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Intestinal metaplasia of the gastric cardia: A prospective study with enhanced magnification endoscopy.

OBJECTIVE: There are no endoscopic features that distinguish intestinal metaplasia of the cardia (CIM) from the normal cardia. Biopsy specimens are therefore randomly obtained from normal-appearing mucosa with significant potential sampling errors. Enhanced magnification endoscopy involves the combined use of magnification endoscopy with acetic acid instillation. This study assessed the value of enhanced magnification endoscopy in detecting CIM. METHODS: Patients undergoing elective upper endoscopy were invited to participate in the study. Patients were included if the squamocolumnar junction and the esophagogastric junction were judged to be at the same level. Enhanced magnification endoscopy was performed with 3% acetic acid instillation. Standard endoscopy was followed by magnification endoscopy and repeated after acetic acid spraying. Surface patterns were characterized before and after acetic acid spraying. The observed surface patterns were compared with histological results obtained from a single targeted biopsy specimen of each pattern. RESULTS: The overall prevalence of CIM was 34.8% (86/247 patients). After excluding 52 patients because of endoscopic evidence of Barrett's esophagus, 195 patients were eligible for participation in the study. In the study group, CIM was detected in 86 patients (44.1%) in targeted biopsy samples. No dysplasia was identified. Enhanced magnification endoscopy detected four different patterns of the mucosal surface: I) round pits, II) reticular, III) villous, and IV) ridged. The yields of detection of intestinal metaplasia according to endoscopic patterns were I) 0%, II) 5.3% (odds ratio = 0.05), III) 57.7% (odds ratio = 7.5, p = 0.0001), and IV) 95.8% (odds ratio = 42.8, p = 0.0001). CONCLUSIONS: CIM is more common than previously reported. Enhanced magnification endoscopy identifies two characteristic endoscopic patterns, villous (pattern III) and ridged (pattern IV), with outstanding clarity and resolution that correlate with histological identification of CIM with a single targeted biopsy sample. Enhanced magnification endoscopy will permit longitudinal studies of an entity that can be identified endoscopically.

Acetic Acid↗

Losses of heterozygosity on chromosomes 9p and 17p are frequent events in Barrett's metaplasia not associated with dysplasia or adenocarcinoma.

OBJECTIVE: Losses of heterozygosity (LOH) on chromosomes 9p and 17p frequently accompany malignant transformation of Barrett's esophagus (BE). They have been reported in adenocarcinoma, dysplasia, and adjacent metaplasia of patients with long-segment BE (LSBE). This study aimed to evaluate and compare the frequency of LOH on 9p and 17p in patients with long- and short-segment BE (SSBE) without dysplasia or adenocarcinoma. METHODS: Matched metaplasia and blood DNA were evaluated for LOH on chromosomes 9p and 17p in patients with a previous diagnosis of BE and no dysplasia or cancer. RESULTS: We included 18 patients (12 long-segment BE and six short-segment BE). The overall prevalence of LOH was 61% (10 of 18), with no significant difference between LSBE (58%) and SSBE (50%). The frequencies of LOH on 9p and 17p were similar (35% and 39%, respectively), with 18% of the patients showing losses at both chromosomes. CONCLUSIONS: LOH on 9p and 17p are highly frequent events in BE, even in the absence of dysplasia and adenocarcinoma. The presence of these abnormalities in non-neoplastic epithelium suggests they might be useful markers for risk stratification within endoscopic surveillance programs.

Adenocarcinoma↗

Detection of cardia intestinal metaplasia: do the biopsy number and location matter?

BACKGROUND AND AIM: Presence of intestinal metaplasia in the gastric cardia (cardia intestinal metaplasia, CIM) has been reported in 5-34% of patients undergoing upper endoscopy and is a topic of interest given the rising incidence of cancer in this location. The aim of this article is to determine the prevalence of CIM in biopsies obtained from two separate locations within the gastric cardia. METHODS: Patients presenting to the endoscopy unit for upper endoscopy for any symptoms were invited to participate in the study. The biopsy protocol included: eight biopsies from the gastric cardia, four from upper cardia (forceps across the squamocolumnar junction), four from lower cardia (within 1 cm of upper cardia), and four each from the gastric body and antrum. All cardia biopsies were stained with hematoxylin and eosin (H&E) and alcian blue at pH 2.5 for the presence of goblet cells and the body/antrum biopsies were stained with Steiner silver stain for Helicobacter pylori detection. In patients testing negative for H. pylori by histology, a serology test was performed. RESULTS: Sixty-five patients have been evaluated by this protocol; median age 54 yr (range: 34-81 yr), 63 males, 53 Caucasians, and 12 African Americans. The detection of CIM was as follows: upper cardia only, 7, both upper and lower cardia, 5, and lower cardia only, 7. Thus, CIM was detected in 12 patients (18%) in the upper cardia biopsies, in 12 patients (18%) in the lower cardia; overall prevalence of CIM was 29% (19 patients). Fifty-eight percent of CIM patients tested positive for H. pylori by either histology or serology. The addition of serology allowed for the detection of eight additional H. pylori-positive CIM patients. CONCLUSIONS: The prevalence of CIM in this study was similar (18%, four biopsies) at each location; however, if both locations were considered (eight biopsies), the prevalence increased to 29%. Thus, CIM prevalence may vary depending on the number of biopsies obtained as well as on the location of biopsies. Use of additional testing detects more patients who are H. pylori positive and should be performed if association of CIM with H. pylori is contemplated. Future endoscopic studies of the gastric cardia should specify the location of biopsies, the number of biopsies obtained, and the tests used to diagnose H. pylori.

Adult↗

Adnexal metaplasia in carcinoma in situ of the skin.

Two cases of epidermoid carcinoma in situ of the skin, one with mucinous metaplasia and the other with sebaceous metaplasia, are reported. These unique cases suggest a spectrum of differentiation possible by neoplastic epidermal keratinocytes, which may help in the understanding of the histogenesis of certain skin neoplasms.

Aged↗

"Small intestinal type" and "colonic type" intestinal metaplasia of the human stomach, and their relationship to the histogenetic types of gastric adenocarcinoma.

Intestinal metaplasia in the non-tumour bearing parts of the gastric mucosa was demonstrated in 24 cases in a material consisting of 27 consecutive patients operated for carcinoma of the stomach. Two mucin histochemical types of intestinal metaplasia could be identified. 1) "Small intestinal type" which was present in all 24 cases, and which was by far the most dominating type. 2) "Colonic type" which occurred in small foci in the gastric mucosa of 11 cases, and which was significantly more frequent in stomachs bearing tumours of presumed intestinal histogenesis, than in those bearing tumours of presumed non-intestinal histogenesis.

Adenocarcinoma↗

Effect of squamous metaplasia on infection of hamster trachea organ cultures with Mycoplasma pneumoniae.

An organ culture system for hamster trachea was developed for maintenance of the ciliated respiratory epithelium during periods of extended cultivation (i.e., greater than 20 days). Evaluation of five serum types showed that horse serum and fetal calf serum were best for the maintenance of epithelial ciliary activity and morphology. Rings that were opened on one side ("split rings") had the best maintenance of the ciliated epithelium as judged by the retention of ciliary activity and normal histological appearance after 3 to 4 weeks in culture. The in vitro induction of squamous metaplasia was achieved by cultivating explants in Waymouth MAB 87/3 (vitamin A-free) medium, without serum. This system allowed a direct comparison of the effects of Mycoplasma pneumoniae infection in two epithelial types, ciliated pseudostratified columnar and keratinizing squamous. Attachment of 14C-labeled mycoplasmas was more than twofold greater in the normal epithelium. Pretreatment of explants with neuraminidase decreased attachment for both squamous and pseudostratified epithelial surfaces to a similar basal level. Recovery of viable organisms from infected tissue of both epithelial types indicated that the organism titer remained essentially constant during the infection period, but was significantly higher for the pseudostratified ciliated epithelium. These results suggest that specific receptor sites for M. pneumoniae are markedly reduced by the induction of squamous metaplasia and, hence, appear to be specific for the normal respiratory surface containing goblet cells and pseudostratified, ciliated epithelial cells.

Animals↗

Gastric antigens in health and disease. Behaviour in early development, senescence, metaplasia, and cancer.

Immunofluorescence studies of the behaviour of gastric antigens in health and disease have shown that during foetal development both gastric and intestinal antigens are present in the gastric superficial mucous epithelium. The intestinal component disappears soon after birth; it re-emerges in senescence and in metaplasia and neoplasia, while the gastric antigen, which normally persists in adult life, is depleted in these circumstances. The loss of adult and the re-emergence of foetal antigen in both metaplasia and neoplasia suggest a possible fundamental relationship between these conditions; the phenotypic variation may reflect cytogenetic liability, which has malignant transformation as a final irreversible step.

Adult↗

Relationship of erosive gastritis to the acid secreting area and intestinal metaplasia, and the healing effect of pirenzepine.

The extent of acid secreting areas and the distribution of intestinal metaplasia in patients with erosive gastritis, and the healing effects of pirenzepine were examined. Studies were done with the endoscopic Congo red-methylene blue test developed in our hospital. Compared with control patients with no gastroduodenal disease, erosive gastritis was associated significantly more frequently with large acid secreting areas, but little or no intestinal metaplasia was detected in the stomach. A double blind trial was carried out, using 100 mg pirenzepine tablets or placebo for three months in 43 patients with erosive gastritis. Endoscopically, complete healing was significantly more frequent in the pirenzepine treated groups three months after the start of the treatment, as compared with the placebo treated group (p less than 0.05).

Adult↗

Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up.

Because early gastric cancer is associated with a much better prognosis than advanced disease, its diagnosis is important. Over a 12 year period (1976-87), a progressive increase in the incidence of early gastric cancer was observed. Twenty four of the 718 (3.3%) consecutive gastric resections for gastric cancer in this period were in patients with early gastric cancer. Six of the 24 were diagnosed in the first six year period (1976-81) and 18 in the second six year period (1982-87) (p less than 0.01). This increase was observed during the prospective phase of the study, when all patients diagnosed on initial biopsy specimen as showing type III intestinal metaplasia underwent follow up endoscopy and biopsy at six to 12 month intervals. Eleven of the 18 with early gastric cancer detected in this period were diagnosed as a direct result of this follow up. We conclude that early gastric cancer can be diagnosed with increasing frequency if patients with type III intestinal metaplasia are closely followed endoscopically.

Follow-Up Studies↗

Complete and incomplete intestinal metaplasia at the oesophagogastric junction: prevalences and associations with endoscopic erosive oesophagitis and gastritis.

BACKGROUND/AIMS: Intestinal metaplasia (IM) is a common finding at the oesophagogastric junction, but the aetiopathogenesis of the different IM subtypes-that is, incomplete IM (specialised columnar epithelium, SCE) and complete IM- and their associations with gastro-oesophageal reflux disease and Helicobacter pylori gastritis are unclear. METHODS: 1058 consecutive dyspeptic patients undergoing gastroscopy were enrolled. The gastric, oesophagogastric junctional, and oesophageal biopsy specimens obtained were stained with haematoxylin and eosin, alcian blue (pH 2.5)-periodic acid Schiff, and modified Giemsa. RESULTS: Complete junctional IM was detected in 196 (19%) of the 1058 subjects, and in 134 (13%) was the sole IM subtype. Incomplete junctional IM (SCE) was detected in 101 (10%) subjects, of whom 62 (61%) also had the complete IM subtype. Of patients with normal gastric histology (n = 426), 6% had complete IM and 7% junctional SCE. The prevalence of both types of IM increased with age in patients with either normal gastric histology or chronic gastritis (n = 611). Epithelial dysplasia was not detected in any patients with junctional IM. In multivariate analysis, independent risk factors for incomplete junctional IM were age (odds ratio (OR) 1.3 per decade, 95% confidence interval (CI) 1.2 to 1.6), endoscopic erosive oesophagitis (OR 1.9, 95% CI 1.1 to 3.2), and chronic cardia inflammation (OR 2.9, 95% CI 1.3 to 6.2), but not gastric H pylori infection (OR 1.0, 95% CI 0.6 to 1.7). In univariate analysis, junctional incomplete IM was not associated with cardia H pylori infection. Independent risk factors for "pure" complete junctional IM (n = 134) were age (OR 1.2 per decade, 95% CI 1.0 to 1.4), antral predominant non-atrophic gastritis (OR 2.6, 95% CI 1.3 to 5.2), antral predominant atrophic gastritis (OR 2.1, 95% CI 1.1 to 5.2), and multifocal atrophic gastritis (OR 7.1, 95% CI 2.5 to 19.8). In univariate analysis, junctional complete IM was strongly associated with chronic cardia inflammation and cardia H pylori infection (p<0. 001). CONCLUSIONS: Both complete and incomplete junctional IM are independent acquired lesions that increase in prevalence with age. Although IM subtypes often occur simultaneously, they show remarkable differences in their associations with gastritis and erosive oesophagitis: junctional complete IM is a manifestation of multifocal atrophic gastritis, while the incomplete form (SCE) may result from carditis and gastro-oesophageal reflux disease. The frequency of dysplasia in intestinal metaplasia at the oesophagogastric junction appears to be low.

Aged↗

Heterotopic gastric mucosa together with intestinal metaplasia and moderate dysplasia in the gall bladder: report of two clinically unusual cases with literature review.

We report the clinicopathological findings of two patients with ectopic gastric mucosa within the gall ladder. The first patient, a 78 year old man, was asymptomatic. He was admitted to hospital for a colon adenocarcinoma. Intraoperatively, a firm nodule was palpable in the gall bladder. Histological examination of the resected specimen revealed a body type gastric mucosa in the submucosa, adjacent to which were extensive pyloric gland and intestinal metaplasia with mild to moderate dysplasia. The remaining gall bladder mucosa demonstrated changes of chronic cholecystitis. The second patient was a 62 year old woman with symptoms of chronic cholecystitis. The preoperative diagnosis was consistent with this diagnosis with a "polyp" at the junction of the neck and cystic duct. Cholecystectomy was performed and the histological examination of the resected specimen showed that the "polyp" consisted of heterotopic gastric mucosa with glands of body and fundus type. In the remaining mucosa, chronic cholecystitis was evident. To the best of our knowledge, this is the first report of a clinicopathological presentation of heterotopic gastric mucosa, pyloric gland type, and intestinal metaplasia with dysplastic changes in the gall bladder. As heterotopic tissue may promote carcinogenesis of the gall bladder, close attention should be paid to any occurrence of such lesions in this anatomical region.

Aged↗

Gastric ciliated metaplasia. A study of 3406 gastrectomy specimens from dwellers of the Atlantic and the Pacific basins.

BACKGROUND: Ciliated cells in gastrectomies from patients dwelling in the Pacific and Atlantic basins have been reported previously. AIM: To compare all the results in an attempt to explain the findings. METHODS: Sections from 3406 gastrectomies were reviewed: 1966 and 1440 from the Atlantic and Pacific basins, respectively. Ciliated cells and intestinal metaplasia (IM) were recorded; IM was classified into focal or extensive IM. The total number of sections/gastrectomy was noted. RESULTS: In the Atlantic basin, 5% of specimens had ciliated metaplasia (CM); it was more frequent in intestinal carcinoma (IC; 9%) than diffuse carcinoma (DC; 3%) or miscellaneous gastric diseases (MGD; 3%). In the Pacific basin, the frequency of specimens with CM was 29%: it was more frequent in IC (43%) than in DC (16%) or MGD (10%). The difference between the frequency of CM in specimens with IC or with DC/MGD in the Atlantic and the Pacific basins was significant (p < or = 0.05). The presence of CM was influenced by age and the extent of IM in both basins, but not by sex or the number of sections investigated. CONCLUSIONS: CM-apparently an independent microscopic marker-was significantly higher in the Pacific than in the Atlantic basin. Environmental carcinogens involved in the evolution of IM and IC seem to be implicated in gastric ciliogenesis. Carcinogens that differ in nature and/or in strength in both basins might activate the latent natural genes encoding ciliated processes in gastric cells in patients subsequently developing gastric carcinoma, more notably of intestinal type.

Adult↗

Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract.

BACKGROUND: Upper gastrointestinal tract intestinal metaplasia (IM) is termed Barrett's oesophagus (BO) or gastric intestinal metaplasia (GIM), depending on its location. BO and GIM are associated with chemical exposure resulting from gastro-oesophageal reflux and chronic Helicobacter pylori infection, respectively. Paneth cells (PCs), characterised by cytoplasmic eosinophilic granules, are found in a subset of IM at these sites, but histology may not accurately detect them. AIM: To determine human defensin 5 (HD5; an antimicrobial peptide produced by PCs) expression in BO and GIM, and to investigate its association with H pylori infection. METHODS: Endoscopic biopsies from 33 patients with BO and 51 with GIM, and control tissues, were examined by routine histology and for H pylori infection and HD5 mRNA and protein expression. RESULTS: In normal tissues, HD5 expression was specific for PCs in the small intestine. Five patients with BE and 42 with GIM expressed HD5, but few HD5 expressing cells in IM had the characteristic histological features of PCs. Most HD5 positive specimens were H pylori infected and most HD5 negative specimens were not infected. CONCLUSIONS: HD5 immunohistochemistry was often positive in IM when PCs were absent by conventional histology. Thus, HD5 immunohistochemistry may be superior to histology for identifying metaplastic PCs and distinguishing GIM from BO. The higher frequency of HD5 expression in GIM than in BO is associated with a higher frequency of H pylori infection, suggesting that in IM PCs may form part of the mucosal antibacterial response.

Adult↗

Tubular metaplasia in Bowman's capsule.

Proximal tubular type metaplasia of the epithelium of Bowman's capsule is described in a fit young adult male. This form of metaplasia is unlike those previously described and could cause initial confusion if encountered in a percutaneous renal biopsy.

Adult↗

Oncocytic metaplasia of the nasopharynx or extra-parotid Warthin's tumour?

A case of oncocytic metaplasia obstructing the Eustachian tube in an elderly patient is described. Histologically, it was similar to Warthin's tumour of the parotid gland. The lymphocytes were predominantly T cell, unlike those of Warthin's tumour which are predominantly B cell. It is proposed that oncocytic metaplasia represents an early stage in the evolution of Warthin's tumour.

Adenolymphoma↗

Immunohistochemical localisation of androgen receptor in apocrine metaplasia and apocrine adenosis of the breast: relation to oestrogen and progesterone receptors.

AIM: To investigate the receptor status of the sex steroid hormones in apocrine metaplasia of the breast. METHODS: 82 cases of apocrine metaplasia, including 18 of the rare lesion apocrine adenosis, were studied immunohistochemically for the expression of androgen receptor, oestrogen receptor, and progesterone receptor proteins on formalin fixed, paraffin embedded tissue sections. The standard avidin biotin complex (ABC) technique was followed and appropriate positive and negative controls were used. RESULTS: All the studied cases (82/82) were positive for androgen receptor, but were negative for oestrogen receptor and progesterone receptor. CONCLUSIONS: Apocrine metaplastic epithelium, unlike the normal breast epithelium, is responsive to androgens, through androgen receptors, rather than to the female sex hormones. This may have clinical implications.

Adult↗

Reduplication cyst of appendix with mucinous carcinoma and Müllerian metaplasia: a case report.

This report describes a case of mucinous carcinoma and Müllerian metaplasia arising within an appendiceal duplication cyst found incidentally during an emergency Caesarian section. Intestinal duplication cysts are rare and although there are occasional reports of malignant transformation, this is the first case where Müllerian metaplasia was found concurrently with a malignancy. There was no previous history of endometriosis and no other abnormalities were found at surgery. Treatment included surgical excision. The patient is alive and well two years after removal of the cyst.

Adenocarcinoma, Mucinous↗

Detection of sulfated glycoproteins in intestinal metaplasia: a comparison of traditional mucin staining with immunohistochemistry for the sulfo-Lewis(a) carbohydrate epitope.

BACKGROUND: Premalignant Barrett's oesophagus (BO) and gastric intestinal metaplasia (IM) show phenotypic variability. Incompletely differentiated sulfomucin rich gastric IM (type III) may have increased malignant potential. The types of sulfated oligosaccharide structures present in IM, BO, and colon have not been fully characterised. AIMS: To compare sulfo-Lewis(a) epitope tissue distribution with high iron diamine (HID) positive sulfomucin in metaplastic, dysplastic, and neoplastic tissues from oesophagus and stomach. METHODS: Sections containing gastric IM or BO (some associated with dysplasia or adenocarcinoma) were stained by the HID/alcian blue (AB) method and immunohistochemically (antibody 91.9H) to detect sulfo-Lewis(a). Based on HID/AB staining, IM was subtyped into type I (complete) or types II and III (incomplete). RESULTS: In total, 125 sections from 38 subjects were studied. Normal squamous oesophagus, normal gastric epithelium, and type I IM were negative for sulfomucin and sulfo-Lewis(a). In type II IM, occasional goblet cells were HID and sulfo-Lewis(a) positive, but sialomucin secreting (AB positive) columnar cells were sulfo-Lewis(a) negative. Type III IM was always sulfo-Lewis(a) positive. Sulfomucin staining in dysplasia and cancer was variable, but HID positive areas were always sulfo-Lewis(a) positive. CONCLUSIONS: Sulfo-Le(a), which is expressed on colonic mucin, is invariably present on sulfomucins in gastric IM and BO. Its presence in incomplete variants of IM and its absence from type I IM emphasises the phenotypic differences between complete and incomplete forms of metaplasia. 91.9H immunostaining is useful in IM subtyping. Characterising the molecular basis of sulfo-Lewis(a) expression may help understand the process of aberrant differentiation.

Adenocarcinoma↗