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Combined irradiation and extensive operations in the treatment of stages I and II carcinoma of the cervix uteri.

Since 1947, carcinoma of the cervix uteri, Stage I, has been treated at the Ochsner Clinic with intracavitary irradiation and a radical hysterectomy--Wertheim type--and pelvic node dissection. If metastasis to the lymph node is demonstrated, external irradiation is administered postoperatively. Carcinoma of the cervix uteri, Stage II, has been treated with intracavitary radium and external radiation, followed by the same surgical procedure. All patients were treated surgically, except those with medical conditions precluding extensive operation. Five and ten year survival rates for Stage I cancer were 81.5 and 68.7 per cent, respectively; for Stage II, these rates were 64.5 per cent and 54.0 per cent, respectively. There were moderate complications from the combined therapy, with a ureteral fistula rate of 1.9 per cent. Although the combined use of irradiation and operation for carcinoma of the cervix uteri has been looked upon in this country with disfavor because of poor healing and complications, we have not found this to be so. With improvement of both radiation therapy and surgical management, these patients can be offered treatment based upon sound physiologic principles and can live in freedom from fear of recurrence in later years. The outlook is good for continued improvement in the complication rate, surgical technique and possibly, chemotherapy.

Adenoma

[Classification of precancerous conditions and cancer of the cervix uteri].

The classification consists of three sections: background processes, precancer states, and cancer of cervix uteri. The background processes depending on the etiological factor and the character of lesion of the epithelium are divided into dyshormonal, inflammatory, and posttraumatic. Groups of the so-called morphological precancer and preclinical forms of cervix uteri cancer are identified.

Carcinoma in Situ

Isolated arteritis of the cervix uteri.

Four patients with arteritis apparently isolated to the cervix uteri are presented and the clinical and pathological significance of this condition is discussed.

Adolescent

[Diagnosis, therapy, and prognosis of primary reticulum cell sarcoma of the cervix uteri (author's transl)].

Until now 12 cases of primary reticulum cell sarcoma of the cervix uteri have been described in the literature. Two more cases are reported. Diagnosis is only possible after exclusion of a systemic disease. Principle rules for therapy cannot be given by these few cases. However it seems that combined surgical and radiological treatment provides the best chances for longer surviving. Experiences in chemotherapeutical treatment of reticulum cell sarcoma of the cervix uteri are not yet published. Four of the 14 patients mentioned in this study died from relapse. The prognosis of this type of cervical tumor seems to be rather good.

Adult

The isozyme pattern of cyclic AMP-dependent protein kinase and the distribution of a cervicovaginal antigen in experimental carcinoma of the cervix uteri of mice.

Tissue-sections from 12 methylcholanthrene-induced carcinomas of the cervix uteri of mice were tested for the presence of an antigen normally confined to the cervicovaginal epithelium. The antigen was detected in 10 of the 12 tumours investigated with indirect immunofluorescence, and in all 7 tumours studied with the more sensitive method of mixed hemagglutination. The concentration of the antigen was generally higher in the well-differentiated areas of the tumours, but it was also found associated with solitary tumour cells, apparently invading the stroma. The presence of CVA in the tumours suggests an origin of the tumour cells from the cervicovaginal epithelium. The cyclic AMP dependent protein kinase (EC 2. 7. 1. 37) in the tumour cytosols was studied by chromatography on agarose and DEAE-cellulose. The enzyme showed the same properties as that from normal vaginal epithelium. The tumour cells thus contain an apparently normal complement of this enzyme, which is believed to be responsible for most of the intracellular actions of cyclic AMP.

Animals

[Quantification of proteinthiols in morphologically normal basal cells and pathological squamous cells of the cervix uteri].

Smears taken from eight probands with carcinoma in situ or invasive carcinoma of the cervix uteri have been stained with DDD and Fast Blue B. The extinctions microspectrometrically measured at 560 nm are directly proportional to the quantity of protein-SH-groups. The extinctions of the total cell (Eges) and of the cell nucleus (EK) are measured in 67 basal cells (BAS), 78 dysplatic cells (DYS), 122 undifferentiated cancer cells (UNIF) and 89 differentiated cancer cells (POLY). From BAS through DYS and UNIF to POLY EK increases by a total of 176%. In all four cell types investigated, linear correlations between EK and Eges have been found to occur with a probability of over 99%. The straight lines ascertained represent a relation between EK and Eges which is obviously very characteristic for each cell type, and it becomes apparent that the measuring points corresponding to each single cell are in each instance so close to the straight line that in most cases a differentiation of the three pathological cell types is possible even without a morphological criterion. The straight lines corresponding to BAS, DYS and UNIF start from a common origin, whereas the straight line corresponding to POLY branches off from the UNIF line only. This is in accordance with the formal genesis of pathological variants observed in the cervical squamous epithelium or in differentiated carcinomas of the squamous epithelium respectively.

Carcinoma, Squamous Cell

[Hormone dependent, functional gynecologic morphology in infancy and adolescence presented on the example of the cervix uteri].

Signs of different activities in the dynamic morphology of the epithelium and mucus of the cervix uteri are demonstrated in the female fetus, newborn, child and adolescent. Besides the morphological description of the ectropium, transitional zone, s.c. "reserve-cells", squamous cell nodes and production and secretion of mucus other investigations were done by allometry, caryometry and histochemistry. The examinations allow insight into the hormonal activities specially of the estrogenes in different periods of female life.

Adolescent

The glycolytic enzyme activity of the human cervix uteri.

The activity of the following enzymes was studied in normal, precancerous, and malignant biopsies from the human cervix uteri: hexokinase (HK), phosphofructokinase (PFK), pyruvate-kinase (PK), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G-6-PDH). In precancerous conditions, i.e., dysplasia and carcinoma in situ without any signs of invasive carcinoma, only PK showed moderate but significant activity increases. A rise in enzyme activity in biopsies histologically classified as carcinoma in situ was found to signal the presence of invasive carcinoma in other parts of the cervix. In invasive carcinomas of the cervix, all the enzymes studied showed a two- to four-fold increase (p less than 0.01) as compared to the normal cervix. The present study failed to reveal significant differences between enzyme activities in biopsies from patients in Stage I, II, and III; no correlation could be established between enzyme activity and prognosis.

Alcohol Oxidoreductases

The cytologic diagnosis of clear cell adenocarcinoma of the cervix uteri.

Four cases are presented of clear cell adenocarcinoma of the cervix uteri. Two are early cases of limited histologic extent and two are more advanced examples. The cytologic features are presented with particular reference to differences between the earlier and the more advanced cases. When the early cases are separated in this manner, a source of diagnostic difficulty, which does not arise in the advanced lesions, is identified and discussed.

Adenocarcinoma

Cytologic characteristics of adenoid cystic carcinoma of the cervix uteri.

Cytologic characteristics of three cases of adenoid cystic carcinoma of the cervix uteri are reviewed. The clusters of malignant cells tend to form large acini and mimic the pattern seen in histologic sections. The resemblance to cells of adenocarcinoma of the endometrium is noted. When the acinar pattern is recognized in cervical smears, adenoid cystic carcinoma of the cervix may be suspected.

Aged

Effect of medroxyprogesterone acetate contraception on cytoplasmic estrogen receptor content of the human cervix uteri.

Specimens of cervical tissue from five women each on 150 mg and 450 mg regimens of medroxyprogesterone acetate (MPA) for contraceptive purposes, were obtained through punch biopsy 15 days after injection. In another group of five women each on the same contraceptive regimens, punch biopsies of the cervix uteri were obtained 30 days after injection. These times corresponded to maximum and optimum blood levels of MPA respectively. Corresponding tissue from the same anatomical position in patients matched, where possible, for age and parity was obtained from hysterectomy specimens to serve as controls. Quantification of estrogen receptor content in the cytoplasm of these tissues was achieved through standard procedures. Analysis of data showed that MPA suppressed estrogen receptor content significantly compared to controls, but that there were no differences in this effect between the two dosages or time of biopsy.

Adult

Follow-up studies in dysplasia and cancer in situ of the cervix uteri.

In order to study when recurrences appear following conization for dysplasia or cancer in situ of the cervix uteri, a series of 477 patients has been investigated. They all underwent conization at Sabbatsberg 1965-1970. Among the 181 cases of dysplasia two developed recurrences one respectively three years after treatment. In the series of 296 patients with cancer in situ thirteen recurrences appeared. Eight of them were detected within the first three years. The other five were spread out during the next four years. About 50% of all patients had been followed-up for five years or more (Table I). The conclusion is reached that a yearly follow-up is necessary for at least ten years. As it is impossible to take care of such an accumulating number of examinations at the Swedish departments of obstetrics and gynecology without extra personnel, the following proposal is made. During the first three years after treatment the examinations are performed at the department where the conization has been performed. After that period the follow-up is limited to vaginal smears taken once every year in connection with the general gynecologic health control.

Adult

Cryosurgical treatment of dysplasia and carcinoma in situ of the cervix uteri.

Fifty-nine patients (age range 18-40 years, mean 28 years) with dysplasia or carcinoma in situ of the cervix uteri were treated with cryosurgery. Healing occurred in 54 patients (91.6%) after one treatment ("double-freeze" technic) and in 2 patients after refreezing. No early or late complications occurred during a follow-up period of 7-37 months. Five of the patients with carcinoma in situ were followed immunologically with determinations of serum TPA (tissue polypeptide antigen), which can be employed as a parameter of malignancy. In all instances, the initially elevated TPA normalized after cryosurgical treatment. Cryosurgery is a simple, painless and safe treatment method in ectocervically localized carcinoma in situ and dysplasia that is particularly suited for out-patient use.

Adolescent

[Cytofotometrically Determined DNA-pattern of premalignant cases of dysplasia of the cervix uteri. Contribution to the problem of morphologic definition and clinical sigificance of these lesions (author's transl)].

24 cases of probably benign and precancerous epithelial lesions of the cervix uteri were analysed cytofotometrically. The specimens were stained after the method of Feulgen. Benign epithelial changes for instance metaplasia, regenerating epithelium, atrophic and parakeratotic epithelium, basal cell hyperplasia and cervix epithelium irritated by inflammation, had normal diploid DNA-pattern. On the contrary premalignant dysplasia of all stages show an aneuploid DNA-content in every case. The cases of dysplasia had no diploid mode, an atypical proliferation with polyploidisation of an atypical way, DNA-stemlines and a broad scattering of DNA-values. Carcinoma in situ had a similar DNA-content. These data confirm the hypothesis premalignant dyplasia is a reality between normal cervical epithelium and carcinoma in situ. For now only severe grades of dysplasia have been treated by operation (i. e. conisation, hystectomy) not the low grade cases of dysplasia. With regard to DNA-histograms of dysplasia of all grades this seems to be unjustified.

Adult

The effects of radiotherapy on immunity in patients with localized carcinoma of the cervix uteri.

To assess the effects of radiotherapy on immune status, a wide range of assessments have been performed on patients with localized carcinoma of the cervix uteri undergoing and initially responding clinically to radical pelvic radiotherapy. Neutrophil function was essentially unchanged by treatment. Absolute neutrophil and lymphocyte counts fell after treatment and remained depressed 3 and 12 months following treatment. The proportions of T and B cells dropped with treatment but recovered to near-presentation levels during the follow-up period even though absolute counts remained depressed. In vitro tests of cellular immunity were depressed by treatment and remained so 3 and 12 months following treatment whereas skin test responses remained normal throughout the assessments. Inhibitory plasma effects were observed in phytohaemagglutinin lymphocyte transformation studies on 4 untreated patients; at follow-up these effects were not evident. A variable response in immune indices has therefore been observed in patients in remission after treatment of localized carcinoma cervix stressing the importance of assessing several aspects of immune function and implying that persistent depression of certain indices does not adversely affect the host tumor response. In two patients relapsing after apparently good initial response all aspects of immunological assessment (except serum immunoglobulin levels and neutrophil function) deteriorated.

Cell Migration Inhibition

Cytochemical studies of respiratory enzymes in carcinoma of the cervix uteri after irradiation by radium and cobalt 60.

Enzymological studies of succinic dehydrogenase and cytochrome oxidase were made on human squamous cell carcinoma of the cervix uteri before, during and after radiation therapy by radium and 60CO. The enzymatic activities of the two enzymes were higher in cells of stage III than in the corresponding cells of stage II. In addition, after treatment, no enzymatic activity could be detected. These changes may be explained on the basis of mitochondrial damage as a result of radiation effect.

Biopsy