Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis.

BACKGROUND: Vonoprazan (VPZ) is a novel potassium-competitive acid blocker that may be clinically beneficial for proton pump inhibitor (PPI)-resistant reflux esophagitis (RE). The aim of this study was to investigate the efficacies of VPZ therapy at 20 mg for 4 weeks in patients with PPI-resistant RE and VPZ maintenance therapy at 10 mg for 8 weeks in patients who have been successfully treated. METHODS: Subjects comprised 24 patients with PPI-resistant RE (Los Angeles classification grade A/B/C/D: 3/7/11/3). After confirming PPI-resistant RE by endoscopy, 20 mg VPZ was administered. Endoscopy was performed 4 weeks after the initiation of VPZ. Symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Maintenance therapy with 10 mg VPZ was performed and endoscopy was conducted after 8 weeks. RESULTS: In 21 (87.5%) out of 24 patients, esophageal mucosal breaks were successfully treated by 20 mg VPZ. The median FSSG score was significantly lower on days 1-7, 14, and 28 after the initiation of VPZ than before its administration. Maintenance therapy with 10 mg VPZ prevented the relapse of esophageal mucosal breaks in 16 (76.2%) out of 21 patients. CONCLUSION: VPZ was effective for most patients with PPI-resistant RE.

Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis.

BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.

The effect of n-3/n-6 polyunsaturated fatty acids on acute reflux esophagitis in rats.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) play various roles in inflammation. However, the effect of PUFAs in the development of reflux esophagitis (RE) is unclear. This study is to investigate the potential effect of n-3/n-6 PUFAs on acute RE in rats along with the underlying protective mechanisms. METHODS: Forty Sprague Dawley rats were randomly divided into four groups (n = 10 in each group). RE model was established by pyloric clip and section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6 groups), or normal saline (control and sham operation groups) was injected intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg, respectively). The expressions of interleukin (IL)-1ß, IL-8, IL-6 and myeloid differentiation primary response gene 88 (MyD88) in esophageal tissues were evaluated by Western blot and immunohistochemistry after 72 h. The malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal tissues were determined to assess the oxidative stress. RESULTS: The mildest macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The expression of IL-1ß, IL-8, IL-6 and MyD88 were increased in all RE groups, while the lowest and highest expression were found in n-3 and n-6 group, respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05), in an ascending trend from n-3, n-6 groups to control group. The lowest and highest SOD levels were found in the control and n-3 group, respectively (P < 0.05). CONCLUSION: n-3 PUFAs may reduce acute RE in rats, which may be due to inhibition of the MyD88-NF-kB pathway and limit oxidative damage.

Decreased n-6/n-3 polyunsaturated fatty acid ratio reduces chronic reflux esophagitis in rats.

AIM: To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation. METHOD: Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1ß, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA. RESULTS: The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1ß, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05). CONCLUSION: Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake.

Risk factors for reflux esophagitis and countermeasures-Diet.

Reflux esophagitis is increasing in Japan in association with cultural and societal changes to a more Western lifestyle. The major cause is reflux of gastric contents, consisting mainly of gastric acid, into the esophagus. For prevention, it is necessary to give attention to the contents of meals, as well as food form and eating habits. More specifically, it is important to improve lifestyle habits related to diet, such as refraining from ingesting foods that stimu- late gastric acid secretion or promote relaxation of the lower esophageal sphincter, which delays gastric emptying. Furthermore, consuming large meals quickly, lying down immediately after eating, and eating solids, each of which delays gastric emptying, should be avoided, as well as acidic foods and hot meals.

Ameliorative effects of Panax quinquefolium on experimentally induced reflux oesophagitis in rats.

BACKGROUND & OBJECTIVES: Reflux oesophagitis (RE), is one of the most prevalent chronic gastrointestinal disorders commonly referred to as gastroesophageal reflux disease (GERD) and requires long term therapy. The present study was designed to investigate the protective effects of Panax quinquefolium (PQ), administered with variable doses, on experimentally induced reflux oesophagitis (RE) in rats. METHODS: Forty two female Sprague-Dawley (180-220 g) rats were randomly divided to receive standardized root powder of PQ (50-200mg/kg, po), standard anti-reflux (omeprazole, 5 mg/kg, ip) and anti-oxidant (α-tocopherol, 16 mg/kg, po). After 45 min drug pretreatment, RE was produced in rats by simultaneous ligation of the pyloric end and forestomach. Several parameters, including macroscopic lesion index, glutathione system, lipid peroxidation (LPO) and tissue myeloperoxidase (MPO) activity were measured. Alterations in ICAM-1, CINC-2 and MCP-1 gene expression were examined through reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: PQ significantly attenuated the severity of the macroscopic signs of RE-induced tissue damage, replenished the depleted GSH level and reduced the RE-associated LPO levels dose dependently. In contrast, omeprazole though effectively improved the mucosal damage, it failed to bring significant attenuation of RE-associated changes in LPO, GSH level and MPO activity. α-Tocopherol significantly ameliorated RE-induced tissue injury and improved LPO level and GSH/GSSG ratio but failed to counteract RE-induced MPO activity. PQ at dose of 100 mg/kg significantly downregulated ICAM-1 and CINC-2 expression whereas it showed no effect over MCP-1 expression. INTERPRETATION & CONCLUSIONS: The present data indicate that PQ protects against RE-induced oesophageal damage via a mechanism that inhibits the influx of inflammatory cell to oesophagus and a consequence excessive oxidative load, opening the avenue to its promising protective role in patients with gastroesophageal reflux disease (GERD).

Should we screen reflux oesophagitis patients for coeliac disease?

OBJECTIVES: Oesophagitis and gastro-oesophageal reflux have been implicated recently in the manifestations of coeliac disease. The aim was to investigate this association in a primary-care setting. METHODS: First, the prevalence of coeliac disease was calculated in 1198 adults with oesophagitis, in 2541 adults with reflux symptoms and in 200 adults suffering from dysphagia; 5459 patients with a history consistent with dyspepsia and 709 patients with a suspicion of coeliac disease served as controls. Second, the prevalence of oesophagitis was estimated in 382 untreated and 232 treated coeliac patients; controls here comprised 5404 patients with dyspeptic symptoms and 2525 patients with reflux symptoms. Third, oesophagitis and oesophageal reflux symptoms were investigated before and after a gluten-free diet was followed in 67 adults with coeliac disease. The diagnosis of coeliac disease was based on small-bowel histology; histological exclusion of the disease was unambiguous in all controls. Oesophagitis was identified by endoscopic inspection. RESULTS: Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. The corresponding percentages were 1.0% in patients with dyspepsia and 12% with suspicion of coeliac disease. The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease, 7.0% in patients with dyspepsia, and 27% in symptomatic reflux disease. In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet. CONCLUSIONS: This study does not support the conception that patients with reflux oesophagitis should be screened vigorously for coeliac disease. The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease.

Clinical response to amino acid-based formula in neurologically impaired children with refractory esophagitis.

OBJECTIVE: Chronic gastrointestinal symptoms and histologic changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux disease (GERD) may be improved by the use of elemental formulas. The aim of our study was to evaluate the efficacy of a dietary trial in neurologically impaired children unresponsive to medical and surgical therapy for GERD. METHODS: Nine children (three boys and six girls; median age, 44 months; range, 13-180 months) affected by cerebral palsy associated with severe mental retardation and with long-standing history of GERD were fed the elemental formula, Neocate, for a minimum of 4 weeks. Before and after the dietary trial, each child underwent endoscopy with esophageal biopsy and a cellobiose/mannitol sugar permeability test. The diagnosis of GERD was based on the microscopic changes of the esophagus. RESULTS: Before the dietary trial, according to conventional histologic criteria, esophagitis was considered moderate in seven children and mild in two. Five of nine patients also had abnormal sugar permeability test results. During and after the dietary trial, seven of nine patients experienced resolution of their long-term symptom complaints. Furthermore, after the dietary trial, both endoscopic ( < 0.01) and histologic ( < 0.05) findings significantly improved. At 6-month follow-up, progressive reintroduction of individual dietary proteins, except for cow's milk protein, did not cause reappearance of the symptoms. CONCLUSIONS: In neurologically impaired children unresponsive to conventional antireflux treatments, a course of a highly restricted diet with an amino acid-based formula may bring an immediate and sustained, endoscopically and histologically proven improvement in long-standing gastrointestinal symptoms and esophagitis.

[Long-term results of conservative management of reflux esophagitis]. / Langzeitergebnisse der konservativen Behandlung der Refluxösophagitis.

Reflux esophagitis is a frequent and chronic disease. Impairment of the quality of life by the reflux symptoms and the risk of complications are the most important indications for a long-term treatment. The base of the treatment of reflux esophagitis is the inhibition of the gastric acid secretion with proton pump inhibitors (PPI) or by H2-receptor antagonist. In general, PPI's are more efficient in the treatment of refluxesophagitis as compared to H2-receptor antagonists blockers regarding the relieve of symptoms and the healing of erosive esophageal lesions. The use of an antacids and procinetics in the long-term treatment is not indicated. The treatment strategy depends on the severity of the symptoms and the esophageal lesions. Patient with mild esophagitis can be treated either with H2-receptor antagonists or with PPI's on demand or continuous. In the case of severe esophagitis, a long-term treatment with PPI's is indicated to avoid complications. Recurrence of esophagitis during a long-term therapy should be treated by PPI's. After healing the long-term treatment should be adapted either by increasing the given dose of the medicament or by a switch to more effective medicaments in acid suppression.

Management of reflux oesophagitis: role of weight loss and cimetidine.

A double blind clinical trial was performed to evaluate the effect of weight loss and cimetidine in the treatment of reflux oesophagitis. Thirty-two patients were evaluated by endoscopy, L.O.S.P. determination, oesophageal scintigraphy and ambulatory 24 hour oesophageal pH monitoring. Patients were randomly allocated into treatment using a regimen of placebo/weight loss or cimetidine/weight loss. Assessments were repeated after 8-12 weeks. A similar weight loss and improvement in symptoms and endoscopy appearances was seen in both groups. In contrast there was no significant change in frequency or duration of reflux on 24-hour pH monitoring or oesophageal scintigraphy or L.O.S.P. We conclude that weight loss may have an important role in the treatment of reflux oesophagitis and should be recommended to patients as an early therapeutic intervention. Cimetidine did not confer any additional benefit to that obtained from weight loss alone.

[Diet in gastrointestinal diseases--1983 status]. / Diät bei Magen-Darm-Erkrankungen--Stand 1983.

In the treatment of gastrointestinal disease, no spectacular novelties have been introduced within the past few years. Dietary fibre, medium chain triglycerides (MCT) and certain formula diets have been established as standard tools in the treatment of various gastrointestinal diseases. Some progress has been noted with the introduction of longterm enteral feeding via needle catheter jejunostomies and longterm home parenteral nutrition. Study of the effects, use, practicability and cost of numerous "traditional" diets has led to a more realistic and critical prescription of diets. There is a general trend towards the prescription of diets only when their influence on the disease or on the abnormal nutritional state is superior to the effects of normal food.

[Current trends in the treatment of reflux esophagitis in childhood]. / Attuali orientamenti nella terapia dell'esofagite da reflusso nell'infanzia.

A problem of some complexity is the management of pathological gastro-esophageal reflux due to the presence of cardio-hiatal malformation, malposition of the cardia and gastric tuberosity, a congenitally short esophagus, and the like. Sometimes, however, there is no demonstrable morphological aleration and the condition, characterized by primitive hypotonia of the LES, goes under the name of infant chalasia of the esophagus. The general policy is to try first a conservative treatment consisting of dietary and postural measures and the administration of metoclopramide and d;ugs that protect the esophageal mucosa; this stage, however, should not be prolonged beyond 6 weeks. The presence of gastro-esophageal reflux associated with hiatal hernia; the presence of severe esophagitis or peptic stenosis of the esophagus and the persistence of symptoms after an adequate period of conservative therapy constitute as many indications for surgical correction. Good results can be obtained by restoring or strengthening the failing function of the LES, as is done quite successfully with funduplication after Nissen or with method of Belsey-Mark IV.

Medical management of patients with reflux esophagitis.

Medical management of reflux esophagitis includes physical manipulations, antacids, and antireflux medications (bethanechol and alginic acid). Their combined usage in the continuous dyspeptic and the problem case help "break the cycle," providing relief for long periods of time. Identification of possible inciting factors in cases of recurrence should be pointed out to the patient so that he will develop an instinctive antireflux behavior. The effect of this combined therapy on the pathophysiology and natural history of the disease remains to be determined.