[Pathophysiology and treatment of reflux esophagitis].

Reflux esophagitis (RE) is characterized by excessive esophageal acid exposure. The number of acid reflux episodes, the way acid comes up after reflux and the delay of acid bolus clearance cause excessive esophageal acid exposure. Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of acid reflux in both healthy subjects (HS) and in patients with RE, but there is no difference in the rate of TLESRs or in the rate of acid reflux during TLESRs above the LES between HS and patients with RE. In patients with severe RE, refluxed acid above the LES rises more easily to the proximal esophagus but it does not clear easily from the esophagus when compared with HS. To cure RE, it is necessary to normalize excessive esophageal acid exposure. In GERD guideline in Japanese Society of Gastroenterology, standard dose proton pump inhibitor (PPI) is recommended as the first-line therapy. The response to a standard dose of PPI in patients with mild RE is 90-95%, and that in patients with severe RE is 80-85%. In case that standard dose of PPI is not effective, it is possible that the change to other PPI, the change of administration method (before a meal) and double-dose PPI therapy are effective.

Effect of rikkunshito on the expression of substance P and CGRP in dorsal root ganglion neurons and voluntary movement in rats with experimental reflux esophagitis.

BACKGROUND: While there are reports that the herbal medicine rikkunshito (RKT) relieves upper gastrointestinal disease symptoms, the effect of RKT on primary afferent neurons is unknown. METHODS: A model of reflux esophagitis (RE) was implemented using male Wistar rats aged 6-7 weeks. Ten days after surgery, the total area of esophageal mucosal erosion sites was determined. Th8-10 dorsal root ganglia (DRG) were dissected out and the expression of substance P (SP), calcitonin gene-related peptide (CGRP), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined in DRG using immunohistochemistry. RKT (0.6%/WV) or omeprazole (OME) (10 mg/kg) was administered for 10 days beginning on the day after surgery. Voluntary movement was measured with an infrared sensor for 22 h each day. KEY RESULTS: RE rats showed esophageal mucosal erosion and significantly increased number of SP/CGRP- and p-ERK1/2-immunoreactive neurons in DRG. Treatment with OME improved the size of erosive lesions in the esophageal mucosa of RE rats, while RKT did not. Treatment with RKT or OME significantly reduced the expression of SP/CGRP and p-ERK1/2 in DRG, and significantly increased voluntary movement in RE rats. CONCLUSIONS & INFERENCES: RKT inhibited the activation of ERK1/2 and decreased the expression of SP and CGRP in DRG of RE rats, which may be associated with the observed amelioration of voluntary movement.

[Clinical observation on acupuncture for treatment of reflux esophagitis of heat stagnation of liver and stomach type].

OBJECTIVE: To observe the clinical therapeutic effect of acupuncture for treatment of reflux esophagitis of heat stagnation of liver and stomach type. METHODS: Sixty-one cases were randomly divided into an acupuncture group (31 cases) and a medication group (30 cases). The acupuncture group was treated with needles at Zusanli (ST 36), Zhongwan (CV 12), Weishu (BL 21) and Neiguan (PC 6) mainly, once a day; and the medication group was treated with oral administration of 20 mg Omeprazole, once a day. The scores of clincial symptoms, comprehensive therapeutic effect, results of gastroscopy and pathology as well as recurrence rate etc. were observed before and after treatment. RESULTS: After treatment, the scores of symptoms significantly decreased in the two groups (both P < 0.01). The total effective rate of the acupuncture group was 90.3% (28/31), and 90.0% (27/30 )in the medication group, there was no statistical difference between two groups (P > 0.05); results of gastroscopy and esophageal mucosa pathology showed no statistical difference between two groups (both P > 0.05), the recurrence rate 12 weeks after treatment of 9.1% in the acupuncture group was lower than that of 42.9% in the medication grou p (P < 0.05). CONCLUSION: Acupuncture has preferable short and long-term therapeutic effects for treatment of reflux esophagitis of heat stagnation of liver and stomach type.

[Study on reflux esophagitis treated by Tongjiang granule].

OBJECTIVE: To study the mechanism of Tongjiang granule on treating GERD. METHOD: The rats in the model group received steel wire ring-cardiamyopexy. A steel wire ring was fixed firmly on cardia. The rats in the control group underwent the cardia-plasty plus pylori ligation plus stomach-empty intestine Roux-en-Y anastomosis. The rats were divided into six groups after operations at random, which were fed up respectively with Tongjiang granule of different dosage and perpulsid. No treatment groups were taken as control. RESULT: The experiment showed that Tongjiang granule could lighten or cure RE in the pathology, decrease the hydrochloric acid in gastric juice, in the meantime, increase the motilin in the animal blood. This study indicated that the effect of Tongjiang granule group from experimental research was better than that of the control group (perpulsid). CONCLUSION: The effects of Tongjiang granule on treating GERD can be achieved by decreasing the hydrochloric acid in gastric juice, increasing the motilin in blood and promoting the gastric impetus in the animal experiment.

Review article: modern technology in the diagnosis of gastro-oesophageal reflux disease--Bilitec, intraluminal impedance and Bravo capsule pH monitoring.

Ambulatory pH monitoring detects abnormal levels of acid reflux in the oesophagus and can be used to correlate patients' symptoms with oesophageal acid exposure. Catheter-based pH testing has several limitations, including issues of sensitivity, specificity, tolerability and the inability to record non-acid reflux events. In an effort to improve upon these drawbacks, several devices have been introduced, including the Bilitec system for measuring duodenogastro-oesophageal reflux; intraluminal impedance monitoring, which detects the distribution, composition and clearing of both acid and non-acid oesophageal reflux; and a wireless pH monitoring device, the Bravo capsule. Initial investigations using the Bilitec system demonstrated that duodenogastro-oesophageal reflux tracked very closely with acid reflux and decreased with proton-pump inhibitor (PPI) therapy, casting doubt on the clinical utility of Bilitec monitoring. Recent evidence revealed a possible role for duodenogastro-oesophageal reflux in a subset of patients who continue to report reflux symptoms in the setting of normalized oesophageal acid exposure on high-dose PPI therapy. When combined with pH monitoring, impedance monitoring enhances the detection and characterization of gastro-oesophageal reflux and may have a role in the evaluation of certain specific gastro-oesophageal reflux disease (GERD) symptoms that persist despite acid suppression therapy. The utility of the Bravo wireless technology for GERD diagnosis has been validated in several studies, with improvements over catheter-based pH monitoring in tolerability, accuracy and sensitivity, as well as the ability to record periods both off and on PPI therapy in a single study. All three diagnostic modalities have advanced the understanding of GERD pathogenesis, but their impact on the clinical management of GERD is still the focus of active investigation.

Bioadhesive oesophageal bandages: protection against acid and pepsin injury.

The rate of acid and pepsin diffusion through solutions of sodium alginate was measured using in vitro techniques. Previous work has demonstrated that solutions of alginate may adhere to the oesophagus for up to 60 min; this work measured their ability to protect the oesophageal epithelial surface from damage caused by refluxed acid and pepsin. Franz diffusion cells were used to measure the rate of acid and pepsin diffusion through an alginate layer. The effect of the type of alginate, alginate concentration and depth of alginate applied were investigated. The rate of both acid and pepsin diffusion was significantly reduced (ANOVA analysis; P<0.05) in the presence of an alginate solution compared to the control. A 2% (w/v) alginate solution with a high guluronic acid component, in a layer of 0.44 mm depth, demonstrated the greatest reduction in acid diffusion with a permeation coefficient 14% than that of a control value. All three alginates demonstrated significant reductions in acid diffusion with both increasing depth and increasing concentration, as expected. Pepsin diffusion was also significantly reduced as the depth and concentration of applied alginate increased. This study demonstrates that an adhesive layer of alginate present within the oesophagus will limit the contact of refluxed acid and pepsin with the epithelial surface.

Increased esophageal chemoreceptor sensitivity to acid in patients after successful reversal of Barrett's esophagus.

When compared to patients with erosive esophagitis, patients with Barrett's esophagus have demonstrated reduced chemo- and mechanoreceptor sensitivity to acid infusion and balloon distension, respectively. However, anecdotal clinical experience suggested an increase in symptom perception in patients after successful elimination of Barrett's epithelium, using multipolar electrocoagulation (MPEC) and high-dose proton pump inhibitor (PPI). To determine perception thresholds to acid infusion, we evaluated eight consecutive patients after a series of MPEC treatments resulted in complete elimination of Barrett's mucosa and compared them to 10 age-matched patients with nonreversed Barrett's esophagus and 10 patients with symptomatic, endoscopy-documented erosive esophagitis (Hetzel-Dent grade 2 or greater). Chemosensitivity was determined by a modified acid perfusion test, where acid perception thresholds were quantified by the lag time to initial typical symptom perception, sensory intensity rating, and an acid perfusion sensory score (APSS). While patients after successful elimination of Barrett's esophagus had similar sensory intensity ratings and APSS as patients with erosive esophagitis, the lag times differed significantly between the groups, and both groups had significantly higher sensory intensity ratings and APSS than patients with nonreversed Barrett's esophagus. In conclusion, patients after complete reversal of Barrett's mucosa are unexpectedly as sensitive to acid as symptomatic patients with erosive esophagitis.

Histamine H2 receptor antagonist-refractory oesophagitis: the efficacy of long-term omeprazole maintenance treatment.

BACKGROUND: Erosive oesophagitis refractory to high dose histamine H2 receptor antagonists (definition: failure to heal fully after > or = 3 months' treatment with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg daily but frequently relapses when the patients are put back on maintenance H2 receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2 g, respectively). AIM: To investigate the efficacy of maintenance omeprazole 20 mg daily in refractory erosive oesophagitis. PATIENTS & METHODS: In this open, sequential study, patients with H2 receptor antagonist-refractory oesophagitis were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole 40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily for up to 4.5 years. RESULTS: Healing on omeprazole occurred in 38 out of 39 patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed (asymptomatic in half) during subsequent maintenance treatment, whereas all had relapsed earlier on high dose H2 receptor antagonists. CONCLUSION: Within the limits of interpretation of an open study, omeprazole 20 mg daily seems effective in maintaining prolonged remission in this group of patients with H2 receptor antagonist-refractory oesophagitis.

Why does sucralfate improve healing in reflux esophagitis? The role of sucrose octasulfate.

In the present investigation, one of sucralfate's major components, sucrose octasulfate (SOS), is shown in vitro to protect human esophageal epithelium against acid injury. This was done by mounting sections of human epithelia obtained at the time of esophagectomy in Ussing chambers and monitoring the change in electric resistance (R) on luminal acidification with 60 mM HCl. Mucosal-to-serosal mannitol fluxes were also performed before and after exposure to HCl. In untreated control tissues luminal acidification progressively reduced R with time and significantly increased tissue permeability to mannitol. In contrast, tissues exposed to 10 mg/ml SOS showed a minimal decrease in R and no significant change in permeability to mannitol (p less than 0.05 compared with control for both factors). Since SOS does not buffer luminal H+, protection by SOS is mediated by a direct action on the tissue. The impact of these results on sucralfate's reported ability to improve healing in reflux esophagitis is discussed.

The effects of omeprazole and ranitidine on 24-hour pH in the distal oesophagus of patients with reflux oesophagitis.

Ambulatory 24-h pH monitoring in the distal oesophagus was performed in seven patients with erosive or ulcerative reflux oesophagitis to compare the effects of omeprazole and ranitidine in the management of gastro-oesophageal reflux disease. In a double-blind, crossover study patients were treated with either 60 mg o.m. omeprazole or 150 mg b.d. ranitidine. The pH measurements were performed before treatment and on the fourteenth day of treatment with either regimen. The total acid exposure time (percentage total time pH less than 4) was abnormal in six out of seven patients before treatment. During treatment with omeprazole the acid exposure time of five patients was normal in comparison with only two patients during ranitidine therapy. However, even with a rather high dose of omeprazole, pathological gastro-oesophageal reflux may still occur.

Inhibitory effect of coffee on lower esophageal sphincter pressure.

We examined the effect of 150 ml of caffeinated instant coffee at two pHs, 4.5 and 7.0, on lower esophageal sphincter pressure in 20 normal volunteers and 16 patients with reflux esophagitis. When ingested alone coffee at pH 4.5 and 7.0 caused a decrease in basal sphincter pressure in normal volunteers from 19.4 +/- 1.5 to 13.7 +/- 1.0 mmHg (P ¿ 0.01) and from 18.7 +/- 1.5 to 16.0 +/- 0.8 mmHg (P < 0.05) respectively. When coffee at pH 4.5 was drunk with a mixed nutrient test meal, the resting sphincter pressure in normal subjects fell after 30-60 min with the nadir, 11.2 +/- 1.0 mmHg, being recorded at 60 min (P < 0.01). Coffee at pH 7.0 with the test meal resulted in a fall in pressure to 14.3 +/- 1.5 mmHg (P < 0.02) at 60 min. In patients with reflux esophagitis, coffee at pH 4.5 lowered lower esophageal sphincter pressure from 9.1 +/- 1.0 to 5.5 +/- 0.6 mmHg (P < 0.005); coffee at pH 7.0 decreased lower esophageal sphincter pressure from 8.5 +/- 1.1 to 6.9 +/- 0.7 mmHg (P < 0.05). In these patients, mean basal pressure, 9.2 +/- 0.8 mmHg, decreased to 5.2 +/- 0.7 mmHg (P < 0.001) 45 min after drinking coffee at pH 4.5 with the test meal. Coffee at the neutral pH caused a fall in pressure from 8.8 +/- 1.1 to 6.5 +/- 0.7 mmHg at 60 min after the test meal. Thus, coffee at either pH 4.5 or 7.0 caused a decrease in fasting and postcibal lower esophageal sphincter pressure in normal volunteers and patients with reflux esophagitis. The magnitude and the duration of the effect were greater after coffee at the lower pH. These data support the clinical belief that coffee may cause or aggravate heartburn by decreasing lower esophageal sphincter pressure.