Explore the vast range of titles available.

The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood. To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB. Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay. Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative. The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Barrett's esophagus results from chronic reflux of both acid and bile. Reflux of gastric and duodenal contents is facilitated through the denervated stomach following esophagectomy, but the development of Barrett's changes in this model and the relationship to gastric and esophageal physiology is poorly understood. To document the development of new Barrett's changes, i.e., columnar metaplasia or specialized intestinal metaplasia (SIM) above the anastomosis, and relate this to the recovery of gastric acid production, acid and bile reflux, manometry, and symptoms. Forty-eight patients at a median follow-up of 26 months (range = 12-67) postesophagectomy underwent endoscopy with biopsies taken 1-2 cm above the anastomosis. The indication for esophagectomy had been adenocarcinoma (n = 27), high-grade dysplasia (n = 2), and squamous cell cancer (n = 19). Physiology studies were performed in 27 patients and included manometry (n = 25), intraluminal gastric pH (n = 24), as well as simultaneous 24-hour esophageal pH (n = 27) and bile monitoring (n = 20). Duodenogastric reflux increased over time, with differences between patients greater than and less than 3 years postesophagectomy for acid (p = 0.04) and bile (p = 0.02). Twenty-four patients (50%) developed columnar metaplasia and of these 13 had SIM. The prevalence of columnar metaplasia did not relate to the magnitude of acid or bile reflux, to preoperative neoadjuvant therapies, or to the original tumor histology. The duration of reflux was most significant, with increasing prevalence over time, with SIM in 13 patients at a median of 61 months postesophagectomy compared with 20 months in the 35 patients who were SIM-negative (p < 0.006). Supine reflux correlated with symptoms. The development of Barrett's epithelium is frequent after esophagectomy, is time-related, reflecting chronic acid and bile exposure, and is not specific for adenocarcinoma or the presence of previous Barrett's epithelium. This model may represent a useful in vivo model of the pathogenesis of Barrett's metaplasia and tumorigenesis.

It has previously been shown that microalbuminuria is a useful disease activity marker for inflammatory bowel disease (IBD). Microalbuminuria correlates strongly with the markers of clinical and laboratory disease activity such as erythrocyte sedimentation rate (ESR), and C reactive protein (CRP). The aim of this study was to discover if microalbuminuria accurately reflects the intestinal inflammation by correlating it with intestinal inflammation using a standard histopathological grading system in patients with ulcerative colitis and Crohn's colitis. Forty two patients with IBD who had undergone endoscopic examination of the entire colon for the assessment of severity and extent of the disease (Crohn's colitis (n = 21), ulcerative colitis (n = 21)) were recruited to the study. Patients with small bowel Crohn's disease were not studied. Twenty four patients had left sided colonic disease and 18 patients had extensive colonic disease. Each patient's colonic biopsy specimens were scored blindly by a histopathologist and a composite score was compiled on the basis of the severity of changes in the enterocytes and crypts and the cellularity of the lamina propria. A clinical disease activity was obtained using the simple index of Harvey and Bradshaw. Microalbuminuria was measured in all patients by an immunoturbiditimetric method. ESR and CRP were also measured, as indicators of acute phase response in the same patients. It was found that patients with active IBD had higher concentrations of microalbuminuria compared with those patients in remission (median 222 micrograms/min (range 40-686 micrograms/min) v median 96 micrograms/min (range 30-376 micrograms/min); p < 0.001)). Significantly higher concentrations of microalbuminuria were also detected in patients with extensive colonic IBD compared with those patients with left sided disease (median 297 micrograms/min (range 132-686 micrograms/min) v median 101 micrograms/min (range 30-433 micrograms/min); p < 0.001)). A strong positive correlation was seen between microalbuminuria and intestinal histopathological score in IBD patient groups with left sided colitis (r = 0.77; p < 0.001) and extensive disease (r = 0.71; p < 0.01). The standard histopathological grading system correlated with the clinical disease activity (r = 0.64; p < 0.005) and CRP (r = 0.62; p < 0.02), however, it did not correlate with ESR. In conclusion, the strong correlation of microalbuminuria with a standard intestinal histopathological grading system suggests that microalbuminuria accurately reflects the severity of colonic inflammation in patients with Crohn's colitis and ulcerative colitis.

BACKGROUND:The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood.AIMS:To examine the expression of the proinflammatory cytokines IL-8 and IL-1b along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-B.PATIENTS ANDMETHODS:Fresh biopsy specimens were collected from patients with reflux esophagitis (n= 15), Barrett's esophagus (n = 35), Barrett's adjacent to adenocarcinoma (n = 8), and esophageal adenocarcinoma (n = 35). IL-8 and IL-1b expression were measured using enzyme-linked immunosorbent assay. NF-B expression was measured by electrophoretic mobility shift assay. RESULTS:Elevated expression of NF-B was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-B. IL-8 and IL-1b were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1b, and NF-B from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1b in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-B positive had significantly higher levels of both IL-8 (p= 0.04) and IL-1b (p= 0.03) compared to adenocarcinoma patients who were NF-B negative. CONCLUSIONS:The proinflammatory cytokines IL-8 and IL-1b are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-B activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-B activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-B/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.The American Journal of Gastroenterology (2005) 100, 1257-1264; doi:10.1111/j.1572-0241.2005.41338.x

Enterobius vermicularis (the pinworm) commonly infests the lumen of the intestine but on rare occasions has been found in the wall or in the tissues outside the gastrointestinal tract. Three such patients have been encountered in whom Enterobius vermicularis was found in the wall of the colon, in the retrocaecal tissues, and on the peritoneum. The pathological lesions and their relationship to the clinical features are discussed. A brief review of the literature is given. It is concluded that Enterobius vermicularis can only penetrate the wall of the gastrointestinal tract if this is diseased. Once in the tissues the worms can cause an inflammatory reaction simulating carcinoma and Crohn's disease, and, by perforation of the intestine, cause a generalized peritonitis.

The clinical and pathological findings in 23 patients with ischaemic lesions of the alimentary tract (ischaemic enterocolitis) are described. These are compared with findings in 13 patients with occlusive thrombosis of the superior mesenteric artery. The pathological features distinguishing the two conditions are discussed. Ischaemic enterocolitis was found to be a relatively common condition (0·6% of necropsies). The occurrence of mucosal fibrosis (a hitherto undescribed feature) has been of help in the biopsy diagnosis of ischaemic lesions of the gut.

A case of bilateral uveal melanoma in a 60-year-old woman in association with primary bilateral ovarian carcinoma is described. This is the first case in which ultrastructural studies have been performed on the ocular tumours. Seven previously described cases are summarised, and the extreme rarity of such reports would suggest that this may indeed be a new syndrome.

Clostridioides difficile infection is a major cause of nosocomial and community illness. In this report from the Emerging Infections Program, associated with the U.S. CDC, the national burden of C. difficile infection is estimated from 2011 through 2017. In 2017, an estimated 462,100 cases of C. difficile infection occurred.

Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens.