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.

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.

Development and evaluation of a double-check support system using artificial intelligence in endoscopic screening for gastric cancer.

BACKGROUND: This study aimed to prevent missing gastric cancer and point out low-quality images by developing a double-check support system (DCSS) for esophagogastroduodenoscopy (EGD) still images using artificial intelligence. METHODS: We extracted 12,977 still EGD images from 855 cases with cancer [821 with early gastric carcinoma (EGC) and 34 malignant lymphoma (ML)] and developed a lesion detection system using 10,994 images. The remaining images were used as a test dataset. Additional validation was performed using a new dataset containing 50 EGC and 1,200 non-GC images by comparing the interpretation of ten endoscopists (five trainees and five experts). Furthermore, we developed another system to detect low-quality images, which are not suitable for diagnosis, using 2198 images. RESULTS: In the validation of 1983 images from the 124 cancer cases, the DCSS diagnosed cancer with a sensitivity of 89.2%, positive predictive value (PPV) of 93.3%, and an accuracy of 83.3%. EGC was detected in 93.2% and ML in 92.5% of cases. Comparing with the endoscopists, sensitivity was significantly higher in the DCSS, and the average diagnostic time was significantly shorter using the DCSS than that by the trainees. The sensitivity, specificity, PPV, and accuracy in detecting low-quality images were 65.8%, 93.1%, 79.6%, and 85.2% for "Blur" and 57.8%, 91.7%, 82.2%, and 78.1% for "Mucus adhesion," respectively. CONCLUSIONS: The DCSS showed excellent capability in detecting lesions and pointing out low-quality images.

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.

Recovery of lower oesophageal barrier function: a pilot study comparing a mixture of atropine and neostigmine and sugammadex: A randomised controlled pilot study.

BACKGROUND: The lower oesophageal sphincter (LOS) barrier serves to prevent regurgitation of gastric contents. Although general anaesthesia depresses its function, its recovery process during emergence from anaesthesia has not been systematically examined. OBJECTIVE: To explore whether recovery of lower oesophageal barrier function differed between patients receiving a mixture of 1 mg atropine and 2 mg neostigmine and those receiving 2 mg kg-1 sugammadex during emergence from anaesthesia. DESIGN: An unblinded randomised controlled pilot study. SETTING: A single university hospital from January 2016 to December 2018. PATIENTS: A total of 20 non-obese adult females undergoing minor surgery. INTERVENTION: The patients were randomly assigned to a group either receiving atropine and neostigmine or sugammadex for reversal of rocuronium. MAIN OUTCOME MEASURES: Through use of the high-resolution manometry technique, the lower oesophageal barrier pressure (PBAR: primary variable) defined as a pressure difference between pressures at the LOS and the stomach was measured at five distinguishable time points during emergence from total intravenous anaesthesia. A mixed effects model for repeated measures was used to test the hypothesis. RESULTS: In all patients baseline PBAR values were positive even under muscle paralysis and general anaesthesia before administration of reversal agents, and did not differ between the groups (P = 0.299). During recovery from muscle paralysis and general anaesthesia, PBAR (mean ±â€ŠSD) significantly increased (P = 0.004) from 17.0 ±â€Š2.9 to 21.0 ±â€Š5.0 mmHg in the atropine and neostigmine group (n = 8) and from 19.1 ±â€Š9.0 to 24.5 ±â€Š12.7 mmHg in the sugammadex group (n = 11). PBAR significantly increased immediately after return of consciousness in both groups, whereas return of muscle tone, lightening of anaesthesia and tracheal extubation did not change it. CONCLUSION: Recovery of the lower oesophageal barrier function does not differ between patients receiving either atropine and neostigmine or sugammadex and is completed after recovery of consciousness from general anaesthesia. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000020500: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000023594&type=summary&language=E.

Computer-aided diagnosis system using only white-light endoscopy for the prediction of invasion depth in colorectal cancer.

BACKGROUND AND AIMS: Endoscopic treatment is recommended for low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC) with submucosal (SM) invasion <1000 µm. However, diagnosis of invasion depth requires experience and is often difficult. This study developed and evaluated a novel computer-aided diagnosis (CAD) system to determine whether endoscopic treatment is appropriate for colorectal lesions using only white-light endoscopy (WLE). METHODS: We extracted 3442 images from 1035 consecutive colorectal lesions (105 LGDs, 377 HGDs, 107 CRCs with SM <1000 µm, 146 CRCs with SM ≥1000 µm, and 300 advanced CRCs). All images were WLE, nonmagnified, and nonstained. We developed a novel CAD system using 2751 images; the remaining 691 images were evaluated by the CAD system as a test set. The capability of the CAD system to distinguish endoscopically treatable lesions and untreatable lesions was assessed and compared with the results from 2 trainees and 2 experts. RESULTS: The CAD system distinguished endoscopically treatable from untreatable lesions with 96.7% sensitivity, 75.0% specificity, and 90.3% accuracy. These values were significantly higher than those from trainees (92.1%, 67.6%, and 84.9%; P < .01, <.01, and <.01, respectively) and were comparable with those from experts (96.5%, 72.5%, and 89.4%, respectively). Trainees assisted by the CAD system demonstrated a diagnostic capability comparable with that of experts. CONCLUSIONS: The CAD system had good diagnostic capability for making treatment decisions for colorectal lesions. This system may enable a more convenient and accurate diagnosis using only WLE.

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.

Efficacy of End-Tidal Capnography Monitoring during Flexible Bronchoscopy in Nonintubated Patients under Sedation: A Randomized Controlled Study.

BACKGROUND: Although appropriate sedation is recommended during flexible bronchoscopy (FB), patients are at risk for hypoventilation due to inadvertent oversedation. End-tidal capnography is expected as an additional useful monitor for these patients during FB. OBJECTIVES: The aim of this study was to evaluate the benefit of additional end-tidal capnography monitoring in reducing the incidence of hypoxemia during FB in patients under sedation. METHODS: Patients undergoing FB under moderate sedation without tracheal intubation were randomly assigned to receive standard monitoring including pulse oximetry or additional capnography monitoring. Bronchoscopy examiners for the only capnography group were informed of apnea events by alarms and display of the capnography monitor. RESULTS: A total of 185 patients were enrolled. Patient characteristics were well balanced between the two groups. Hypoxemia (at least one episode of pulse oximeter oxygen saturation [SpO2] < 90%) was observed in 27 out of 94 patients in the capnography group (29%) and in 42 out of 91 patients in the control group (46%; p = 0.014), resulting in an absolute risk difference of -17.4% (95% confidence interval, -31.1 to -3.7). In the capnography group, hypoxemia duration was shorter (20.4 vs. 41.7 s, p = 0.029), severe hypoxemic events (SpO2 < 85%) were observed less frequently (16 [17%] vs. 29 [32%], p = 0.019), and the mean lowest SpO2 value was higher (90.5 vs. 87.6%, p = 0.002). CONCLUSION: End-tidal capnography monitoring can reduce the incidence and duration of hypoxemia during FB in nonintubated patients under sedation.

Real-time Endoscopy-Guided Measurement of Rectal Mucosal Admittance Is a Novel and Safe Method for Predicting Ulcerative Colitis Relapse.

Background: There are known associations between inflammatory bowel disease (IBD) and changes in mucosal paracellular permeability. We recently developed a novel catheter that can measure mucosal admittance (MA). Methods: Patients with ulcerative colitis (UC) in clinical remission underwent real-time MA measurement during colonoscopy between June 2014 and July 2015 and were prospectively followed. MA measures were taken from normal-appearing mucosa using the Tissue Conductance Meter (TCM). We examined relationships between mucosal admittance, clinical parameters at the time of MA measurement, and disease relapse during the follow-up period using the Cox proportional hazards model. Results: We measured baseline MA in 54 patients with UC during remission, with no complications. Of these, 23 patients relapsed during the subsequent follow-up period, at a median of 25.8 ± 7.6 months. Rectal MA was the only predictor of disease relapse in multivariate analysis (P = 0.027). The optimal rectal MA cutoff value for relapse was 781.0 (area under the receiver operating characteristic curve, 0.712), and in patients who showed lower than normal cutoff values, there was a significantly higher likelihood of relapse compared with other patients (log-rank test, P < 0.001). Conclusions: High rectal MA measured by TCM is associated with long-term sustained remission. Real-time rectal MA measurement using a novel endoscopy-guided catheter could be a safe and useful means of predicting prognosis for patients with UC in remission.

Evaluation of Esophageal Mucosal Integrity in Patients with Gastroesophageal Reflux Disease.

BACKGROUND: Impaired esophageal mucosal integrity plays a role in causing symptoms of gastroesophageal reflux disease (GERD). Recently, the assessment of esophageal baseline impedance (BI) using the multichannel intraluminal impedance-pH (MII-pH) test was suggested as a surrogate technique for the study of esophageal mucosal integrity and was reported to be useful in distinguishing GERD from non-GERD. However, measuring BI requires a 24-h testing period, is complicated, and causes considerable patient discomfort. SUMMARY: Recently, endoscopy-guided catheters that can measure mucosal impedance (MI) and mucosal admittance (MA), which is the inverse of impedance, were developed, and their usefulness in measuring MI and MA for the diagnosis of GERD has been reported. In these studies, esophageal MI values were significantly lower in patients with GERD than in those without GERD. In contrast, esophageal MA was significantly higher in patients with GERD than in those without. Furthermore, we reported that MA is inversely correlated with BI and correlated with acid exposure time. Key Messages: Endoscopy-guided real-time measurement of MI and MA may allow the estimation of mucosal integrity and may be a useful diagnostic tool for patients with GERD in a manner similar to 24-h MII-pH monitoring.

Endoscopic-Guided Measurement of Mucosal Admittance can Discriminate Gastroesophageal Reflux Disease from Functional Heartburn.

OBJECTIVES: A novel catheter that can measure mucosal admittance (MA), the inverse of impedance, was developed recently. In this pilot study, we aimed to clarify the usefulness of measuring MA for diagnosing gastroesophageal reflux disease (GERD). METHODS: We conducted two prospective studies. In the first study, esophageal MA was evaluated in 120 participants (24 with erosive esophagitis, 82 with heartburn but non-erosive esophagitis, and 14 healthy volunteers) and compared with the endoscopic findings. In the second study, multichannel intraluminal impedance combined with pH (MII-pH) tests was conducted followed by an MA measurement in 33 patients with non-erosive esophagitis and proton pump inhibitor (PPI)-refractory heartburn. Based on the MII-pH test results, patients were divided into GERD or functional heartburn (FH). MA was compared between the GERD and FH groups and also compared with the baseline impedance (BI) and acid exposure time (AET). RESULTS: Median MA at the distal esophagus was significantly higher in patients with erosive esophagitis compared with that in patients with non-erosive esophagitis and healthy volunteers (46.8, 13.1 and 6.5, respectively, P<0.01). In patients with PPI-refractory heartburn, the median MA at the distal esophagus was significantly higher in patients with GERD than those with FH (19.3 vs. 7.2, P<0.05). There was a negative correlation between MA and BI, and a positive correlation between MA and AET at the distal esophagus (r=-0.46 and r=0.53, P<0.05). CONCLUSIONS: Real-time measurement of MA is useful to distinguish GERD from non-GERD.

Endoscopy-Guided Evaluation of Duodenal Mucosal Permeability in Functional Dyspepsia.

OBJECTIVES: The pathophysiology of functional dyspepsia (FD) is not fully understood. Impaired duodenal mucosal integrity characterized by increased mucosal permeability and/or low-grade inflammation was reported as potentially important etiologies. We aimed to determine the utility of a recently developed simple catheterization method to measure mucosal admittance (MA), the inverse of mucosal impedance, for evaluation of duodenal mucosal permeability in patients with FD. METHODS: We conducted two prospective studies. In the first study, duodenal MA of 23 subjects was determined by catheterization during upper endoscopy, and transepithelial electrical resistance (TEER) of duodenal biopsy samples in Ussing chambers was measured to assess the correlation between MA and TEER. In the second study, duodenal MA of 21 patients with FD fulfilling the Rome III criteria was compared with that of 23 healthy subjects. RESULTS: The mean MA and TEER values were 367.5±134.7 and 24.5±3.7 Ω cm2, respectively. There was a significant negative correlation between MA and TEER (r=-0.67, P=0.0004, Pearson's correlation coefficient). The mean MA in patients with FD was significantly higher than that in healthy subjects (455.7±137.3 vs. 352.1±66.9, P=0.002, unpaired t-test). No procedure-related complications were present. CONCLUSIONS: We demonstrated the presence of increased duodenal mucosal permeability in patients with FD by MA measurement using a simple catheterization method during upper endoscopy.

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.

End-tidal capnographic monitoring to detect apnea episodes during flexible bronchoscopy under sedation.

BACKGROUND: Apnea developing as a result of oversedation is a potential clinical problem in patients undergoing flexible bronchoscopy (FB) under sedation. However, there are no reports of evaluation using a standardized method of the frequency of occurrence of apnea episodes during FB under sedation. The aim of this study was to investigate the frequency of apnea episodes during FB under sedation in the clinical setting by end-tidal capnography. METHODS: This study was a single-institution retrospective review of a prospectively maintained database and medical records, including capnographic data, from April 2015 to March 2016. We enrolled patients who were sedated with midazolam and underwent diagnostic FB under end-tidal capnographic monitoring. Apnea was defined as cessation of airflow for more than 10 s. RESULTS: Data from a total of 121 eligible patients were analyzed. A total of 131 apnea episodes (median duration 33 s) were recorded in 59 patients (48.8%). Prolonged apnea episodes lasting for more than 30 s occurred in 24 patients (19.8%). Furthermore, 55 apnea episodes (42.0%) were followed by a decline of the SpO2 by ≥4% from the baseline. CONCLUSIONS: In this study, end-tidal capnography revealed the occurrence of apnea episodes at a high frequency in patients undergoing FB under sedation in the clinical setting.