Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.

Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.

Histological quality of polyps resected using the cold versus hot biopsy technique.

BACKGROUND AND STUDY AIMS: The monopolar hot biopsy technique is a widespread method of removing and cauterizing small colonic polyps. Due to the insulated cups of the biopsy forceps, it also allows adequate histological interpretation of the resected specimen. In our experience, polyps removed using the monopolar hot biopsy technique have been less histologically interpretable in comparison with polyps removed using cold biopsy forceps. The aim of this study was to assess and compare the diagnostic quality of polyps obtained using the hot biopsy and cold biopsy techniques. PATIENTS AND METHODS: This was a prospective study of consecutive patients undergoing colonoscopy with removal of polyps using either hot biopsy or cold biopsy techniques. One experienced endoscopist using the same techniques carried out the biopsies. An experienced gastrointestinal pathologist, blinded to the technique used, evaluated the specimens for diameter, artifacts, cautery damage, tissue fragmentation, and general histological and diagnostic quality. Statistical analysis was carried out using the chi-squared test, Fisher's exact test, and Student's t-test. RESULTS: Forty-three consecutive patients (84 % men; mean age 63.8 +/- 15 years) underwent 88 biopsies (45 hot biopsies and 43 cold biopsies). There were no statistically significant differences between the two study groups with regard to demographic data, indications for colonoscopy, endoscopic findings, or polyp size. Cautery damage, architectural distortion, and tissue fragmentation occurred more frequently in polyps resected using the hot biopsy technique ( P < 0.001). CONCLUSIONS: The quality of the specimens removed by cold biopsy was generally better than when using hot biopsy technique. Histological evaluation is more difficult in polyps resected with the hot biopsy technique in comparison with the cold biopsy technique. When the nature of polyps affects the patient's management, a biopsy may be obtained before polyp coagulation.

Placement of PEG tubes through previously placed self-expanding esophageal metal stents.

BACKGROUND: Self-expanding metal stents are frequently used to palliate patients with malignant dysphagia and close tracheoesophageal fistulae. Despite proper stent positioning and deployment, in a subset of patients there is no improvement in dysphagia, closure of tracheoesophageal fistulae, or resolution of anorexia. Such patients may require a PEG tube. It has been suggested that PEG placement through a preexisting esophageal stent is problematic because of the risks of gastrostomy tube impaction within the stent and resultant stent migration. METHODS: Case records were retrospectively reviewed of 9 consecutive patients with indwelling esophageal self-expanding metal stents undergoing attempted PEG. OBSERVATIONS: PEG tube placement was successful in all patients. In 1 patient, the stent migrated distally into the stomach during PEG placement. This was managed endoscopically without further complication. CONCLUSIONS: PEG placement in patients with previously placed esophageal self-expanding metal stents is a relatively safe and feasible procedure, although stent migration may occur.

Gastrointestinal infections in children.

Gastrointestinal infections in children are a major cause of morbidity and mortality worldwide. Children living in developing countries are particularly susceptible to infectious diarrhea because of poor standards of hygiene and sanitation. Although the magnitude of diarrheal illnesses in developed countries is less, costly hospital admissions are still frequent. The causal agent of infectious diarrhea is most frequently related to age, geographical location, lifestyle habits, use of antibiotics, associated medical conditions, social circumstances, and degree of immune competence. In this article we present some of the most important articles published in the field during the last year. The role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer disease has been shown in adults and children. Information about the natural history of H. pylori, symptomatology, and diagnostic therapeutic approaches for children are being generated constantly; we discuss some of the most relevant information in this review.

Investigation of diarrhea in AIDS.

Chronic diarrhea is a common problem in patients with acquired immune deficiency syndrome (AIDS), resulting in significant morbidity and potential mortality. In the early stages of immunodeficiency, human immunodeficiency virus (HIV)-infected patients are susceptible to infection with the same enteric pathogens that cause diarrhea in immunocompetent hosts, but with progressive immunodeficiency, these patients become susceptible to numerous opportunistic disorders. The main factor to consider when tailoring the work-up of diarrhea in the HIV-infected patient is the immune status, which is reflected by the total CD4 lymphocyte cell count. A CD4 count of less than 100 cells/microL is significantly correlated with opportunistic disorders. For the HIV-infected patient with diarrhea, repeated stool studies to investigate for bacteria, ova and parasites should be the first step. When either upper or lower gastrointestinal tract symptoms are present and stool studies are negative, endoscopy directed to the probable organ of involvement is appropriate. If localizing symptoms are absent, the most appropriate next test is sigmoidoscopy with biopsies. Not infrequently, despite extensive evaluation, the cause of diarrhea in patients with AIDS remains unexplained. Recently, the widespread use of highly active antiretroviral therapy, including protease inhibitors, has led to a change in the epidemiology of diarrhea in AIDS patients. As their immune status improves, HIV-infected patients treated with combination therapy become less prone to opportunistic disorders. However, diarrhea appears to be frequent because several antiretroviral agents can themselves cause diarrhea.

Diagnosis and treatment of esophagitis in AIDS.

At least 30% of patients with AIDS experience esophageal symptoms at some point during the course of HIV infection. The aim of this review is to provide a practical approach to the evaluation and therapy of esophagitis in AIDS.

Special histologic stains are rarely beneficial for the evaluation of HIV-related gastrointestinal infections.

During a 28-month period, endoscopic mucosal biopsy specimens from all HIV-infected patients were submitted for routine histologic evaluation. Immunoperoxidase staining for cytomegalovirus and herpesvirus antigens (esophagus), mycobacterial and fungal staining, and Gram staining of mucosal biopsy specimens were done. Special fungal and acid-fast stains were selectively performed in patients with absolute CD4 cell counts of less than 200 cells per microliter (200 x 10(6)/L) and/or with diarrhea and or wasting syndrome. Treatment was based on the endoscopic and histologic findings, and long-term follow-up was performed. The 121 symptomatic HIV-infected patients underwent 221 upper and/or lower endoscopies with 285 biopsy sites. The sensitivity and specificity of H&E staining for the diagnosis of gastrointestinal cytomegalovirus were 97% and 100%, respectively. The results of fungal and mycobacterial stains neither altered therapy nor identified previously undiagnosed infections in any patient. Long-term follow-up revealed no patient in whom an infection was missed on routine H&E, which affected outcome. Routine H&E staining is accurate for the diagnosis of gastrointestinal opportunistic infections in HIV-infected patients. Special histologic stains for fungal, mycobacterial, and viral infections did not increase the diagnostic yield or alter medical therapy but doubled the costs.

Cocaine-associated ischemic colitis.

Cocaine use can result in various gastrointestinal complications, including gastric ulcerations, retroperitoneal fibrosis, visceral infarction, intestinal ischemia, and gastrointestinal tract perforation. We report cocaine-associated colonic ischemia in three patients and review the literature. Including ours, 28 cases have been reported, with a mean patient age of 32.6 years (range, 23 to 47 years); 53.5% were men and 46.5% were women. The interval between drug ingestion and onset of symptoms varied from 1 hour to 2 days. Cocaine is a potentially life-threatening cause of ischemic colitis and should be included in the differential diagnosis of any young adult or middle-aged patient with abdominal pain and bloody diarrhea, especially in the absence of estrogen use or systemic disorders that can cause thromboembolic events, such as atrial fibrillation.

Cyclooxygenase-2 inhibitor celecoxib: a possible cause of gastropathy and hypoprothrombinemia.

Gastrointestinal side effects from nonsteroidal anti-inflammatory drugs (NSAIDs) result mainly from inhibition of the enzyme cyclooxygenase (COX)-1; it is responsible for the synthesis of prostaglandin E2, which leads to increased mucosal blood flow, increased bicarbonate secretion, and mucus production, thus protecting the gastrointestinal mucosa. In inflammation, COX-2 is induced, causing synthesis of the prostaglandins in conditions such as osteoarthritis and rheumatoid arthritis. Two NSAIDs (celecoxib and rofecoxib) with very high specificity for COX-2 and virtually no activity against COX-1 at therapeutic doses have been approved for clinical use. In trials of celecoxib and rofecoxib, only 0.02% of patients had clinically significant gastrointestinal bleeding, compared to a 1% to 2% yearly incidence of severe gastrointestinal side effects with NSAIDs. Our patient had arthritis of the hips and chronic atrial fibrillation and was on warfarin therapy for stroke prevention; less than a week after starting celecoxib therapy, gastrointestinal bleeding and hypoprothrombinemia occurred.

Esophageal ulcer caused by cytomegalovirus: resolution during combination antiretroviral therapy for acquired immunodeficiency syndrome.

A 36-year-old man with a 5-year history of untreated human immunodeficiency virus (HIV) infection had odynophagia for 14 days. Fifteen days earlier, he had begun taking trimethoprim-sulphamethoxazole and combination antiretroviral therapy that included lamivudine, zidovudine, and nelfinavir. He had no history of opportunistic infection. The CD4 lymphocyte count was 67/microL and HIV-RNA level was 359,396 copies/mL. Esophagogastroduodenoscopy revealed a large, well-circumscribed esophageal ulceration 31 cm from the incisors. Histopathologic examination of esophageal biopsy specimens showed cytopathic changes diagnostic of cytomegalovirus (CMV). In situ DNA hybridization was positive for CMV. While combination antiretroviral therapy was continued, the esophageal symptoms resolved within 4 days of endoscopy without specific therapy for CMV. Follow-up endoscopy 4 weeks later revealed a normal-appearing esophagus, and the patient has remained symptom-free for 10 months.

Declining prevalence of opportunistic gastrointestinal disease in the era of combination antiretroviral therapy.

OBJECTIVE: Opportunistic disorders (OD) are the most frequent GI manifestations of the acquired immunodeficiency syndrome (AIDS). Since the introduction of highly active antiretroviral therapy (HAART), there appears to be have been a reduction in the incidence of many of these OD; however, the effect of HAART on the prevalence of GI OD has not been well studied. METHODS: From 4/95 through 3/98, all HIV (HIV)-infected patients undergoing GI endoscopy were prospectively identified; mucosal biopsies were obtained in a standardized fashion and histological specimens were examined by a single GI pathologist. Patients were divided into three groups based on the time of evaluation: group I: 4/95 to 3/96; group II: 4/96 to 3/97; and group III: 4/97 to 3/98. RESULTS: A total of 166 patients (90% men; mean age 36+/-10 yr; median CD4 lymphocyte count 62 cells/microl, range 2-884, median viral RNA level 1,357 copies/ml, range undetectable to 7,721,715) underwent 279 upper and/or lower endoscopies during the study period. There were no statistical differences in patients' demographics and indications for endoscopy although the CD 4 lymphocyte count was higher in group III. The percentage of patients receiving HAART at the time of endoscopy increased from 0% to 57% over the three periods (p<0.01), and the percentage of patient receiving combination antiretroviral therapy increased from 37% to 82% over the study period (p<0.01). In contrast, the prevalence of OD decreased from 69% (group I) to 13% (group III) (p<0.01), whereas the prevalence of non-OD, including a normal endoscopy increased from 31% to 87% (p<0.01). CONCLUSIONS: GI OD now seem to be an uncommon problem in HIV-infected patients undergoing endoscopy despite a low CD4 lymphocyte count, and this reduction of OD was associated with the use of HAART.

Diagnosis of esophageal ulcers in acquired immunodeficiency syndrome.

The esophagus is one of the most common sites of gastrointestinal involvement in human immunodeficiency virus (HIV)-infected patients, with at least 30% of the patients having esophageal symptoms at some point during the course of HIV infection. Esophageal ulcers are commonly caused by infections such as cytomegalovirus (CMV) or may be idiopathic. The clinical presentation of the various causes of esophageal ulcers are similar; therefore, a thorough endoscopic and histological workup is imperative to make a diagnosis and, consequently, to provide appropriate therapy. The widespread use of more effective antiretroviral therapy appears to have led to a decline in gastrointestinal opportunistic disorders in patients with acquired immunodeficiency syndrome (AIDS), including those involving the esophagus. Unfortunately, there are several reports of resistance of HIV-1 to multiple antiretroviral agents, and thus it is possible we will observe an increase in various opportunistic disorders again. The aim of this article is to provide a practical approach to the clinical, endoscopic, and histopathologic evaluation of esophageal ulcers in patients with AIDS.