A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

BACKGROUND AND AIM: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. METHODS: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). RESULTS: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. CONCLUSIONS: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Differences Between Patients with Heartburn Refractory to Vonoprazan and Those Refractory to Proton Pump Inhibitors.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, demonstrates more potent acid inhibition than proton pump inhibitors (PPIs). This study aimed to evaluate the effect of vonoprazan in patients with unproven gastroesophageal reflux disease (GERD) by comparing patients with vonoprazan-refractory heartburn with those with PPI-refractory heartburn. METHODS: This study included 104 consecutive patients with vonoprazan- or PPI-refractory heartburn (52 patients each), no erosive esophagitis on endoscopy and who underwent combined multichannel intraluminal impedance-pH (MII-pH) testing with vonoprazan/PPI discontinuation. Patients' backgrounds, symptom scores from four questionnaires, MII-pH results and high-resolution manometry results were compared between the two groups. RESULTS: The vonoprazan group demonstrated significantly higher GERD symptoms and scores of abdominal pain and diarrhea on the Gastrointestinal Symptom Rating Scale questionnaire. MII-pH results revealed that the vonoprazan group demonstrated 40.4%, 17.3%, and 42.3% and the PPIs group exhibited 26.9%, 17.3%, and 55.8% of abnormal acid reflux [true non-erosive reflux disease (NERD)], reflux hypersensitivity and functional heartburn, respectively. The vonoprazan group demonstrated higher true NERD rates but with no significant difference (p = 0.307). Among the vonoprazan group, eight patients with true NERD underwent another MII-pH test on vonoprazan, and all cases demonstrated normal acid exposure times (0.0% [0.0-0.3]). CONCLUSION: Patients with unproven GERD with vonoprazan-refractory heartburn demonstrated more symptoms, including not only GERD symptoms but also functional dyspepsia and irritable bowel syndrome symptoms, than those with PPI-refractory heartburn.

Two onset types of achalasia and the long-term course to diagnosis.

BACKGROUND: Recently, the incidence of achalasia has been increasing, but its cause remains unknown. This study aimed to examine the initial symptoms and the course of symptoms and to find new insights into the cause and course of the disease. METHODS: Altogether, 136 patients diagnosed with achalasia by high-resolution manometry (HRM) were enrolled. Questionnaires and chart reviews were conducted to investigate the initial symptoms, time from onset to diagnosis, and comorbidities, as well as the relationship between HRM results, time to diagnosis, and symptom severity. RESULTS: In total, 67 of 136 patients responded to the questionnaire. The median ages of onset and diagnosis were 42 and 58 years, respectively. The median time from onset to diagnosis was 78.6 months, with 25 cases (37.3%) taking > 10 years to be diagnosed. The symptom onset was gradual and sudden in 52 (77.6%) and 11 (16.4%) patients, respectively. Of the 11 patients with acute onset, three (27.3%) developed anhidrosis at the same time. There was no correlation between the time from onset to diagnosis and esophageal dilatation, resting LES pressure, or mean integrated relaxation pressure (IRP). No correlation was also found between the degree of symptoms and resting LES pressure or IRP. CONCLUSION: Esophageal achalasia can have acute or insidious onsets. This finding may help to elucidate the cause of achalasia.

Impact of ineffective esophageal motility on chemical clearance in patients with gastroesophageal reflux symptoms.

Ineffective esophageal motility (IEM) is the most common manometric abnormality in gastroesophageal reflux disease (GERD). However, the impact of IEM on esophageal chemical clearance has not been fully investigated. This study aimed to determine the impact of IEM on esophageal chemical clearance in patients with GERD. A total of 369 patients with GERD symptoms who underwent upper endoscopy and high-resolution manometry (HRM) test were retrospectively analyzed. The relationship between IEM and erosive esophagitis was examined. In addition, the impact of IEM on chemical clearance was examined in patients who underwent an additional combined multichannel intraluminal impedance-pH (MII-pH) test. Esophageal chemical clearance capability was evaluated via postreflux swallow-induced peristaltic wave (PSPW) index and acid clearance time (ACT). Of 369 patients, 181 (49.1%) had esophageal motility disorders, of which 78 (21.1%) had IEM. The proportion of IEM patients in those with erosive esophagitis and those without were 16.2% and 21.7%, respectively, and no significant difference was observed (P = 0.53). After excluding patients other than those with IEM and normal esophageal motility, 64 subsequently underwent MII-pH test. The median values of the PSPW index in the IEM and normal esophageal motility group were 11.1% (4.2%-20.0%) and 17.1% (9.8%-30.6%), respectively. The PSPW index was significantly lower in the IEM group than in the normal esophageal motility group (P < 0.05). The median ACT values in the IEM group and normal esophageal motility group were 125.5 (54.0-183.5) seconds and 60.0 (27.2-105.7) seconds, respectively. The ACT was significantly longer in the IEM group than in the normal esophageal motility group (P < 0.05). In conclusion, IEM was found to be associated with chemical clearance dysfunction as measured against the PSPW index and ACT. As this condition could be a risk factor for GERD, future treatments should be developed with a focus on chemical clearance.

The Effect of Ineffective Esophageal Motility on Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Ineffective esophageal motility (IEM) is the most common gastrointestinal motility disorder. Studies have reported that IEM is related to gastroesophageal reflux disease (GERD). However, the relationship between IEM and GERD remains uncertain. This study aims to clarify this relationship retrospectively. METHODS: We analyzed 195 subjects who underwent high-resolution manometry between January 2011 and September 2016. Of these subjects, 72 had normal esophageal motility (NEM) and 26 had IEM. We investigated differences in the clinical characteristics, severity and duration of GERD symptoms, and comorbid extra-esophageal symptoms of the subjects. Comorbid extra-esophageal symptoms were assessed with the Gastrointestinal Symptom Rating Scale questionnaire. Investigation-defined GERD was diagnosed when erosive esophagitis or abnormal multichannel intraluminal impedance was present. RESULTS: We found no significant difference in the prevalence of IEM between patients with and without GERD (37.5 and 21.1%, respectively; p = 0.174). There were no differences in age, gender, body mass index, presence of hiatal hernia, or duration of GERD between the groups. Compared to patients with NEM, those with IEM were significantly less likely to have comorbid extra-esophageal symptoms (p < 0.05). CONCLUSION: There is no association between IEM and GERD.

Clinical Characteristics of Esophageal Motility Disorders in Patients With Heartburn.

BACKGROUND/AIMS: Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms. METHODS: Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group. RESULTS: Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05). CONCLUSIONS: The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.

The use of 13C-erythromycin as an in vivo probe to evaluate CYP3A-mediated drug interactions in rats.

(14)C-erythromycin breath test has been utilized to evaluate the extent of CYP3A activity in vivo. However, its radioactivity sometimes impedes its clinical application. In this study, we employed erythromycin labeled with (13)C ((13)C-EM), a nonradioactive stable isotope, as an in vivo probe of breath test to evaluate CYP3A-mediated drug interactions in rats. A physiologically based pharmacokinetic (PBPK) model to describe (13)CO(2) exhalation altered by drug interactions was newly constructed. Rats received an intravenous or oral administration of (13)C-EM with or without a CYP3A inhibitor or inducer, that is, ketoconazole (KCZ) or dexamethasone (DEX), respectively. Breath samples were taken at designated times, measured with an infrared spectrophotometer, and the Δ(13) CO(2) value (‰) in each sample was obtained. The C(max) and AUC(0-t) of Δ(13) CO(2) were significantly decreased with KCZ and increased with DEX. The PBPK model in this study successfully described the (13)CO(2) exhalation after (13)C-EM administration in the absence and presence of drug interactions. In conclusion, this study proposed a simple and rapid in vivo methodology to utilize (13)C-EM for the quantitative analysis of CYP3A inhibition and induction. This method using small animals may be useful in early drug development processes.