006, P = 0.001) compared to healthy volunteers. The frequency of eating between meals in the primary clinic group was significantly (P < 0.05) higher than that in the tertiary clinic group. Conclusions It may be important for clarification of healthcare-seeking behavior to determine the difference in both impairment of physical quality of life and eating attitudes between tertiary clinic and primary clinic FD outpatients in Japan.

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan

Background/Aims There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. Methods We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G>A), preproghrelin (3056T>C), Leu72Met (408C>A), Gln90Leu (3412T>A) and G-protein β3 (825C>T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. Results There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. Conclusions The Leu72Met (408C>A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

Classification of patients who experience a higher distress level to transoral esophagogastroduodenoscopy than to transnasal esophagogastroduodenoscopy

In Japanese routine clinical practice, endoscopy is generally carried out without sedation. The present study aimed to identify the factors essential for appropriate selection of transnasal esophagogastroduodenoscopy (TN‐EGD) as an alternative to unsedated transoral esophagogastroduodenoscopy (TO‐EGD).