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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Relationship between gastroesophageal reflux disease (GERD) and constipation: laxative use is common in GERD patients.

BACKGROUND: The relationship between gastroesophageal reflux disease (GERD) and constipation has not yet been examined in Japan. We herein analyzed the use of laxatives by GERD and non-GERD patients to clarify the relationship between GERD and constipation. METHODS: This was a retrospective observational study designed to examine the use of laxatives by GERD and non-GERD patients. A total of 118 patients (mean age 69.7 years, 50 males) with reflux esophagitis (RE) and non-erosive reflux disease (NERD) who received maintenance acid-suppressive therapy for more than 1 year were included in the GERD group (83 RE patients, 35NERD patients). Similarly, 61 patients (mean age 69.4 years, 28 males) who received regular acid-suppressive therapy for reasons other than GERD were included in the non-GERD group. We also investigated demographic factors associated with the onset of GERD, including body mass index (BMI), age, and sex. RESULTS: The frequency of laxative use was significantly higher in the GERD group (38.1%) than in the non-GERD group (21.3%). No significant differences were observed in dose frequencies between the groups. The type of laxative used also did not significantly differ between the groups. Furthermore, no significant differences were noted in sex, age, or BMI between the groups. CONCLUSIONS: The use of laxatives was significantly more common in GERD patients than in non-GERD patients. The present results suggest that a relationship exists between GERD and constipation.

Stimulated saliva secretion is reduced in proton pump inhibitor-resistant severe reflux esophagitis patients.

BACKGROUND: Salivary secretion in patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with PPI-resistant severe reflux esophagitis were investigated. METHODS: We recruited 22 PPI-resistant and 22 PPI-responsive severe reflux esophagitis patients who were not infected with Helicobacter pylori. Saliva secretion testing and esophageal manometry using high-resolution manometry were performed. 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 as well as the pH of saliva after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA. RESULTS: The amount of saliva secreted was significantly lower in the PPI-resistant group than in the PPI-responsive group, with medians (25th-75th percentile) of 3.7 (2.2-6.8) and 4.9 (4.0-7.8) mL, respectively (p = 0.029). Salivary pH was significantly lower in the PPI-resistant group [6.9 (6.7-7.2)] than in the PPI-responsive group [7.2 (7.1-7.4), p = 0.001]. Salivary pH after acid loading was significantly lower in the PPI-resistant group [5.6 (5.3-5.9)] than in the PPI-responsive group [6.4 (6.1-6.5), p = 0.002]. The salivary EGF concentration was significantly higher in the PPI-resistant group [3211.5 (1865.0-4121.5)] than in the PPI-responsive group [1816.0 (1123.5-2792.3), p = 0.041]. No significant differences were observed in the proportion of esophageal motility abnormalities. CONCLUSION: Stimulated saliva secretion was reduced in PPI-resistant severe reflux esophagitis patients.

Saliva secretion is reduced in proton pump inhibitor-responsive non-erosive reflux disease patients.

BACKGROUND: There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with NERD were examined. METHODS: Thirty-one PPI-responsive NERD patients and 31 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 amount 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 amount of saliva secreted was significantly lower in the NERD group than in the control group, with medians (25th-75th percentile) of 4.0 mL/3 min (2.0-6.0) and 6.0 (3.9-8.0), respectively (p = 0.0131). Salivary pH was significantly lower in the NERD group (7.0 [6.8-7.2]) than in the control group (7.2 [7.0-7.3], p = 0.0100). Salivary pH after acid loading was significantly lower in the NERD group (5.8 [5.4-6.2]) than in the control group (6.3 [6.1-6.5], p = 0.0002). The difference in pH of stimulated saliva after acid loading (1.2 [0.9-1.5], p = 0.0021) was significantly higher in the NERD group than in the control group (0.8 [0.7-1.1]). The salivary EGF concentration was significantly higher in the NERD group (2513.0 pg/mL [1497.5-5005.0] than in the PPI-responsive group (1641.0 [1139.8-2092.0], p = 0.0032). CONCLUSION: Stimulated saliva secretion was reduced in PPI-responsive NERD patients.

Risk of hemorrhage and stricture significantly increases in elderly patients with proton pump inhibitor (PPI)-resistant reflux esophagitis.

BACKGROUND: To examine the clinical characteristics, including complications, of patients older than 75 years of age with proton pump inhibitor-resistant reflux esophagitis. METHODS: Patients who were resistant to standard-dose proton pump inhibitors were enrolled in the present study. Eligible patients (n = 26) were divided into those who were older (n = 11) and younger (n = 15) than 75 years of age. Clinical characteristics including complications (hemorrhage and stricture), body mass index, the severity of reflux esophagitis, Helicobactor pylori infection, gastric mucosal atrophy, hiatal hernia, kyphosis, and the use of antithrombotic agents were examined. The efficacy of 20 mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis was also investigated. RESULTS: The severity of reflux esophagitis was significantly higher in the elderly group than in the non-elderly group. No other significant differences were observed between the groups. The proportion of patients with hemorrhage was significantly larger in the elderly group than in the non-elderly group. Similarly, the proportion of patients with stricture was significantly larger in the elderly group than in the non-elderly group. Nine out of 10 patients in the elderly group and all patients in the non-elderly group achieved healing after the 4-week administration of 20 mg vonoprazan. No significant differences were observed in healing rates between the groups. CONCLUSION: Among patients with proton pump inhibitor-resistant reflux esophagitis, the rates of severe reflux esophagitis and complications (hemorrhage and/or stricture) were significantly higher in elderly patients than in non-elderly patients. Regardless of age, 20 mg vonoprazan was effective for proton pump inhibitor-resistant reflux esophagitis.

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".

Persistent Postprandial Regurgitation vs Rumination in Patients With Refractory Gastroesophageal Reflux Disease Symptoms: Identification of a Distinct Rumination Pattern Using Ambulatory Impedance-pH Monitoring.

OBJECTIVES: Up to 20% of patients with refractory gastroesophageal reflux disease (GERD) might have postprandial rumination. The aim of this study was to distinguish persistent GERD-related postprandial regurgitation from rumination in patients with refractory GERD undergoing ambulatory multichannel intraluminal impedance-pH (MII-pH) monitoring. METHODS: We first characterized 24-hour and postprandial MII-pH patterns in 28 consecutive patients with confirmed rumination syndrome (positive clinical and high-resolution manometry/impedance). We compared such MII-pH patterns with those from 30 patients with typical GERD symptoms (10 nonerosive reflux disease, 10 hyperactive esophagus, and 10 functional heartburn) and 27 healthy controls. Using ROC curves, we selected the best MII-pH parameters to prepare an MII-pH rumination score. We prospectively tested the performance of the new MII-pH rumination score in 26 consecutive patients with refractory GERD (predominant regurgitation). RESULTS: Compared with GERD controls, patients with rumination were more often females, younger, and had significantly more postprandial early nonacid reflux episodes with high proximal extent. Postprandial reflux in ruminators had a distinct nadir pH profile over time (from nonacid to acid). Despite increased reflux events, baseline impedance in ruminators was similar to that in healthy subjects. Ruminators marked postprandial symptoms earlier and much more often than patients with GERD. An MII-pH-based rumination score (using postprandial nonacid reflux/hour and Symptom Index) diagnosed rumination in 46% of patients with refractory GERD and persistent regurgitation (sensitivity 91.7% and specificity 78.6%). DISCUSSION: Postprandial rumination is very common in refractory GERD with persistent regurgitation. A simple MII-pH score detects rumination in these patients with high sensitivity and specificity.