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      Objective Quantification of Grade of Atypia in Epithelial Tumors of the Stomach by Image Processing

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          Abstract

          An image processing technique to extract tubular and nuclear areas from histological specimens stained with hematoxylin was established. Two indices representing tubular density and nucleus‐to‐cytoplasm ratio of glands were examined in intestinal‐type tumor of the stomach. In specimens clearly stained with hematoxylin, significant differences of brightness among nuclei, cytoplasm and stroma can be obtained. Image processing by computer enabled us to identify nuclei, cytoplasm and stroma by utilizing the differences of brightness among them. Both indices tended to increase with severity of histological atypia and their values in the tubular adenoma group were significantly different from those in the tubular adenocarcinoma group (P< 0.05). Therefore, these two indices could be regarded as valid and objective measures of the grade of histological atypia. Eighty‐four percent of tubular adenoma and tubular adenocarcinoma cases were classified correctly with the discriminant formula and critical value calculated from the two indices on the basis of measurement of the images magnified by 40 times. There is, however, still a non‐negligible overlap of discriminant scores between the tubular adenoma group and tubular adenocarcinoma group. More indices representing histological atypia will be required to allow objective differential diagnosis between malignant and benign lesions.

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          Most cited references15

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          The value of morphometry to classic prognosticators in breast cancer.

          In 271 breast cancer patients with adequate follow-up for at least 5.5 and maximally 12 years, the value of morphometry to classic prognosticators of breast cancer (tumor size and axillary lymph node status) was assessed. Previous studies had indicated the value of this quantitative microscopic technique. Apart from quantitative microscopic features, subjective qualitative features such as nuclear and histologic grade were assessed as well. Univariate life-table analysis showed the significance (p less than 0.001) of several features such as lymph node status, tumor size, nuclear and histologic grade, and several morphometric variables (mitotic activity index, mean and standard deviation of nuclear area). Cellularity index was also significant (p = 0.02). Survival analysis with Cox's regression model, using a stepwise selection as well as backwards elimination, pointed to three features: mitotic activity index, tumor size, and lymph node status. Mitotic activity was the most important prognostic feature, but the combination of these three features in a multivariate prognostic index had even more prognostic significance. Kaplan-Meier curves showed that the 5-year survival of lymph node-negative patients (n = 146) is 85%, versus 93% in patients with a "good prognosis index" (n = 150). For lymph node-positive patients (n = 125), 5-year survival was 55%, compared with 47% in the "high index" (poor prognosis) patients (n = 121). Logistic discriminant analysis with 5.5-year follow-up as a fixed endpoint (191 survivors and 80 nonsurvivors) essentially gave the same results. Application of two instead of one decision threshold (e.g., numerical classification probability 0.60 and 0.40) decrease the number of false-negative and false-positive outcomes, however, with a number of patients falling in the class "uncertain." Thus, in agreement with other studies, morphometry significantly adds to the prognosis prediction of lymph node status and tumor size. Mitotic activity index is the best single predictor of the prognosis. An additional index advantage is that the multivariate model results in a continuous index variable that can be subdivided in many classes with an increasing risk of recurrence, so that more refined clinical therapeutic decision making is possible in individual patient care. The morphometric techniques are inexpensive and fairly simple and therefore can be applied in most pathology laboratories.
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            Morphometric analysis of gallbladder adenocarcinoma: discrimination between carcinoma and dysplasia.

            To characterize the cytological features of well differentiated adenocarcinoma of the gallbladder, a comparative morphometric analysis was made using 35 histologically classified cases of invasive well differentiated adenocarcinoma, 13 cases of mild dysplasia, 19 cases of severe dysplasia, and 22 control gallbladders. The variables analyzed were nucleocytoplasmic (N/C) ratio and nuclear area (N.A.). Both the mean values of N/C ratio and N.A. demonstrated a progressive increase from control to mild dysplasia, to severe dysplasia and to carcinoma. The differences were statistically significantly different. Discriminant analysis was made with a set for learning and a set for testing, selected from the 89 lesions with random numbers. Using this discriminant function, all the cases except one carcinoma were discriminated as carcinoma, and all the cases of control, adenoma, and mild dysplasia were discriminated as benign lesions. However, cases of severe dysplasia were subdivided into benign or malignant. These results indicate that morphometric analysis clearly differentiates carcinomas from benign lesions, and that the dysplastic mucosal lesions can be divided into benign and malignant, although some difficult borderline lesions exist.
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              Morphometric distinction of low- and high-grade dysplasias in gastric biopsies.

              Substantial agreement has previously been demonstrated between qualitative and morphometric grading of gastric dysplasia. In the present study, a further attempt is made to quantitatively define the dysplastic changes in relation to associated benign or malignant changes of gastric mucosa. In total, 232 cases were studied and were associated with benign peptic ulcer (89 cases), histologically proven gastric cancer (88 cases), and gastritis-associated mild, moderate, and severe dysplasias (55 cases). The analysis showed that one discriminant function consisting of seven morphometric features is sufficient to separate the regenerative and cancer-associated cases. The classification results obtained on the basis of this discriminant function in both training and testing sets are encouragingly similar, indicating that the classification is reliable. This was further confirmed by the results of the application of this rule in the mild, moderate, and severe dysplasia biopsies (the above-mentioned gastritis-associated cases) used in a previous study. The quantitative analysis permits two grades, instead of three, to be distinguished: low-grade and high-grade dysplasia.
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                Author and article information

                Journal
                Jpn J Cancer Res
                Jpn. J. Cancer Res
                10.1111/(ISSN)1349-7006a
                CAS
                Japanese Journal of Cancer Research : Gann
                Blackwell Publishing Ltd (Oxford, UK )
                0910-5050
                1876-4673
                February 1991
                : 82
                : 2 ( doiID: 10.1111/cas.1991.82.issue-2 )
                : 199-205
                Affiliations
                [ 1 ]Division of Pathology, Tsuchiura Kyohdoh Hospital, 11‐7 Manabe Shin‐tnachi, Tsuchiura 300
                [ 2 ]Pathology Department, Institute of Basic Medical Sciences, University of Tsukuba, 1‐1‐1 Ten‐noudai, Tsukuba 303
                Author notes
                [*] [* ]To whom correspondence should be addressed
                Article
                CAE199
                10.1111/j.1349-7006.1991.tb01829.x
                5918377
                1900823
                f75e61c3-31e7-4e0e-ad70-779131abeb4a
                History
                Page count
                References: 18, Pages: 7
                Categories
                Article
                Custom metadata
                2.0
                February 1991
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.6.9 mode:remove_FC converted:04.11.2015

                gastric tumor,morphometry,image processing
                gastric tumor, morphometry, image processing

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