Improving the Diagnostic Yield of High-Resolution Esophageal Manometry for GERD: The "Straight Leg-Raise" International Study.

BACKGROUND & AIMS: The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET). METHODS: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%. RESULTS: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected. CLINICALTRIALS: gov ID: NCT04813029.

Diabetes medications and risk of HCC.

Type 2 diabetes mellitus is a recognized risk factor for HCC in patients with liver disease, independent from the etiology of their liver disease. Hence, prevention and treatment of type 2 diabetes mellitus and its underlying cause, insulin resistance, should be considered a treatment target for patients with liver disease. The drug armamentarium for diabetes is wide and consists of agents with insulin-sensitizing activity, agents that stimulate insulin secretion, insulin itself, and agents that reduce gastrointestinal and urinary glucose absorption. From an endocrinology perspective, the main goal of treatment is the achievement of euglycemia; however, in patients at risk of, or with known underlying liver disease, the choice of diabetic medication as it relates to potential hepatic carcinogenesis remains complex and should be carefully considered. In the last decade, increasing evidence has suggested that metformin may reduce the risk of HCC, whereas evidence for other classes of diabetic medications, particularly some of the newer agents including the sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, is fewer and often inconsistent. In this review, we aim to summarize the current evidence on the potential effects of the most widely used diabetic agents on liver cancer tumorigenesis.

Association between esophageal motor disorders and pulmonary involvement in patients affected by systemic sclerosis: a retrospective study.

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.

Esophageal dysmotility in patients with eosinophilic esophagitis: pathogenesis, assessment tools, manometric characteristics, and clinical implications.

Eosinophilic esophagitis (EoE) represents a growing cause of chronic esophageal morbidity whose incidence and prevalence are increasing rapidly. The disease is characterized by eosinophilic infiltrates of the esophagus and organ dysfunction. Typical symptoms include dysphagia, chest pain, and bolus impaction, which are associated to mechanical obstructions in most patients. However, up to one in three EoE patients has no visible obstruction, suggesting that a motor disorder of the esophagus may underlie symptoms. Although potentially relevant for treatment refractoriness and symptomatic burden, esophageal dysmotility is often neglected when assessing EoE patients. The first systematic review investigating esophageal motility patterns in patients with EoE was published only recently. Accordingly, we reviewed the pathogenesis, assessment tools, manometric characteristics, and clinical implications of dysmotility in patients with EoE to highlight its clinical relevance. In summary, eosinophils can influence the amplitude of esophageal contractions via different mechanisms. The prevalence of dysmotility may increase with disease duration, possibly representing a late feature of EoE. Patients with EoE may display a wide range of motility disorders and possible disease-specific manometric pressurization patterns may be useful for raising a clinical suspicion. Intermittent dysmotility events have been found to correlate with symptoms on prolonged esophageal manometry, although high-resolution manometry studies have reported inconsistent results, possibly due to the suboptimal sensitivity of current manometry protocols. Motor abnormalities may recover following EoE treatment in a subset of patients, but invasive management of the motor disorder is required in some instances. In conclusion, esophageal motor abnormalities may have a role in eliciting symptoms, raising clinical suspicion, and influencing treatment outcome in EoE. The assessment of esophageal motility appears valuable in the EoE setting.

Recent insights on functional heartburn and reflux hypersensitivity.

PURPOSE OF REVIEW: Rome IV experts have proposed that gastroesophageal reflux disease (GERD) should be diagnosed only in patients with abnormal esophageal acid exposure, and that reflux hypersensitivity (RH) and functional heartburn (FH) both should be considered functional conditions separate from GERD. Although past and recent evidence support that FH can be completely distinguished from GERD, the concept that RH is not GERD is highly questionable. This review attempts to provide current data on these issues. RECENT FINDINGS: Many recent investigations have provided new data on the different pathophysiological features characterizing RH and FH. Major differences have emerged from analyses of impedance-pH monitoring studies using the novel impedance metrics of baseline impedance (an index of mucosal integrity) and the rate of postreflux swallow-induced peristaltic waves (a reflection of the integrity of esophageal chemical clearance). SUMMARY: The better ability to interpret impedance-pH tracings together with earlier data on the different prevalence of microscopic esophagitis in RH and FH patients, and recent studies documenting poor therapeutic efficacy of pain modulators and good results of antireflux surgery for RH support recategorization of RH within the GERD world. Further research is needed to correctly phenotype patients who have heartburn without mucosal breaks, and to guide their effective management.

Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients With Eosinophilic Esophagitis.

BACKGROUND: An association has been reported between achalasia and eosinophilic esophagitis (EoE). We performed a retrospective study of high-resolution manometry (HRM) patterns in a large cohort of patients with EoE. MATERIAL AND METHODS: We collected data from consecutive patients with a new diagnosis of EoE from 2012 through 2019 undergoing HRM during the initial assessment at different centers in Italy. Demographic, clinical, endoscopic and histological characteristics were recorded at baseline and during management. Diagnoses of EoE and esophageal motility disorders were made according to established criteria. Treatments offered included proton pump inhibitors and topical steroids for EoE, and pneumatic dilation and myotomy for achalasia. Response to therapy was defined as less than 15 eosinophils per high power field in esophageal biopsies. RESULTS: Of 109 consecutive patients (mean age 37 years, 82 male), 68 (62%) had normal findings from HRM. Among 41 patients with motor disorders, 24 (59%) had minor motor disorders and 17 (41%) presented with major motor disorders, including 8 with achalasia (1 with type 1, 4 with type 2, and 3 with type 3). Achalasia and nonachalasia obstructive motor disorders had 14.7% prevalence among patients with EoE. Achalasia was more frequent in women, with longer diagnostic delay and abnormal esophagogram (P < .05) compared with EoE without achalasia or obstructive motor disorders. Clinical features and endoscopic findings did not differ significantly between patients with EoE with vs without achalasia and obstructive motor disorders. A higher proportion of patients without achalasia and obstructive motor disorders responded to topical steroids than patients with these features (P < .005). Invasive achalasia management was required for symptom relief in 50% of patients with achalasia and obstructive motor disorders. CONCLUSION: Achalasia and obstructive motor disorders are found in almost 15% of patients with EoE, and esophageal eosinophilia might cause these disorders. Patients with EoE who do not respond to standard treatments might require targeted muscle disruption.

Course of oesophageal varices and performance of noninvasive predictors following Hepatitis C Virus clearance in compensated advanced chronic liver disease.

BACKGROUND: In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS: Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS: Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS: In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.

Eradication of hepatitis C virus infection disclosing a previously hidden, underlying autoimmune hepatitis: Autoimmune hepatitis and HCV.

Chronic hepatitis C virus (HCV) infection and autoimmune disorders show a complex interplay, with HCV often being identified as the trigger of autoimmune phenomena or diseases. While there is evidence of successful HCV treatment with direct-acting antivirals (DAA) in patients with concomitant HCV and autoimmune hepatitis (AIH), there are also sparse reports of AIH developing during, or following, DAA treatment. Here we report a case of a patient with suspected concomitant HCV and AIH who underwent liver biopsy but showed no histological hallmarks of autoimmunity. The patient later developed a hepatitic flare following DAA-induced viral clearance, and a second liver biopsy showed features compatible with AIH. Response to corticosteroid and azathioprine treatment was seen. This reports demonstrates that patients with features of auto-reactivity and HCV after DAA-induced viral clearance require careful follow-up.

Improvement in hepatitis C virus patients with advanced, compensated liver disease after sustained virological response to direct acting antivirals.

BACKGROUND: The outcome of patients with chronic hepatitis C virus infection (HCV) and advanced, compensated liver disease after sustained virological response (SVR) to direct-acting antivirals (DAAs) has not yet been completely depicted. We aimed to assess the clinical, biochemical and instrumental outcome of patients with advanced, compensated chronic HCV-related liver disease with DAA-induced SVR to DAAs and who had at least 1-year follow-up. MATERIALS AND METHODS: Fifty-two patients with cirrhosis (n = 27) and fibrosis stage F3 (n = 25) followed up for a median of 60 weeks after successful DAA treatment were included. Laboratory work-up, including APRI and FIB-4 scores, liver transient elastography and measurement of the spleen bi-polar diameter were carried out before treatment and at the end of follow-up. RESULTS: Liver stiffness decreased (P < 0.0001) from a median baseline of 15.2 kPa (12.0-20.0) to 9.3 kPa (7.5-12.0) at follow-up. A liver stiffness value suggestive of the presence (ie, ≥21.0 kPa) of clinically significant portal hypertension was found in 13 patients (25.0%) at baseline and in seven patients (13.5%) at follow-up (P = 0.037). Both APRI (P < 0.0001) and FIB-4 score (P = 0.025) progressively decreased, while platelet count increased (143 × 109 /L [117-176] to 153 × 109 /L [139-186], P = 0.003), and spleen bi-polar diameter decreased (120 mm [112-123] to 110 mm [102-116], P = 0.0009) from baseline to the end of follow-up. CONCLUSIONS: In patients advanced, compensated chronic liver disease, liver stiffness significantly improves in the long-term after SVR, and this improvement is accompanied by an amelioration of indirect indices of liver fibrosis and function, and by a decrease in parameters of portal hypertension.

Effects of bariatric surgery on the esophagus.

PURPOSE OF REVIEW: Bariatric surgery is the best therapeutic approach to patients with morbid obesity, but there is mounting evidence that it is associated with esophageal dysfunctions, including gastroesophageal reflux disease (GERD) and motor disorders. In the present review, we summarize the existing information on the complex link between bariatric surgery and esophageal disorders. RECENT FINDINGS: Although high-quality studies on these effects are lacking, because of evident methodological flaws and retrospective nature, the review of published investigations show that pure restrictive procedures, such as laparoscopic adjustable gastric banding (LAPG) and laparoscopic sleeve gastrectomy (LSG), are associated with de novo development or worsening of GERD. Moreover, LAGB is the procedure with the greatest frequency of esophageal motor disorders, including impairment of LES relaxation and ineffective esophageal peristalsis associated with esophageal dilation. LSG seems to be less associated with esophageal dysmotility, although evidence derived from studies with objective measurements of esophageal dysfunction is limited. Finally, RYGB seems to be the best procedure for improvement of GERD symptoms and preservation of esophageal function. SUMMARY: Overall, the restrictive-malabsorptive approach represented by RYGB must be preferred to pure restrictive operations in order to avoid the negative consequences of bariatric surgery on esophageal functions.

Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD.

OBJECTIVES: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. METHODS: Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. RESULTS: Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE). CONCLUSIONS: IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity.

Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6µgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3µgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8µgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water.

Measurement of oro-caecal transit time by magnetic resonance imaging.

OBJECTIVES: To assess prospectively the agreement of orocaecal transit time (OCTT) measurements by lactulose hydrogen breath test (LHBT) and magnetic resonance imaging (MRI) in healthy subjects. METHODS: Volunteers underwent abdominal 1.5-T MRI using axial and coronal single-shot fast-spin-echo T2-weighted sequences, having fasted and after lactulose ingestion (10 g/125 mL). Imaging and H2 excretion gas-chromatography were performed concurrently every 15 min up to 180 min. MR images were analyzed using semiautomatic segmentation to calculate small bowel gas volume (SBGV) and visually to detect bolus arrival in the caecum. Agreement between MRI- and LHBT-OCTT was assessed. RESULTS: Twenty-eight subjects (17 men/11 women; mean age ± standard deviation 30 ± 8 years) were evaluated. Two H2 non-producers on LHBT were excluded. OCTT measured by MRI and LHBT was concordant in 18/26 (69 %) subjects (excellent agreement, k = 0.924). Median SBGV was 49.0 mL (interquartile interval 44.1 - 51.6 mL). In 8/26 (31 %) subjects, MRI showed that the lactulose bolus was in the terminal ileum and not the caecum when H2E increased on LHBT. Median OCTT measured by MRI was significantly longer than OCTT measured by LHBT [135 min (120 - 150 min) vs. 127.5 min (105 - 150 min); p = 0.008]. Above baseline levels, correlation between [H2] and SBGV was significant (r = 0.964; p < 0.001). CONCLUSIONS: MRI provides valid measurements of OCTT and gas production in the small bowel. KEY POINTS: • MRI is a valid technique to measure OCTT. • Excellent agreement between MRI and LHBT was found. • Measuring gas production using MRI may provide evidence of small bowel fermentation.

Food Intolerances, Food Allergies and IBS: Lights and Shadows.

This narrative review delves into the intricate relationship between irritable bowel syndrome (IBS) and food intolerances. IBS, a chronic functional gastrointestinal disorder, is characterized by symptoms like abdominal pain and altered bowel habits. The prevalence of IBS has increased globally, especially among young adults. Food and dietary habits play a crucial role in IBS management. About 85-90% of IBS patients report symptom exacerbation linked to specific food consumption, highlighting the strong connection between food intolerances and IBS. Food intolerances often exhibit a dose-dependent pattern, posing a challenge in identifying trigger foods. This issue is further complicated by the complex nature of gastrointestinal physiology and varying food compositions. This review discusses various dietary patterns and their impact on IBS, including the low-FODMAP diet, gluten-free diet, and Mediterranean diet. It highlights the importance of a personalized approach in dietary management, considering individual symptom variability and dietary history. In conclusion, this review emphasizes the need for accurate diagnosis and holistic management of IBS, considering the complex interplay between dietary factors and gastrointestinal pathophysiology. It underlines the importance of patient education and adherence to treatment plans, acknowledging the challenges posed by the variability in dietary triggers and the psychological impact of dietary restrictions.