Relationship between pharyngeal or esophageal reconstruction and esophageal pressure after swallowing.

BACKGROUND: High-resolution manometry, which measures esophageal luminal pressure changes after swallowing, could shed more light on food-transport dynamics after pharyngeal/esophageal reconstruction. This prospective cohort study assessed the influence of two head-and-neck and esophageal tumor-resection and reconstruction approaches on esophageal pressure. METHODS: The cohort consisted of 17 patients who underwent esophageal/pharyngeal resection/reconstruction for cancer and then participated in postoperative high-resolution manometry. Five healthy controls also underwent manometry for comparison. RESULTS: Partial pharyngectomy with patch grafts associated with smooth and continuous esophageal/pharyngeal movement. By contrast, surgery that removed the thoracic esophagus led to complete loss of peristalsis and poor food transport. CONCLUSIONS: High-resolution manometry effectively characterized the changes in food-transport dynamics caused by pharyngeal/esophageal resection/reconstruction. These findings suggest that continuous and smooth movement of the pharynx and esophagus is important for swallowing and high resolution manometry could be useful in patients after pharyngeal/esophageal resection/reconstruction.

Efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease.

BACKGROUND: To evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease. METHODS: On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 8 weeks by 30 patients (11 men, mean age: 67.8) with non-erosive reflux disease who responded well to maintenance therapy using proton pump inhibitor and answered "very satisfied" or "satisfied" to an overall satisfaction survey (5-grade scale). The degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin levels before breakfast was examined before and after on-demand therapy. The number of vonoprazan tablets taken and the frequency (regular, temporary, rare) of its administration were also investigated. RESULTS: All patients completed 8-week on-demand therapy with 20-mg vonoprazan. Comparisons of patient satisfaction levels before and after therapy revealed no significant differences in the number of patients who were very satisfied and satisfied with the therapy. Furthermore, there were no significant differences in score of symptoms or gastrin levels before and after therapy. During 8-week on-demand therapy, patients took 11 tablets (median) (7.0-18.0 tablets: 25-75 percentiles), and 30.0% of patients (n = 9) took vonoprazan on a regular basis (at least 2 tablets a week). CONCLUSION: On-demand therapy with 20-mg vonoprazan exerted equivalent effects to continuous PPI maintenance therapy for patients with non-erosive reflux disease.

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.

The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects.

BACKGROUND: A study in Japan has found that nizatidine (NIZ) is more effective than other histamine H2 receptor agonists (H2RAs) in treating reflux esophagitis (RE), although the NIZ group included a greater number of patients with severe RE. As there was no difference in the level of acid suppression among H2RAs, it is possible that NIZ has other effects on esophageal acid exposure (EAE) besides acid suppression. In this study, the effect of NIZ on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux was evaluated in healthy subjects. METHODS: In 10 healthy subjects, while in a sitting position, esophageal motility and a pH study were measured for 3 hours after a meal on 2 separate days at least 2 weeks apart. Participants received an oral dose of 150 mg of NIZ, 60 min before the meal on one day and a placebo on the other. Both studies were preceded by a week of treatment with either NIZ (150 mg, bid) or a placebo and the order of treatment was randomized. RESULTS: Basal LES pressure in the NIZ group (14.1 mmHg, median) was significantly greater than that of the placebo group (8.5 mmHg). The rate of TLESRs in the NIZ group (22.0/3 h) for the postprandial 3-hour period was significantly less than that of the placebo group (16.5/3 h) and the rate of acid reflux during TLESRs (24.7%) and the EAE (0.2%) in the NIZ group for the postprandial 3-hour period was also significantly less than that of the placebo group (74.4% and 2.8%, respectively). CONCLUSION: NIZ significantly reduces acid reflux by inhibiting both the rate of TLESRs and acid reflux during TLESRs.

Characteristics of symptomatic reflux episodes in patients with non-erosive reflux disease who have a positive symptom index on proton pump inhibitor therapy.

BACKGROUND AND AIM: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. METHODS: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24-hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. RESULTS: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. CONCLUSIONS: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception.

Predictors of a better outcome of pneumatic dilatation in patients with primary achalasia.

OBJECTIVE: Pneumatic dilatation (PD) has been widely used in the treatment of primary achalasia. The aim of this study was to evaluate the effectiveness of PD and its predictive factors in Japanese patients with primary achalasia. METHODS: Fifty-five consecutive patients were treated using PD (Rigiflex balloon dilator). Diagnosis was established through radiographic and/or esophageal manometry. All patients underwent a pre-designed clinical evaluation prior to and 6 months after PD treatment. We defined success of PD as 6 months or more of clinical remission, with a total score (0-4) or=1 and the score for each item 40-year age group was 85.7%, while the <40-year age group achieved a rate of only 38.5%. Multivariate logistic regression analysis also demonstrated that older age was the only independent factor associated with the success of PD. There was no perforation related to PD. CONCLUSIONS: PD is a safe and effective treatment for achalasia, particularly in older patients who experience a better outcome than younger patients.

Eosinophilic esophagitis: a case report with a review of the literature.

Eosinophilic esophagitis (EE) is an allergic inflammatory condition of the esophagus and is characterized by dense eosinophilic infiltration of the esophagus. There has been a dramatic increase in the diagnosis of EE in Western countries in recent years; however, in Japan, there are very few reports of EE. We present a rare case of EE in a 70-year-old Japanese woman, who had dysphasia for 2 years, but which worsened over a 6-month period. Laboratory examinations showed peripheral eosinophilia (1279/µl). Significant thickening of the esophageal wall was observed on computed tomography scan and many circular rings appeared when an esophagogastroduodenoscopy was carried out. From these circular rings, EE was suspected and a biopsy was then taken from the esophagus. As the histologic findings from the esophageal biopsy showed that >25 eosinophils existed per high-power field, the patient was diagnosed with EE. Oral corticosteroid (prednisolone 30 mg/day) therapy was administered and after 3 days of treatment her symptoms almost disappeared. EE needs to be considered as a differential diagnosis if patients with non-erosive reflux disease have dysphagia but do not respond to high-dose proton pump inhibitor therapy.

The appearance of rosette-like esophageal folds ("esophageal rosette") in the lower esophagus after a deep inspiration is a characteristic endoscopic finding of primary achalasia.

BACKGROUND: In healthy subjects who inspire deeply the lower esophagus usually opens, and the esophageal palisade vessels (EPVs) become visible. However, in patients with achalasia, the full extent of the EPVs does not become visible and, in addition, rosette-like esophageal folds appear in the lower esophagus. The aim of this study was to investigate whether or not these changes at the lower esophagus are characteristic findings of achalasia. METHODS: A total of 34 patients with achalasia and no esophageal dilatation following deep inspiration were compared with 34 sex- and age-matched control subjects. Following a deep inspiration, the lower esophagus of all study cohorts was evaluated on (1) whether or not the full extent of the EPVs was visible, (2) whether or not rosette-like esophageal folds appeared in the lower esophagus, and (3) whether or not there were any gastric lesions. RESULTS: One patient had secondary achalasia, and the remaining 33 patients had primary achalasia. In the control subjects, the full extent of the EPVs was clearly visible after a deep inspiration, and no esophageal folds appeared in the lower esophagus. In contrast, in the achalasia patients, EPVs were not observed in all patients after a deep inspiration, and rosette-like esophageal folds appeared in 33 of the 34 patients. CONCLUSION: After a deep inspiration, the non-visibility of the EPVs and the appearance of rosette-like esophageal folds at the lower esophagus, which we have called "esophageal rosette", are characteristic endoscopic findings of primary achalasia.

Acid and non-acid reflux in Japanese patients with non-erosive reflux disease with persistent reflux symptoms, despite taking a double-dose of proton pump inhibitor: a study using combined pH-impedance monitoring.

BACKGROUND: Combined multi-channel intra-luminal impedance and pH (Mll-pH) monitoring can detect gastro-esophageal reflux and identify acid and non-acid reflux (NAR) events. It can be used for patients with persistent symptoms who are having proton pump inhibitor (PPI) therapy. The aim of this study is to determine the frequency of acid reflux and NAR and to establish their relationship with persistent reflux symptoms in Japanese patients with non-erosive reflux disease (NERD) who are on a double-dose of PPI therapy. METHODS: Thirteen patients with NERD, with persistent reflux symptoms, despite taking PPI at least twice daily, were included in this study. Twenty-four-hour combined Mll-pH monitoring was carried out on all patients and reflux episodes were detected by impedance channels, located at 3, 5, 7, 9, 15 and 17 cm above the lower esophageal sphincter (LES) and classified into acid reflux and NAR, based on pH data from 5 cm above the LES. A positive symptom index (SI) was declared, if at least half of the symptoms were preceded by reflux episodes within 5 min. RESULTS: A total of 916 liquid reflux episodes were detected, and a total of 171 symptoms were recorded. Eight (4.7%) of 171 symptoms were related to acid reflux, and 68 (39.8%) were related to NAR. Seven (53.8%) patients had a positive SI and in these seven patients, a total of 79 symptoms were recorded. 5 (6.3%) of the 79 symptoms were related to acid reflux and 44 (55.7%) were related to NAR. CONCLUSIONS: Persistent reflux symptoms, in SI-positive patients with NERD on double-dose PPI therapy, are more likely to be associated with primarily non-acid reflux.

Mechanisms of excessive esophageal acid exposure in patients with reflux esophagitis.

The pathophysiology of excessive esophageal acid exposure, including the way refluxed acid extends towards the proximal esophagus, in patients with reflux esophagitis (RE), is not yet clear. For 3 h after a meal, concurrent esophageal manometry and pH monitoring was carried out on 14 patients with severe RE, 15 patients with mild RE, and 15 healthy subjects. At 2 cm above the proximal margin of the lower esophageal sphincter (LES) there was no difference between the three groups in the total number of acid-reflux episodes, the rate of transient LES relaxations (TLESRs), or the rate of acid reflux during TLESRs. The rate of acid reflux at 7 cm above the proximal margin of the LES, during TLESRs, in patients with severe RE (50.9%, median) was, however, significantly higher than in patients with mild RE (35.7%) and healthy subjects (15.4%). In addition, the rate of acid reflux during TLESRs in patients with mild RE was significantly higher than in healthy subjects. Both the amplitude and the success rate of primary peristalsis in patients with severe RE were significantly lower than those of healthy subjects and patients with mild RE but there was no difference between healthy subjects and patients with mild RE. The cause of excessive acid exposure in patients with RE is the difference in the way refluxed acid extends towards the proximal esophagus and acid bolus clearance, not the number of acid-reflux episodes.