Hiroto Miwa

Background: Functional dyspepsia (FD) is a common gastrointestinal disorder that significantly impacts patients' quality of life. Over a decade ago, the Asian Neurogastroenterology and Motility Association (ANMA) and the Asian Pacific Association of Gastroenterology (APAGE) jointly developed the first Asian consensus report on FD. In this consensus report, members of ANMA and APAGE provide updated recommendations on the definition, diagnosis, epidemiology, pathophysiology, and management of FD, focusing on Asian populations. Methods: The task force members conducted a systematic literature review and used a modified Delphi process to develop updated consensus statements. Based on members' feedback, statements that failed to reach at least 80% consensus in the first round of voting were revised. Revisions included rephrasing for clarity, incorporating additional evidence, and subgroup voting during a second round of discussion at a hybrid meeting. Results: The task force developed 32 statements covering key aspects of FD. Major updates include new insights into the pathophysiology and emerging treatment options. The task force acknowledged that the limited scope and heterogeneity of available studies limit definitive conclusions about the utility of some emerging therapies such as probiotics and potassium‐competitive acid blockers in FD management. Conclusions: The second Asian Consensus Report on FD provides updated evidence‐based recommendations to improve the diagnosis and management of FD in clinical practice, particularly in the Asian setting.

Background: This multicenter retrospective study evaluated the long-term outcomes of functional dyspepsia (FD) and factors associated with treatment resistance over a 3-year period after treatment initiation. Methods: A total of 111 patients diagnosed with FD according to the Rome IV criteria and confirmed by upper endoscopy to have no organic disease were retrospectively analyzed. First-line therapy included acid-suppressive drugs, prokinetics, and the Kampo medicine rikkunshito, whereas second-line therapy comprised anxiolytics or antidepressants for refractory cases. Gastrointestinal symptoms, psychological distress, and health-related quality of life were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale (HADS), and Short Form-8. Symptom improvement was evaluated at 1 and 3 years. Results: The improvement rates at 1 and 3 years were 50.5% and 80.2%, respectively. At baseline, the non-improvement group had significantly higher HADS-Depression and GSRS-Abdominal Pain scores (p < 0.05). Multivariate analysis identified HADS-Depression (odds ratio [OR] = 0.676, p = 0.019) and GSRS-Abdominal Pain (OR = 0.461, p = 0.038) as independent predictors of treatment resistance. Conclusions: The present findings indicate that FD often requires prolonged therapy, and baseline depressive symptoms and abdominal pain predict poor long-term outcomes, emphasizing the need for early psychological assessment and integrated management.

Junji Chen, Tadayuki Oshima, Takashi Kondo, Toshihiko Tomita, Hirokazu Fukui, Shinichiro Shinzaki, and Hiroto Miwa. J Neurogastroenterol Motil 2023;29:446-54. https://doi.org/10.5056/jnm22184

Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms are distressing for patients with quiescent Crohn’s disease (qCD) and worsen their quality of life. In the present study, we assessed the effect of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on the intestinal environment and clinical features in patients with qCD. Eleven patients with qCD, who met the Rome III diagnostic criteria for IBS-D, received BBG9-1 (24 mg) orally three times daily for 4 weeks. Indices of the intestinal environment (fecal calprotectin level and gut microbiome) and clinical features (CD/IBS-related symptoms, quality of life and stool irregularities) were evaluated before and after treatment. Treatment with BBG9-1 tended to reduce the IBS severity index in the studied patients (p = 0.07). Among gastrointestinal symptoms, abdominal pain and dyspepsia tended to be improved by the BBG9-1 treatment (p = 0.07 and p = 0.07, respectively), and IBD-related QOL showed a significant improvement (p = 0.007). With regard to mental status, the patient anxiety score was significantly lower at the endpoint of BBG9-1 treatment than at the baseline (p = 0.03). Although BBG9-1 treatment did not affect the fecal calprotectin level, it suppressed the serum MCP-1 level significantly and increased the abundance of intestinal Bacteroides in the study patients. The probiotic BBG9-1 is able to improve IBD-related QOL with a reduction of anxiety score in patients with quiescent CD and IBS-D-like symptoms.

Patients with quiescent inflammatory bowel disease (IBD) frequently suffer diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms, such as abdominal pain or stool irregularities. Here, we assessed the effect of ramosetron, a serotonin type 3 (5-HT₃) receptor antagonist, on IBS-D-like symptoms in patients with quiescent IBD. Seventy patients with quiescent IBD, who met the Rome III diagnostic criteria for IBS-D, were randomly assigned to receive either ramosetron (5 μg; n = 35) or a placebo (n = 35) orally once daily for 4 weeks. The primary endpoint was the responder rate for global assessment of relief from overall IBS-D-like symptoms. The responder rates for relief of abdominal pain/discomfort and improvement of bowel habits were also evaluated. The responder rate for relief from overall IBS-D-like symptoms at the final evaluation point was significantly higher in the ramosetron group (35.5%) than in the placebo group (11.4%) (p = 0.037). The responder rate for improvement of bowel habits was significantly higher in the ramosetron group (38.7%) than in the placebo group (14.3%) (p = 0.028). The reduction of stool frequency was significantly greater in the ramosetron group than in the placebo group (p = 0.044). Ramosetron is effective for relief of overall IBS-D-like symptoms in patients with quiescent IBD.

This study aimed to evaluate the relationship of esophageal epithelial permeability with mast cell infiltration and IgG4 deposits as well as chemokine levels in eosinophilic esophagitis (EoE) patients before and after treatment. Biopsies from controls and EoE patients before and after treatment were analyzed. Hematoxylin and eosin staining was used to show eosinophil infiltration. Paracellular permeability of the esophageal epithelium was assessed using surface biotinylation. Immunohistochemical staining was performed to examine mast cell infiltration and IgG4 deposits. Gene expression of chemokines was evaluated by qRT-PCR. Esophageal epithelial infiltration of mast cells, IgG4 deposits, and permeability were significantly increased in EoE patients. Levels of interleukin-13, calpain-14, and eotaxin-3 mRNAs were significantly upregulated, while filaggrin, serine peptidase inhibitor Kazal type 7 (SPINK7), and involucrin mRNAs were significantly downregulated in EoE patients. In patients achieving histologic remission diagnosed by eosinophil counts, a subset of EoE patients with unchanged permeability after treatment showed increases in mast cell infiltration, IgG4 deposits, and interleukin-13, calpain-14, filaggrin, and SPINK7 expression, with decreased eotaxin-3 and involucrin. Other EoE patients with decreased permeability displayed decreased eotaxin-3, involucrin, and mast cell infiltration, no IgG4 deposits, and increased IL-13, calpain-14, filaggrin, and SPINK7. Increased permeability of the esophagus in EoE patients without eosinophil infiltration after treatment was associated with mast cell infiltration and IgG4 deposits.

Shaoqi Duan, Nobuko Imamura, Takashi Kondo, Hirosato Kanda, Yoko Kogure, Takuya Okugawa, Masashi Fukushima, Toshihiko Tomita, Tadayuki Oshima, Hirokazu Fukui, Koichi Noguchi, Yi Dai, and Hiroto Miwa. J Neurogastroenterol Motil 2022;28:255-64. https://doi.org/10.5056/jnm21204

The subtypes of functional dyspepsia (FD) differ depending on whether the Rome III criteria or the Rome IV criteria are used. We investigated the ability to diagnose FD patients using the Rome III and IV criteria. The subtypes of FD were evaluated using the Rome questionnaire. The Gastrointestinal Symptom Rating Score, health-related quality of life (HR-QOL; SF-8), and psychological scores (HADS, STAI) were evaluated. The questionnaire was collected from a total of 205 patients, and 54.1% were FD patients. The ratio of FD patients under the Rome III criteria was 19% for epigastric pain syndrome (EPS), 38% for postprandial distress syndrome (PDS), and 43% for an overlap of EPS and PDS, but under the Rome IV criteria overlap decreased to 17% and PDS increased to 64%. Patients whose subtype changed from overlap under the Rome III criteria to PDS under the Rome IV criteria were compared with PDS patients whose subtype did not change between the Rome III and IV criteria. The comparison showed that the former had significantly lower early satiation rates and significantly higher acid reflux and abdominal pain scores, demonstrating that EPS symptoms due to acid reflux after meals were clearly present. As a result of changing from the Rome III criteria to the Rome IV criteria, the number of overlap patients decreased, and the number of PDS patients increased.

Goals: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. Background: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. Study: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. Results: Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. Conclusions: In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.