A 25-year analysis of deaths from uterine cancer in Louisville, Kentucky.
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Biomedical subjects
Publications and source records attributed to W M Christopherson.
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It is postulated that squamous cell carcinoma, adenocarcinoma, and mixed adenosquamous cell carcinoma of the uterine cervix all have a common cell or origin, the subcolumnar reserve cell. The relative frequency with which the various types of carcinoma in situ are seen is in part explained by the ubiquitous nature of squamous metaplasia in the region of the transformation zone in women of reproductive age. It is suggested that squamous metaplasia is the soil on which most squamous carcinomas of the cervix evolve. The relatively low frequency with which adenocarcinoma and adenosquamous carcinoma in situ are encountered may also be dependent on their less accessible location in the endocervix.
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The revolutionary changes in the mores and practices of adolescent sexuality have not as yet resulted in a significant increase in the rates of cervical cancer precursors in a study of 29,600 young women under age 21. The study represents women from families of low socioeconomic status. Over a 21-year period no cases of carcinoma in situ nor of invasive cervix cancer occurred. The dysplasia rate was low (0.9/1000), and when prerevolutionary and revolutionary periods were compared, there were no significant differences in the rates. Cryocautery was successful in ablating dysplasia, as was follow-up without treatment. An attempt will be made to continue to monitor these young women of the sexual revolution since the effects of their past and current participation might not be discernible for years to come.
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Carcinoma in situ is defined as the early stage of cancer and must therefore be initiated by an as yet unknown carcinogen(s). Progression of the lesion to invasive carcinoma is reported to occur in a high proportion of nontreated cases. Reserve cell proliferations are frequently associated with both dysplasia and carcinoma in situ, and it is suggested that these are the cells from which both lesions arise. Dysplasia may result from both carcinogenic and noncarcinogenic stimuli. Since dysplasia usually either regresses or remains stabilized over a prolonged period, it is suggested that it is more frequently associated with noncarcinogenic stimuli. Microinvasive carcinoma is limited to lesions with no more than 5 mm. of stromal invasion as measured from the surface. Confluence of growth and lymphatic-like space invasion should not interdict the diagnosis. Microinvasive carcinoma thus defined rarely gives rise to lymph node metastasis or eventuates in death. The diagnosis cannot be made from punch biopsy specimens. Only if pathologists adhere to a standard nomenclature can follow-up studies be used successfully to identify the natural behavior of each type of lesion in this spectrum.
Two strains of mice, CF-LP and Swiss-Webster random-bred, were evaluated for liver neoplasia after administration of oral contraceptive steroids. No increased incidence of hepatocellular tumors was found beyond the variation expected by chance. The overall tumor incidence in treated and untreated groups was identical. No significant increase in tumor size was observed in the treated animals. Liver weights progressively increased in several of the treated groups. In both treated and untreated animals hepatocellular neoplasia was usually accompanied by intracytoplasmic inclusions similar to those observed in human liver tumors. Vascular lesions were observed in some of the animals receiving large doses of contraceptive steroids. While these may be the result of local toxicity, their similarity to lesions observed in benign liver tumors warrants further investigation. No evidence was found to suggest that contraceptive steroids act as initiators of liver neoplasia.
Tissue specimens from a series of 46 hepatic tumors occurring in young female oral contraceptive users were tested for alpha1-antitrypsin deposition, utilizing immunocytochemical and histochemical methods. In two instances serum alpha1-antitrypsin phenotyping was also performed. Immunoreactive alpha1-antitrypsin deposits were demonstrated in benign lesions, including 56% of cases of focal nodular hyperplasia and 68% of cases of liver-cell adenoma, and in 89% of cases of malignant hepatoma. There was good correlation between alpha1-antitrypsin deposits and variable amounts of finely granular, or globular, diastase-resistant periodic acid-Schiff positivity within tumor cells. While quantitative differences in alpha1-antitrypsin deposits between benign and malignant cell proliferations were not observed, a qualitative continuum that linked all tumors in the study group was found. The findings suggest that alpha1-antitrypsin deficiency is not related to the hepatic tumors developing in oral contraceptive users. The tumor tissue deposits of alpha1-antitrypsin observed represent a marker protein, the significance of which is undefined.
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A registry of liver tumors was started in late 1973 in an attempt to assess the relationship of these tumors to oral contraceptives or to other environmental factors. This report is concerned with the pathological aspects and the possible pathogenesis of the first 101 tumors accessioned. There were 44 instances of focal nodular hyperplasia, 40 adenomas, four unclassified but probably benign tumors, and 13 hepatocellular carcinomas. Eighty-one patients took oral contraceptives; six were associated with pregnancy; three had taken estrogens for long periods of time; one had a thecoma; four never took sex steroids; and in five the history was unknown. Tumor rupture and intrahepatic hemorrhage were frequent complications. It is possible that the vascular lesions associated with focal nodular hyperplasia could play a part in their pathogenesis as well as with rupture. Foci of adenomatous hyperplasia may be related to the development of adenomas. The association of these tumors with sex steroids could be coincidental. The fact that none of the patients had cirrhosis of liver fibrosis, and that androgenic anabolic steroid therapy has been associated with hepatocellular carcinomas in males, suggests that further study of the problem is necessary.
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A group of 205 women with endometrial carcinoma was matched for age, parity, and year of operation with a group of 205 women who had had hysterectomies for benign disease. In the former group, 32 patients had used conjugated estrogens, while in the latter group 12 had used this hormone, yielding a relative risk of 3.1 (P = 0.0008). Users of other forms of systemic estrogens showed similar elevations in relative risk. Relative risk was related to duration of use, progressing from no evidence of risk among those using the hormone for less than 5 years to an 11.5-fold greater risk for those using it for 10 years or more. Risk was also related to the strength of the medication. The relative risk for users of the 1.25-mg tablets was 12.7 as compared to a two- to fourfold greater risk among users of lesser strength tablets.
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Primary hepatic tumors developed in 13 young women who had been ingesting contraceptive steroids. Nine tumors were benign, and four malignant. Six tumors ruptured spontaneously and caused life-threatening hemorrhage. Benign tumors were successfully resected in eight women. One woman died during hepatic resection for malignant hepatoma; in two other cases of hepatocellular carcinoma, tumors were nonresectable. In two patients, the tumor was left in situ after neoplasm had been excluded by biopsy. The increase of such tumors in women of childbearing age warrants the suspicion that these contraceptive steroid hormones play an etiologic role.