The place of quantitation in diagnostic gastrointestinal pathology.
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Adolescent↗
Biomedical subjects
P W Hamilton
Publications and source records attributed to P W Hamilton.
A combination of cytological and architectural morphometry in assessing regenerative hyperplasia and dysplasia in ulcerative colitis.
Morphometry and stereology were used to assess the cytological and architectural characteristics of regenerative and dysplastic colorectal mucosal abnormalities in ulcerative colitis. Reproducibility of measurements was assessed and found to be good, confirming the objective and reproducible nature of morphometric analysis. Discriminant analysis between the morphometric features of regenerative mucosal change and low-grade dysplasia revealed the significant cytological and architectural variables from which a cytological and architectural score were derived. The architectural score was capable of classifying all of the cases into their correct diagnostic category, although a combination of the two scores provided better separation of cases. Probability density analysis was carried out so that probabilities of group membership could be allocated to cases, given their cytological and architectural scores. Discriminant analysis was also applied to low- and high-grade dysplasia. Important cytological and architectural variables were identified and used separately to derive scoring systems. In combination, the dual scoring of lesions was capable of separating low- from high-grade dysplasia, although overlap was still evident. Again, probability density analysis allowed the allocation of cases into one or other category, although a closer examination showed that such a rule could not successfully classify a new set of low- and high-grade dysplasia cases. Quantitative histological analysis of mucosal abnormalities is shown to be of use in the objective diagnosis of reactive and dysplastic change in patients with ulcerative colitis. The use of simple scoring systems and probability based allocation of cases promotes the future role of morphometric techniques in the diagnostic laboratory.
Bayes Theorem↗
Quantitative histological study of mucosal inflammatory cell densities in endoscopic duodenal biopsy specimens from dyspeptic patients using computer linked image analysis.
Inflammatory cell counting in endoscopic biopsy sections was carried out on duodenal mucosal samples from defined sites in patients with duodenal ulcer, duodenitis but no ulcer, non-ulcer dyspepsia, and asymptomatic controls using computer linked image analysis. The variables measured included polymorphonuclear and mononuclear cells per mm of superficial epithelium and per mm2 lamina propria. Duodenal ulcer crater margin and mucosal biopsy specimens from endoscopically inflamed mucosa in the group with duodenitis but no ulcer showed significantly higher inflammatory cell counts than endoscopically normal non-ulcer dyspepsia and control mucosa. Biopsy specimens from non-ulcer dyspepsia patients showed significantly higher lamina propria polymorphs than control group mucosa. Endoscopically normal duodenal ulcer and duodenitis but no ulcer mucosa also showed significantly higher acute and chronic inflammatory cell counts than controls. The prevalence of Helicobacter pylori in duodenal biopsy specimens was low (0-22%) and unrelated to local inflammatory response. Despite histological appearances, duodenal biopsy specimens from non-ulcer dyspepsia patients showed significantly higher inflammatory cell infiltration than control specimens, suggesting that at least some represent part of a spectrum of subclinical peptic disease.
Adult↗
The role of morphometry in predicting prognosis in pancreatic islet cell tumors.
Morphometry of 31 pancreatic islet cell tumors was examined to determine the value of this technique in assessing tumor behavior. Patients were followed for a mean period of 5.1 years (range, 1 month-14 years) after diagnosis. Initially 17 localized and nine metastatic tumors were studied. Discriminant analysis was carried out on these cases and identified nuclear/cytoplasmic ratio and number of nuclei/mm2 as the significant discriminatory features. These were combined to derive a classification rule which was capable of correctly identifying localized and metastatic tumors in 92% of cases. The classification rule was applied subsequently to an additional five test cases, all of which were classified successfully. The failure of increased nuclear size and pleomorphism to correlate with malignancy in these tumors was confirmed. Tumors which metastasized had significantly greater gross diameters than localized lesions, but overlap existed. Mitotic counts were not a helpful discriminatory feature. Morphometry may be useful in improving histologic assessment of pancreatic islet cell tumor behavior.
Adenoma, Islet Cell↗
Superficial gastritis and Campylobacter pylori in dyspeptic patients--a quantitative study using computer-linked image analysis.
The purpose of this study was the quantitative assessment of mucosal inflammation and its relationship to Campylobacter pylori in gastric antral and body biopsies from patients with dyspepsia and controls. The study groups comprised patients with duodenal ulcer (DU; n = 20), duodenitis (DUN; n = 20), non-ulcer dyspepsia (NUD; n = 20). Using a semi-automatic, computer-linked image analyser (Kontron: MOP Videoplan), mucosal acute and chronic inflammatory cell densities were measured in defined gastric sites for each patient group and expressed as number per mm2 of lamina propria and number per mm length of epithelium. Measurements were also made on a group of asymptomatic controls (n = 9) who fulfilled strict exclusion criteria. All biopsies were analysed for the presence of Camplyobacter pylori (CP) with a Giemsa stain. Data between groups were compared using the Mann-Whitney U-test. In the antrum and body, the mononuclear cell count was significantly higher in lamina propria in DU patients than in DUN, NUD and controls. In the body, DU laminia propria mononuclear cell counts were higher than those of DUN and controls. Prevalence rates for CP for DU, DUN, and NUD were 94, 89, and 50 per cent for antral and 88, 83, and 56 per cent for body biopsies. Significant differences were present between CP-positive and negative subjects in the NUD group. Antral and body inflammation within these clinical groups shows a wide variation. Higher inflammatory cell counts in the DU group may reflect the prevalence of CP colonization.
Adult↗
Investigation of the relationship between gastric antral inflammation and Campylobacter pylori using graphic tablet planimetry.
Gastric antral endoscopic pinch biopsies from a group of dyspeptic patients were analysed for acute and chronic inflammatory cell numbers in the lamina propria and surface epithelial layer using computer-linked graphic tablet planimetry, and independently graded for Campylobacter pylori (CP) infection using a visual scoring system with grade 1 assessed as patchy epithelial infection and grade 2 as a continuous layer of organisms on the mucosal surface extending into gastric pits. The study group consisted of 36 patients (18 duodenitis; 18 non-ulcer dyspepsia). Within the 140 biopsies analysed, grade 1 and 2 biopsies had significantly higher acute and chronic inflammatory cell counts than CP-negative biopsies (grade 0) in lamina and surface epithelium (P less than 0.001). Acute inflammatory cell counts were significantly higher in the surface epithelium in grade 1 (P less than 0.05) and grade 2 biopsies (P less than 0.001) but chronic inflammatory cells were only higher in grade 1 (P less than 0.01). No significant differences were present between grade 1 and grade 2 biopsies for any parameter. This study confirms that highly significant quantitative differences in the inflammatory status are related to the presence of CP.
Acute Disease↗
Assessment of oesophagitis by histology and morphometry.
Morphometric measurements of nuclear area, nuclear concentration and nucleolar dimensions in defined tissue zones of orientated oesophageal biopsy sections were compared between three patient groups--asymptomatic/normal endoscopy (n = 8); symptomatic reflux/normal endoscopy (n = 17); and symptomatic/endoscopic oesophagitis (n = 15). No significant differences could be shown for any mean parameter between clinical groups. In a further group of 16 patients, identical morphometric measurements were made in non-orientated grasp biopsies and correlated with prolonged ambulatory pH data. No significant correlations could be shown between nuclear parameters and acid reflux measurements. These results suggest that morphometric measurement cannot be recommended as a diagnostic tool in the diagnosis of oesophagitis, although it may be useful in the assessment of individual therapeutic response in clinical trials.
Adult↗
Architectural morphometry in ulcerative colitis with dysplasia.
Semi-automatic image analysis was used to assess the architectural features of normal colorectal mucosa and ulcerative colitis with and without dysplasia. Eight measured and derived morphometric variables were compared with the histological grading. The main data-set variation was due to: (1) the area of mucosa and epithelium per unit length of muscularis mucosae; (2) mean mucosal and epithelial height; and (3) the percentage epithelium and number of crypts per unit length of muscularis mucosae. Discriminant analysis using the variables mean epithelial height and mean lamina propria area per unit length of muscularis mucosae separated normals (n = 10) from high-grade dysplasia (8). The classification rule allocated low-grade dysplasia (8) to the high-grade category and 60% of regeneration cases (10) to the normal mucosa group. Scatter plots of the two discriminating variables separated normal and regenerative mucosa from dysplasia. Histological review of overlapping cases allowed redesignation of a high-grade dysplasia lesion as low grade. Architectural morphometry may be of use in assessing premalignant mucosal changes in ulcerative colitis as a guide to patient surveillance and therapy.
Colitis, Ulcerative↗
A morphometric assessment of transitional mucosa in the colon.
Quantitative morphometric analysis was used in 10 resection specimens to assess so-called transitional mucosa immediately adjacent to colorectal carcinoma. Eleven nuclear and cellular variables were measured from the malignant epithelial area and from zones of increasing distance (1 cm) from the lesion. In addition, mean mucosal height was assessed for each zone. Morphometrical differences between the mucosa immediately adjacent to the malignant epithelium and that taken at some distance from it were determined by Mann-Whitney U tests. Transitional mucosa showed increased mucosal height but no nuclear differences from normal mucosa. Other work has shown that there are nuclear morphometric differences associated with premalignant conditions in the colon. Thus, the suggestion that transitional mucosa represents early neoplastic change cannot be supported.
Adult↗
Classification of normal colorectal mucosa and adenocarcinoma by morphometry.
Semi-automatic image analysis was used to make a morphometrical assessment of 15 nuclear and cellular variables in normal (n = 20) and malignant (n = 30) colorectal epithelium. Principal components analysis on the matrix of correlations between variables identified four main sources of variation within the dataset. These were, in decreasing order of importance: (1) nuclear size, nuclear cytoplasmic ratio and nuclear position within the cell; (2) the variability of nuclear size; (3) nuclear elongation and polarity; (4) nuclear shape and its variation. Discriminant analysis was conducted between histologically normal mucosa (n = 10) and adenocarcinoma in ulcerative colitis (n = 20). Using stepwise variable selection, the mean nuclear cytoplasmic ratio (normal, mean 20.4 (s.d. +/- 2.0); tumour, mean 39.7 (s.d. +/- 7.0)) and the coefficient of variation of nucleus to cell apex distance (normal, mean 19.2 (s.d. +/- 7.5); tumour, mean 47.8 (s.d. +/- 9.1)) were chosen as discriminating features. They were used to derive a discriminant function which gave perfect discrimination between the two groups. Scatter plots of these two variables confirmed complete separation of normal mucosa from adenocarcinoma and provided a simple method of applying the discriminant function. Discriminatory performance did not deteriorate when the function was applied to further normals (n = 10) and adenocarcinoma (n = 10). This study highlights the descriptive differences between normal and malignant colorectal epithelium and shows that case allocation may be made to these two lesion categories using a morphometrically-derived classification rule.
Adenocarcinoma↗
Morphometrical analysis in ulcerative colitis with dysplasia and carcinoma.
Semi-automatic image analysis was used to assess the epithelium in ulcerative colitis with dysplasia and carcinoma. There were three main sources of variation within the dataset: (1) nuclear size, nuclear cytoplasmic ratio and nuclear stratification; (2) the variation of nuclear size; and (3) nuclear shape and polarity. Discriminant analysis chose the mean nuclear cytoplasmic ratio % and the coefficient of variation of nucleus to cell apex distance to derive a scoring system which completely separated normal mucosa (n = 20) and carcinoma (n = 30). The classification rule allocated all high grade dysplasia to the tumour category. Scores for regeneration and low grade dysplasia overlapped with each other and the normal and tumour groups. Scatter plots of the two discriminating variables showed good separation of regeneration and high grade dysplasia, and a degree of overlap with low grade dysplasia. The scatter plots allowed identification of overlapping and misallocated cases, requiring review of their histology and redesignation of the diagnosis in five cases. This study confirms quantitatively the visual criteria used in grading mucosal changes and their trend from regeneration through dysplasia to carcinoma. It underlines the necessity of assessing not only cytological but also architectural and inflammatory components when diagnosing regeneration and low grade dysplasia. Mucosal morphometry may be of use in confirming high grade dysplasia which is an indication for colectomy.
Adenocarcinoma↗