Evaluation of the effects of medium-term (57-day) omeprazole administration and of omeprazole discontinuation on serum gastrin and serum chromogranin A concentrations in the horse.

BACKGROUND: Rebound gastric hyperacidity (RGH) secondary to hypergastrinemia has been suggested to contribute to the rapid recurrence of equine squamous gastric disease (ESGD) in horses after discontinuation of omeprazole. HYPOTHESIS/OBJECTIVES: To evaluate changes in serum gastrin and chromogranin A (CgA) concentrations in response to medium-term (57-day) omeprazole treatment and after omeprazole discontinuation. ANIMALS: Fourteen mature Thoroughbred racehorses in simulated race training. METHODS: Horses received 2.28 g of oral omeprazole PO q24h for 57 days within a 61-day period, excluding a withholding period applied mid-protocol during which treatment was stopped as part of a concurrent study. Serum samples were collected on day 0 before omeprazole treatment, on day 1 of each week of the treatment period, and for an additional 5 weeks after discontinuation of treatment. Serum gastrin and CgA concentrations were analyzed using radioimmunoassay (RIA) and ELISA, respectively. RESULTS: Median serum gastrin concentrations increased 2.5-fold from baseline to day 7 (P < .001) but did not increase further during the omeprazole treatment period. Median serum gastrin concentrations returned to baseline within 2 to 4 days after administration of the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum gastrin concentrations increased in response to omeprazole treatment but returned to baseline within 2 to 4 days after the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. Our results do not support the use of tapering protocols in horses.

Changes in Calprotectin (S100A8-A9) and Aldolase in the Saliva of Horses with Equine Gastric Ulcer Syndrome.

Equine gastric ulcer syndrome (EGUS) is a highly prevalent disease that affects horses worldwide. Within EGUS, two different forms have been described: equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD). The associated clinical signs cause detrimental activity performance, reducing the quality of life of animals. Saliva can contain biomarkers for EGUS that could be potentially used as a complementary tool for diagnosis. The objective of this work was to evaluate the measurements of calprotectin (CALP) and aldolase in the saliva of horses as potential biomarkers of EGUS. For this purpose, automated assays for the quantification of these two proteins were analytically validated and applied for detecting EGUS in a total of 131 horses divided into 5 groups: healthy horses, ESGD, EGGD, combined ESGD and EGGD, and horses with other intestinal pathologies. The assays showed good precision and accuracy in analytical validation, and they were able to discriminate between horses with EGUS and healthy horses, especially in the case of CALP, although they did not show significant differences between horses with EGUS and horses with other diseases. In conclusion, salivary CALP and aldolase can be determined in the saliva of horses and further studies are warranted to elucidate the potential of these analytes as biomarkers in EGUS.

Gastrojejunostomy as a treatment for gastric outflow disorders in four adult horses.

Four adult horses with histories of moderate abdominal pain and inappetence were diagnosed with delayed gastric emptying and gastric impaction attributed to pyloroduodenal obstruction (three cases) or duodenitis (one case). A stapled side-to-side gastrojejunostomy was performed on all horses. Two horses returned to work and survived ≥3 years. One horse was euthanased 6 months post-surgery due to recurrent abdominal pain, and one was found dead 5 months postsurgery after an unattended foaling.

A Comparison of the Efficacy of Two Omeprazole Formulations in the Treatment of Equine Gastric Ulcer Syndrome in Racehorses: A Blinded, Randomized Clinical Trial.

Equine gastric ulcer syndrome (EGUS) is the most common disease of the stomach in horses and treatment is based on the oral administration of omeprazole for at least 28 days. Aim of this study was to compare the efficacy of two formulations of oral omeprazole-powder paste and gastro-enteric resistant granules-in the treatment of naturally occurring gastric ulcers in racehorses. Thirty-two adult racehorses, aged between 2 and 10 years old, with clinical signs of EGUS were included in this blinded, randomized clinical trial. Two gastroscopies were performed to evaluate gastric lesions in the squamous or glandular mucosa before and after 28 days of treatment. After the first gastroscopy, 2/32 horses were excluded because affected by equine squamous gastric disease (ESGD) 1/4. The remaining horses were divided into 4 groups, and were treated with 2 formulations of omeprazole (gastroenteric resistant granules, group 1, or powder paste, group 3) or with 2 placebo formulations (granules, group 2, or paste, group 4). Treatments were performed in the placebo horses affected by ESGD or equine glandular gastric disease after the T28 gastroscopy control. No differences were found between groups at T0. Differences were found between T0 vs. T28 for granular (P = .002) and powder paste (P = .01) formulations. No differences were detected between the two groups receiving omeprazole formulations at T28 (0.34) and between T0 vs. T28 for either of the groups receiving placebo treatments. For all the variables, the size of the effect was greater than 0.5, proving that the treatments had a considerable effect. Gastro-enteric resistant granules and powder paste omeprazole showed similar efficacy in the treatment of ESGD. The glandular mucosa responded poorly to treatment with omeprazole.

Changes in Management Lead to Improvement and Healing of Equine Squamous Gastric Disease.

Equine squamous gastric disease (ESGD) is common in horses and poses a serious welfare problem. Several risk factors have been identified and ESGD is routinely treated with omeprazole. Fourteen mares, previously used as embryo recipients and diagnosed with ESGD, were selected. Horses were confined to individual stalls, exercised once daily, and fed ad libitum hay, 1 kg of a low starch compound complementary feed and a mineral supplement. Half of the horses received a compound containing hydrolysed collagen (supplement) and the other half did not (control). At the start of the study, ESGD scores were 3.57 and 3.36 for the supplement and control group, respectively. After 4 weeks, the ESGD grades were significantly reduced in both groups (1.89 and 1.43, respectively, p < 0.01), and healing (ESGD < 2) occurred in 7 out of 14 horses. No treatment effect was observed (p = 0.75), and it was concluded that the change in husbandry overshadowed any potential effect of the compound. Severe ESGD can improve, and even heal, with the provision of a diet of ad libitum forage and a small amount of a compound complementary feed, without the use of omeprazole. A predictable daily routine, with a limited number of dedicated caretakers, may have contributed to the improvement of gastric health.

Changes in Proteins in Saliva and Serum in Equine Gastric Ulcer Syndrome Using a Proteomic Approach.

Changes in the salivary proteome in 12 horses with the two diseases included in equine gastric ulcer syndrome (EGUS), equine glandular gastric disease (EGGD) (n = 6) and equine squamous gastric disease (ESGD) (n = 6), were evaluated using a high-resolution LC-MS/MS analysis of TMT-labelled peptides and compared to 10 healthy control horses. Serum was also analysed for comparative purposes. The comparison between the horses with EGGD and controls showed significant changes in 10 salivary proteins, whereas 36 salivary proteins were differently abundant between ESGD and control groups. The most upregulated proteins in the case of EGGD were related to immune activation whereas, in horses with ESGD, the most significantly changed proteins were associated with squamous cell regulation and growth. Compared to serum, saliva showed a higher number of proteins with significant changes and a different pattern of changes. The proteins identified in our study, in addition to providing new information about the pathophysiological mechanisms in these diseases, could have the potential to be novel biomarkers for the diagnosis or monitoring of EGGD and ESGD.

Equine Squamous Gastric Disease: Prevalence, Impact and Management.

This narrative review explores the etiopathogenesis, clinical signs, diagnosis and treatment of ESGD (equine squamous gastric disease) and discusses the impact of this commonly encountered condition on the equine industry. ESGD refers specifically to peptic injury of the squamous mucosa of the stomach. Prevalence is highest in performance horses, but the disease has been documented across many breeds and ages, including in feral horses and foals. The pathogenesis of ESGD is well understood. Intensive management and exercise are important factors that contribute to a disruption of the normal stratification of gastric pH. This results in exposure of the vulnerable squamous mucosa to acid, leading to ulceration. Clinical signs are variable and there is little evidence to support a direct association between reported signs and the presence or absence of lesions seen on gastroscopy. Management is aimed at acid suppression and mitigation of known risk factors.

Effect of omeprazole and sucralfate on gastrointestinal injury in a fasting/NSAID model.

BACKGROUND: Equine gastric ulcer syndrome (EGUS) is a common and significant cause of morbidity in horses, with a range of clinical signs, including inappetence, colic and poor performance. Hospitalised horses are exposed to factors that may induce EGUS, including fasting and nonsteroidal anti-inflammatory drug (NSAID) administration, and may be at risk for development of squamous (ESGD) and glandular gastric disease (EGGD). Prophylactic anti-ulcer medication is often prescribed for these patients, but drug selection is complicated by different aetiology and response to treatment of ESGD and EGGD. OBJECTIVES: To establish the efficacy of sucralfate or omeprazole used prophylactically in horses exposed to a combined feed-fast and NSAID administration EGUS induction protocol. We hypothesised that these drugs would be equally effective for prevention of gastric lesions in the experimental cohort. STUDY DESIGN: Randomised crossover experimental design. METHODS: Horses (n = 14) received either omeprazole (1 mg/kg PO q24h) or sucralfate (20 mg/kg PO q8h) while undergoing the feed-fast/NSAID protocol, allowed an 8-week washout period, and then administered the alternate treatment. Serial gastroscopy, ultrasound and haematology documented treatment effects. RESULTS: ESGD and EGGD score increased over time under both treatments. There was a significant effect of treatment on EGGD scores (P < .001), with post-treatment EGGD scores higher for horses receiving sucralfate (median 3; IQR 2.25,3) than omeprazole (1; 1,1). The effect of treatment on ESGD scores just achieved significance (P = .05), with post-treatment ESGD scores higher for sucralfate (4; 3,4) than omeprazole (2; 2,3). MAIN LIMITATIONS: This study was performed in healthy horses, and response to treatment may differ in horses with clinical illness. Additional investigation in a larger population may be required to detect significant differences in other clinical parameters. CONCLUSIONS: Omeprazole was superior to sucralfate for mitigating gastric lesion severity in healthy horses exposed to a feed-fast/NSAID model.

Chronic severe pyloric lesions in horses: 47 cases.

BACKGROUND: The clinical findings and outcome associated with chronic severe equine pyloric lesions have not been well described previously. OBJECTIVES: To describe the history, clinical signs, endoscopic and ultrasound results, laboratory data, treatment, pathological findings and survival of horses with chronic severe pyloric lesions. STUDY DESIGN: Retrospective case series. METHODS: Medical records from horses treated at clinics in Czech Republic and Germany in which chronic severe pyloric lesions were confirmed endoscopically and/or on post-mortem examination were reviewed. RESULTS: Forty-seven horses were identified, median age 3 years (range 0.8-16 years). There were 3 geldings, 23 mares and 19 stallions and the majority were Warmbloods (60%). The most common presenting signs were poor body condition (40; 87%), slow eating (39; 83%), recurrent colic (35; 74%) and selective appetite (30; 64%). The most consistent laboratory abnormality was hypoalbuminaemia (10; 36%). Slow gastric emptying was confirmed in 29 individuals during gastroscopy and/or ultrasonography. Endoscopy revealed distal oesophagitis in 9 of 47 horses, and severe equine squamous gastric disease in all cases. Pyloric lesions were depressed, flat or raised fibrinosuppurative pyloric ulcers and were seen in 45 (2 pylori were not seen endoscopically). Thirty-two cases were treated, with 28 responding well initially. All treated cases received anti-ulcer medication and four underwent gastrojejunostomy. Clinical signs recurred after medical treatment in at least 11 cases. Only 18 of 44 cases (41%) survived long term (3 were lost to follow-up). Horses diagnosed at 3 years of age or younger were significantly less likely to survive more than 6 months than older horses (27.8% vs. 72.2%, P<0.001). MAIN LIMITATIONS: The study is retrospective, some records were incomplete and case identification was subjective. CONCLUSIONS: Chronic severe pyloric lesions can be associated with delayed gastric emptying identified with ultrasonography and/or endoscopy. The prognosis is poor in young horses.

Effect of Changing Diet on Gastric Ulceration in Exercising Horses and Ponies After Cessation of Omeprazole Treatment.

Diet is an accepted risk factor for equine squamous gastric disease (ESGD), but there is little published evidence for the benefit of dietary change (DC). This study evaluated the effect of DC with or without initial omeprazole medication. Twelve pairs of exercising horses with ESGD Grade 2/4 (EM) and 17 pairs with ESGD Grade ≥3/4 (ES), were monitored. Paired horses had similar management, feeding times, workloads, and initially feed or forage. One of each pair was randomly assigned, postgastroscopy (Scope1), to a specified restricted starch ration; the other remained on their original diet. Omeprazole (4 mg/kg per os SID) was given to all ES pairs for 4 weeks. Gastroscopies were scored, without dietary knowledge, after 4 and 10 weeks (Scopes 2 and 3). Workloads remained similar throughout. McNemar's tests identified any changes in ESGD grade. Within the EM group, DC had no additional effect. For the ES group remaining on their original diet, there was significant improvement in ESGD grade from Scopes 1 to 2 (P < .001) but a worsening between Scopes 2 and 3 (P = .005), with Scope 3 being no different from Scope 1 (P = .08) reflecting no apparent long-term medication benefit. For the DC group, there was significant improvement in ESGD grade from Scopes 1 to 2 (P < .001) and between Scopes 1 and 3 (P = .003); In addition, there was no significant difference between Scopes 2 and 3 (P = .32). Although limited by the small number of pairs evaluated, this study provides evidence that appropriate DCs can be a beneficial management strategy for ESGD.

Diagnostic accuracy of blood sucrose as a screening test for equine gastric ulcer syndrome (EGUS) in weanling foals.

BACKGROUND: Equine gastric ulcer syndrome is an important cause of morbidity in weanling foals. Many foals are asymptomatic, and the development of an inexpensive screening test to ensure an early diagnosis is desirable. The objective of this study was to determine the diagnostic accuracy of blood sucrose for diagnosis of EGUS in weanling foals. RESULTS: 45 foals were studied 7 days before and 14 days after weaning. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL); glandular lesions (GDL); squamous lesions (SQL) and clinically significant gastric lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using ROC curves and calculating the AUC. For each lesion type, sucrose concentration in blood was compared to gastroscopy; and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Cut-off values were selected manually to optimize Se. Because of concerns over the validity of the gold standard, additional Se, Sp, and lesion prevalence data were subsequently estimated and compared using Bayesian latent class analysis. Using the frequentist approach, the prevalence of GL; GDL; SQL and CSL before weaning was 21; 9; 7 and 8% respectively; and increased to 98; 59; 97 and 82% respectively after weaning. At the selected cut-off, Se ranged from 84 to 95% and Sp ranged from 47 to 71%, depending upon the lesion type and time of sampling. In comparison, estimates of Se and Sp were consistently higher when using a Bayesian approach, with Se ranging from 81 to 97%; and Sp ranging from 77 to 97%, depending upon the lesion type and time of sampling. CONCLUSIONS: Blood sucrose is a sensitive test for detecting EGUS in weanling foals. Due to its poor specificity, it is not expected that the sucrose blood test will replace gastroscopy, however it may represent a clinically useful screening test to identify foals that may benefit from gastroscopy. Bayesian latent class analysis represents an alternative method to evaluate the diagnostic accuracy of the blood sucrose test in an attempt to avoid bias associated with the assumption that gastroscopy is a perfect test.

Comparison of aloe vera and omeprazole in the treatment of equine gastric ulcer syndrome.

BACKGROUND: Anecdotally, aloe vera is used to treat gastric ulceration, although no studies have yet investigated its efficacy in horses. OBJECTIVES: To test the hypothesis that aloe vera would be noninferior to omeprazole in the treatment of equine gastric ulcer syndrome. STUDY DESIGN: Randomised, blinded clinical trial. METHODS: Forty horses with grade ≥2 lesions of the squamous and/or glandular mucosa were randomly assigned to one of two groups. Horses received either aloe vera inner leaf gel (17.6 mg/kg bwt) b.i.d. or omeprazole (4 mg/kg bwt) s.i.d. for approximately 28 days, after which a repeat gastroscopic examination was performed to determine disease resolution. Horses with persistent lesions were offered a further 28 days of treatment with omeprazole (4 mg/kg bwt s.i.d.) and were re-examined on completion of treatment. RESULTS: Efficacy analyses were based on 39 horses that completed the trial. Equine squamous gastric disease (ESGD) was observed in 38 horses; improvement and healing rates in these horses were 56% and 17%, respectively, in the aloe vera group, and 85% and 75%, respectively, in the omeprazole group. Healing was less likely to occur in horses with prolonged gastric emptying. Equine glandular gastric disease (EGGD) was less common than ESGD (n = 14) and numbers were too small to perform meaningful statistical analyses. The hypothesis that aloe vera would be noninferior to omeprazole was not supported. MAIN LIMITATIONS: No placebo control group was included. Limited numbers preclude any comment on the efficacy of aloe vera in the treatment of EGGD. CONCLUSIONS: Treatment with aloe vera was inferior to treatment with omeprazole.

Diagnostic accuracy of blood sucrose as a screening test for equine gastric ulcer syndrome (EGUS) in adult horses.

BACKGROUND: Equine gastric ulcer syndrome (EGUS) is common in adult horses, particularly those involved in performance disciplines. Currently, detection of EGUS by gastroscopy is the only reliable ante mortem method for definitive diagnosis; however it is unsuitable as a screening test because it is expensive, time consuming, and is not readily available to most veterinarians. Sucrose permeability testing represents a simple, economical alternative to gastroscopy for screening purposes, and the feasibility of this approach in the horse has been previously reported. The aim of this study was to determine the diagnostic accuracy of blood sucrose as a screening test for EGUS in a large group of adult horses with and without naturally occurring gastric disease. RESULTS: One hundred and one adult horses with or without naturally occurring gastric ulceration were studied. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL), glandular lesions (GDL), squamous lesions (SQL), and clinically significant lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using receiver operator characteristics (ROC) curves and calculating the area under the curve (AUC). For each lesion type, sucrose concentration in blood was compared to gastroscopy, as the gold standard, and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Ulcer grading was performed blindly by one observer; and the results were validated by comparing them with that of two other observers, and calculating the level of agreement. Cut-off values were selected manually to optimize Se. The prevalence of GL, GDL, SQL, and CSL was 83, 70, 53 and 58% respectively. At the selected cut-offs, Se ranged from 51 to 79% and Sp ranged from 43 to 72%, depending upon the lesion type and time of sampling. CONCLUSIONS: Blood sucrose is neither a sensitive or specific test for detecting EGUS in this population of adult horses with naturally occurring gastric ulceration. Further studies aimed at evaluating the performance characteristics of the test in different study populations are warranted. Given the limitations of endoscopy, due consideration should also be given to alternative methods for comparison of blood sucrose with a gold standard.