Biomedical subjects
Publications and source records attributed to J M Monaghan.
The nuclear DNA contents in subbasal (nonreplicating) cells of 161 vulvar biopsies from 31 patients were studied by Feulgen staining, integrated scanning microspectrophotometry (densitometry) and subsequent "four-quarter" analysis of the measurements. The results showed a constancy of the nuclear DNA content in the nonreplicating cells, regardless of the patient or the biopsy site.
Significant premalignant disease of the cervix was found in 37% of women referred to a colposcopy clinic because of a smear that showed no more than mildly atypical cells, and in 49% of women whose smears showed mild dyskaryosis. This did not seem to be related to the number of times the abnormal smear had been repeated and was not confined to patients whose smears had been reported by only one laboratory. In another group of 102 women whose first abnormal smear was graded as atypical: 10 had cervical intraepithelial neoplasia; 9 still had abnormal smears and 27 had been lost to follow-up, possibly because the potential importance of this finding was not recognised by the doctor to whom the smear report had been returned. Women with midly atypical or mildly dyskaryotic smears are at considerable risk of having cervical intraepithelial neoplasia. All patients with a smear report showing dyskaryosis of any degree of severity should be referred for colposcopy. Those with atypical cytology should be referred for colposcopy if a second smear, repeated after 3 months, is not normal.
This report analyses 1234 patients with CIN and non-condylomatous wart virus infection (NCWVI) managed by CO2 laser ablation in the Regional Department of Gynaecological Oncology, Queen Elizabeth Hospital, Gateshead from 1979 to 1983. Thirty-five patients (3%) were lost to follow-up. Of the 1157 patients currently under review and with at least 1 year of follow-up, 44 (3.8%) were laser treatment failures. This group is analysed and the results compared with other series.
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A selected group of 51 patients with histological features of cervical warty atypia was observed for 1 year. Initial features were compared with a cohort of 50 patients with CIN. Twenty-four patients showed resolution of the warty atypia, in 19 it remained unchanged, and in eight patients CIN or microinvasive disease was present on repeat biopsy. The DNA patterns obtained by tissue imprint of the initial biopsies and subsequent integrated densitometry, using a Vickers M85 scanning densitometer, showed that warty atypias could be objectively distinguished from CIN, but that the method could not predict the group of warty atypias that would resolve. There was no clinical feature or group of features which allowed a means of predicting the outcome of such lesions.
Three experiments describing applications of cell kinetic techniques to the human cervix are presented. The mitotic index is shown not to be associated with histologic differentiation, node metastasis, or survival rates in cervical squamous carcinoma, although inherent sources of inaccuracy may be a contributory factor. The second experiment, a new application of the metaphase arrest technique to cervical epithelium, allows an estimation of cell production rates in normal, dysplastic, wart-affected cervical epithelium, and in invasive carcinoma. Confidence limits are wide, rendering individual values imprecise in isolation. The third project describes a modification of in vitro labeling of cervical biopsy specimens using tritiated thymidine followed by autoradiography. Labeling indexes are produced for normal and pathological cervical epithelium. Although successful labeling was not achieved in every case, the labeling index for cervical intraepithelial neoplasia (CIN stage III) is significantly greater than for normal epithelium. The metaphase arrest technique appears to be the most applicable of the three to the study of the human cervix, yielding a useful parameter of cell proliferative activity. The labeling index gives an indication of activity that is useful for comparative studies, but that does not provide data regarding actual proliferative rates. More sophisticated experiments using radioactive materials are ethically inadmissable.
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Seventy-three patients with adenocarcinoma of the cervix were seen between 1969 and 1983. This represented 8.1% of all carcinoma of cervix seen during that period. Survival rates in stage Ib were significantly worse for those with poorly differentiated lesions and for those with involved pelvic lymph nodes. Age at presentation appeared to decline over the period of the study. When the patients with stage Ib lesions were compared with a group of stage Ib squamous carcinomas treated in the same unit, there was no difference in age at presentation, node metastasis rates, or survival. Four patients had cervical intraepithelial neoplasia (CIN) in addition to adenocarcinoma.
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A total of 94 patients with cervical warty atypia have been treated, on an outpatient basis, using the carbon dioxide laser. The treatment was quickly and painlessly performed. Ten patients (10.6%) had a persisting warty atypia. These treatment failures were not related to age, parity, lesion size, or method of contraception.
In order to study cell proliferation in intact human cervical epithelium, a technique involving metaphase arrest has been utilized. Metaphase accumulation is observed following intraepithelial administration of vincristine sulphate, at a predetermined optimum dose of 50 micrograms/ml. A significant delay before the onset of stathmokinetic activity is demonstrated; thereafter linearity of accumulation is apparent over a 4-hr period following injection. The technique appears applicable to the estimation and comparison of cell production rates in vivo of normal cervical epithelium, cervical intraepithelial neoplasia, wart-affected cervical epithelium and early invasive carcinoma. However, individual values are likely to be imprecise in isolation, indicating the need to study relatively large numbers of subjects in each group. Some practical difficulties are discussed.
A report is given of 160 patients with vulval carcinoma who were managed by one Oncologist (J.M.M.) in a regional gynaecological oncology department. Prognosis was closely related to nodal metastases which were in turn related to tumour size and degree of differentiation. These factors may be a guide to the need to carry out pelvic node dissection during radical surgical treatment. The place of radical surgery is emphasized and the need for postoperative staging suggested.
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A total of 423 patients with cervical intraepithelial neoplasia (CIN) have been treated with a carbon dioxide laser in the out-patient colposcopy clinic. Thirty patients required two or more treatments. Outcome has been assessed in 408 patients followed for more than 1 year. Sixteen patients (4%) have had a recurrence of CIN. Failures were not related to age, parity or size of lesion.
The clinical history and treatment of 17 patients with multicentric primary carcinomas of the cervix and vulva is presented. There is a significant association between vulval intraepithelial neoplasia and cervical neoplasia. The concept of multicentricity in relation to invasive and intraepithelial neoplasia of the cervix and vulva is critically reviewed.
Cellular imprints from 30 colposcopic biopsies were analyzed for their intranuclear DNA content using Feulgen staining and microspectrophotometry. Biopsies from ten areas of normal epithelium were compared with those from ten cervical intraepithelial neoplasias (CIN) and ten noncondylomatous warty atypias (NCWA). The normal biopsy prints showed an expected diploid-tetraploid stem cell line. Warty atypias and CIN could be distinguished by their aneuploid Feulgen-stained cells and the polypoid densitometry pattern of the warty atypias. The significance of these findings in relation to cervical neoplasia is discussed.