Factors associated with prevalence and severity of erosive tooth wear in patients with reflux oesophagitis.

BACKGROUND: Extrinsic factors for erosive tooth wear (ETW) have been widely reported, but the intrinsic factors for wear remain unclear. OBJECTIVES: The aim of this study was to evaluate the factors associated with the prevalence of ETW in patients with reflux oesophagitis (RO). To prevent severe ETW with RO, factors associated with severity of ETW were also evaluated. METHODS: A total of 270 patients with RO were recruited. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffering capacity were assessed prior to endoscopy. Subjects were asked to complete a medical condition and oral self-care questionnaire. Univariate and multivariate analyses were employed to identify factors collectively associated with the prevalence and severity of ETW. RESULTS: A total of 212 cases were categorized as patients with ETW (148 with mild ETW and 64 with severe ETW). Multivariate analyses indicated that saliva secretion, severity of RO and proton pump inhibitor (PPI) resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. The odds ratio of saliva secretion and BMI were less than 1, meaning that higher saliva secretion resulted in a lower prevalence of ETW and lower BMI was associated with severe ETW. CONCLUSION: Saliva secretion, severity of RO and PPI resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. Lower saliva secretion and BMI were significant factors for ETW.

In females, salivary secretion was significantly lower in patients with severe reflux esophagitis than in healthy controls.

BACKGROUND: The salivary secretion in patients with mild reflux esophagitis (RE) and non-erosive reflux disease is significantly lower in females, but not in males. However, sex differences in salivary secretion in patients with severe RE remain unknown. Therefore, the present study investigated sex differences in saliva secretion in patients with severe RE. METHODS: Subjects consisted of 23 male patients with severe RE, 24 male healthy controls (HCs), 26 female patients with severe RE, and 25 female HCs. Saliva secretion was assessed as follows: each patient chewed sugarless gum for 3 min prior to endoscopy, and the amount and pH of saliva secreted before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: In males, no significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between severe RE patients and HCs. In females, the amount of saliva secretion (severe RE: 2.4 [1.8-4.1], HCs: 5.3 [3.4-7.5], p = 0.0017), salivary pH (severe RE: 7.0 [6.7-7.3], HCs: 7.2 [7.1-7.3], p = 0.0455), and the acid-buffering capacity (severe RE: 5.9 [5.3-6.2], HCs: 6.2 [6.1-6.5], p = 0.0024) were significantly lower in severe RE patients than in HCs. CONCLUSION: Among females, the salivary secretion was significantly lower in severe RE patients than in HCs. This reduction in salivary secretion may contribute to the pathophysiology of severe RE in females.

Characteristics of proton pump inhibitor-resistant severe reflux esophagitis and efficacy of vonoprazan in elderly (older than 75 years) and non-elderly groups.

Background and Aim: Previous studies on age differences in proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) have found that stenosis and bleeding complications were significantly more common in the elderly than in the non-elderly. We sought to examine differences between two groups of elderly (75 years or older) and non-elderly (<75 years) patients with (PPI)-resistant severe RE and also the efficacy of vonoprazan (VPZ) in these patients. Methods: There were 14 patients in the elderly group and 15 in the non-elderly group. Information was obtained on patient background (sex, body mass index [BMI], gastric mucosal atrophy, and the presence of hernia and collagen disease), and all patients underwent the saliva secretion test and esophagogastroduodenoscopy (EGD). The saliva secretion test (amount of saliva secreted, salivary pH, and the acid-buffering capacity) was performed by chewing sugar-free gum for 3 min before EGD. The efficacy of VPZ in both groups was also assessed. Results: Saliva secretion, sex, BMI, and the presence of gastric mucosal atrophy did not significantly differ between the two groups. The number of hernias larger than 4 cm was significantly higher in the elderly PPI-resistant group, and significantly more patients had collagen disease in the non-elderly group. The efficacy of VPZ was not significantly different between the two groups; however, 10 patients in the non-elderly group had collagen disease, and 4 did not achieve esophageal mucosal healing even with VPZ 20 mg. Conclusion: The number of large hernias (>4 cm) was significantly higher in the elderly group, while significantly more non-elderly patients had collagen disease. In the non-elderly group with scleroderma, the efficacy of VPZ 20 mg may not be sufficient.

Esophageal Motility Disorders: Diagnosis and Treatment Strategies.

BACKGROUND: Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions, resulting in dysphagia and noncardiac chest pain. High-resolution manometry (HRM) is essential for the diagnosis of primary EMD; however, the recognition of EMD and HRM by general practitioners in Japan is limited. This review summarizes the diagnosis of and treatment strategies for EMD. SUMMARY: HRM is a specific test for the diagnosis of EMD, whereas endoscopy and barium swallow as screening tests provide characteristic findings (i.e., esophageal rosette and bird's beak sign) in some cases. It is important to note that manometric diagnoses apart from achalasia are often clinically irrelevant; therefore, the recently updated guidelines suggest additional manometric maneuvers, such as the rapid drink challenge, and further testing, including functional lumen imaging, for a more accurate diagnosis before invasive treatment. Endoscopic/surgical myotomy, pneumatic dilation, and botulinum toxin injections need to be considered for patients with achalasia and clinically relevant esophagogastric junction outflow obstruction. KEY MESSAGE: Since the detailed pathophysiology of EMD remains unclear, their diagnosis needs to be cautiously established prior to the initiation of invasive treatment.

Patients with gastroesophageal reflux disease (both reflux oesophagitis and non-erosive reflux disease): Prevalence and severity of erosive tooth wear and saliva properties.

BACKGROUND: The prevalence between erosive tooth wear (ETW) in association with reflux oesophagitis (RO) has been reported. However, the severity of both diseases and the relationship between ETW and non-erosive reflux disease (NERD) is unclear. OBJECTIVES: The prevalence and severity of ETW were investigated in RO, NERD and healthy controls. METHODS: 135 patients with RO, 65 with NERD and 40 healthy controls were recruited for this case-control study. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffer capacity were assessed prior to endoscopy. The prevalence and severity of ETW, saliva properties among each group were analysed using Pearson's chi-squared test. RESULTS: A total of 135 cases (56.3%) were categorised as the patient with ETW (55 with mild RO, 49 with severe RO and 31 with NERD). There was a significant relationship between the prevalence of RO and ETW, while there was no significant correlation between the prevalence of NERD and ETW. There was a significant difference related to the severity between RO and ETW. For salivary secretion, there was a significant difference between with and without ETW in patients with mild RO, severe RO and NERD. There was a significant difference between with and without ETW for salivary buffer capacity in patients with mild and severe RO. CONCLUSION: There was a significant association of the prevalence and severity between RO and ETW. Clinical signs such as ETW and salivary buffer capacity depended on the severity of RO.

Among females older than 50 years, saliva secretion is significantly lower in non-erosive reflux disease patients than in healthy controls.

BACKGROUND: Saliva secretion is significantly lower in patients with non-erosive reflux disease (NERD) than in healthy controls (HC). A previous study on HC showed that saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with NERD than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with NERD. METHODS: Subjects older than 50 years were included in the present study and consisted of 20 male patients with NERD, 19 male HC, 25 female patients with NERD, and 23 female HC. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: In males, no significant differences were observed in the amount of stimulated saliva secretion or salivary pH between NERD patients and HC. However, the acid-buffering capacity (NERD: 6.1 [5.9-6.5], HC: 6.4 [6.2-6.6]) was significantly lower in NERD patients than in HC. In females, the amount of stimulated saliva secretion (NERD: 2.6 [2.0-4.1], HC: 5.8 [3.7-7.5]), salivary pH (NERD: 7.0 [6.8-7.2], HC: 7.2 [7.0-7.2]), and the acid-buffering capacity (NERD: 5.8 [5.4-6.2], HC: 6.2 [6.0-6.5]) were significantly lower in NERD patients than in HC. CONCLUSION: Among females older than 50 years, saliva secretion was significantly lower in NERD patients than in HC. This reduction in saliva secretion may contribute to the pathophysiology of NERD in females.

Esophageal Dilation in Patients with Achalasia Is a Predictive Factor for the Inability to Traverse the Esophagogastric Junction with a Manometric Catheter.

INTRODUCTION: The insertion of a high-resolution manometry (HRM) catheter into the stomach is essential for accurate manometric diagnoses; however, it is impossible in some cases due to the inability to traverse the esophagogastric junction (EGJ). Predictive factors for these patients have not been investigated in detail, necessitating time-consuming and burdensome procedures for investigators and patients. Therefore, the present study investigated the percentage of and risk factors for failed intubation at the EGJ. METHODS: We initially reviewed the medical charts of consecutive HRM procedures performed at our hospital between September 2018 and January 2023. Patient characteristics and the findings of endoscopy and esophagography (where available) were compared between successful and failed procedures. A multivariate logistic regression analysis was conducted to identify predictive factors for the inability to traverse the EGJ. We then validated the predictive factors identified by reviewing consecutive procedures performed between February 2023 and August 2023. RESULTS: Among the 781 procedures performed, 55 (7.0%) failed due to the inability to traverse the EGJ. Achalasia was the most common disorder in these procedures. An older age and dilated esophagus of >34 mm were independent predictive factors for the inability to traverse the EGJ in patients with treatment-naïve achalasia. In the validation study, 7 out of 68 procedures (10.3%) failed due to the inability to traverse the EGJ. A flowchart using the findings of endoscopy and an esophageal diameter of >34 mm predicted the inability to traverse the EGJ with a sensitivity of 71.4% and specificity of 86.9%. CONCLUSION: Based on an esophageal diameter >34 mm and endoscopic findings, we predicted the inability to traverse the EGJ in more than 70% of patients. A multi-center prospective study is warranted in the future.

Lemborexant Attenuates Regurgitation without Worsening Objective Parameters on Reflux Monitoring in Patients with Gastroesophageal Reflux Disease and Insomnia: A Single-Arm Proof-of-Concept Study.

INTRODUCTION: Esophageal hypersensitivity is associated with gastroesophageal reflux disease (GERD). Since sleep disturbance causes esophageal hypersensitivity, hypnotics may ameliorate GERD. However, zolpidem prolongs esophageal acid clearance. Lemborexant is a new hypnotic with higher efficacy and fewer adverse events than zolpidem. Therefore, the present study investigated the effects of lemborexant on GERD. METHODS: Patients with heartburn and/or regurgitation and insomnia who did not take acid suppressants or hypnotics in the last month were recruited. Symptom assessments using GerdQ and reflux monitoring were performed before and after a 28-day treatment with 5 mg lemborexant at bedtime. The primary outcome was a change in the total GerdQ score, excluding the score for insomnia. Secondary outcomes were changes in each GerdQ score and the following parameters on reflux monitoring: the acid exposure time (AET), number of reflux events (RE), acid clearance time (ACT), and post-reflux swallow-induced peristaltic wave (PSPW) index. RESULTS: Sixteen patients (age 45.0 [33.3-56.0], 11 females [68.8%]) completed the intervention (1 patient did not tolerate the second reflux monitoring). The total GerdQ score, excluding the score for insomnia, did not significantly change (8.0 [6.0-9.0] before vs. 7.0 [6.3-9.0] after p = 0.16). GerdQ showed the significant attenuation of regurgitation (2.0 [2.0-3.0] vs. 1.0 [0-2.8] p = 0.0054) but not heartburn (2.5 [1.0-3.0] vs. 1.0 [0.3-2.0] p = 0.175). No significant differences were observed in AET, RE, ACT, or PSPW index before and after the intervention. CONCLUSION: Lemborexant attenuated regurgitation without the worsening of objective reflux parameters. A randomized placebo-controlled study is warranted in the future.

Significantly Lower Saliva Secretion in Females With Gastroesophageal Reflux Disease and Healthy Subjects Than in Males.

OBJECTIVE: Saliva secretion in healthy subjects is lower in females than in males. The present study investigated sex differences in saliva secretion in patients with gastroesophageal reflux disease (GERD) and healthy controls. METHODS: This case-control study included 39 (male/female: 16/23) with non-erosive reflux disease (NERD), 49 (25/24) patients with mild reflux esophagitis, 45 (23/22) with severe reflux esophagitis (A1), and 46 (24/22) healthy controls. Saliva secretion was examined as follows: before endoscopy, patients chewed sugar-free gum for three minutes, and the amount and pH of saliva before and after acid loading as an index of acid-buffering capacity were evaluated. The relationships between saliva secretion and body mass index, height, and weight were also examined. RESULTS: The amount of saliva secreted was significantly lower in females than in males in all four groups (NERD, mild reflux esophagitis, severe reflux esophagitis, and healthy controls). Salivary pH and acid-buffering capacity were similar in all groups. The amount of saliva secreted positively correlated with height and body weight, albeit more strongly with height. CONCLUSION: A sex difference in saliva secretion exists in GERD patients, similar to healthy controls. Saliva secretion was significantly lower in female GERD patients than in male GERD patients.

Orientation of Lower Esophageal Sphincter Pressure Using Three-Dimensional High-Resolution Manometry in Patients with Achalasia: A Pilot Study.

BACKGROUND: This study was performed to evaluate the orientation of lower esophageal sphincter (LES) pressure in patients with untreated achalasia using three-dimensional high-resolution manometry (3D-HRM). METHODS: The study involved 20 patients with untreated achalasia (10 men, 60 [47-74] years of age). The 3D-HRM assembly had 32 standard channels and 12 3D channels. During basal LES pressure measurements, the orientations of the LES high- and low-pressure zones were evaluated at end-expiration. The directional relationships between the orientation of the LES high- and low-pressure zones were also evaluated. RESULTS: The LES high-pressure zones were located on the greater curvature side in nine (45%) patients, from the greater curvature to posterior wall side in six (30%), and from the greater curvature to anterior wall side in five (25%). The LES high-pressure zones were located mainly on the greater curvature side, but there were some variations of the orientation among the patients. The LES low-pressure zones were most frequently located from the lesser curvature to the posterior wall side in 11 (55%) patients, from the lesser curvature to anterior wall side in 6 (30%), on the posterior wall side in 2 (10%), and on the anterior wall side in 1 (5%). Significant differences were found in the directional relationships between the orientation of the LES high- and low-pressure zones (P = 0.0053). CONCLUSIONS: This is the first report from Japan focusing on the LES pressure orientation using 3D-HRM. Such evaluation may be useful for clarifying the pathophysiology of achalasia.

Saliva Secretion Is Significantly Lower in Female Patients with Mild Reflux Esophagitis than in Female Healthy Controls.

INTRODUCTION: Saliva secretion is significantly lower in patients with mild reflux esophagitis than in healthy controls. A previous study on healthy controls showed that stimulated saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with mild reflux esophagitis than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with mild reflux esophagitis. METHODS: Twenty-five male patients with mild reflux esophagitis, 25 male healthy controls, 24 female patients with mild reflux esophagitis, and 24 female healthy controls were recruited for this case-control study. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 minutes prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: No significant differences were observed in the amount of stimulated saliva secretion, salivary pH, or the acid-buffering capacity between male patients with mild reflux esophagitis and healthy controls. No significant differences were noted in salivary pH between female patients with mild reflux esophagitis and healthy controls; however, the amount of stimulated saliva secretion was significantly lower (p = 0.0023) in the former (2.5 [1.9-4.1]) than in the latter (4.6 [3.2-6.6]), while the acid-buffering capacity was slightly lower (p = 0.0578) in the former (5.9 [5.7-6.2]) than in the latter (6.2 [6.0-6.5]). CONCLUSION: The amount of stimulated saliva secretion was significantly lower in female patients with mild reflux esophagitis than in female healthy controls. This reduction in saliva secretion may affect the pathophysiology of mild reflux esophagitis in females.

Differences in salivary secretion and epidermal growth factor concentrations in mild reflux esophagitis and non-erosive reflux disease.

BACKGROUND: Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio. METHODS: Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA. RESULTS: No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups. CONCLUSION: After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups.

High-resolution manometry with additional maneuvers using the Starlet system: normative thresholds and diagnostic yields for relevant esophagogastric junction outflow disorders.

BACKGROUND: Chicago classification version 4.0 suggests additional maneuvers, such as upright testing, multiple rapid swallows (MRS), and the rapid drink challenge (RDC), for high-resolution manometry (HRM) to minimize ambiguity in the diagnosis of esophageal motility disorders. The present study investigated normative thresholds for these new metrics using the Starlet system as well as their diagnostic yields for relevant esophagogastric outflow disorders (EGJOD). METHODS: In study 1, 30 asymptomatic volunteers prospectively performed HRM including MRS and RDC in the supine/upright positions. We calculated normative thresholds for the new metrics, such as upright integrated relaxation pressure (IRP), upright intrabolus pressure (IBP), and IRP during RDC (RDC-IRP). In study 2, we retrospectively analyzed the HRM tracings of 82 patients who underwent HRM in both positions at our hospital to assess the diagnostic yields of HRM metrics. RESULTS: Based on the results of study 1, we adopted the following normative thresholds: upright IRP < 20 mmHg, upright IBP < 21 mmHg, and RDC-IRP < 16 mmHg. In study 2, 45 patients with dysphagia or chest pain were included in the analysis to identify predictive factors for clinically relevant esophagogastric outflow disorders (true EGJOD). Supine/upright IRP, RDC-IRP, and pan-esophageal pressurization > 20 mmHg during RDC (RDC-PEP) predicted true EGJOD with RDC-PEP with the highest sensitivity of 91.7%. CONCLUSIONS: HRM with additional maneuvers may facilitate the diagnosis of clinically relevant EGJOD.

Proton Pump Inhibitor Treatment Has Little Effects on Secretion of Saliva in Patients with Proton Pump Inhibitor-Responsive Mild Reflux Esophagitis and Non-Erosive Reflux Disease.

INTRODUCTION: The secretion of saliva, which is triggered by acid reflux into the esophagus via the esophagosalivary reflex, plays a crucial role in the defensive mechanisms of the esophagus. The volume of saliva secreted in patients with gastroesophageal reflux disease (GERD) is reduced. However, the effects of proton pump inhibitors (PPI) on the secretion of saliva have rarely been reported. Therefore, the present study investigated changes in the volume and pH of saliva after the cessation of PPI. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients previously diagnosed with mild reflux esophagitis (RE) or non-erosive reflux disease (NERD) controlled with PPI (including vonoprazan) who performed the salivary secretion test before and after a 2-week cessation of PPI. The volume, pH, and pH after acid loading (buffering capacity) of saliva were compared before and after the cessation of PPI. RESULTS: Thirty-two patients (25 NERD, 7 mild RE) were included. The second saliva test was performed a median interval of 14 months [12.0-15.3] after the first test. No significant differences were observed in the volume of saliva secreted before and after the cessation of PPI (before 4.0 mL [2.7-6.0] vs. after 4.0 mL [2.3-5.9], p = 0.894). No significant differences were noted in pH or changes in pH after acid loading before and after the cessation of PPI (pH: before 7.1 ± 0.24 vs. after 7.0 ± 0.24, p = 0.1. Delta pH after acid loading: before 1.0 [0.8-1.2] vs. after 1.0 [0.8-1.2], p = 0.844). CONCLUSION: The cessation of PPI did not appear to affect the volume, pH, or buffering capacity of saliva in patients with PPI-responsive mild RE and NERD.

Evaluation of the circumferential location of mild reflux esophagitis (Grade A and B) in the lower esophagus.

Background and Aim: Discrepancies have been reported in the circumferential locations of mild mucosal breaks. We investigated their locations using a new method. Methods: This is a retrospective study. Eighty patients (Grade A/B: 53/27) with mild mucosal breaks in the lower esophagus were examined. Since the 3 o'clock position corresponded to the right wall of the lower esophagus using our method with sufficient accuracy, the circumferential locations of mucosal breaks were identified as times on a clock face, which were changed to circular data to calculate the mean direction. The circumferential distribution of mucosal breaks was evaluated in the single lesion group (single group) and multiple lesion group (multiple group). Results: Forty-eight of 80 patients had 1 mucosal break, while 32 had ≥2 mucosal breaks. Circumferential locations markedly differed between the single and multiple groups. In the single group, mucosal breaks were exclusively distributed between 2 and 7 o'clock, with 50% in the 3 o'clock direction (right wall). In the multiple group, 81 mucosal breaks were distributed circumferentially, not uniformly; however, at least 1 lesion was located between 2 and 7 o'clock in 91% of subjects. Therefore, a factor for the development of mucosal breaks from the right to posterior wall was present in both groups. Conclusion: In the single group, mucosal breaks were localized from the right to posterior wall, mainly in the right wall. In the multiple group, mucosal breaks were located circumferentially, but often between the right lateral and posterior wall. These two distributions significantly differed.Clinical trial registration: This is a retrospective study, so it was not registered.

Smaller CO2 injection volume and lower gastric pressure induce bothersome symptoms in drug-resistant functional dyspepsia patients with less frequent belching.

BACKGROUND: The relationship between bothersome symptoms and gastric pressure or CO2 injection volumes in drug-resistant functional dyspepsia (FD) patients remains unknown; therefore, this relationship was examined in drug-resistant FD and non-FD patients. METHODS: Thirty drug-resistant FD patients and 30 non-FD patients were recruited. Gastric pressure was assessed using an external pressure transducer, and the CO2 injection volume was measured using an endoscopic CO2-supplied device and flow meter. The following variables were examined: gastric pressure at baseline and gastric pressure and the CO2 injection volume when patients initially felt abdominal tension and bothersome symptoms following the CO2 injection. The relationship between belching and bothersome symptoms was also investigated. RESULTS: No significant differences were observed in basal gastric pressure between the groups. Initial and bothersome symptoms in the upper abdomen in drug-resistant FD patients developed at a significantly lower gastric pressure and significantly smaller CO2 injection volume than in non-FD patients. The frequency of belching was significantly lower in the drug-resistant FD group than in the non-FD group. CONCLUSION: Bothersome symptoms in drug-resistant FD patients develop at a lower gastric pressure and smaller CO2 injection volume than in non-FD patients. These patients also had difficulties with belching.

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.

Saliva secretion is reduced in mild reflux esophagitis patients.

BACKGROUND: Salivary secretion in patients with mild reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with mild reflux esophagitis were investigated. METHODS: Thirty-eight mild reflux esophagitis patients and 38 control subjects were recruited for this case-control study. Saliva secretion testing was performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA. RESULTS: The volume of saliva secreted was significantly (p = 0.0412) lower in the mild reflux esophagitis group than in the control group, with medians (25th-75th percentile) of 4.2 mL/3 min [2.6-6.2] and 6.0 [3.9-8.0], respectively. No significant differences were observed in salivary pH (the mild reflux esophagitis group: 7.1 [6.9-7.2], the control group 7.2 [7.1-7.3]). Salivary pH after acid loading was significantly (p = 0.0009) lower in the mild reflux esophagitis group (5.9 [5.5-6.3]) than in the control group (6.3 [6.2-6.5]). No significant differences were noted in salivary EGF concentrations (the mild reflux esophagitis group: 1739.0 pg/mL [1142.3-3329.0], the control group: 1678.0 [1091.8-2122.5]. CONCLUSION: The secretion volume and acid-buffering capacity of stimulated saliva were reduced in patients with mild reflux esophagitis.