Helen H. Wang

Prevalence of metaplasia at the gastro-oesophageal junction

Specialised columnar epithelium (SCE), a form of intestinal metaplasia usually found in Barretts oesophagus, cannot be distinguished endoscopically from normal gastric epithelium. Endoscopists seldom obtain biopsy specimens from a normal-appearing gastro-oesophageal junction, and therefore short segments of SCE in this region may go unrecognised. We studied patients who had short segments of SCE at the gastro-oesophageal junction. All patients scheduled for elective endoscopic examinations in our general endoscopy unit, irrespective of indication, were questioned for symptoms of gastro-oesophageal reflux disease. At endoscopy, severity of oesophagitis was graded, and biopsy specimens obtained from the squamocolumnar junction, irrespective of its appearance or location in the oesophagus. Among 142 patients without endoscopically apparent Barretts oesophagus, 26 (18%) were found to have SCE. All patients with SCE were white, and the male/female ratio was 1.9. In contrast, non-whites accounted for 14% of the 114 patients without SCE and the male/female ratio was 0.8. The groups did not differ significantly in the frequency of symptoms and endoscopic signs of gastrooesophageal reflux. We conclude that adults frequently have unrecognised segments of SCE at the gastro-oesophageal junction; this may underlie the rising frequency of cancer of the gastrooesophageal junction in the USA and Europe.

Phenotype of Barrett's esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction : An immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45MI

The pathogenesis of short segment Barretts esophagus (SSBE) and intestinal metaplasia (IM) of the gastroesophageal junction (IMGEJ) are poorly understood. Also, these conditions are difficult to distinguish from one another based solely on endoscopic and pathologic criteria. Therefore, the aim of this study was to evaluate the immunophenotypic features of SSBE and IMGEJ and to compare the results with lesions of known etiologies: long segment BE (LSBE) caused by reflux disease and Helicobacter pylori-induced IM of the gastric antrum (IMGA). Routinely processed mucosal biopsy specimens from 11 patients with LSBE, 17 with SSBE, 10 with IMGEJ, 16 with IMGA, 17 with a normal nonmetaplastic GEJ, and 7 patients with a normal gastric antrum were immunohistochemically stained with monoclonal antibodies to: Das1, an antibody shown to react specifically with colonic goblet cells; 45M1, an antibody that recognizes the M1 gastric mucin antigen; and cytokeratin (CK) 7 and 20, antibodies that have previously been reported to show specific staining patterns in BE versus IMGA. Also evaluated was nonintestinalized mucinous epithelium from LSBE, SSBE, and also the normal GEJ and gastric antrum. LSBE, SSBE, and IMGEJ showed similar prevalences of Das1 (91% versus 88% versus 100%) and 45M1 reactivity (100% versus 100% versus 100%), and a similar pattern of CK7/20 reactivity (diffuse strong CK7 staining of the surface and crypt epithelium, and strong surface and superficial crypt CK20 staining) (91% versus 94% versus 90%). In contrast, although 45M1 reactivity in IMGA (93%) was similar to that of the other three groups, IMGA showed a significantly lower prevalence of Das1 positivity (13%, p < 0.001), and only a 14% prevalence of the CK7/20 staining pattern that was predominant in the other three groups (p < 0.001). Das1, 45M1, and CK7/20 staining were similar in nonintestinalized “cardia-type” mucinous epithelium from LSBE, SSBE, and the GEJ, but all were distinct from the normal gastric antrum. In summary, the immunophenotypic features of SSBE and IMGEJ are similar and closely resemble those seen in classic LSBE, but are distinct from IMGA. This may indicate that IM in LSBE, SSBE and at the GEJ have similar biologic properties. Based on our data, SSBE and IMGEJ cannot be distinguished on the basis of their immunophenotype.

Molecular pathophysiology and physical chemistry of cholesterol gallstones.

Cholesterol gallstones are one of the most prevalent and most costly digestive diseases in the developed countries. Although precipitation of cholesterol from supersaturated bile is the first irreversible physical-chemical step in cholesterol gallstone formation, hepatic hypersecretion of biliary cholesterol is the primary defect in the formation of cholesterol gallstones. The other common abnormalities of the hepatobiliary system in gallstone patients include accelerated cholesterol nucleation/crystallization, gallbladder hypomotility, hypersecretion and accumulation of mucins, high efficiency of intestinal cholesterol absorption and slow intestinal motility. Family and twin studies in humans as well as gallstone prevalence investigations in different strains of inbred mice have clearly demonstrated that a complex genetic basis could determine individual predisposition to develop cholesterol gallstones in response to environmental factors such as high dietary cholesterol. In this review, we summarize progress in understanding the molecular pathophysiology of cholesterol gallstone formation with particular reference to most recent advances in the physical-chemistry of bile and the physiology of biliary lipid secretion.

Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction.

Pancreatic acinar metaplasia (PAM), defined as nodules of glandular tissue forming acini composed of cells with coarse apical eosinophilic granules, with or without mucous cells, was recently recognized in gastric mucosa, but its significance is not known. As part of a study on intestinal metaplasia at the gastroesophageal junction (GEJ), we evaluated the prevalence and clinical and histologic correlates of PAM in biopsy specimens from the gastroesophageal squamocolumnar junction. All adult patients having elective upper gastrointestinal endoscopy over a 6-month period were invited to participate. Clinical data and endoscopic findings were recorded. Biopsy specimens, obtained from both sides of the apparent squamocolumnar junction, were processed routinely and reviewed (without knowledge of the clinical data) to evaluate types of epithelium, types and degree of inflammation, and the presence of PAM. The presence or absence of PAM was then correlated with the other histologic findings and with the clinical and endoscopic data. The study comprised 155 patients (79 women, 76 men; 139 white patients, nine black patients, and seven patients of other ethnic groups). Their mean age was 52 years (range: 18-89 years). PAM was present in 37 patients (24%). PAM was not associated with any of the reported symptoms, endoscopic evidence of esophagitis or columnar epithelium in the distal esophagus, or any of the histologic features evaluated, including active esophagitis, intestinal metaplasia at the GEJ, active and chronic gastritis, intestinal metaplasia in the stomach, and Helicobacter infection. Although PAM is present in a considerable proportion (24%) of patients with mucosal biopsy specimens from the squamocolumnar junction, it appears to be an incidental finding unrelated to clinical or histologic abnormalities. We therefore suggest a congenital, rather than an acquired, origin for this entity.

Epidemiology of lymphomatoid papulosis

Background. Lymphomatoid papulosis is a rare skin disease with malignant potential. Its epidemiology is largely unknown.

Predictive value of fine‐needle aspiration of the thyroid in the classification of follicular lesions

Background. Fine‐needle aspiration has been less valuable in the diagnosis of follicular lesions than for other neoplasms of the thyroid. It has been observed that follicular carcinoma is found in microfollicular, but not macrofollicular lesions, and this has served as a guide to management for many surgeons. The authors attempted to determine what cytologic parameters might usefully distinguish these types of follicular lesion.

The Clinical Significance of Right-sided Colonic Inflammation in Patients with Left-sided Chronic Ulcerative Colitis

Background:Rarely, patchy right colonic inflammation has been observed in patients with left sided chronic ulcerative colitis (CUC), but the clinical significance of this finding is unknown. Therefore, the aim of this study was to evaluate the clinical and pathologic features and natural history of CUC patients with left-sided colitis combined with patchy right colonic inflammation and to compare the clinical course to a control group of patients with isolated left-sided CUC. Methods:Twelve patients with clinically and pathologically confirmed left-sided CUC, but also with patchy right colonic inflammation, were identified from a cohort of 352 consecutive patients with CUC who underwent colonoscopy at the Brigham and Womens Hospital between 1996 and 2000. In this cohort, 127 patients had left-sided colitis. As the first study to use controls in this setting, 35 consecutive patients with left-sided CUC, but without patchy right colonic inflammation, were selected and evaluated during the same time period. In all patients, the medical records were reviewed for a wide variety of clinical, endoscopic, and pathologic features. The mean follow-up time for the study and control groups was 105 ± 128 and 112 ± 80 months, respectively. Results:Patients in the study group were significantly older than the control group at the time of diagnosis (47 ± 17 years vs 35 ± 14 years, p = 0.048), but the two groups had a similar gender distribution (25% male vs 40% male), prevalence of extraintestinal manifestations (25% vs 11%), frequency of nonsteroidal anti-inflammatory drug use (75% vs 50%), family history of colitis (27% vs 15%), current tobacco use (8% vs 3%), history of appendectomy (8% vs 0%), and overall severity of disease (33% vs 46%). None of the patients in the study group, and only one control patient, had disease progression to pancolitis. One study patient developed high-grade dysplasia in the rectum that required a colectomy. None of the study or control patients developed clinical or pathologic features of Crohns disease. Conclusions:Rarely patients with left-sided CUC may have patchy right colonic inflammation. The clinical features and natural history of patients with left-sided CUC and patchy right colonic inflammation is similar to patients with isolated left-sided CUC.

Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors and represents a failure of biliary cholesterol homoeostasis in which the physical–chemical balance of cholesterol solubility in bile is disturbed.

Value of cytology in detecting intestinal metaplasia and associated dysplasia at the gastroesophageal junction

Tissue sampling is essential for detecting intestinal metaplasia in the distal esophagus (Barretts esophagus), because symptoms and endoscopy are not reliable in making this diagnosis. The utility of cytology in this process is unknown. All adult patients having elective upper gastrointestinal endoscopy over a 6-month period were invited to participate in a prospective study whose aim was to determine the prevalence of intestinal metaplasia in the distal esophagus in an adult population with diverse upper gastrointestinal symptoms. Clinical data and endoscopic findings were recorded. Brush cytology and biopsy specimens were obtained from both sides of the apparent squamocolumnar junction. The cytology specimens were processed routinely, stained with the Papanicolaou technique, and reviewed blinded to the clinical information and the histological findings in the corresponding biopsy specimens. One hundred fifty-five patients (81 women, 74 men; 137 whites, 11 blacks, 7 others; mean age, 52 years) were included. Glandular epithelium/cells were present on both histology and cytology in 147 specimens. Thirty-two patients (22%) showed intestinal metaplasia on histology. Of the cytology specimens from these 32 patients, 6 contained definite goblet cells (19%), 7 probable goblet cells, and 19 no goblet cells. Goblet cells and probable goblet cells were observed on cytology in 7 and 11 additional specimens, respectively. One was from a patient known to have intestinal metaplasia in the esophagus. Follow-up endoscopy with biopsy was performed in two of these latter 18 patients and did not show intestinal metaplasia. One case of high-grade dysplasia, two of low-grade dysplasia, and three indefinite for dysplasia were diagnosed on histology. All three cases of dysplasia were also identified on cytology. The three indefinite cases on histology were considered reactive in two and unremarkable in one on cytology. Low-grade dysplasia was diagnosed on cytology alone on two cases. Follow-up endoscopy with biopsy was performed in one patient, and low-grade dysplasia was found. Cytology using the Papanicolaou stain is not as sensitive and specific as histology for detecting intestinal metaplasia in the distal esophagus. However, it may be at least as useful as tissue sampling in detecting dysplasia.

Growth factor expression and proliferation kinetics in periampullary neoplasms in familial adenomatous polyposis

Background. Patients with familial adenomatous polyposis develop periampullary adenomas at a high rate. However, little is known regarding the factors that control the growth, the natural history, or the malignant potential of these tumors.