Tailoring the wrap: intraoperative functional lumen imaging probe (FLIP) during hiatal hernia repair.

INTRODUCTION: The introduction of the functional lumen imaging probe (FLIP) has provided objective, real-time feedback on the geometric variations with each component of a hiatal hernia repair (HHR). The utility of this technology in altering intraoperative decision-making has been scarcely reported. Herein, we report a single-center series of intraoperative FLIP during HHR. METHODS: A retrospective review of electronic medical records between 2020 and 2022 was conducted and all patients undergoing non-recurrent HHR with FLIP were queried. Patient and hernia characteristics, intraoperative FLIP values and changes in decision-making, as well as early post-operative outcomes were reported. Both diameter and distensibility index (DI) were measured at 40 ml and 50 ml balloon inflation after hiatal dissection, after hiatal closure, and after fundoplication when indicated. RESULTS: Thirty-three patients met inclusion criteria. Mean age was 62 ± 14 years and mean BMI was 28 ± 6 kg/m2. The majority (53%) were type I hiatal hernias. The largest drop in DI occurred after hiatal closure, with minimal change seen after fundoplication (mean DI of 4.3 ± 2. after completion of HH dissection, vs 2.7 ± 1.2 after hiatal closure and 2.3 ± 1 after fundoplication when performed). In 13 (39%) of cases, FLIP values directly impacted intraoperative decision-making. Fundoplication was deferred in 4/13 (31%) patients, the wrap was loosened in 2/13 (15%); the type of fundoplication was altered to achieve adequate anti-reflux values in 2/13 (15%) patients, and in 1/13 (3%) the wrap was tightened. CONCLUSION: FLIP measurements can be used intraoperatively to guide decision-making and alter management plan based on objective values. Long-term outcomes and further prospective studies are required to better delineate the value of this technology.

Anti-reflux mucosectomy (ARMS) for refractory gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common diseases seen by gastroenterologists worldwide. A significant proportion of patients have a suboptimal response to acid inhibitors, especially proton pump inhibitors and potassium-competitive acid blockers. Due to concerns regarding the safety of long-term medication, many patients are unwilling to take lifelong medication. Endoscopic antireflux management offers a minimally invasive option for GERD patients. In recent decades, there have been several endoscopic antireflux therapies, including radiofrequency therapy, transoral fundoplication, and mucosal resection or mucosal ablation. Of these, antireflux mucosectomy (ARMS) is an effective and safe therapy for refractory GERD. This review provides an updated summary of antireflux mucosectomy.

Efficacy and safety of pantoprazole and itopride in patients with overlap of gastroesophageal reflux disease and dyspepsia: A prospective, open-label, single-arm pilot study.

Background and Aim: Combining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping dyspepsia, but data regarding this is lacking. Methods: This single-center, prospective study evaluated the efficacy and safety of 6-week treatment with fixed-drug combination (FDC) of pantoprazole (PPI) and itopride (prokinetic) in 50 patients with ≥3 month history of GERD and overlapping dyspepsia refractory to pantoprazole. Efficacy was assessed as reduction in GERD symptom assessment scale (GSAS) distress score for 15 symptoms from baseline to week 6. Adverse events (AEs) were monitored up to week 6. Results: Although heartburn was the most common symptom at week 6 (26.8%), its frequency significantly decreased from baseline (84.0%; P <0.01). A similar trend was observed for other symptoms: pressure/discomfort inside chest (19.5%), belching (14.6%), regurgitation (12.2%), bloating (9.8%), flatulence (9.8%), early satiety (7.3%), acidic/sour taste in mouth (7.3%), nausea (7.3%), frequent gurgling in stomach/belly (4.9%), and pressure/lump in throat (2.4%). Mean distress scores of all symptoms markedly decreased at week 6. Three AEs (n = 2) of moderate intensity were reported. Conclusion: The FDC of pantoprazole and itopride showed favorable efficacy and safety in patients with GERD and overlapping dyspepsia refractory to pantoprazole monotherapy. Nevertheless, further studies are warranted.

Development of a new endoscopy system to visualize bilirubin for the diagnosis of duodenogastroesophageal reflux.

OBJECTIVES: Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. METHODS: The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. RESULTS: Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P < 0.05). The esophageal Bil value and NNRE were significantly positively correlated (P = 0.031). The area under the receiver operating characteristic curve for the differential diagnosis of RH was 0.817. CONCLUSION: The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

Esophageal chemical clearance and mucosa integrity values in refractory gastroesophageal reflux disease patients with different esophageal dynamics.

OBJECTIVES: Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes. MATERIALS AND METHODS: 201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors. RESULTS: PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (p < 0.05 for both comparisons). PSPWI with esophageal peristalsis abnormality was lower than EGJ injury (p = 0.049), while MNBI showed no statistical difference. PSPWI, MNBI and their combination have auxiliary diagnostic values for esophageal peristalsis [area under the curves (AUCs): 0.683, 0.656, 0.708)] while only their combination for EGJ injury (AUC: 0.610). And they positively correlated with esophageal motility while negatively correlated with ineffective swallows and acid reflux events. CONCLUSIONS: PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.

Clinical Effect of Shugan Hewei Prescription Combined with Vonoprazan on Refractory Gastroesophageal Reflux Disease Due to Qi Depression and Phlegm Obstruction / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and adverse effects of Shugan Hewei prescription combined with vonoprazan in the treatment of refractory gastroesophageal reflux disease （RGERD） due to qi depression and phlegm obstruction. MethodEighty RGERD patients who met the inclusion criteria underwent 24-hour pH impedance and high-resolution esophageal manometry and electronic gastroscopy. The 80 patients were randomly assigned to an observation group （Shugan Hewei prescription， one bag each time， twice a day + vonoprazan， 20 mg each time， once a day） and a control group （vonoprazan， 20 mg each time， once a day） by the random number table method. The treatment in both groups lasted for 4 weeks. The clinical efficacy was examined. The scores of TCM symptoms （pharyngeal discomforts such as phlegm obstruction， retrosternal discomfort， and belching）， somatic symptoms， quality of life， and improvement of esophageal mucosa under gastroscopy were observed in both groups before treatment and after treatment for 2 and 4 weeks. ResultSeventy-five patients completed the trial were included in this study， including 38 patients in the observation group and 37 patients in the control group. The total response rate in the observation group was 89.47%（34/38）， which was higher than that （62.16%，23/37） in the control group （χ2=13.014， P<0.01）. After treatment， the scores of esophageal mucous membrane， reflux disease symptoms， TCM symptoms， gastroesophageal reflux disease health-related quality of life scale （GERD-HRQL）， and somatic self-rating scale （SSS） decreased in both groups（P<0.05）. Moreover， the observation group outperformed the control group in alleviating heartburn， acid reflux， throat discomforts， midnight coughing， nausea and dry vomiting， mucousy mouth， and insomnia in the patients with GERD （P<0.05，P<0.01）. However， the two groups showed no statistically significant differences in the improvement of esophageal mucosa after treatment. ConclusionThe combination of Shugan Hewei prescription with vonoprazan was superior to vonoprazan alone in treating RGERD regarding clinical symptoms， physical signs， quality of life， and somatic symptoms， without causing obvious adverse effects.

Comparison of 180° anti-reflux mucosectomy versus 270° anti-reflux mucosectomy for treatment of refractory gastroesophageal reflux disease: a retrospective study.

BACKGROUND: Anti-reflux mucosectomy (ARMS) is a novel endoscopic treatment for refractory gastroesophageal reflux disease (rGERD). Several studies have validated its safety and effectiveness, but postoperative dysphagia remains in concern. Since the influence of different resection ranges on efficacy and complications of ARMS has rarely been studied, this study aimed to compare outcomes of 180°ARMS and 270°ARMS in treatment of rGERD. METHODS: This study was conducted from August 2017 to September 2020. 39 eligible patients underwent either 180° ARMS or 270° ARMS and followed up at 6 months postoperation. Primary outcome measure was assessed by Gastroesophageal Reflux Disease Questionnaire (GERD-Q). Secondary outcomes included quality of life, PPI use, gastroesophageal flap valve grade, presence of reflux esophagitis, acid exposure time (AET), distal contractile integral (DCI), and integrated relaxation pressure (IRP) measured by high-resolution manometry (HRM) and complication rate. Per-protocol analysis was performed. RESULTS: Among 39 patients, 18 underwent 180° ARMS, while 21 underwent 270° ARMS. At postoperative 6 months follow-up period, primary outcome showed no significant difference between two groups (p = 0.34). Similarly, no significant difference was demonstrated between groups regarding most secondary outcomes except for fewer complaints of newly dysphagia in 180° ARMS group. No other serious complications were observed in both groups. CONCLUSION: Although 180° ARMS and 270° ARMS could be equally effective for treatment of rGERD, 180° ARMS might be more recommended due to lower incidence of newly post-procedural dysphagia.

EZH2-mediated suppression of CLDN1 leads to barrier dysfunction in PPI-refractory gastroesophageal reflux disease.

BACKGROUND: PPI-refractory gastroesophageal reflux disease (RGERD) is characterized as the existence of reflux symptoms resistant to optimized PPI treatment. Alleviated mucosal integrity has been regarded as one of the mechanisms of RGERD. METHODS: RNA sequencing analysis and GSEA were performed. Human biopsy samples, cell lines, and rat models were recruited. Trans-epithelial electrical resistance (TEER) was tested and a FITC-dextran flux assay was performed to detect barrier permeability. Tissue morphology was evaluated using HE staining, while gene expression was measured by qRT-PCR, western blotting, flow cytometry, immunofluorescence, immunohistochemistry, and chromatin immunoprecipitation (ChIP) analysis. RESULTS: The tight junction protein Claudin-1 is significantly weakened in the RGERD epithelium, while levels of EZH2-mediated H3K27me3 were increased. Forced EZH2 expression in epithelial cells led to H3K27me3 accumulation and Claudin-1 suppression, which consequently caused epithelial barrier dysfunction. Notably, studies on esophagogastroduodenal anastomosis (EGDA) rat models showed the attenuation of Claudin-1 level and barrier function could be rescued by an Ezh2 inhibitor GSK126. ChIP analysis followed by qPCR (ChIP-qPCR) revealed H3K27me3 suppressed CLDN1 via accumulating at the TSS area. CONCLUSION: For the first time, we explored the attenuated tight junction of RGERD, demonstrating a potential underlying mechanism that EZH2-mediated H3K27me3 could impair esophageal epithelial barrier function by suppressing the transcription of CLDN1.

Magnetic sphincter augmentation in treating refractory gastroesophageal reflux disease: A systematic review and meta-analysis.

OBJECTIVE: In this systematic review and meta-analysis we aimed to determine the efficacy and safety of magnetic sphincter augmentation (MSA) in the management of refractory gastroesophageal reflux disease (rGERD). METHODS: Literature search was conducted in PubMed, the Cochrane Library, EMBASE, Web of Science, OpenGrey and ClincalTrials.gov for single-arm studies evaluating the efficacy and safety of MSA in rGERD or comparative studies with proton pump inhibitor (PPI) or laparoscopic Nissen fundoplication (LNF) serving as the control published until April 2020. Primary outcome was the rate of postoperative PPI use, and secondary outcomes included postoperative GERD-health-related quality of life (GERD-HRQL), normalization of acid exposure time (AET) and incidence of procedure-related adverse events (AE). RESULTS: Ten single-arm studies, one randomized controlled trial and three cohort studies involving 1138 participants were included. Post-MSA PPI withdrawal, significant GERD-HRQL improvement and AET normalization were achieved in 87.0%, 88.0% and 75.0% of the patients, respectively. The incidence of postoperative dysphagia was 29% and endoscopic dilation was required in 7.4% of patients undergoing MSA. MSA showed a better efficacy in symptom control than PPI (PPI cessation: 91% vs 0%; GERD-HRQL improvement: 81% vs 8%) and similar effectiveness but a lower risk of gas-bloat syndrome (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.51-0.93, P = 0.01) and better reserved ability to belch (RR 1.48, 95% CI 0.76-2.86, P = 0.25) compared with LNF. CONCLUSIONS: MSA was an effective and safe therapy for rGERD. Well-designed randomized trials that compare the efficacy of MSA with other therapies are needed.

Esophagogastric junction contractile integral abnormalities in patients with proton pump inhibitor-refractory symptoms.

OBJECTIVES: Esophagogastric junction contractile integral (EGJ-CI) is a novel indicator to evaluate quantitatively the esophagogastric junction (EGJ) barrier function. We aimed to assess the role of EGJ-CI in patients with refractory gastroesophageal reflux disease (GERD) symptoms and the correlation between EGJ-CI and impedance-pH monitoring characteristics. METHODS: In total 82 patients with proton pump inhibitors (PPIs)-refractory gastroesophageal reflux symptoms (heartburn or regurgitation) were enrolled. These patients were further divided into two groups based on their EGJ-CI value (39 mmHg·cm). The mean nocturnal baseline impedance (MNBI) was measured to explore its association with EGJ-CI. RESULTS: The median EGJ-CI in patients with PPI-refractory symptoms was 30.8 mmHg·cm. EGJ-CI was inversely correlated with acid exposure time and reflux episodes; while it was positively correlated with MNBI, distal contractile integral, lower esophageal sphincter basal pressure and integrated relaxation pressure. Patients were further divided into the high (n = 27) and low (n = 55) EGJ-CI groups using a cut-off value of 39.0 mmHg·cm. Patients with a low EGJ-CI had a lower MNBI level than those with a high EGJ-CI (2703 Ω vs 3545 Ω, P = 0.034). CONCLUSIONS: In patients with PPIs-refractory symptoms, EGJ-CI is associated with acid exposure and conventional high-resolution manometry parameters. EGJ-CI may play an important role in the diagnosis and treatment of patients with refractory GERD.

Caracterización de los trastornos manométricos esofágicos en pacientes con enfermedad por reflujo gastroesofágico refractario con síntomas esofágicos / Characterization of esophageal motility disorders in refractory gastroesophageal reflux disease patients with esophageal symptoms

Resumen Introducción: La enfermedad por reflujo gastroesofágico (ERGE) refractaria puede conducir a complicaciones potenciales como la esofagitis persistente, estenosis esofágica, anillo de Schatzki y esófago de Barrett. Este estudio describe la motilidad en pacientes con ERGE refractaria y su relación con síntomas esofágicos. Método: Se realizó un estudio observacional analítico a partir de una cohorte retrospectiva en pacientes con diagnóstico de ERGE refractaria y síntomas esofágicos a quienes se les realizó manometría esofágica de alta resolución más impedanciometría. Se describen las características clínicas y demográficas, y la asociación entre los trastornos manométricos y los síntomas esofágicos. Resultados: Se incluyeron 133 pacientes (edad promedio: 54,1 ± 12,5 años). La pirosis y regurgitación (69,2 %) y la disfagia esofágica (13,5 %) fueron los síntomas más comunes. La motilidad normal (75,2 %), el aclaramiento completo del bolo (75,2 %) y la motilidad esofágica inefectiva (MEI) (18 %) fueron los hallazgos manométricos más frecuentes. La unión gastroesofágica tipos II y IIIb estuvieron presentes en el 35,3% y 33,8 % de los casos, respectivamente. La aperistalsis (3,8 %) y el esófago en martillo neumático (Jackhammer; 0,8 %) fueron infrecuentes. El aclaramiento incompleto del bolo se asoció con disfagia esofágica (p = 0,038) y a MEI (p = 0,008). Ningún síntoma esofágico se relacionó significativamente con trastornos de motilidad. Conclusiones: Los resultados de nuestro estudio sugieren que los trastornos de motilidad son infrecuentes en los pacientes con ERGE refractaria. Adicionalmente, sugieren que la presencia de alteraciones de motilidad esofágica no se relaciona con la presencia de síntomas esofágicos y, por tanto, que el tipo de síntoma presentado no permite predecir la existencia de dichos trastornos.

Abstract Introduction: Refractory gastroesophageal reflux disease (GERD) can lead to potential complications such as persistent esophagitis, esophageal stricture, Schatzki ring, and Barrett's esophagus. This study describes motility in patients with refractory GERD, and its association with esophageal symptoms. Materials and methods: An analytical observational study was carried out in a retrospective cohort of patients diagnosed with refractory GERD and esophageal symptoms who underwent high-resolution esophageal manometry and impedance testing. Clinical characteristics, demographics, and the association between motility disorders and esophageal symptoms are described. Results: 133 patients were included (mean age 54.1 ± 12.5 years). Heartburn and regurgitation (69.2%), and esophageal dysphagia (13.5%) were the most common symptoms. Normal motility (75.2%), complete bolus clearance (75.2%), and ineffective esophageal motility (IEM) (18%) were the most frequent manometric findings. Type II and IIIb gastroesophageal junction were observed in 35.3% and 33.8% of the cases, respectively. Esophageal aperistalsis (3.8%) and Jackhammer esophagus (0.8%) were rare findings. Incomplete bolus clearance was associated with esophageal dysphagia (p=0.038) and IEM (p=0.008). No esophageal symptoms were significantly related to motility disorders. Conclusions: The results of the present study suggest that motility disorders are rare in patients with refractory GERD. They also suggest that esophageal motility disorders are not associated with the presence of esophageal symptoms and, therefore, the type of symptom experienced does not allow predicting the existence of such disorders.

Low FODMAPs diet or usual dietary advice for the treatment of refractory gastroesophageal reflux disease: An open-labeled randomized trial.

BACKGROUND: The low FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols) diet improves lower gastrointestinal symptoms. Patients suffering from proton pump inhibitor (PPI) refractory gastroesophageal reflux disease (GERD) have limited treatment options. We investigated the efficacy of a low FODMAPs diet in patients with PPI refractory GERD. METHODS: This multicenter, randomized, open-label study compared the efficacy of a 4-week low FODMAPs diet and usual dietary advice (ie, low-fat diet and head of bed elevation) in patients with symptomatic PPI refractory GERD, defined by a Reflux Disease Questionnaire (RDQ) score >3 and abnormal pH-impedance monitoring on PPIs. The primary endpoint was the percentage of responders (RDQ ≤3) at the end of the diet. RESULTS: Thirty-one patients (55% women, median age 45 years) were included, 16 randomized in the low FODMAPs diet group and 15 in the usual dietary advice group. Adherence to the assigned diet was good, with a significant difference in the FODMAPs intake per day between the low FODMAPs diet (2.5 g) and the usual dietary advice group (13 g) (p < 0.001). There was no difference in response rates (RDQ score ≤3) between the low FODMAPs diet (6/16, 37.5%) and usual dietary advice (3/15, 20%) groups (p = 0.43). Total RDQ score and dyspepsia subscore decreased significantly over time in both groups (p = 0.002), with no difference according to the assigned diet group (p = 0.85). CONCLUSION: Low FODMAPs diet and usual dietary advice have similar but limited beneficial effects on symptoms in patients with PPI refractory GERD.

Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease.

INTRODUCTION: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. METHODS: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. RESULTS: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0-0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1-3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7-34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4-74.3%], p < 0.01). CONCLUSIONS: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

The pharmacotherapeutic management of gastroesophageal reflux disease (GERD).

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a very common worldwide condition, affecting about 15-20% of the whole population, and representing a major burden for health-care systems. Because of its frequency, health physicians - family doctors as well as specialists - should be aware of the different pharmacotherapeutic approaches in managing GERD, according to disease severity. AREAS COVERED: Authors summarize the pharmacological management of GERD in adults, present the different pharmaceutical classes, and review the evidence on efficacy for each treatment according to the most common clinical scenarios: non-erosive gastroesophageal reflux disease (NERD), erosive esophagitis (EE), and proton-pump inhibitor (PPI) refractory GERD. They also provide an overview of treatments under development. EXPERT OPINION: To date, PPIs remain the most effective treatment option for both NERD and EE. However, Potassium-Competitive Acid blockers (PCAB) may be considered, with at least similar efficacy in Asian populations. Preliminary data suggest that PCABs could be superior to classic PPIs in patients with severe EE, and may also be of particular interest in the management of PPI-refractory GERD patients. Their definitive role in GERD management, however, still remains to be determined based on properly designed and conducted randomized clinical trials.

[Clinical characteristics and esophageal function tests of refractory gastroesophageal reflux disease].

Objective: To analyze the clinical characteristics and pathogenesis of refractory gastroesophageal reflux disease(RGERD). Methods: The patients with acid regurgitation, heartburn and extraesophageal symptoms were enrolled in the study from November 2015 to September 2017 at Peking University Third Hospital. All the subjects filled the informed consent.Questionnaire, SCL-90, SAS and SDS scales were recorded. A 24 hour pH-impedance monitoring and esophageal high resonance manometry were carried out. According to the response to proton pump inhibitor(PPI), the patients were divided into RGERD and non-RGERD(NRGERD)groups. The clinical characteristics were compared between these two groups. Logistic regression was used to analyze the risk factors of RGERD. Results: One hundred and nineteen patients were finally enrolled in the study including 61 RGERD (51.3%) and 58 NRGERD patients (48.7%).The body mass index (BMI) and rates of, typical GER symptoms including acid regurgitation in RGERD patients were significantly lower than those in NRGERD patients (P<0.05).While the atypical GER symptoms such as poststernal discomfort or chest pain were more common in RGERD group (P<0.05).RGERD patients presented less acid reflux events and lower proximal segment reflux ratio than NRGERD patients. No obvious differences were found in the manometry metrics between these two groups. The scores of somatization, depression and hostility in RGERD patients by SCL-90 scales were significantly higher than those in NRGERD patients (P<0.05), and depression score was an independent risk factor for RGERD [OR=3.915 (95%CI 1.464-10.466), P =0.007]. Conclusions: RGERD patients present more atypical symptoms and pathological non-acid reflux.Depression is an independent risk factor for RGERD.

Treatment of Refractory Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common disorder that is treated with lifestyle modification, weight loss, and medications, such as proton pump inhibitors (PPIs). An empiric course of PPI therapy is an effective and cost-effective strategy for the management of GERD. However, in some patients, PPI therapy and lifestyle changes are inadequate to control symptoms. When there is persistence of symptoms despite empiric therapy, patients are labeled as having refractory GERD. This label underestimates the wide differential diagnosis of foregut pathology that can mimic symptoms of GERD. A careful history of symptoms, response to PPI therapy, adherence, compliance, and timing helps elucidate if medication has been helping. When patients are refractory, alternative etiologies of GERD must be considered. Many of these alternatives can be determined on an upper endoscopy or with complementary testing, such as high-resolution esophageal manometry or gastric emptying testing as symptoms dictate. When an alternative cause is not found and index endoscopy is normal, additional testing with either traditional pH or impedance testing can be completed based on prior examination results and response to therapy. Further therapy, including medical, endoscopic, or surgical, can then be targeted at the etiology.

New treatment method for refractory gastroesophageal reflux disease (GERD): C-BLART (clip band ligation anti-reflux therapy)-a short-term study.

OBJECTIVES: C-BLART (clip band ligation anti-reflux therapy) has been reported as a new alternative endoscopic treatment for refractory gastroesophageal reflux disease (GERD). This study evaluated the short-term efficacy of C-BLART for controlling GERD symptoms, esophageal acid exposure, esophagitis, and quality of life. METHODS: Patients with refractory GERD were recruited for a nonrandomized concurrent comparison, with 60 patients in the C-BLART with tailored PPI use group and 43 patients in the BID proton pump inhibitor (PPI) group. The primary outcomes were esophageal acid exposure and the lower esophageal sphincter (LES) pressure. The GERD-Q score, esophagitis grade, and adherence degree were also recorded. Crossover from the BID PPI group to the C-BLART with tailored PPI use group was allowed after 6 months. RESULTS: The LES pressure and GERD-Q score improved more in the C-BLART with tailored PPI use group (P < 0.001) after 6 months, with no significant difference in the decrease in esophagitis compared with the baseline endoscopic results (P = 0.268). Treatment with PPIs had been halted in 43% of the patients at 6 months after C-BLART. At 12 months after C-BLART, the DeMeester score showed a significant improvement compared with the baseline measurements (P = 0.025). The GERD-Q score and LES pressure did not significantly improve compared with the baseline values (P = 0.102, P = 0.184) in C-BLART with tailored PPI use group. At 6 to 12 months, n = 6 (10%) patients had undergone laparoscopic fundoplication to control their symptoms in all the patients after C-BLART. CONCLUSION: C-BLART is a novel treatment for controlling refractory GERD symptoms, esophageal acid exposure, and LES pressure according to this short-term analysis, safely performed endoscopically to create an anti-reflux barrier with ligated bands. Despite improvements in DeMeester score, LES pressure, and GERD-Q scores in the C-BLART with tailored PPI use group, many patients continue to demonstrate objective evidence of GERD.

Short-term effects of Da Vinci robot Nissen fundoplication in the treatment of refractory gastroesophageal reflux disease / 中国胸心血管外科临床杂志

@#Objective    To investigate the short-term effects of Da Vinci robot-assisted Nissen fundoplication in the treatment of refractory gastroesophageal reflux disease (rGERD), and to evaluate the safety and efficacy of its surgical treatment. Methods    A total of 40 patients with rGERD treated by Da Vinci robot-assisted surgery from October 2016 to November 2019 in our hospital were collected. There were 23 males and 17 females at age of 34-76 (61±23) years. The related clinical data were retrospectively analyzed, and the operation skills of Da Vinci robot-assisted Nissen fundoplication with rGERD were summarized. Results    There was no perioperative death or serious complication such as esophagogastric fistula. Postoperative reflux symptoms were significantly improved. DeMeester scores after surgery (39.79±35.01 points vs. 2.61±2.40 points, P=0.029), lower esophageal sphincter pressure (8.74±7.21 mm Hg vs. 24.56±8.76 mm Hg, P=0.020), integrated relaxation pressure (7.29±7.21 mm Hg vs. 16.49±9.99 mm Hg, P=0.023), distal contractile integral (600.49 ± 665.30 mm Hg·s·m vs. 510.99 ± 580.60 mm Hg·s·m, P=0.042), GERD-Q scale score (12.98±2.39 points vs. 7.59±1.11 points, P=0.033) were significantly improved compared with those before surgery. Postoperative dysphagia was found in 2 patients. And dysphagia was alleviated after diet adjustment and other treatments. Conclusion    Da Vinci robot-assisted Nissen fundoplication is a safe and effective treatment for rGERD.

Sintomas persistentes ao tratamento com inibidor da bomba de prótons são devidos à doença do refluxo gastroesofágico refratária ou decorrentes de outras afecções? / Are the persistent symptoms to proton pump inhibitor therapy due to refractory gastroesophageal reflux disease or to other disorders?

ABSTRACT BACKGROUND: Gastroesophageal reflux disease (GERD) is a clinical condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Transient lower esophageal sphincter relaxation is the main pathophysiological mechanism of GERD. Symptoms and complications can be related to the reflux of gastric contents into the esophagus, oral cavity, larynx and/or the lung. Symptoms and other possible manifestations of GERD are heartburn, regurgitation, dysphagia, non-cardiac chest pain, chronic cough, chronic laryngitis, asthma and dental erosions. The proton pump inhibitor (PPI) is the first-choice drug and the most commonly medication used for the treatment of GERD. The most widespread definition of Refractory GERD is the clinical condition that presents symptoms with partial or absent response to twice-daily PPI therapy. Persistence of symptoms occurs in 25% to 42% of patients who use PPI once-daily and in 10% to 20% who use PPI twice-daily. OBJECTIVE: The objective is to describe a review of the current literature, highlighting the causes, diagnostic aspects and therapeutic approach of the cases with suspected reflux symptoms and unresponsive to PPI. CONCLUSION: Initially, the management of PPI refractoriness consists in correcting low adherence to PPI therapy, adjusting the PPI dosage and emphasizing the recommendations on lifestyle modification change, avoiding food and activities that trigger symptoms. PPI decreases the number of episodes of acid reflux; however, the number of "non-acid" reflux increases and the patient continues to have reflux despite PPI. In this way, it is possible to greatly reduce greatly the occurrence of symptoms, especially those dependent on the acidity of the refluxed material. Response to PPI therapy can be evaluated through clinical, endoscopic, and reflux monitoring parameters. In the persistence of the symptoms and/or complications, other causes of Refractory GERD should be suspected. Then, diagnostic investigation must be initiated, which is supported by clinical parameters and complementary exams such as upper digestive endoscopy, esophageal manometry and ambulatory reflux monitoring (esophageal pH monitoring or esophageal impedance-pH monitoring). Causes of refractoriness to PPI therapy may be due to the true Refractory GERD, or even to other non-reflux diseases, which can generate symptoms similar to GERD. There are several causes contributing to PPI refractoriness, such as inappropriate use of the drug (lack of patient adherence to PPI therapy, inadequate dosage of PPI), residual acid reflux due to inadequate acid suppression, nocturnal acid escape, "non-acid" reflux, rapid metabolism of PPI, slow gastric emptying, and misdiagnosis of GERD. This is a common cause of failure of the clinical treatment and, in this case, the problem is not the treatment but the diagnosis. Causes of misdiagnosis of GERD are functional heartburn, achalasia, megaesophagus, eosinophilic esophagitis, other types of esophagitis, and other causes. The diagnosis and treatment are specific to each of these causes of refractoriness to clinical therapy with PPI.

RESUMO CONTEXTO: A doença do refluxo gastroesofágico (DRGE) é a condição clínica que se desenvolve quando o refluxo do conteúdo gástrico provoca sintomas incômodos e/ou complicações. O relaxamento transitório do esfíncter inferior do esôfago é o principal mecanismo fisiopatológico da DRGE. Os sintomas e complicações podem estar relacionados ao refluxo do conteúdo gástrico para o esôfago, cavidade oral, laringe e/ou pulmão. Os sintomas e outras possíveis manifestações da DRGE são pirose, regurgitação, disfagia, dor torácica não-cardíaca, tosse crônica, laringite crônica, asma e erosões dentárias. O inibidor da bomba de prótons (IBP) é o medicamento de primeira escolha e o mais comumente utilizado para o tratamento da DRGE. A definição mais difundida de DRGE Refratária é a condição clínica que apresenta sintomas com resposta parcial ou ausente ao tratamento com IBP duas vezes ao dia. A persistência dos sintomas ocorre em 25% a 42% dos pacientes que utilizam IBP uma vez ao dia e em 10% a 20% dos que utilizam IBP duas vezes ao dia. OBJETIVO: O objetivo é apresentar uma revisão da literatura atual, salientando as causas, aspectos diagnósticos e abordagem terapêutica dos casos com sintomas suspeitos de refluxo e não responsivos ao IBP. CONCLUSÃO - Inicialmente, o manejo da refratariedade ao IBP consiste em corrigir a baixa aderência à terapia com IBP, ajustar a dosagem do IBP e reforçar as recomendações sobre modificação do estilo de vida, evitando alimentos e atividades que desencadeiem os sintomas. O IBP diminui o número de episódios de refluxo ácido, no entanto o número de refluxos "não-ácidos" aumenta e o paciente continua apresentando refluxo apesar do IBP. Desta forma, é possível reduzir consideravelmente a ocorrência de sintomas, especialmente aqueles dependentes da acidez do material refluído. A resposta à terapia com IBP pode ser avaliada através de parâmetros clínicos, endoscópicos e de monitorização do refluxo. Na persistência dos sintomas, outras causas de DRGE Refratária devem ser suspeitadas. Em seguida, deve ser iniciada a investigação diagnóstica, que é apoiada por parâmetros clínicos e exames complementares, como endoscopia digestiva alta, manometria esofágica e monitorização ambulatorial do refluxo (pHmetria esofágica ou impedancio-pHmetria esofágica). As causas de refratariedade à terapia com IBP podem ser devidas à DRGE Refratária verdadeira ou mesmo a outras doenças não relacionadas ao refluxo, que podem gerar sintomas semelhantes à DRGE. Existem várias causas de refratariedade ao IBP, como uso inadequado da droga (falta de aderência do paciente à terapia com IBP, dosagem inadequada de IBP), refluxo ácido residual devido à supressão ácida inadequada, escape ácido noturno, refluxo "não-ácido", metabolismo rápido do IBP, esvaziamento gástrico lento e diagnóstico equivocado de DRGE. Este representa uma causa frequente de insucesso do tratamento clínico e neste caso, o problema não é o tratamento, mas sim o diagnóstico. As causas de diagnóstico equivocado da DRGE são pirose funcional, acalásia, megaesôfago, esofagite eosinofílica, outros tipos de esofagite e outras causas. O diagnóstico e o tratamento são específicos para cada uma dessas causas de refratariedade ao tratamento clínico com IBP.

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.