Efficacy of Rikkunshito for Functional Heartburn: A Prospective Pilot Study.

BACKGROUND: Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit fromrikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn. METHODS: Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration. RESULTS: One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027). CONCLUSIONS: The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients.

Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy.

BACKGROUND: This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid blocker (P-CAB) therapy. METHODS: This study included 23 patients with reflux-related symptoms despite P-CAB therapy. Esophageal impedance-pH monitoring was performed on P-CAB and the following potential determinants of reflux perception were investigated: reflux nadir pH value; change in pH (baseline-nadir); bolus clearance time; reflux extent; proportions of acid, weakly acidic, and weakly alkaline reflux episodes; and proportions of liquid and mixed reflux episodes. RESULTS: Overall, ≥ 90% of all and symptomatic reflux episodes were weakly acidic reflux and 63% of symptomatic reflux episodes were reflux episodes with pH ≥ 5. There were no significant differences regarding potential determinants between symptomatic and asymptomatic reflux episodes. However, the proportion of symptomatic reflux episodes was significantly greater with pH < 5 (13.8%) than with pH ≥ 5 (9.5%) (P = 0.0431). In reflux episodes with pH < 5, the proportion of symptomatic reflux episodes was significantly greater in proximal sites (20.6%) than in distal sites (10.6%) (P = 0.0178). Conversely, in reflux episodes with pH ≥ 5, there was no significant difference regarding reflux perception according to reflux extent (proximal: 9.6% vs. distal: 9.0%, P = 0.9337). CONCLUSIONS: In patients with P-CAB-resistant NERD, reflux symptoms were mainly caused by reflux episodes with pH ≥ 5 on P-CAB therapy. The proportions of symptomatic reflux episodes among reflux sites differed according to reflux pH value; thus, the mechanisms of reflux perception may differ according to reflux pH value.

Differences in clinical characteristics between conservative-treatment-response group and refractory (surgical-treatment) group in patients with jackhammer esophagus.

BACKGROUND: Jackhammer esophagus (JE) is a rare disease with unclear clinical features. The objective of this study was to retrospectively compare the clinical characteristics of patients with JE whose symptoms were controlled with conservative treatment, such as observation or medication, versus those who were required surgical treatment, such as surgical myotomy or per oral endoscopic myotomy. METHODS: Eighteen patients with JE were included in this study. The patients were divided into two groups: patients who responded to conservative treatment (C group) and patients who were refractory to conservative treatment and underwent surgery (S group). Patient age, sex, disease duration before treatment, symptoms, esophagogastroduodenoscopic (EGD) findings, esophagographic findings, esophageal wall thickness on computed tomography, number of swallows with hypercontractile peristalsis in 10 water swallows, and maximum distal contractile integral (DCI) were compared between the groups. RESULTS: Thirteen of 18 patients (72%) were in the C group and five of 18 (28%) were in the S group. There were no significant differences in age, sex, disease duration before treatment, symptoms, EGD findings, esophagographic findings, esophageal wall thickness, or number of swallows with hypercontractile peristalsis between the groups. On Starlet high-resolution manometry, the median maximum DCI value was significantly higher in the S group (32,651 mmHg-s-cm) than in the C group (17,926 mmHg-s-cm) (P = 0.0136). CONCLUSIONS: JE treatment should be carefully considered because some patients require surgery, whereas others are controlled with conservative treatment alone. A higher DCI value in patients with JE may predict resistance to conservative treatment.

Validity of the Cutoff Value for Integrated Relaxation Pressure Used in the Starlet High-Resolution Manometry System.

BACKGROUND: In a previous study that used the Starlet high-resolution manometry system to assess integrated relaxation pressure (IRP) in healthy adults, the predicted cutoff value was about 26 mm Hg. However, some patients with achalasia have an IRP value of <26 mm Hg. This study examined the validity of the Starlet IRP cutoff value in patients with achalasia. METHODS: Among 37 patients with achalasia, the percentage of patients with a Starlet IRP value ≥26 mm Hg was calculated. Patients were then classified as IRP-high (IRP ≥26 mm Hg) and IRP-low (IRP <26 mm Hg), and the groups were compared in relation to basal lower esophageal sphincter (LES) pressure, Chicago classification achalasia subtype, and esophagography subtype. RESULTS: Twenty (54%) of the 37 patients had an IRP of ≥26 mm Hg. Basal LES pressure was significantly higher in the IRP-high group than in the IRP-low group. Chicago classification Type II achalasia was most common in the IRP-high group, whereas Type I was most common in the IRP-low group. No significant difference was noted in the distribution of esophagography subtypes between groups. CONCLUSIONS: It is difficult to determine an IRP cutoff value with Starlet. When diagnosing achalasia with Starlet, comprehensive assessment must consider findings other than IRP values. In addition, IRP was associated with Chicago classification type.

Possible new endoscopic finding in patients with achalasia: "Gingko leaf sign".

BACKGROUND: The diagnosis of achalasia can occasionally be difficult because of the low prevalence of apparent endoscopic abnormal findings, such as dilation and food residue, and lack of "esophageal rosette" in some patients. We have found a new endoscopic finding "Gingko leaf sign", which consists of not being able to see the full extent of the esophageal palisade vessels and a Gingko leaf-shaped morphology of a longitudinal section of the esophagogastric junction at the end of a deep inspiration, in some achalasia patients without "esophageal rosette". The aim of the study was to investigate the prevalence of "Gingko leaf sign" in these patients. METHODS: We retrospectively compared the prevalence of "Gingko leaf sign" between 11 achalasia patients without "esophageal rosette" and 22 age-/gender-matched healthy subjects. The diagnoses of achalasia were based on the results of high-resolution manometry. We also investigated the characteristics of the patients with "Gingko leaf sign". RESULTS: All the patients had "Gingko leaf sign", in contrast to none of the healthy subjects (p < 0.001). Four of 11 patients did not require any therapy. Six of seven patients did not relapse after balloon dilatation, but one patient required per-oral endoscopic myotomy 8 months after balloon dilatation. CONCLUSION: All our achalasia patients without "esophageal rosette" had "Gingko leaf sign". It is possibly a useful endoscopic finding in achalasia patients without "esophageal rosette".

Efficacy of long-term maintenance therapy with 10-mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis.

BACKGROUND: To investigate the efficacy of long-term (52 weeks) maintenance therapy by 10-mg vonoprazan administration for proton pump inhibitor-resistant reflux esophagitis continued from the preceding study. METHODS: Sixteen patients with proton pump inhibitor-resistant reflux esophagitis (mean age 70.9 years, eight males) in whom endoscopic healing was achieved by 20-mg vonoprazan administration for 4 weeks and maintenance of remission was maintained by 10-mg vonoprazan administration for 8 weeks were enrolled. Endoscopy was performed at 52 weeks after the initiation of maintenance therapy with 10-mg vonoprazan to evaluate whether there was any recurrence of reflux esophagitis. Changes in the gastric mucosa were investigated at 52 weeks. Symptoms were assessed using the frequency scale for the symptoms of gastroesophageal reflux disease and the fast gastrin level at 8 and 52 weeks following the maintenance therapy. RESULTS: Endoscopic remission was maintained at 52 weeks in 15 (93.8%) of the 16 patients with proton pump inhibitor-resistant reflux esophagitis. One patient relapsed with grade C of reflux esophagitis. There were no significant differences in the symptom score at 8 and 52 weeks, nor the gastrin level at 8 and 52 weeks. There was no change in the stomach on endoscopy at 52 weeks. CONCLUSION: Long-term maintenance therapy by 10-mg vonoprazan administration is very effective for proton pump inhibitor-resistant reflux esophagitis patients in whom endoscopic healing was maintained by 8 weeks maintenance therapy with 10-mg vonoprazan administration.

Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease.

BACKGROUND: The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). METHODS: Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. RESULTS: One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. CONCLUSIONS: The pathogenesis of -P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB.

Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis.

BACKGROUND: The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). METHODS: On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. RESULTS: One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. CONCLUSION: On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE.

Endoscopic diagnosis of hiatus hernia under deep inspiration is not consistent with esophageal manometric diagnosis.

BACKGROUND: To investigate the relationship between endoscopic and esophageal manometric hiatus hernia (HH). METHODS: Forty-six gastroesophageal reflux disease patients with endoscopic HH under maintenance therapy were recruited. Endoscopy was performed on all patients in a fully conscious state. Endoscopic HH was defined as apparent separation greater than 1 cm of the lower margin of the esophageal palisade vessels and the diaphragm hiatus on endoscopy under deep inspiration. Esophageal manometry was conducted using high-resolution manometry (HRM). The length between the lower margin of the lower esophageal sphincter and pulmonary inversion point was measured 10 times. The mean and maximum of the length was then calculated. RESULTS: The mean HH length on HRM was 0 cm (0-0) [median (25th to 75th percentile)], 0 cm (0-0), 0.5 cm (0-1.1), and 2.2 cm (1.3-2.5) in the groups with endoscopic HH lengths of 1-2, 2-3, 3-4, and 4-5 cm, respectively. The maximum HH length on HRM was 0 cm (0-0), 0 cm (0-0), 0.8 cm (0-1.4), and 2.4 cm (1.5-2.9) in the 1-2, 2-3, 3-4, and 4-5 cm endoscopic HH groups, respectively. The mean and maximum HH lengths increased significantly in the group with an endoscopic HH length of 4-5 cm compared with the other groups, but did not differ significantly among the 1-2, 2-3, and 3-4 cm groups. Of patients with endoscopic HH less than 3 cm, few had esophageal manometric HH greater than 2 cm. CONCLUSIONS: Endoscopic diagnosis of HH under deep inspiration is not consistent with esophageal manometric diagnosis, leading to overdiagnosis.

Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis.

BACKGROUND: Vonoprazan (VPZ) is a novel potassium-competitive acid blocker that may be clinically beneficial for proton pump inhibitor (PPI)-resistant reflux esophagitis (RE). The aim of this study was to investigate the efficacies of VPZ therapy at 20 mg for 4 weeks in patients with PPI-resistant RE and VPZ maintenance therapy at 10 mg for 8 weeks in patients who have been successfully treated. METHODS: Subjects comprised 24 patients with PPI-resistant RE (Los Angeles classification grade A/B/C/D: 3/7/11/3). After confirming PPI-resistant RE by endoscopy, 20 mg VPZ was administered. Endoscopy was performed 4 weeks after the initiation of VPZ. Symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Maintenance therapy with 10 mg VPZ was performed and endoscopy was conducted after 8 weeks. RESULTS: In 21 (87.5%) out of 24 patients, esophageal mucosal breaks were successfully treated by 20 mg VPZ. The median FSSG score was significantly lower on days 1-7, 14, and 28 after the initiation of VPZ than before its administration. Maintenance therapy with 10 mg VPZ prevented the relapse of esophageal mucosal breaks in 16 (76.2%) out of 21 patients. CONCLUSION: VPZ was effective for most patients with PPI-resistant RE.

Pathogenesis of Double-Dose Proton Pump Inhibitor-Resistant Non-Erosive Reflux Disease, and Mechanism of Reflux Symptoms and Gastric Acid Secretion-Suppressive Effect in the Presence or Absence of Helicobacter pylori Infection.

BACKGROUND: Various mechanisms have been suggested to be responsible for contributing to the occurrence of proton pump inhibitor (PPI)-resistant non-erosive reflux disease (NERD). The aims of this study were to clarify the pathogenesis of PPI-resistant NERD. METHODS: Fifty-three patients with NERD, who had persistent reflux symptoms despite taking double-dose PPI, were included in this study. After excluding eosinophilic esophagitis (EoE) and primary esophageal motility disorder, esophageal impedance-pH monitoring was carried out. In symptom index (SI)-positive patients, the mechanism of SI positivity and the percent time with intragastric pH >4 were investigated according to the presence or absence of Helicobacter pylori infection. RESULTS: One of the 53 patients had EoE, and 4 had primary esophageal motility disorder. Twenty-three and 2 patients were SI-positive for liquid and gas-only reflux respectively. Of 17 SI-positive, H. pylori-negative patients, 5 were SI-positive for acid reflux, whereas all of the H. pylori-positive patients were SI-positive for non-acid reflux. The percent time with intragastric pH >4 was significantly lower in the H. pylori-negative patients than in the H. pylori-positive patients. CONCLUSIONS: The pathogenesis of double-dose PPI-resistant NERD was identified in 57%. In some of H. pylori-negative patients, acid-related symptoms were observed. However, in H. pylori-positive patients, these symptoms were excluded by taking double-dose PPI.

Proton pump inhibitors are associated with lower gastrointestinal tract bleeding in low-dose aspirin users with ischaemic heart disease.

BACKGROUND: Impact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship. METHODS: Retrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography. RESULTS: 538 patients were enrolled (males, 74.4%; mean age 67.4±10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15-0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10-0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08-0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06-1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43-55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01-21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02-0.88). CONCLUSIONS: In low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding.