Immunohistochemical Assessment of GDNF and Chromogranin A Expression in Erosive and Granulomatous Lesions in Glandular Region of Equine Stomach.

The equine stomach consists of two separate non-glandular and glandular sections. Despite the incidence of most lesions in the non-glandular region, both stomach parts are prone to lesions. In this study, 41 hybrid-native horses, including 24 stallions and 17 mares, were examined over five years. In total, 27 horses (65.85%) that were sampled had lesions, including erosion, granuloma, or both on the glandular region of the stomach. Occurrence of gastric erosive and granulomatous lesions had no significant relationship with the age and gender of horses or the sampling season (P>0.05). Moreover, parasites Gastrophilus and Habronema were mainly the primary cause of gastric erosive and granulomatous lesions respectively. In Periodic Acid Schiff (PAS) stained tissue sections, the inflammation severity in granulomatous lesions was higher and statistically significant, compared to erosive lesions (P<0.05). Immunohistochemistry revealed negative expression of glial cell line-derived neurotrophic factor in gastric lesions, while its expression was relatively positive in normal stomachs. Interestingly, based on counting cells and evaluation of expression intensity, Chromogranin A expression in neuroendocrine glandular cells had a significant relationship with the increase of severity and depth of the lesions (P<0.05). The results indicated that the glial cell line-derived neurotrophic factor does not affect the pathogenesis of equine gastric lesions while confirming the role of increment of gastric neuroendocrine cells in lesion progress. Furthermore, the increased expression of Ki67 and p53 proteins in granulomatous lesions, compared to other groups, may be associated with the proliferation and control process of the cells in measures regarding the formation and healing of the lesion.

Design, synthesis, biological evaluation, and computational studies of novel thiazolo-pyrazole hybrids as promising selective COX-2 inhibitors: Implementation of apoptotic genes expression for ulcerogenic liability assessment.

A novel series of thiazolo-pyrazole hybrids has been prepared and assessed for their in vitro COX-1/COX-2 inhibitory activity. Compound 6c exhibited the most selective COX-2 inhibition profile (SI of 264) not far of Celecoxib (294). In-vivo anti-inflammatory activity revealed that compound 6d exhibited the highest activity (97.30% inhibition of edema) exceeding reference standard Indomethacin (84.62% inhibition of edema). The ulcerogenic liability tested, using gross, microscopic, biochemical analysis and apoptotic genes expression, showed that compound 6b matched the optimal candidate activity (ulcer index = 120, selectivity index of ~ 162 and 77% in-vivo inhibition of edema). Meanwhile, compound 6 m (ulcer index = 0) showcased the highest safety profile. Molecular modeling analysis and drug likeness studies presented appreciated agreement with the biological evaluation.

Assessment of the Gastroprotective Effect of the Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), Against the Gastric Mucosal Ulceration Induced by Ethanol in Experimental Rats.

The chaga medicinal mushroom (Inonotus obliquus) was traditionally used to treat various ailments. To establish the pharmacological properties of I. obliquus, studies were performed to show the antiulcer activity of the ethanolic extract. The ethanolic extract of I. obliquus was prepared. The antiulcer activity of I. obliquus was determined using gastric ulcerated rats (ulceration induced by ethanol). The ethanolic extract of I. obliquus (200 mg/kg) did not cause any sign of toxicity or sensitivity to rats when the extracts were administered by oral feed. Oral administration of ethanolic extract of I. obliquus exhibited antiulcer activity in all models used. The ethanolic extract of I. obliquus showed an effective antiulcer activity, which could be due to the presence of various biologically active compounds. This confirmed the traditional uses of I. obliquus in the treatment of ailments.

Assessment of the antinociceptive and ulcerogenic activity of the tapentadol-diclofenac combination in rodents.

Preclinical Research & Development The objective of the present study was to evaluate the tapentadol-diclofenac combination in three dose-ratios in the mouse acetic acid-induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose-response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid-induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co-administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid-induced visceral pain test with an acceptable gastric damage profile in mice.

Synthetically modified bioisosteres of salicyl alcohol and their gastroulcerogenic assessment versus aspirin: biochemical and histological correlates.

The present study was conducted to synthesize nitrogen containing derivatives of salicyl alcohol and to investigate in vivo their ulcerogenic potential in comparison with aspirin in rats. The compounds [4-(2-hydroxybenzyl) morpholin-4-iumchloride (I)] and [1,4-bis(2-hydroxybenzyl) piperazine-1,4-diium chloride (II)] were synthesized and their chemical structures were characterized using spectral data. In our previous study (Ali et al., Afr J Pharm Pharmacol 7:585-596, 2013), both compounds showed anti-inflammatory, antinociceptive, and antipyretic properties in standard animal models and a greater binding affinity for cyclooxygenase-2 versus cyclooxygenase-1 in molecular docking and dynamics analysis. For in vivo studies, animals were randomly divided into four groups. The synthetic compounds (both at 100 or 150 mg/kg), aspirin (150 mg/kg), or saline vehicle was administered orally, once daily for 6 days and then tested for ulcerogenic activity. At the end of the procedure, gastric juice and tissues were collected and subjected to biochemical and histological analyses. The results of the study revealed that in the case of the aspirin-treated group, there was a significant increase in gastric juice volume, free acidity, total acidity, and ulcer score and a decrease in gastric pH. Moreover, histological examination of the gastric mucosa of the aspirin-treated group indicated morphological changes while neither of the synthetic compounds showed any significant ulcerogenic or cytotoxic properties. The results of the present study suggest that both compounds are free from ulcerogenic side effects and may represent a better alternative to aspirin.

Ulcerogenic risk assessment of diets for pigs in relation to gastric lesion prevalence.

BACKGROUND: Gastric ulcers in fattening pigs from intensive pork production can cause sudden deaths on farm and the grinding intensity of the diet appears to be among the risk factors. The objective of this work is to adopt the latest laboratory tests and thresholds for the ulcerogenic risk assessment of diets from experimental reports and verify the class of risk in relation to gastric lesion prevalence in reared finishers. RESULTS: Specificity and accuracy of feed safety tests based on the ulcerogenic risk of feed associated with the particle size distribution of diets were calculated on the occurrence of gastric lesions observed at a slaughterhouse: 41 lard-type hogs, fed with two diets [pelleted (n = 21 pigs) vs. mixed meal (n = 20 pigs)], analyzed at the laboratory of our Institute, were involved. Gross inspection at the abattoir allowed the identification of the development of macroscopic gastric lesions in the pigs (13/21) fed with a pelleted complete diet, ranked in Class 1 (high ulcerogenic risk) on laboratory assessment. Breakdown of gastric lesion severity: hyperkeratosis (13/13), mucosal erosions (11/13) and bleeding ulcers (2/13). This occurrence was compared to the morphology of stomach mucosa from 20 finishers fed with a mixed meal diet, ranked in Class 3 (low ulcerogenic risk), in which no gastric lesions were observed. Very fine particle (VFP) mass (<0.4 mm) according to cut off thresholds (>36%) for the safety ranking of diets, showed: 100% positive predictive value (PPV); 100% specificity; 88.1% accuracy; 72.2% sensitivity. CONCLUSIONS: Three factors emerged: the elevated mass (42.6%) of <0.4 mm particles in the pelleted complete diet confirmed the associated risk rank in Class 1 assessed by laboratory procedures, as gastric lesions were selectively observed in 61.9% of finishers fed with the high risk diet; in these animals, macroscopic gastric lesions occurred within four weeks and showed a sub-clinical course, independently of severity; proper sieving analysis is necessary to define the VFP proportion in feedstuffs with certainty, as an adequate measure to assess the ulcerogenic risk class of the diet.

Cost-effectiveness of endoscopic surveillance of gastric ulcers to improve survival.

BACKGROUND: Endoscopic surveillance of presumed-benign gastric ulcers may detect missed malignancy, but its impact on long-term outcomes is uncertain. OBJECTIVE: To estimate the clinical benefits and cost-effectiveness of follow-up surveillance. DESIGN: State-transition model. SETTING: To simulate the clinical course of presumed-benign gastric ulcers, we estimated prevalence and incidence of undetected gastric cancer, surveillance effectiveness, stage-specific disease mortality rates, and costs from clinical studies and databases. PATIENTS: This study involved 60-year-old men diagnosed with presumed-benign gastric ulcers. INTERVENTION: Follow-up endoscopic surveillance. MAIN OUTCOME MEASUREMENTS: Lifetime gastric cancer risk, life expectancy, quality-adjusted life expectancy, lifetime costs, and incremental cost-effectiveness ratios. RESULTS: For a cohort of 60-year-old men with presumed-benign gastric ulcers and a 2.6% prevalence of undetected malignancy, the lifetime gastric cancer risk was 4.4%. Surveillance improved (undiscounted) life expectancy by 10.0 days and increased discounted quality-adjusted life expectancy by 3.4 days at a cost of $146,700 per quality-adjusted life year (QALY). Surveillance cost less than $50,000 per QALY if the undetected gastric cancer prevalence was 6.5%, and it cost less than $100,000 per QALY if the prevalence was greater than 3.5%, endoscopy costs were 40% lower, or the disutility associated with gastric cancer was 30% lower. Probabilistic sensitivity analysis suggested that at a willingness-to-pay threshold of $100,000 per QALY, the probability that surveillance was cost effective was 25.2%. LIMITATIONS: Data from multiple sources with varied study designs were used. CONCLUSION: Endoscopic surveillance of presumed-benign gastric ulcers may improve overall survival. However, unless the prevalence of having undetected malignancy exceeds 6%, surveillance is unlikely to be cost-effective.

Nonclinical safety assessment of the histone deacetylase inhibitor vorinostat.

Vorinostat (SAHA, Zolinza), a histone deacetylase inhibitor, is assessed in nonclinical studies to support its approval for cutaneous T-cell lymphoma. Vorinostat is weakly mutagenic in the Ames assay; is clastogenic in rodent (ie, CHO) cells but not in normal human lymphocytes; and is weakly positive in an in vivo mouse micronucleus assay. No effects are observed on potassium ion currents in the hERG assay up to 300 microM (safety margin approximately 300-fold the approximately 1 microM serum concentration associated with the 400 mg/d maximum recommended human dose. No rat respiratory or central nervous system effects are found at 150 mg/kg (>2-fold maximum recommended human dose). No cardiovascular effects, including effects on QTc interval, are observed after a single oral dose (150 mg/kg) in dogs. Vorinostat is orally dosed daily in rats (controls, 20, 50, or 150 mg/kg/d) and dogs (controls, 60, 80, or 100/125/160 mg/kg/d) for 26 weeks with a 4-week recovery. Rat vorinostat-related adverse findings are decreased food consumption, weight loss, and hematologic changes; a no observed adverse effects level is not established. In dogs, adverse effects are primarily gastrointestinal; the no observed adverse effects level is 60 mg/kg/d (approximately 6-fold maximum recommended human dose). Toxicities are reversible and can be monitored in the clinic.

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres.

BACKGROUND AND AIM: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. METHODS: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 +/- 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. RESULTS: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. CONCLUSIONS: The FSSG score reflects the severity of the endoscopic findings of GERD.

[Analysis of the clinical benefits and cost-effectiveness of performing a systematic second-look gastroscopy in benign gastric ulcer]. / Estudio del beneficio clínico y de coste-efectividad tras efectuar sistemáticamente una segunda gastroscopia en la úlcera gástrica benigna.

INTRODUCTION: We analyzed the need to routinely perform a second gastroscopy after an initial diagnosis of benign gastric ulcer. METHOD: A total of 226 consecutive cases of gastric ulcer were reviewed. Sensitivity (S), specificity (Sp), positive and negative predictive value (PPV and NPV) and the accuracy of the initial gastroscopy plus biopsy were analyzed, both overall and according to the initial endoscopist's experience (attending or resident physician). The diagnostic accuracy of the initial and second-look gastroscopies was compared. The number of second endoscopies required to diagnose a new case of malignant gastric ulcer and their cost was calculated, both overall and according to the endoscopist's experience. RESULTS: There were 178 benign ulcers (79%) and 48 malignant ulcers (21%). The initial gastroscopy (S: 87.2%; Sp: 100%; PPV: 100%; PNV: 96.7%; accuracy: 96.7%) was performed by an attending physician in 74% of the patients and by a resident physician in the remaining 26%. Diagnostic accuracy was higher for attending physicians than for residents (98.2% vs. 94.8%; p=0.18). The accuracy of second-look endoscopy was 100%, with a significant improvement when compared with the initial procedure (p=0.035). Three new cases of MALT lymphoma and three new cases of gastric adenocarcinoma were diagnosed and could be treated with curative intent. The number of second gastroscopies required to diagnose a new case of malignant gastric ulcer and their economic cost was: 37.3 (4,675 Euros) for the whole group, 55.2 (6,845 Euros) for attending physicians and 19.3 (2,393 Euros) for residents. CONCLUSIONS: Initial gastroscopy showed high diagnostic accuracy, which was slightly lower when performed by resident physicians. Second-look gastroscopy significantly improved the results, confirming the clinical benefit of this procedure in diagnosing potentially curable malignant lesions. The mean cost of each new diagnosis of malignancy was 4,675 Euros, which was three times lower if the initial gastroscopy was performed by a less experienced endoscopist.

[Assessment of rate of hydroxyl anions production by Helicobacter pylori in stomach].

Production of hydroxyl anions by tissue samples of pylorus mucous membrane obtained from 45 patients with gastric or duodenal ulcers was investigated. The production was estimated using the recently developed method based on measurement of rate of pH change in urea-containing reaction mixture. The rate of [OH-] generation as a result of H. pylori metabolism accounted on pylorus square varied from 0.4 to 1318.9 mcmol [OH-]/min, and in 90.2% of cases it did not exceed 128.1 mcmol [OH-]/min. This rate is comparable to mean rate of [H+] generation in stomach of healthy man--114.2-238.4 mcmol [H+]/min. Obtained results allow to conclude that this bacterium may participate in regulation of stomach acid-base balance.

[Comparative assessment of the strength properties of the mucous membrane of the stomach in patients with peptic ulcer and the effect of quamatel on ulcer cicatrization in experiment].

The article reviews the research work of the authors on the strength properties of the mucous membrane of the stomach in patients with peptic ulcer and in experiment with quamatel application. Experiments were performed in laboratory animals and resected stomachs of patients with duodenal or stomach ulcer and complications requiring scheduled surgical treatment. The results of the research into the maximum tension (durability) of the stomach mucous membrane, antrum, and the periulcer area are described. For both localizations of the ulcer, the mucous membrane of the antrum was found to exhibit the least durability, while the highest durability was exhibited by the mucous membrane of the periulcer area. In the case of bulbar ulcer, the durability of the mucous membrane was shown to decrease with an increase in the number of aggravations. An inverse relationship between the strength properties and the intensity of hydrochloric acid production was observed.

Accuracy of the initial endoscopic diagnosis in the discrimination of gastric ulcers: is endoscopic follow-up study always needed?

BACKGROUND: Endoscopic follow-up study of gastric ulcers has been recommended routinely because of the possibility that a gastric neoplasm will be missed in the initial endoscopy. Some authors, most of them reporting data from areas of low gastric carcinoma incidence, have questioned this policy because of the low numbers of curable cancers detected and the high cost of such a program. GOALS: To assess the accuracy of endoscopy diagnosis of gastric ulcers, and to evaluate the efficacy and cost of a gastric ulcer follow-up endoscopic program in an area with an intermediate incidence rate of gastric cancer. STUDY: A retrospective study was used to identify all the gastroscopies in which a gastric ulcer had been diagnosed during a 6-year period. The endoscopic impression was compared with the histologic diagnosis, sensitivity, specificity, positive and negative predictive values, and the likelihood ratio. Patients who completed a follow-up program also were reviewed. For each neoplasm discovered, the number of endoscopies and global cost were calculated. RESULTS: In the 741 gastroscopies performed, 547 gastric ulcers were diagnosed in 529 patients. Biopsies were taken in 330 patients, in whom 341 gastric ulcers were found. At the index endoscopy, 41 gastric neoplasms (12.4%) were diagnosed. The accuracy of endoscopic malignancy diagnosis was as follows: positive predictive value of 0.68, negative predictive value of 0.98, sensitivity of 0.82, and specificity of 0.95. The likelihood ratio was 16. A total of 117 patients completed the follow-up program. Three new cases of gastric cancer (2.6%) were identified. In these three cases, the initial opinion of the endoscopist was uncertain. In the authors' experience, the cost of each gastric cancer diagnosed has been $4.653 (U.S. dollars). CONCLUSIONS: The endoscopic impression correlates with the histologic diagnosis even in a area of intermediate gastric cancer incidence. Endoscopic follow-up study may be restricted to cases of uncertain or malignant endoscopic impression.

[Post-treatment assessment of Helicobacter pylori eradication, by polymerase chain reaction in gastric biopsies]. / Evaluación de la erradicación postratamiento del Helicobacter pylori por reaccion en cadena de la polimerasa en biopsias gástricas.

BACKGROUND: The pre-treatment detection of H.p. in the stomach of patients is easily achieved with routine methods. Conversely, with conventional methods, it is difficult to detect the presence of H.p. after treatment. OBJECTIVE: To estimate the actual percentage of successfully treated patients by using a more sensitive and specific technique (PCR) in the same biopsies where standard methods were negative for H.p. MATERIALS AND METHODS: We selected 97 treated patients (31 Gastric Ulcers/66 Duodenal Ulcers, 62 male/35 female, age: 49 +/- 14 years), in whom success of treatment was defined by histological means and CLO Test. In the same gastric biopsies H.p-DNA PCR was performed. Different therapeutic schemes were utilized, but all included Proton Pump Inhibitors + ATB. Eight weeks after the end of the treatment, without medication, the patients were controlled as follows: 5 biopsies per patient, 2 of antrum, 2 of corpus (in different zones) and 1 for CLO Test. H.p. eradication was defined on histological grounds (gastric biopsy histology: 10% formaldehide buffer fixation, paraffin inclusion, Giemsa, HE staining and inmunohistochemistry), CLO Test (Delta West Pty. Ltd. Bentley, Australia) and by the absence of H.p.-DNA by PCR (amplification of a 296 bp of the species-specific antigen of H.p. and visualization of the amplified product in agarose gel with Ethidium Bromide and UV light). RESULTS: [table: see text] CONCLUSIONS: The higher sensitivity of PCR (10(3) fold more than conventional methods) allowed us in this group of patients to detect 13% of false eradication. It would be necessary to follow up this group of patients in order to know whether they develop or not clinical symptoms and/or histological evidence of disease. If such a case PCR could become an important tool for treatment evaluation.

Gastric ulcers at endoscopy: brush, biopsy, or both?

OBJECTIVES: All gastric ulcers discovered at endoscopy are potentially malignant. Concurrent use of both histological biopsy and cytological brushing has been advocated as a means of increasing the diagnostic yield for neoplasia at the time of initial endoscopy. The purpose of this analysis was to determine the impact of these diagnostic strategies on the cost-effectiveness of detecting malignancy in patients with a gastric ulcer. METHODS: The diagnostic performance of biopsy and brushings in detecting gastric malignancy was estimated from a meta-analysis of published reports. Nondiscounted direct costs were determined from patient resource consumer profiles from the perspective of a Canadian hospital. A decision tree was used to compare diagnostic strategies (biopsy alone, brushing alone, or biopsy and brushing) in a hypothetical cohort of patients found to have a gastric ulcer at endoscopy. Effectiveness was expressed as diagnostic days saved. RESULTS: No strategy achieved dominance. The brushing strategy was the most cost-effective, but its cost-effectiveness ratio was only slightly lower than that of biopsy. Cost differences between the biopsy and brushing strategies were small (less than $6 per case). Performing both biopsy and brushing slightly improved the true-positive rate but resulted in a doubling of the false-positive rate, which in turn led to unnecessary laparotomies. The impact of the high false-positive rate was also seen in the incremental cost of performing both brushings and biopsy ($168-$423 per case). CONCLUSIONS: For gastric ulcers discovered at endoscopy, the preferred strategy is to perform either cytological brushing or histological biopsy. The previously recommended strategy of performing both cytological brushing and histological biopsy should be reconsidered.

Gastroduodenal mucosa in peptic ulcer: endoscopic and histological assessment.

This study aimed to assess the prevalence of endoscopic and histological gastroduodenitis as well as helicobacter-like organisms in patients with peptic ulcer. After diagnostic endoscopy, gastroduodenal biopsy specimens were taken from thirty patients (n = 30) with clinical and endoscopic diagnosis of peptic ulcer (duodenal ulcer = 25, gastric ulcer = 5). Endoscopic gastroduodenitis occurred in 18 patients (60%). Histological gastritis was detected in the gastric body or antrum in 25 (83%) and duodenitis in 17 (57%) patients. There was significant correlation between endoscopic and histological gastritis (p < 0.05). Helicobacter-like organisms occurred in 73% of the patients with peptic ulcer and in 88% of the antral biopsy specimens showing antral gastritis. Presence of helicobacter-like organisms was in particular associated with acute on chronic gastritis compared to chronic gastritis (p < 0.01). Moreover the patients with gastritis were found to belong to the older age group and 81.8% had blood group O +ve (p < 0.01 and p < 0.05 respectively). We conclude that presence of helicobacter-like organisms in patients with peptic ulcer is significantly associated with acute on chronic gastritis.

Interobserver variation in assessment of gastroduodenal lesions associated with non-steroidal anti-inflammatory drugs.

Video endoscopic images were used to investigate whether gastroenterologists could agree on the definition of lesions within the stomach seen at endoscopy, with particular reference to those seen in patients taking non-steroidal anti-inflammatory drugs. Seven experienced endoscopists, unaware of the patients' clinical history or drug consumption, recorded their classification for 93 randomised video images of gastric lesions. There was complete agreement in the diagnosis of ulceration for nine images from patients who were not taking non-steroidal anti-inflammatory drugs; eight of nine were classified as deep ulcers, with 86% agreement for this subclassification. By contrast, the overall agreement for lesions in patients taking non-steroidal anti-inflammatory drugs was only 55%. Only nine of 44 ulcers were subclassified as deep, and there was considerable cross classification of non-haemorrhagic erosions and ulcers. In conclusion, ulcers that occur in patients taking non-steroidal anti-inflammatory drugs differ from those in patients who are not taking these drugs in that they are often more superficial and difficult to distinguish from erosions. The prognostic importance of these lesions is, therefore, uncertain.

Endoscopy, gastric ulcer, and gastric cancer. Follow-up endoscopy for all gastric ulcers?

The practice of following benign-appearing gastric ulcers until healing was critically evaluated in a retrospective manner by reviewing all gastric ulcers that were followed with serial endoscopy and all gastric cancers diagnosed at the University of Alabama at Birmingham. The stated purpose of following ulcers to healing is to detect those gastric cancers that may be masquerading as benign ulcer and were not correctly diagnosed at initial endoscopy. Over a five-year period, 148 gastric ulcers were followed with serial endoscopy and in no case was an unsuspected carcinoma found at follow-up endoscopy. In addition, of 67 gastric cancers diagnosed between 1979 and 1986, 62 were suspected of being malignant by the endoscopist at initial examination for an accuracy of 92%. The accuracy rate based solely on biopsy and/or brush cytology was 94%. When endoscopic and biopsy and/or cytology impressions were combined, only one case of gastric carcinoma was not suspected. The overall accuracy was 99%. These results suggest that if either the endoscopic impression or the biopsy and cytology is suspicious for malignancy, then follow-up endoscopy until healing should be done. On the other hand, if, at the initial examination, the ulcer appears benign and biopsy plus cytology are negative, then serial endoscopy has a low benefit relative to its cost.

Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer.

In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer.

Quality of gastric ulcer healing: histological and ultrastructural assessment.

It has long been assumed that the mucosa in areas of grossly 'healed' gastric or duodenal ulcers returns to normal, either spontaneously or after treatment. This assumption is based almost entirely upon visual, superficial examination by endoscopy. Few, if any, histological and ultrastructural studies examined the deeper mucosa in the areas of grossly healed ulcers. In several experimental studies, we analysed the development, evolution, and healing of acetic acid-induced gastric ulcers in rats and assessed the histological and ultrastructural features (structure and cellular composition) of the gastric mucosa in areas of grossly healed ulcers. The gastric mucosa of grossly 'healed' ulcers showed re-epithelialization of the mucosal surface at every study interval (2 weeks, 2, 3, and 4 months), but the subepithelial mucosa displayed prominent abnormalities. Two patterns of scarring were distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% thinner than normal mucosa) with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; and (b) the mucosa displayed a marked dilation of gastric glands with poor differentiation of the glandular cells and a reduction in the supportive microvascular network. It is theorized that these abnormalities could interfere with oxygenation, nutrient supply, and mucosal resistance and defence; therefore, they could be a basis for ulcer recurrence. These observations indicate that the quality of mucosal structural restoration rather than the speed of ulcer healing is the most important factor in determining risk of ulcer recurrence. The clinical relevance of these findings is supported by a preliminary study in which marked histological abnormalities were found in the subepithelial mucosa in patients with 'healed' duodenal ulcers.