Comparison of eotaxin-3 biomarker in patients with eosinophilic oesophagitis, proton pump inhibitor-responsive oesophageal eosinophilia and gastro-oesophageal reflux disease.

BACKGROUND: Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) is a recently described entity which resembles oeosinophilic oesophagitis (EoE), yet responds to acid suppressive treatment. AIM: To determine whether EoE shares similar staining features with PPI-REE or with gastro-oesophageal reflux disease (GERD). METHODS: This retrospective study consisted of patients with an established diagnosis of EoE, PPI-REE, or GERD identified from a database during a 1-year period. Immunohistochemistry (IHC) analysis was performed specifically targeting eotaxin-3 antibodies. All sections were qualitatively (intensity) and quantitatively (percentage of cells stained) assessed independently by two blinded pathologists. RESULTS: The cohort consisted of three groups of patients: EoE (n = 22), PPI-REE (n = 23) and GERD (n = 23) for a total of 68 patients. Study demographics included mean age 39 (14) years, 75% male and 77% Caucasian. There was a significant difference in the eotaxin-3 staining among EoE, PPI-REE and GERD groups [mean score (s.d.): 1.2 (1.2), 0.8 (1.0), 0.3 (0.7), P = 0.006]. Staining scores of EoE patients were significantly higher compared with GERD (P = 0.002) and a trend towards significance was seen between EoE and PPI-REE (P = 0.054). There was also a significant difference in EoE staining intensity score among the three groups (P = 0.006). Intensity scores of EoE were significantly higher compared with GERD [1.0 (0.9) vs. 0.22 (0.52), P < 0.001]. There was no significant difference between EoE and PPI-REE groups [1.0 (0.0) vs. 0.52 (0.75) P = 0.094]. CONCLUSIONS: A difference in eotaxin-3 staining was seen in the three groups of patients with oesophageal eosinophilia. Eotaxin-3 can distinguish EoE from GERD, but not from proton pump inhibitor responsive-oesophageal eosinophilia.

Prevalence of eosinophilic esophagitis in a United States military health-care population.

Eosinophilic esophagitis (EoE) is a rapidly emerging chronic immune-mediated condition affecting children and adults, both genders, and all races. A large variation in the prevalence of EoE exists in the literature. The aim of this study is to establish the prevalence of EoE in a military health-care population in the United States using a comprehensive electronic medical record search. Using the International Classification for Diseases-9 code for EoE (530.13), the total number of EoE patients enrolled in the military health-care system from October 1, 2008 to September 30, 2009 including active-duty military, dependents of military personnel, and retirees were identified. For each case of EoE identified, demographic data (age, gender, and race) and geographic location was obtained. The overall prevalence of EoE was calculated as well as the prevalence within subgroups. The geographic regional locations were reported per the U.S. Census Bureau regions (Northeast, South, Midwest, and West). A total of 987 EoE patients were identified from 10,180,515 military health-care beneficiaries, establishing an overall prevalence of 9.7 per 100,000 (95% confidence interval [CI] 9.1-10.3). Seven hundred twenty-eight out of 7,707,372 adult patients were identified, establishing a prevalence of 9.5 per 100,000 (95% CI 8.8-10.1). Two hundred fifty-nine out of 2,473,143 pediatric patients were identified, establishing a prevalence of 10.5/100,000 (95% CI 9.2-11.8). EoE was more prevalent in males (odds ratio [OR] 2.03 [95% CI 1.78-2.32]) and higher in Caucasian versus African Americans (18.1 vs. 5.2/100,000, OR 3.47 [95% CI 2.40-5.03]). EoE was more prevalent in the Western region of the United States compared with the Northeast, South, and Midwest regions, with a prevalence of 11.9 versuss 5.2, 9.6, and 9.2 per 100,000, respectively. When comparing Northern with Southern states, there was an increased prevalence in the North (10.9 vs. 7.2/100,000, P < 0.05). In this large nationwide study, increase in prevalence of EoE was seen in younger adults, with a higher prevalence in Caucasians. Geographically, the western United States had a significantly higher prevalence with a slightly higher prevalence in the Northern latitude.

Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings.

BACKGROUND: Some patients with a phenotypic appearance of eosinophilic oesophagitis (EoE) respond histologically to PPI, and are described as having PPI-responsive oesophageal eosinophilia (PPI-REE). It is unclear if PPI-REE is a GERD-related phenomenon, a subtype of EoE, or a completely unique entity. AIM: To compare demographic, clinical and histological features of EoE and PPI-REE. METHODS: Two databases were reviewed from the Walter Reed and Swiss EoE databases. Patients were stratified into two groups, EoE and PPI-REE, based on recent EoE consensus guidelines. Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least a 6-week course of treatment. RESULTS: One hundred and three patients were identified (63 EoE and 40 PPI-REE; mean age 40.2 years, 75% male and 89% Caucasian). The two cohorts had similar dysphagia (97% vs. 100%, P = 0.520), food impaction (43% vs. 35%, P = 0.536), and heartburn (33% vs. 32%, P = 1.000) and a similar duration of symptoms (6.0 years vs. 5.8 years, P = 0.850). Endoscopic features were also similar between EoE and PPI-REE; rings (68% vs. 68%, P = 1.000), furrows (70% vs. 70%, P = 1.000), plaques (19% vs. 10%, P = 0.272), strictures (49% vs. 30%, P = 0.066). EoE and PPI-REE were similar in the number of proximal (39 eos/hpf vs. 38 eos/hpf, P = 0.919) and distal eosinophils (50 vs. 43 eos/hpf, P = 0.285). CONCLUSIONS: EoE and PPI-responsive oesophageal eosinophilia are similar in clinical, histological and endoscopic features and therefore are indistinguishable without a PPI trial. Further studies are needed to determine why a subset of patients with oesophageal eosinophilia respond to PPI.

Reflux episodes detected by impedance in patients on and off esomeprazole: a randomised double-blinded placebo-controlled crossover study.

BACKGROUND: Combined with 24-h pH monitoring, the use of impedance is the most sensitive method available for detecting oesophageal reflux. Normal values for impedance have been previously established in healthy controls studied on and off proton pump inhibitors (PPI). AIMS: To determine the effects of PPIs on the total number of reflux episodes in the distal oesophagus measured by impedance in patients with and without gastro-oesophageal reflux disease (GERD). METHODS: In this prospective randomised double-blinded placebo controlled crossover study, all patients underwent two 24-h pH with impedance studies at least 2 weeks apart. Based on a randomisation scheme, patients received either 40 mg of esomeprazole twice daily for 1 week or identical capsule placebo for 1 week, then all patients were crossed over to the other treatment arm. GERD was defined by the validated Johnson-DeMeester score. Reflux by impedance was defined as a 50% decrease from baseline in retrograde movement of liquid between two impedance sites. RESULTS: Sixty-three patients were enrolled and 41 patients completed the study [mean age 52 ± 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African American]. Overall, there was no significant decrease in the total number of distal impedance episodes with esomeprazole compared with placebo (mean change 6.1 ± 22, P = 0.100). When analysed separately by GERD status, among GERD-positive patients, there was a significant decrease in distal impedance episodes while on esomeprazole compared with placebo (mean change -16 ± 22, P = 0.023), but not in GERD-negative patients (mean change -0.35 ± 20, P = 0.872). CONCLUSION: Esomeprazole decreases significantly the number of reflux episodes detected by impedance, but only in patients with GERD.

Safety of dilation in adults with eosinophilic esophagitis.

Esophageal dilation is an effective therapy for dysphagia in patients with stenosing eosinophilic esophagitis (EoE). Historically, there have been significant concerns of increased perforation rates when dilating EoE patients. More recent studies suggest that improved techniques and increased awareness have decreased complication rates. The aim of this study was to explore the safety of dilation in our population of EoE patients. A retrospective review of all adult EoE patients enrolled in a registry from 2006 to 2010 was performed. All patients who underwent esophageal dilation during this time period were identified and included in the analysis. Our hospital inpatient/outpatient medical records, radiology reports, and endoscopy reports were searched for evidence of any complication following dilation. Perforation, hemorrhage, and hospitalization were identified as a major complication, and chest pain was considered a minor complication. One hundred and ninety-six patients (41 years [12]; mean age [standard deviation], 80% white, 85% male) were identified. In this cohort, 54 patients (28%) underwent 66 total dilations (seven patients underwent two dilations, one patient underwent three dilations, and one patient underwent four dilations). Three dilation techniques were used (Maloney [24], Savary [29] and through-the-scope [13]). There were no major complications encountered. Chest pain was noted in two patients (4%). There were no endoscopic features (rings, furrows, plaques) associated with any complication. Type of dilator, size of dilator, number of prior dilations, and age of patient were also not associated with complications. Endoscopic dilation using a variety of dilators can be safely performed with minimal complications in patients with EoE.

Randomised clinical trial: the effect of baclofen in patients with gastro-oesophageal reflux--a randomised prospective study.

BACKGROUND: Baclofen, a GABA(B) agonist, has been shown to reduce transient lower oesophageal sphincter relaxations (TLESRs), a major cause of gastro-oesophageal reflux disease (GERD). AIM: To examine the effect and tolerability of baclofen in GERD patients over a 2-week period. METHODS: Forty-three GERD patients with abnormal 24-h pH tests were prospectively randomised to receive baclofen or placebo in a double-blind fashion for 2 weeks. Oesophageal manometry, 24-h pH monitoring, and a standard questionnaire was administered, before and after treatment. RESULTS: Thirty-four patients completed the study. In the baclofen group there were significant decreases in 24-h pH score (P = 0.020), percent of upright reflux episodes (P = 0.016), percent total time pH <4 (P = 0.003), number of reflux episodes (P = 0.018), number of reflux episodes longer than 5 min (P = 0.016), number of postprandial reflux episodes (P = 0.045), and percentage of time pH <4 (P = 0.003). No significant changes in reflux parameters were noted in the placebo group. Patients receiving baclofen had significantly less belching (P = 0.038), regurgitation (P = 0.036) and overall symptom score (P = 0.004) whereas placebo patients had less heartburn (P = 0.001), chest pain (P = 0.002), regurgitation (P = 0.017) and overall symptom score (P = 0.000). However, there were no significant differences in changes of reflux parameters or symptoms when comparing the two groups. Drowsiness did not limit baclofen use. CONCLUSIONS: Baclofen was associated with a significant decrease in percent upright reflux by 24-h pH monitoring and a significant improvement in belching, regurgitation and overall symptom score. Baclofen may be more effective in patients with predominantly upright reflux and belching.

Correlation between eosinophilic oesophagitis and aeroallergens.

BACKGROUND: Aeroallergens have been implicated in the pathogenesis of eosinophilic oesophagitis. AIM: To determine whether a seasonal variation exists in the diagnoses of eosinophilic oesophagitis and whether there is a correlation with seasonal pollen count. METHODS: A retrospective review was performed from January 2006 to November 2008 to identify eosinophilic oesophagitis patients. Cases were classified by endoscopic date. Daily pollen counts for grass, trees and weeds were obtained from a certified counting station. Per cent of eosinophilic oesophagitis cases were collated seasonally and compared with mean pollen counts for grass, trees and weeds during the same time period. RESULTS: A total of 127 eosinophilic oesophagitis cases were identified (median age 41, range 19-92 years, 84% men). The highest percentage of cases (33.0%; Binomial P = 0.022) was diagnosed in the spring, while the least percentage (16%; Binomial P = 0.0.010) occurred in the winter. There was a significant association between per cent eosinophilic oesophagitis cases diagnosed seasonally and mean grass pollen count (r(s) = 1.000, P < 0.01), but not with trees (r(s) = 0.400, P = 0.600) or weeds (r(s) = 0.800, P = 0.200). CONCLUSIONS: A seasonal variation was seen in the diagnosis of eosinophilic oesophagitis which correlated with pollen counts. These findings have important implications regarding the pathogenesis of eosinophilic oesophagitis, suggesting a potential role for aeroallergens.

Prevalence of esophageal dysmotility in a cohort of patients with esophageal biopsies consistent with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is increasingly being diagnosed in adults presenting with dysphagia, food impactions, and chest pain. Studies to date provide conflicting data on the association of EoE and esophageal dysmotility. The objective of this study was to evaluate the prevalence of esophageal dysmotility in a cohort of patients with biopsies consistent with EoE at a military treatment facility. This is a prospective evaluation of consecutively identified patients at our institution diagnosed with EoE from March 1, 2005 to June 1, 2007. Thirty-two patients with biopsies consistent with EoE completed a symptom survey and 30 underwent esophageal manometry. The majority of EoE patients (23/30, 77%) had a normal end-expiratory lower esophageal sphincter (LES) pressure (normal range 10-35), whereas six patients had a low-normal LES pressure (6-9 mm Hg) and one patient had a decreased LES pressure (<5 mm Hg). Five patients (15.6%) were diagnosed with a nonspecific esophageal motor disorder (NSEMD). Two patients had high mean esophageal amplitude contractions >180 mm Hg (188 mm Hg, 209 mm Hg). No patient was diagnosed with nutcracker esophagus or diffuse esophageal spasm. Patients with and without NSEMD reported a similar degree of swallowing difficulty, heartburn, belching, chest pain, regurgitation, symptoms at night, and total symptom score. Likewise, eosinophil count on mucosal biopsy was similar between patients with and without a NSEMD. In this cohort, we found the prevalence of an NSEMD to be similar to that of a 10% prevalence found in a gastroesophageal reflux population.

Characterization of esophageal striated muscle in patients with achalasia.

Many studies have been conducted analyzing the manometric properties of patients with achalasia, but the striated portion of the esophagus has never been analyzed and is often overlooked. We retrospectively reviewed 120 manometric tracings (20 achalasia, 100 controls) performed between 1994 and 1997 and excluded tracings from patients with chronic cough and nutcracker esophagus. The data were assessed for age, sex, symptoms, duration of symptoms, lower esophageal sphincter pressure, gastroesophageal gradient, upper esophageal sphincter pressure, smooth muscle contraction amplitude and duration, striated muscle contraction amplitude and duration, length from upper esophageal sphincter to maximal striated muscle contraction, and esophageal length. The maximum striated muscle contraction amplitude was significantly decreased in achalasia patients with a median amplitude of 45 mm Hg (range 12-95) vs 76 mm Hg (range 30-210) in the control group (P = 0.002). Although the wave forms were similar, the maximum striated muscle contraction duration and the distance from the upper esophageal sphincter in achalasia patients was not significantly different from controls. The length of the esophagus was significantly longer in achalasia patients with a median value of 25 cm (range 21-30) vs 21 cm (range 17-26) in the control group (P < 0.001). Patients with achalasia have significantly lower maximum striated muscle contraction amplitudes and longer esophagi, but the duration of the contractions and the configuration of the wave forms are not different.

The effect of oral decontamination with clindamycin palmitate on the incidence of bacteremia after esophageal dilation: a prospective trial.

BACKGROUND: Antibiotic prophylaxis to prevent bacterial endocarditis is recommended in high-risk patients undergoing esophageal dilation, a high-risk procedure. Some studies suggest that the oropharynx is the source of bacteremia. A topical antibiotic mouthwash, which reduces bacterial colonization of the oral flora, might decrease bacteremia rates and would be an attractive alternative to systemic administration of antibiotics. METHODS: Adults undergoing outpatient bougienage for a benign or malignant esophageal stricture were randomized in a clinician-blinded fashion to either pre-procedure clindamycin mouthwash or no treatment. Subjects were stratified by type of dilator used. Blood cultures were obtained immediately after the first esophageal dilation and 5 minutes after the last dilation. RESULTS: Fifty-nine patients were enrolled: 30 in the treatment arm and 29 in the no-treatment arm. There were 7 positive blood cultures: 5 in the treatment arm and 2 in the no-treatment arm. The identified organisms were Streptococcus viridans (2), Staphylococcus mucilaginous (2), Lactobacillus (2), and Actinomyces odontolyticus (1). Patients with bacteremia reported greater subjective difficulty with dysphagia (p = 0.01) irrespective of stricture diameter, procurement of biopsies, or dilator type. CONCLUSIONS: The percentage of cases with bacteremia for all dilations performed in this manner was 12% (95% CI [5.3, 23.6]), much lower than previously cited. All organisms in this study were oral commensals. There appears to be no effect of a clindamycin mouthwash on reducing bacteremia after esophageal dilation.

Lectin binding to human colonocytes is predictive of colonic neoplasia.

OBJECTIVE: The aim of this study was to determine whether lectin binding to exfoliated human colonocytes could be used as a noninvasive test for colorectal polyps or cancer. METHODS: Colonocytes were harvested from 31 patients (10 controls, 10 with adenomatous polyps, and 11 with cancer), incubated with a panel of fluorescent-labeled lectins, and assayed by flow cytometry. RESULTS: The lectins jacalin (JAC) and wheat germ agglutinin (WGA) were useful in predicting the presence of a colorectal neoplasm (p = 0.0018 for JAC and p = 0.0099 for WGA). For JAC, sensitivity reached 81% with a specificity of 80%, and for WGA the sensitivity and specificity were both 75%. CONCLUSIONS: Lectin binding to human colonocytes can predict the presence of malignant and premalignant lesions of the colon, and has potential as a noninvasive screening tool for colorectal neoplasms.

Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: prevalence and clinical data.

BACKGROUND & AIMS: Adenocarcinoma of the esophagus and esophagogastric junction (EGJ) is increasing, the earliest lesion being specialized intestinal metaplasia (SIM). This study determined the prevalence and demographic features of patients with SIM, dysplasia, and cancer in the esophagus and EGJ. METHODS: Two antegrade biopsy specimens were taken distal to the squamocolumnar junction (SCJ) and any tongues of pink mucosa proximal to the SCJ. Patients were categorized endoscopically and histologically as having long-segment (LSBE) or short-segment Barrett's esophagus (SSBE), EGJ-SIM, or a normal EGJ. RESULTS: Of 889 patients studied, 56 were undergoing esophagoduodenoscopy screening or surveillance and were not included in the prevalence calculation. The overall prevalence of SIM was 13.2%, with 1.6% LSBE, 6.0% SSBE, and 5.6% EGJ-SIM. Dysplasia or cancer was noted in 31% of LSBE, 10% of SSBE, and 6.4% of EGJ-SIM patients (P

Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short and long segment Barrett's esophagus.

OBJECTIVE: Short segment Barrett's esophagus (SSBE) is defined as the presence of specialized intestinal metaplasia (SIM) in the distal 2-3 cm of the esophagus. Although gastroesophageal reflux and heartburn is very common in these patients, the pathophysiology of the development of a short segment of SIM versus a longer segment of Barrett's epithelium is not clear. The aim of this study was to assess the extent of gastroesophageal reflux in short versus long segments of SIM. METHODS: Of 203 consecutive patients undergoing endoscopy with two biopsies performed just distal to the squamocolumnar junction, 28 patients were identified as having SSBE as evidenced by SIM on biopsy. Twenty-two SSBE patients underwent esophageal manometry and 24-h dual pH monitoring, and the results were compared with 18 long segment Barrett's esophagus (LSBE) patients and 15 patients with normal 24-h pH studies. RESULTS: SSBE and LSBE patients were significantly older than normal subjects (p < 0.0001). Also, lower esophageal sphincter pressure was significantly greater in SSBE patients compared with LSBE patients (12.3 +/- 1.6 vs 5.2 +/- 1.0 mm Hg,p < 0.0008). LSBE patients had a significantly lower distal esophageal peristaltic amplitude as compared with normals (p < 0.012). At 5 cm proximal to the LES, SSBE patients had significantly lower total 24-h pH scores, percent upright and percent supine reflux as compared with LSBE patients. Similarly, when measured at the proximal LES (0 cm), SSBE patients had significantly lower 24-h pH scores when compared with LSBE patients (p < 0.03), whereas percent upright and percent supine reflux were not significantly different. Both LSBE and SSBE patients had a greater degree of GER measured at 5 cm above and just proximal to the LES when compared with normals. CONCLUSION: As a group, SSBE patients have more competent LES sphincters and less gastroesophageal reflux at 0 and 5 cm above the LES as compared with patients with LSBE. These data indicate that the degree and length of acid exposure in the esophagus are important factors in the pathogenesis of SIM involvement of the esophagus.

Evaluation of liver histology, ALT elevation, and HCV RNA titer in patients with chronic hepatitis C.

OBJECTIVE: Hepatic histological evaluation is currently the gold standard to determine the degree of liver injury in chronic hepatitis C. It is unclear whether degree of serum ALT elevation or quantitative hepatitis C virus (HCV) RNA can predict level of histological damage. METHODS: Fifty nine biopsies from 44 patients with chronic hepatitis C were reviewed. The amount of liver damage was quantified using the Histology Activity Index (HAI) and was compared with serum ALT and, in 26 biopsies, quantitative HCV RNA (branched DNA amplification, Quantiplex, Chiron). RESULTS: A statistically significant linear relationship was noted between degree of ALT elevation and amount of liver injury based on HAI score (p < 0.05) although this relationship was not statistically strong (rs = 0.4900). No significant correlation was noted between serum ALT and HCV RNA titer (rs = 0.4044) or between quantitative HCV RNA titer and HAI score (rs = 0.3506). No individual component of the HAI correlated with ALT or HCV RNA. CONCLUSIONS: Although there is a correlation between serum ALT and degree of hepatic injury based on HAI score, this relationship is weak and probably of no clinical use. There is no significant correlation between HCV RNA and serum ALT or HCV RNA and degree of hepatic injury in individual patients. Hepatic histological evaluation continues to be required for clinical assessment of patients with chronic hepatitis C.

Utility of parameters measured during pneumatic dilation as predictors of successful dilation.

OBJECTIVES: The ability to immediately predict the long term outcome of a pneumatic dilation in achalasia has not been well studied. This study prospectively compared immediate postpneumatic dilation parameters with long term efficacy to determine if any factors predicted a favorable long term outcome. METHODS: Twenty-nine previously undilated achalasia patients underwent graduated pneumatic dilation with Hurst-Tucker dilators (diameters 2.7, 3.3, 3.7, and 4.1 cm). Dilations began with the smallest dilator followed by an observation period of at least 6 wk to determine clinical response. If no clinical improvement was noted, the next size dilator was used. Immediate postdilation parameters studies included: 1) severity of pain during dilation, 2) amount of blood on the dilator, 3) insufflation pressures during dilation, 4) esophageal emptying of gastrograffin (30 ml), and 5) esophageal emptying of barium sulfate (90 ml). RESULTS: None of the postdilation parameters studied predicted which patients would have good long term results. Pain during dilation increased with increasing dilator size. CONCLUSIONS: The degree of pain associated with a pneumatic dilation, the amount of blood noted on the dilator, the difference in pressure required to inflate the dilator at the beginning versus the end of dilation, and the amount of esophageal emptying immediately postdilation did not predict long term outcome.

Effect of cigarette smoking on gastroesophageal reflux measured by 24-h ambulatory esophageal pH monitoring.

OBJECTIVE: We reassessed the effect of cigarette smoking on gastroesophageal reflux because two previous ambulatory 24-h pH monitoring studies showed equivocal results and did not relate heartburn to changes in pH reflux events. METHODS: Our protocol design considered nicotine's pharmacokinetic half-life; 14 smokers with heartburn and esophagitis abstained from smoking for 48 h before and during an ambulatory 24-h esophageal pH monitoring study (24-h pH). After resuming their smoking habits for 48 h or more, they underwent a second 24-h pH study and smoked 20 regular, filtered Marlboro cigarettes. Acid reflux was defined as a drop in intraesophageal pH to a value < 4 at 5 cm above the lower esophageal sphincter and was measured as percent exposure and reflux events (total N, those > or = 5 min, and longest event). Heartburn episodes were noted by the patients and were correlated later to acid reflux events. RESULTS: Cigarette smoking significantly increased the percentage time that the pH was < 4 during a 24-h period from 7.35 to 11.1% (medians; p < 0.007). This increased exposure occurred predominantly during the day while in the upright posture and resulted from significant increases in both reflux events and those parameters that measure acid clearance (T events > or = 5 min and longest event). While smoking, the patients noted a 114% increase in daytime heartburn episodes that immediately followed a pH reflux event (3.5 to 7.5 episodes, medians; p < 0.009). CONCLUSIONS: Smoking 20 cigarettes has a greater effect on acid reflux and heartburn than purported.

Analysis of 3,294 cases of upper gastrointestinal bleeding in military medical facilities.

OBJECTIVES: Upper gastrointestinal bleeding (UGIB) remains a commonly encountered medical emergency with significant morbidity and mortality. Most large studies detailing the specific incidence, demographic, and mortality data were performed more than a decade ago. This study analyzes 3,294 cases of UGIB from 139 military medical treatment facilities over a 12-month period. METHODS: A retrospective chart review of Department of Defense military medical treatment facilities for UGIB was performed from October 1990 through September 1991. Core data such as demographic information were analyzed, as well as specific data relating to UGIB. RESULTS: The incidence of UGIB was 36 per 100,000 population with a male-to-female ratio of 2.18 and a mean age of 52 +/- 19.65 yr. The number of cases increased with age; 44.5% of all patients were > or = 60 yr old. The overall mortality was 7.0% (231 of 3294), and death rates were similar among males and females (7.1% vs. 6.8%) with an odds ratio of 1.03 (CI: 0.77-1.402). Mortality increased with age in both genders; 73.2% of deaths occurred in patients more than 60 yr old. Comorbid illness was noted in 50.9% (1675 of 3294) of patients, with similar occurrence in males (48.7%) and females (55.4%). One or more comorbid illnesses were noted in 98.3% of the patients who died, and in 72.3% of cases, they were the primary cause of death. Bleeding was the primary cause of death in 18.6% of patients. Upper endoscopy was performed in 68.8% of cases, therapeutic endoscopy in 12.6%, repeat endoscopy in 10.7%, and surgery in 4.4%. Blood transfusions were administered in 47.3% of cases, with most patients receiving < 5 units of blood. Rebleeding after initial hemostasis was noted in 7.1% of cases. Factors related to increased mortality include age > 60 (p < 0.001), transfusion requirement > 5 U (p < 0.001), presence of comorbid illness (p < 0.001), rebleeding after initial hemostasis (p < 0.005), surgery (p < 0.001), and UGIB occurring during hospitalization (p = 0.027). CONCLUSIONS: We conclude: 1) The incidence of UGIB is 2-fold greater in males than in females, in all age groups; however, the death rate is similar in both sexes. 2) The mortality rate in this study is slightly lower than in most previous studies and may be more reflective of the average mortality in the community at large. 3) In UGIB patients, comorbid illness and not actual bleeding is the major cause of death. 4) Upper endoscopy was performed less often in this study than in other studies, and there were fewer blood transfusions; however, rebleeding and mortality rates remained similar.

The effect of indomethacin on the secretion of human salivary epidermal growth factor.

Ulceration associated with nonsteroidal anti-inflammatory drug (NSAID) use is a common problem in elderly patients. The postulated cause of NSAID ulceration is multifactorial but is probably related to the inhibition of the cyclo-oxygenase pathway and a subsequent decrease in mucosal prostaglandin levels. Epidermal growth factor (EGF), on the other hand, has been shown to be gastroprotective, stimulating DNA synthesis, and preventing ASA-induced gastric ulceration. Since EGF is important in gastric mucosal protection, we questioned whether the potential ulcerogenic properties of indomethacin were related in part to decreasing salivary EGF. Twenty healthy male volunteers with no gastrointestinal complaints received indomethacin 50 mg P.O. t.i.d. for 3 consecutive days. Saliva and serum were collected before indomethacin treatment and repeated 2 h after the last indomethacin dose. Stimulated salivary samples were collected for 15 min in fasted subjects and assayed for EGF, whereas serum indomethacin levels were determined by high-performance liquid chromatography. EGF levels significantly decreased by 33% after indomethacin (p < 0.03), and this decrement was linearly related to serum indomethacin concentrations (r = 0.58; p < 0.048). Salivary output did not change after indomethacin treatment. Based on this data, we concluded that indomethacin's ulcerogenic properties may be related to its prostaglandin inhibitory properties as well as its ability to decrease salivary EGF output.

beta-Carotene inhibits rectal mucosal ornithine decarboxylase activity in colon cancer patients.

Colonic adenocarcinoma affects approximately 6% of adults in many Western countries. beta-Carotene (BC), a safe, inexpensive, and widely available compound, has been proposed as a cancer chemopreventive agent. To evaluate whether BC shows promise as an inhibitor of colonic carcinogenesis, we studied 20 male subjects who had previously undergone resection of colonic adenocarcinoma. Each subject received beta-carotene, 30 mg orally, daily for 6 months. Rectal mucosa was sampled at multiple intervals prior to, during, and following BC administration. Mucosal ornithine decarboxylase (ODC) activity and serum and mucosal BC concentrations were determined at each interval. ODC activity was inhibited by 44% (P < 0.05) and 57% (P < 0.01) after 2 and 9 weeks, respectively, of BC administration and remained low compared with baseline even 6 months following discontinuation of BC. Serum and mucosal BC concentrations increased as expected during BC administration and remained elevated for 6 months following BC discontinuation. The demonstrated inhibition of rectal mucosal ODC activity in these patients with resected colon cancer suggests that BC may prove useful as a cancer chemopreventive agent.