The role of endotoxin in the pathogenesis of progressive liver disease is receiving increasing attention, but remains controversial. Similarly, although alcoholic hepatitis is now recognized as the transitional link between alcoholic fatty liver and advanced alcoholic liver disease, the aetiology of liver cell necrosis in alcoholic hepatitis is not known. Rats fed a nutritionally adequate liquid alcohol diet according to the formula of Lieber and DeCarli developed fatty livers. Littermates fed an identical diet and challenged with small IV doses (1 microgram/g body weight) of E. coli lipopolysaccharide endotoxin (LPS) developed focal necrotizing hepatitis. Control littermates fed an identical calorie balanced but alcohol free diet and challenged with identical doses of LPS did not develop any liver lesions. The hepatocyte necrosis with associated inflammatory changes induced by LPS in fatty livers has some features of early human alcoholic hepatitis and suggests that progressive alcohol induced damage may be multifactorial in origin.

The identification of intestinal metaplasia (IM) in the esophagus is necessary for the selection of patients with Barrett esophagus (BE) for surveillance. We studied 108 esophageal biopsy and resection specimens, clinically diagnosed as BE, and stained them for CDX2, villin, HepPar-1, and cytokeratin (CK) 7 to investigate sensitivity for identifying IM. H&E-stained sections showed definite goblet cells in 94 cases. CDX2 and villin were positive in all 94 cases. Of 38 cardia- and 9 fundic-type mucosa samples associated with BE, 13 (34%) and 0 (0%) displayed CDX2 positivity and 21 (55%) and 1 (11%) displayed villin positivity, respectively. HepPar-1 was positive in 54 (57%) of 94 cases with IM and negative in the associated cardia- and fundic-type mucosa. A full-thickness CK7 staining pattern was present in 90 (96%) of samples with IM and 22 (58%) and 0 (0%) of the associated cardia- and fundic-type mucosa, respectively. None of 20 control samples of morphologically normal gastric mucosa stained for CDX2 or villin. CDX2 and villin are sensitive markers for early-stage IM and can supplement the histologic identification of this premalignant condition in the esophagus.

Barrett esophagus (BE) is an established precursor of esophageal adenocarcinoma (AdenoCa). One hundred and one cases of BE diagnosed by esophageal biopsy and resections were examined morphologically for dysplasia. These were categorized as BE without dysplasia (n=25), indefinite for dysplasia (IND, n=17), low-grade dysplasia (LGD, n=18), high-grade dysplasia (HGD, n=15), and AdenoCa (n=26). Immunostaining for p16 (INK4A/CDKN2A), Cyclin D1 (CCND1), Ki-67, and alpha-methylacyl-CoA racemase (AMACR) was employed to assess their potential as diagnostic discriminators. Abnormal p16 expression (negative, cytoplasmic, or combined cytoplasmic and nuclear staining) was present in all categories, rising from 68% in BE without dysplasia to 100% in AdenoCa, with cytoplasmic staining only showing a significant correlation with the severity of dysplasia. Cyclin D1 expression was present in almost all cases, but high expression (>50% cells positive) was displayed mostly in HGD and AdenoCa (46.7% and 42.3%, respectively). Ki-67 index increased with the severity of dysplasia and labeling extended from the lower third of the crypts to the superficial epithelium. The frequency of AMACR-positivity was 12% in BE, 47.1% in IND, 44.4% in LGD, 93.3% in HGD, and 96.2% in AdenoCa. The intensity and extent of AMACR staining also increased with the severity of dysplasia. Aberrant p16 and high-cyclin D1 expression may reflect early genetic events during the progression of Barrett-associated carcinogenesis. Cytoplasmic staining of p16 is specific. It may represent a different pathway of p16 dysfunction. The pattern and extent of Ki-67 staining and AMACR overexpression are useful additional parameters for identifying dysplasia in BE.

A case of amebic meningoencephalitis recognized in an adult Zambian is described. This is the first authenticated case from Africa. The morphologic features of the organism, its ability to form cysts in tissue, and the granulomatous tissue response denote that the ameba is an hartmannellid rather than a Naegleria. Free-living amebas of the family Hartmannellidae have not been incriminated before as a cause of primary amebic meningoencephalitis in man. To our knowledge this is the only case where such an ameba was responsible for fulminating meningoencephalitis. The presence of the amebas in a cellulocutaneous abdominal lesion suggests hematogenous dissemination.