Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Esophageal motor abnormalities in gastroesophageal reflux disorders.

Gastroesophageal reflux disease (GERD), a prevalent condition with multifactorial pathogenesis, involves esophageal motor dysmotility as a key contributing factor to its development. When suspected GERD patients have an inadequate response to proton-pump inhibitor (PPI) therapy and normal upper endoscopy results, high-resolution manometry (HRM) is utilized to rule out alternative diagnosis such as achalasia spectrum disorders, rumination, or supragastric belching. At present, HRM continues to provide supportive evidence for diagnosing GERD and determining the appropriate treatment. This review focuses on the existing understanding of the connection between esophageal motor findings and the pathogenesis of GERD, along with the significance of esophageal HRM in managing GERD patients. The International GERD Consensus Working Group introduced a three-step method, assessing the esophagogastric junction (EGJ), esophageal body motility, and contraction reserve with multiple rapid swallow (MRS) maneuvers. Crucial HRM abnormalities in GERD include frequent transient lower esophageal sphincter relaxations, disrupted EGJ, and esophageal body hypomotility. Emerging HRM metrics like EGJ-contractile integral and innovative provocative maneuver like straight leg raise have the potential to enhance our understanding of factors contributing to GERD, thereby increasing the value of HRM performed in patients who experience symptoms suspected of GERD.

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry.

Background/Aims: This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). Methods: Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. Results: Codeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. Conclusions: In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Esophageal secondary peristalsis following acid infusion and chemical clearance correlate with mucosal integrity and acid sensitivity in GERD patients.

Background: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. Objectives: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. Design: This was an investigator-initiated, prospective, cross-sectional study. Methods: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. Results: A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007). Conclusion: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Esophageal Hypervigilance and Visceral Anxiety Contribute to Symptom Severity of Laryngopharyngeal Reflux.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a clinical conundrum without a diagnostic gold standard. The Esophageal Hypervigilance and Anxiety Scale (EHAS) is a questionnaire designed for cognitive-affective evaluation of visceral sensitivity. We hypothesized that esophageal hypervigilance and symptom-specific anxiety have an etiopathological role in generation of LPR symptoms, especially when gastroesophageal reflux disease (GERD) cannot explain these symptoms. METHODS: Consecutive patients with LPR and/or GERD symptoms lasting >3 months were prospectively enrolled and characterized using the Reflux Symptom Index, GERD questionnaire, and EHAS. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring off acid suppression for phenotyping GERD and assessment of reflux burden, using conventional metrics (acid exposure time and number of reflux episodes) and novel metrics (mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index). RESULTS: Of 269 enrolled patients (mean age 47.1 years, 21-65 years, 60.6% female), 90 patients were with concomitant GERD and LPR symptoms, 32 patients were with dominant LPR symptoms, 102 patients were with dominant GERD symptoms, and 45 were controls. Patients with concomitant GERD and LPR symptoms had higher EHAS than those with dominant GERD symptoms and controls ( P ≤ 0.001); patients with dominant LPR symptoms had higher EHAS than controls ( P = 0.007). On Pearson correlation, EHAS positively correlated with the Reflux Symptom Index. DISCUSSION: Esophageal hypervigilance and symptom-specific anxiety may be more important than reflux burden in LPR symptom perception.

Artificial intelligence facilitates measuring reflux episodes and postreflux swallow-induced peristaltic wave index from impedance-pH studies in patients with reflux disease.

BACKGROUND/AIM: Reflux episodes and postreflux swallow-induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index. METHODS: Consecutive patients underwent 24-h impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter-rater agreement of data between manual and AI interpretations. RESULTS: We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter-rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921). CONCLUSIONS: AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.

Effects of the GABA(B) agonist baclofen on volitional swallowing in normal subjects.

The GABA(B) receptor agonist baclofen is known to suppress the rate of spontaneous swallowing but not pharyngeal muscle contraction. The extent to which baclofen may alter volitional swallowing is not currently known. We investigated the effects of baclofen in healthy subjects, hypothesizing that baclofen exposure would alter volume-regulation and/or piecemeal deglutition behaviors during volitional swallowing attempts. Pharyngeal high-resolution manometry impedance (P-HRM-I) protocol was used to assess swallowing function of 22 healthy adult volunteers (median 29 years) who were investigated on two occasions, receiving 40 mg baclofen (oral) 1 h before study, or placebo (randomized). Standard swallow function variables recommended by the pharyngeal HRM Working Group were derived for 5 ml, 10 ml, and 20 ml volumes of thin and extremely thick liquid challenges. Multiple swallow behaviors, comprising two swallows <5 s apart, were characterized. The spontaneous swallow rate was also determined. Baclofen exposure had no overall significant effect on swallow variables. Upper esophageal sphincter pressure was weaker during exposure to baclofen, during both the pre-deglutitive and post-deglutitive phases of the swallow (p < 0.05 during thick liquid swallows). Piecemeal swallows, where the bolus is separated in two potions, were significantly more common during 20 ml boluses (p = 0.002). Baclofen decreased the frequency of piecemeal deglutition overall. Baclofen has limited to no effect on volitional swallowing measures, however, does reduce the likelihood of initiation of piecemeal deglutition to large volume challenges.

Current advances in the diagnosis and management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined.

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden in Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility.

Background/Aims: Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients. Methods: Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR. Results: Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P = 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006). Conclusion: Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

Modifications decrease hepatic steatosis in Taiwanese with metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a growing global problem associated with increasing obesity prevalence. Lifestyle modifications are currently recommended, including weight reduction, exercise, and diet control. This study evaluated the short-term effect of lifestyle modifications on transient elastography (TE) values in an obese population with MAFLD. Thirty-two MAFLD patients were recruited for this prospective study and all subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using TE with controlled attenuated parameter (CAP) and liver stiffness measurements (LSM). The mean age was 38.7 years old (10 males). The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m2 vs. 29.4 kg/m2 ), waist (103.19 cm vs. 95.75 cm), and hip circumference (111.67 cm vs. 104.75 cm), and blood pressure (128/78 mmHg vs. 119/71 mmHg) significantly improved before and after the intervention, respectively. Aspartate aminotransaminase (24.06 U/L vs. 18.91 U/L), alanine aminotransaminase (33 U/L vs. 23.72 U/L), creatinine (0.75 mg/dl vs. 0.70 mg/dl), cholesterol (176.41 mg/dl vs. 166.22 m/dl), gamma-glutamyl transferase (26.59 IU/L vs. 19.81 IU/L), and low-density lipoprotein cholesterol (115.63 mg/dl vs. 103.19 mg/dl) also improved after the 3-month intervention. The average CAP significantly decreased after intervention (297.5 dB/m vs. 255.0 dB/m), however, no significant difference in LSM was observed (5.24 kPa vs. 4.82 kPa). The current study suggests that short-term lifestyle modification can effectively improve hepatic steatosis, and TE may serve as a monitoring tool for therapeutic intervention.

Improvement of patient-reported outcomes in patients achieving sustained virologic response with direct-acting antivirals for hepatitis C virus infection.

BACKGROUND: Patient-reported outcome (PRO) in patients with chronic hepatitis C virus (HCV) infection (CHC) after successful direct-acting antiviral (DAA) therapy remains elusive. The study aimed to investigate the impact of DAA therapy on health-related quality of life (HRQoL). We also assess the associated factors predictive of HRQoL change after sustained virologic response (SVR) to HCV therapy. METHODS: CHC patients receiving DAA therapy were prospectively recruited. They completed paired HRQoL assessments which included Short-Form-36 (SF-36), Pittsburgh Sleep Quality Index (PSQI) score, Taiwanese Depression Questionnaire score, and State Trait Anxiety Inventory (STAI) score before treatment and at Week 12 off-treatment. Clinical data and characteristics were compared in a paired manner. RESULTS: A total of 158 patients achieved SVR (SVR rate: 96.6%) were enrolled into the final analysis. Improvement of depression, anxiety, digestive symptoms, and SF-36 items of vitality, body pain, physical functioning, emotional functioning, social functioning, and mental health were demonstrated among SVR patients. Sleep quality, or other SF-36 items were not significantly changed after the treatment. Multivariate analysis revealed that improvement of sleep quality, depression, and anxiety were associated with better HRQoL. CONCLUSION: SVR to HCV therapy by DAA significantly improved PROs including HRQoL.

Esophageal Bolus Domain Pressure and Peristalsis Associated With Experimental Induction of Esophagogastric Junction Outflow Obstruction.

BACKGROUND/AIMS: Intrabolus pressures are important for esophageal bolus transport and may detect obstructed bolus flow. This study measured the effect esophageal outflow obstruction experimentally induce by a leg-lift protocol. METHODS: Twenty-five gastroesophageal reflux disease patients referred for esophageal manometry and a normal motility diagnosis were included. Supine liquid swallows were tested. Leg-lift protocol generated esophageal outflow obstruction by increasing abdominal pressure. Esophageal pressure topography and intrabolus pressure metrics were calculated. These included, (1) mid-domain bolus distension pressure during esophageal emptying (DPE, mmHg) and (2) ramp pressure (mmHg/sec), generated by compression of the bolus between the peristaltic contraction and esophagogastric junction (EGJ). RESULTS: EGJ relaxation pressure was increased by leg-lift from 13 (11-17) to 19 (14-30) mmHg (P < 0.005) and distal contractile integral also increased from 1077 (883-1349) to 1620 (1268-2072) mmHg∙cm∙sec (P < 0.001) as a physiological response to obstruction. All bolus pressures were increased by leg lift; DPE increased from 17 (15-20) to 27 (19-32) mmHg (P < 0.001), and ramp pressure increased from 3 (1-4) to 5 (2-9) mmHg/sec (P < 0.05). CONCLUSION: Measuring pressures within the intrabolus domain can quantify changes related to obstruction to outflow and may serve as adjunct measures for confirming a diagnosis EGJ outflow obstruction.

Analysis of contractile segment impedance during straight leg raise maneuver using high-resolution impedance manometry increases diagnostic yield in reflux disease.

BACKGROUND: Contractile segment impedance (CSI) obtained from high-resolution impedance manometry (HRIM) is a measure of mucosal integrity that predicts gastroesophageal reflux disease (GERD). While straight leg raise (SLR) maneuver augments esophageal peristaltic vigor, it remains unclear whether SLR affects CSI values. This study was aimed to evaluate whether CSI with SLR is feasible and useful to complement the diagnosis of GERD. METHODS: We prospectively recruited 48 patients with typical GERD symptoms who underwent esophagogastroduodenoscopy, HRIM with SLR maneuver, and multichannel intraluminal impedance-pH (MII-pH) testing. The capability of mean nocturnal baseline impedance (MNBI), resting baseline impedance (RBI), CSI with or without SLR maneuver in predicting GERD was assessed using receiver operating characteristics (ROC) analysis. KEY RESULTS: Among 20 GERD patients and 28 non-GERD patients, all values of impedance-based metrics were lower in GERD patients compared to non-GERD patients (p < 0.001). For GERD identification, area under receiver operating characteristic curve (AUROC) values of CSI with SLR maneuver, CSI, MNBI, and RBI were 0.901, 0.858, 0.865, and 0.797. Particularly in ineffective esophageal motility (IEM) patients, SLR maneuver increased mean distal contractile integral from 436 to 828.7 mmHg.s.cm (p = 0.018) and enhanced AUROC values of CSI for GERD identification from 0.917 to 0.958. CONCLUSIONS & INFERENCES: CSI measurement during HRIM appears to be a reliable, time-saving, and less invasive tool for complementing GERD diagnosis. Our results also suggest a simple SLR maneuver during HRIM could enhance diagnostic accuracy of CSI for GERD identification especially in IEM patients.

Effects of menthol on esophageal motility in humans: Studies using high-resolution manometry.

BACKGROUND/AIM: The cold receptor, transient receptor potential melastatin 8 (TRPM8), has been reported to be expressed in esophageal vagal afferents. Esophageal infusion of menthol modulates esophageal perception in reflux patients via TRPM8, but the effects of menthol on esophageal motility are not well investigated. This study aimed to test the hypothesis whether the infusion of menthol into the esophagus could affect esophageal peristaltic characteristics. METHODS: Eighteen healthy adults (men 13, mean age 27) underwent high-resolution manometry (HRM) using a catheter with the injection port located in mid-esophagus. Primary peristalsis was performed with ten wet swallows, while secondary peristalsis was generated by 10 rapid air injections. Two different sessions were randomly performed including acute administration of menthol (3 mM) and the placebo. RESULTS: Menthol significantly decreased upper esophageal (UES) pressure of primary peristalsis than the placebo (p = 0.019). There was no difference in distal contractile integral (p = 0.33), distal latency (p = 0.86), basal lower esophageal sphincter pressure (p = 0.19), or 4-second integrated relaxation pressure (p = 0.75) between menthol and placebo. Menthol significantly decreased the frequency of secondary peristalsis subsequent to the administration of menthol during rapid injections with 20 mL air (p = 0.04). CONCLUSIONS: Intraluminal infusion of menthol reduces UES basal pressure and inhibits peristaltic frequency of secondary peristalsis. The data suggest that the triggering of secondary peristalsis is probably modulated by TRPM8-sensitive mechanoreceptors; however, the activation of TRPM8 from menthol does not alter esophageal motility following deglutition or distension-induced secondary peristalsis.

Esophageal acid burden in reflux patients with normal endoscopy: Does esophageal peristalsis matter?

BACKGROUND: A majority of patients with gastroesophageal reflux disease (GERD) have normal endoscopy. We aimed to investigate whether esophageal primary and secondary peristalsis influence esophageal reflux parameters in patients with normal endoscopy. METHODS: We enrolled consecutive patients with typical reflux symptoms and normal endoscopy. All patients underwent High resolution manometry (HRM) and 24-h impedance-pH studies off therapy. During HRM, secondary peristalsis was evaluated using ten 20-mL rapid air infusions into the esophagus, while primary peristalsis was evaluated using ten 5-mL water swallows. RESULTS: A total of 43 patients completed the study; 13 patients had normal motility, 20 had ineffective esophageal motility (IEM), and 10 had absent contractility. Acid exposure time (AET) (total, supine, and upright) was significantly higher in those with absent primary peristalsis (absent contractility) compared to normal motility (P = 0.001; 0.01; 0.007) and IEM (P = 0.002; 0.02; 0.03). Supine AET was significantly higher in patients without secondary peristalsis compared to those with secondary peristalsis (P = 0.04). CONCLUSION: In the setting of normal endoscopy, acid reflux burden is more profound in patients with absent primary peristalsis, as well as in patients lacking a secondary peristaltic response to esophageal air distension.

Oesophageal hypervigilance and visceral anxiety relate to reflux symptom severity and psychological distress but not to acid reflux parameters.

BACKGROUND: The pathogenesis of gastro-oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive-affective evaluation of visceral sensitivity. AIMS: To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD. METHODS: Patients with chronic reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient-reported outcomes, including EHAS, GERD questionnaire (GERDQ), State-Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded. RESULTS: We enrolled 105 patients, aged 21-64 years (mean, 48.8), of whom 58.1% were female; 27 had non-erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient-reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05). CONCLUSIONS: EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.

Effects of codeine on esophageal peristalsis in humans using high resolution manometry.

BACKGROUND AND AIM: Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension-induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults. METHODS: Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20-43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid-esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed. RESULTS: Codeine significantly increased 4-s integrated relaxation pressure (IRP-4s) (P = 0.003) and shortened distal latency (DL) (P = 0.003) of primary peristalsis. The IRP-4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305). CONCLUSIONS: In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.

Application of a novel straight leg raise test during high-resolution manometry can predict esophageal contractile reserve in patients with gastroesophageal reflux disease.

BACKGROUND/AIM: Increased intra-abdominal pressure from abdominal compression augments esophageal peristalsis during high-resolution manometry (HRM), and straight leg raise (SLR) while supine increases intra-abdominal pressure. We determined if water swallows performed during SLR can mimic contraction reserve seen with multiple rapid swallows (MRS). METHODS: Consecutive patients evaluated for GERD symptoms completed validated GERD questionnaires, esophageal HRM, and upper endoscopy. Distal contractile integral (DCI) was analyzed during single water swallows (10 × 5 mL), MRS (5 × 2 mL), and during SLR (5x5 mL). Peristaltic breaks were measured using software tools with a 20 mm Hg isobaric contour. Univariate correlational analyses were performed to compare esophageal motor patterns and DCI values during single water swallows, MRS, and SLR. RESULTS: Of 103 study patients (mean age: 46.7 ± 12.3 years, 56.3% female), 50 (48.5%) had ineffective esophageal motility (IEM). Contraction reserve was observed on MRS in 62% with IEM, and 35.8% with normal motility (p = 0.008). DCI was significantly higher during SLR compared to mean single swallow DCI in both IEM and normal motility patients (p < 0.001 for each comparison). In IEM patients, SLR significantly reduced swallows with peristaltic breaks (6.1 ± 3.7 vs 3.6 ± 3.6; p < 0.001) and shortened the length of the largest break (4.8 ± 3.4 vs 3.0 ± 3.0 cm; p < 0.001). DCI response following MRS correlated with DCI with swallows during SLR, with a correlational coefficient (Pearson's r) of 0.70 (p < 0.001). CONCLUSIONS: Swallowing against the resistance of increased intra-abdominal pressure from SLR improves esophageal body peristaltic performance and predicts esophageal body contraction reserve.

Association between use of proton pump inhibitors and colorectal cancer: A nationwide population-based study.

BACKGROUND: Proton pump inhibitors (PPIs) use is associated with hypergastrinemia and gut microbiota alteration. Concern over the risk that these factors may increase chances of colorectal cancer (CRC) has risen. To investigate the association between PPIs use and CRC using a large population-based cohort and examine whether the PPIs may differ regarding the risk of CRC. METHODS: We conducted a nationwide cohort study using a database from Taiwan National Health Insurance followed up longitudinally from 1999 through 2011. Patients with PPIs use were compared with non-use controls at a 1:1 ratio, for age, sex, comorbidities, and medications. We performed Cox proportional-hazards regression analysis to estimate the association between PPIs use and the development of CRC. RESULTS: Among the 45382 eligible PPIs users, 172 (0.4%) developed CRC during a median follow-up of 5.4 years. PPIs use was associated with a higher risk of CRC with an adjusted HR of 2.03 (95% CI 1.56-2.63, P<0.001). The risk increased with more frequent use of PPIs (HR 1.59, 95% CI 1.19-2.14; 2.59, 95% CI 1.84-3.65 and 4.33, 95% CI 2.75-6.80 for ≤30 cDDD per year, 30-90 cDDD per year, and ≥90 cDDD per year, respectively). There was also a statistically significant trend toward an increased risk with long-term PPIs use for more than one year. All PPIs, except pantoprazole and rabeprazole, were associated with an increased risk of CRC. CONCLUSIONS: The present study suggests that PPIs use might increase the risk of CRC in a dose-dependent manner.