Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury.

BACKGROUND & AIMS: Reflux esophagitis is believed to be caused by the caustic effects of refluxed gastric acid on esophageal epithelial cells. However, caustic chemical injuries develop rapidly whereas esophagitis might not appear until weeks after the induction of reflux in animal models. We studied early histologic events in the development of reflux esophagitis in a rat model and performed in vitro experiments to determine whether exposure to acidified bile salts causes esophageal epithelial cells to secrete chemokines that might contribute to inflammation. METHODS: At various time points after esophagoduodenostomy, the rat esophagus was removed and inflammatory changes were analyzed by histologic analyses. Human esophageal squamous cell lines were exposed to acidified bile salts to evaluate their effects on cytokine production and immune-cell migration. RESULTS: Reflux esophagitis started at postoperative day 3 with lymphocytic infiltration of the submucosa that progressed to the epithelial surface-these findings contradicted those expected from a caustic chemical injury. Basal cell and papillary hyperplasia preceded the development of surface erosions. Exposure of squamous cells to acidified bile salts significantly increased the secretion of interleukin-8 and interleukin-1beta; conditioned media from these cells caused significant increases in the migration rates of T cells and neutrophils. CONCLUSIONS: These findings support, but do not prove, an alternative concept for the development of reflux esophagitis in which refluxed gastric juice does not directly damage the esophagus, but rather stimulates esophageal epithelial cells to secrete chemokines that mediate damage of esophageal tissue.

The current spectrum of gastric polyps: a 1-year national study of over 120,000 patients.

OBJECTIVES: To use a large pathology database (Caris Diagnostics) to analyze the frequency and associations of gastric polyps in a nationwide US population. METHODS: A total of 121,564 esophagogastroduodenoscopy (EGD) procedures from private practices in 36 states in the Caris Diagnostics database from 1 April 2007 to 31 March 2008 were searched for the endoscopic designations of polyp, nodule, and mass, and for the pathological diagnoses that commonly present as gastric polyps. Pertinent demographic data, clinical indications for EGD, and information regarding Helicobacter pylori infection, reactive gastropathy, chronic inactive gastritis, and intestinal metaplasia were also obtained. RESULTS: A total of 78,909 of the 121,564 patients who underwent EGD had gastric biopsies. The prevalence of gastric polyps in the EGD population was 6.35%; 77% were fundic gland polyps, 17% hyperplastic polyps/polypoid foveolar hyperplasia, 0.69% adenomas, and 0.1% inflammatory fibroid polyps. Malignant neoplasms were slightly >2%. None of the benign gastric polyps had a significant positive association with concurrent H. pylori infection; intestinal metaplasia was detected in the background of 52.2% of carcinoids, 29.6% of adenomas, 20.1% of xanthomas, and 13% of adenocarcinomas and hyperplastic polyps. Adenomas were rarely associated with synchronous adenocarcinomas. CONCLUSIONS: The relative prevalence of fundic gland polyps in this population was much higher than that reported earlier, most likely because of the widespread use of proton pump inhibitors. H. pylori- and atrophy-associated polyps, including adenomas, were less common than in earlier series.

Lymphocytic disorders of the gastrointestinal tract: a review for the practicing pathologist.

Increased numbers of intraepithelial lymphocytes (lymphocytosis) can be found in the esophagus, stomach, small intestine, and colon in a variety of clinical circumstances. This review, directed at practicing pathologists, portrays the normal resident lymphocyte population in the mucosa of each segment of the digestive tract and discusses the different situations that may result in quantitative or qualitative alterations of intraepithelial lymphocytes. Esophageal lymphocytosis has not been fully characterized and its clinical significance, if any, awaits definition. Thus, this diagnosis is presently discouraged. In the stomach, it is particularly important to exclude Helicobacter pylori infection and celiac sprue before diagnosing lymphocytic gastritis. Duodenal lymphocytic infiltrates, inextricably tied with alterations of the villous architecture of the mucosa, are often caused by gluten sensitivity. However, similar morphologic changes may be caused by a vast array of other conditions that must be carefully considered and excluded. Lymphocytic and collagenous colitis are most often unexplained, but their frequent association with autoimmune conditions or certain medications deserve a thorough investigation in each case. Using a combination of histologic and clinical clues, a cause for the intraepithelial lymphocytic infiltration can be identified in many instances. As some of the associated conditions are amenable to effective treatment, the importance of diligently seeking such associations before resorting to a diagnosis of primary lymphocytosis is emphasized.

Helicobacter pylori seroprevalence in symptomatic veterans: a study of 7310 patients over 11 years.

BACKGROUND AND AIMS: The prevalence of Helicobacter pylori infection has been decreasing in the USA, but recent data are lacking. This study evaluates the seroprevalence for anti-H. pylori antibodies in symptomatic veterans tested over the past 11 years. MATERIALS AND METHODS: The same serum anti-H. pylori IgG detection system has been used at a tertiary care Veterans Affairs hospital since late 1996. Results of all tests performed from 1997 to 2007 were analyzed. RESULTS: Of 7310 unique patients tested, 3982 (54.5%) were positive. Seropositivity declined from 70.8% in 1997 to 48.6% in 2002, then reached a plateau around 50%. A strong birth cohort effect was present, from a seropositivity of 72.7% for the veterans born before 1920 to 22% for those born between after 1980. CONCLUSIONS: Despite a constant birth cohort effect, H. pylori seropositivity among symptomatic veterans leveled down at approximately 50% after declining steadily from 1997 to 2002.

Disseminated Kaposi sarcoma with osseous metastases in an HIV-positive patient.

Kaposi sarcoma is a neoplasm commonly associated with human herpesvirus 8 and HIV/AIDS. We present a 44-year-old African immigrant woman who presented to the emergency department after several months of abdominal pain. She was found to be HIV positive, and computed tomography demonstrated numerous lesions of the lungs, liver, and spleen, gastric wall thickening, and several lytic lesions of the spine. Fluoroscopy-guided biopsy of a lytic lesion of the spine yielded the diagnosis of Kaposi sarcoma. AIDS-related Kaposi sarcoma with osseous involvement is rare, with approximately 30 cases reported in the literature. When osteolytic lesions are encountered in an HIV-positive patient, Kaposi sarcoma should remain in the differential.

Chemoprevention of intestinal polyps in ApcMin/+ mice fed with western or balanced diets by drinking annurca apple polyphenol extract.

The Western diet (WD) is associated with a higher incidence of colorectal cancer (CRC) than the Mediterranean diet. Polyphenols extracted from Annurca apple showed chemopreventive properties in CRC cells. A multifactorial, four-arm study by using wild-type (wt) and Apc(Min/+) mice was carried out to evaluate the effect on polyp number and growth of APE treatment (60 µmol/L) ad libitum in drinking water combined with a WD or a balanced diet (BD) for 12 weeks. Compared with APE treatment, we found a significant drop in body weight (P < 0.0001), severe rectal bleeding (P = 0.0076), presence of extraintestinal tumors, and poorer activity status (P = 0.0034) in water-drinking Apc(Min/+) mice, more remarkably in the WD arm. In the BD and WD groups, APE reduced polyp number (35% and 42%, respectively, P < 0.001) and growth (60% and 52%, respectively, P < 0.0001) in both colon and small intestine. Increased antioxidant activity was found in wt animals fed both diets and in Apc(Min/+) mice fed WD and drinking APE. Reduced lipid peroxidation was found in Apc(Min/+) mice drinking APE fed both diets and in wt mice fed WD. In normal mucosa, mice drinking water had lower global levels of DNA methylation than mice drinking APE. APE treatment is highly effective in reducing polyps in Apc(Min/+) mice and supports the concept that a mixture of phytochemicals, as they are naturally present in foods, represent a plausible chemopreventive agent for CRC, particularly in populations at high risk for colorectal neoplasia.

The diagnostic value of the duodenal biopsy: a clinico-pathologic analysis of 28,000 patients.

BACKGROUND: Duodenal biopsies are frequently obtained to investigate malabsorption, diarrhoea, and anemia. The proportion of patients who have duodenal biopsies and their diagnostic yield are unclear. AIMS: To determine what proportion of patients undergoing esophagogastroduodenoscopy in a private setting has duodenal biopsies and to evaluate the diagnostic yield relative to clinical indications and endoscopic findings. METHODS: Records of patients who had duodenal biopsies diagnosed at a United States gastrointestinal pathology laboratory in a single year were analysed. RESULTS: 28,210 patients with and 75,175 without duodenal biopsies were studied. Duodenal biopsy patients were younger (52 years versus 58 years, p<0.001) and more likely to be female (OR 1.46; p<0.0001); 87% of children and 27% of adults had duodenal biopsies. Suspicion of malabsorption or sprue, diarrhoea, anemia, and weight loss were strong predictors of duodenal biopsy. More than 80% of patients had normal duodenum, except those biopsied for sprue, 64% of whom had normal findings. Marsh II-IIIc lesions were diagnosed in 23% of patients with suspected sprue, but in 3.0% of those with diarrhoea, weight loss, or anemia, and in 1.5% of patients with dyspepsia or GERD. CONCLUSIONS: A clinical suspicion of sprue produces the highest yield of histopathologic abnormalities; women are biopsied more often than men despite having less duodenal pathology.

Management of gastric polyps: a pathology-based guide for gastroenterologists.

1-4% of patients who undergo gastric biopsy have gastric polyps. These lesions may be true epithelial polyps, heterotopias, lymphoid tissue, or stromal lesions. Hyperplastic polyps, which arise in patients with underlying gastritis, and fundic-gland polyps, which are associated with PPI therapy, are the most common gastric polyps; however, prevalence varies widely relative to the local prevalence of Helicobacter pylori infection and use of PPI therapy. Some polyps have characteristic topography, size, and endoscopic appearance. Approximately 20% of biopsy specimens identified endoscopically as polyps have no definite pathological diagnosis. Evaluation of the phenotype of the gastric mucosa that surrounds a lesion will provide significant information crucial to the evaluation, diagnosis and management of a patient. The presence of a gastric adenoma should prompt the search for a coexistent carcinoma. The endoscopic characteristics, histopathology, pathogenesis, and management recommendations of polyps and common polypoid lesions in the stomach are discussed in this Review.

Esophagitis dissecans superficialis ("sloughing esophagitis"): a clinicopathologic study of 12 cases.

Esophagitis dissecans superficialis (EDS) is a term applied to a rare endoscopic finding characterized by sloughing of large fragments of the esophageal squamous mucosa that may be coughed up or vomited. Although EDS has been reported in association with certain medications and esophageal strictures, most cases remain unexplained and the histopathologic features of EDS are inadequately described. We undertook this study to define useful diagnostic criteria based on the examination of a series of well-characterized cases of EDS. To identify patients with EDS, we searched our endoscopy and pathology databases, reviewed the esophageal biopsy specimens from candidate cases, and correlated them with pertinent clinical information. Twelve patients (11 men and 1 woman) had endoscopic and histologic findings of EDS and 9 had the histologic features without the endoscopic correlates. Biopsies from confirmed EDS patients showed sloughing and flaking of superficial squamous epithelium with occasional bullous separation of the layers, parakeratosis, and varying degrees of acute or chronic inflammation. Fungal elements were identified in 3 patients, but were not associated with acute inflammation. None of the EDS patients were on bisphosphonate therapy or had bullous skin disorders. Follow-up endoscopy in 5 patients showed complete resolution of the esophageal abnormalities in 4 and mild esophagitis in one. In spite of its sometimes, dramatic presentation, EDS is a benign condition that resolves without lasting esophageal pathology. Although an association with medications, skin conditions, heavy smoking, and physical trauma has been reported, the pathogenesis of EDS remains unexplained.