Robert N. Creadick

Intraepithelial (Stage O) cancer of the cervix

Abstract The concepts of the detection, diagnosis, and treatment of intraepithelial cancer in our clinic are presented. The data are based on 485 patients with intraepithelial cancer of the cervix studied during the past 13 years from Jan. 1, 1947, through Dec. 31, 1959.

Clinical problems in stage 0 (intraepithelial) cancer of the cervix

Abstract A report is given of 275 patients with intraepithelial (Stage 0) squamous-cell cancer of the cervix or cervical stump, who have had diagnosis and treatment in our clinic during the past eight and one-half years. An attempt is made, by the use of descriptive tables, to place Stage 0 cancer in its proper perspective in the entire problem of malignancies of the female generative tract, as these malignancies are seen by our group. From this small series, we can draw no valid conclusions. This series is simply the basis for consideration of an attempt to formulate how properly to manage the problem of Stage 0 cancer. A review of the clinical material, as shown in the various tables, adds little noteworthy data to those of the 1952 report. Although the figures are not of statistical value, Table I shows that the incidence of intraepithelial cancer in the gynecologic patients was 0.58 per cent and in the obstetric patients the incidence was 0.57 per cent. No significant alterations are found for age (Tables III and IV), for race and economic status, for marital status, or parity (Tables V, VI, and VII). Table VIII shows clearly that Stage 0 cancers were found in cervices and in cervical stumps in which no clinical manifestations of disease were apparent to the examiners. If evidences of disease were present, they were in no way pathognomonic of Stage 0 cancer. A comparison of treatment Tables IX, X, and XI in the original report of 1952 with treatment Tables X and XI in this present report shows among the clinicians of our department a definite trend to vaginal hysterectomy with conservation of the ovaries in our younger age groups. The majority feels that vaginal hysterectomy with removal of an adequate vaginal cuff is the operation of choice. It should be noted in Table X that of 237 gynecologic patients with intraepithelial cancer of the cervix, 57 are being followed with no further definitive treatments than multiple punch biopsies for 7 patients and cold-knife cone biopsies for 50 patients. Discrepancies between the total figures for certain categories in the treatment Table X in this report and those in the treatment Tables IX and X in the original 1952 report are due to elimination from this series of a number of patients treated and followed elsewhere (uncontrolled and lost). Table XI shows that of 38 obstetric patients with intraepithelial cancer of the cervix, 10 have received no more definitive treatments than multiple punch biopsies and 11 no more definitive treatments than cold-knife conizations. The figures in Tables X and XI state a calculated risk we have assumed in following these patients who have not had definitive treatment. Another expression of this assumed risk is found in Table XII which shows that 7 gynecologic patients with Stage 0 cancer of the cervix were permitted to become pregnant one or more times before definitive treatments were given. It is important to note that only one of these 7 patients has continued to show genital smear atypicalities. This patient had multiple biopsies only and not cervical conization. Table XIII gives the data on the 11 patients, in a total of 38 obstetric patients who had Stage 0 cancer, who became pregnant after the diagnosis was established. Of these 11 patients, but 3 at the present time had had definitive operative treatment. Eight patients are being followed. One obese, hypertensive patient died following vaginal hysterectomy. No other significant complications occurred as a result of operations for diagnosis or treatment of Stage 0 cancer. Resuturing of the cervix for hemostasis was done in several patients who continued to bleed following cold-knife conization. Routine soundings control the problem of cervical stenosis. One patient, of the 275 patients, had a depressive psychosis prior to diagnosis and definitive therapy and committed suicide despite psychiatric care. It is not felt that the diagnosis and treatment hastened her action. No patient in this series has developed drug addiction. In the discussion, an effort is made to show some of the problems of Stage 0 cancer as they involve many of the specialists of hospital technical practice as well as those of our own service. A short summary is given of the clinical records of two patients in whom invasive squamous-cell cancer of the vagina was demonstrated years after definitive diagnosis and hysterectomy for intraepithelial cancer of the cervix. These two patients are subjects for many varied speculations. To our knowledge none of the patients who are being followed without definitive treatment has developed invasive squamous-cell cancer of the cervix. The follow-up is an important feature in the study of Stage 0 cancer of the cervix or of the cervical stump. It is essential that all patients whether they have had conservative or definitive treatment be followed with adequate diagnostic techniques. Heavy obligations are assumed by anyone who elects to treat the lesion whether by conservative or definitive therapeutic methods. The “pooling” of data from many clinics must be expedited in order to clarify the confusion which now exists in criteria both for diagnosis and for the methods of treatment. Data are presented on the number of follow-up visits and the duration of the follow-up periods for 60 of 75 patients who have Stage 0 cancer and who have had but multiple punch biopsies and cold-knife cervical conizations. The number of follow-up visits per patient ranges from 1 to 14, totaling 289 for the 60 patients. The duration of the follow-up periods ranged from 2 months to 6 years. No patient in this series who has had definitive treatment for Stage 0 cancer of the cervix continues to show atypicalities in genital smears. Three gynecologic and 2 obstetric patients who had multiple punch biopsies or coldknife cervical conizations of the cervix have persistent cytologic atypiae. The two obstetric patients have recently delivered and 2 of the gynecologic patients desire further pregnancies. The third gynecologic patient is 74 years of age and has severe cardiac disease. It is important that two groups of patients in this series be followed closely for academic as well as for clinical reasons. The first group is comprised of those patients who had microscopic foci of invasion found in tissue specimens subjected to multiple block sectioning. There were 7 of these patients, 6 gynecologic and one obstetric. To date, none of these patients has clinical evidence of invasive cancer. The second group is comprised of those patients who have not yet had definitive treatment. Patient 4 in Table XII is an outstanding example in this category. Faithful in follow-ups and with understanding, she refuses further diagnostic or treatment procedures. The diagnostic multiple punch biopsies were made just four years ago. The patient remains adamant in her intention to have another child. Periodic infertility on the husbands part has increased the difficulty of the situation.

Maternal, fetal, and environmental factors in prematurity☆

Abstract This study of certain factors associated with premature births included 2,521 prematures among 29,561 deliveries at three hospitals in North Carolina during the years 1954 through 1961. Using four broad socioeconomic classes, it was observed that the incidence of prematurity was considerably higher in women under 20 years of age and in the less favored socioeconomic classes. Birth order per se did not exert a significant influence on the incidence of prematurity. On the other hand, maternal height did correlate with prematurity, the shorter women having higher rates. Selected complications during pregnancy occurred progressively more frequently from the most favored to the least favored socioeconomic group. In general, the complications studies were associated with an increase in the incidence of prematurity so that both socioeconomic status and complications affected premature rates.

Parental, fetal, and environmental factors in perinatal mortality☆

Abstract The parental, fetal, and environmental factors associated with 279 perinatal deaths and 398 controls have been examined. From the data it is quite evident that socioeconomic factors are of primary importance in perinatal mortality. The difference in perinatal mortality between the white and non-white groups disappeared when adjusted for socioeconomic factors. The fathers occupation and the mothers education showed significant differences in relation to perinatal mortality even when adjusted for race, age, and parity. The fathers occupation and mothers education were considered as indices of the socioeconomic status of the family. The mothers age was found to be a highly significant factor in perinatal mortality even when adjusted for race, age, and parity. The technique used in obtaining the data for the present study did not yield reliable information in regard to the nutritional status of the mother. Birth interval, parity, previous obstetric complications, and previous perinatal mortality did not appear to be significant in relation to perinatal mortality when adjusted for race, age, and parity. No correlation was noted between the level of the maternal hemoglobin and perinatal mortality. Certain complications of pregnancy such as toxemia, premature separation of the placenta, placenta previa, and other antepartum bleeding were associated with extremely high perinatal mortality rates. In this study the type of delivery appeared to have no relationship to perinatal mortality when other variables were considered.

The follow-up of patients with cancer of the cervix treated by radical hysterectomy and radical pelvic lymphadenectomy.

Abstract In Table V the 197 cancers are divided into the various stages and the salvage for each stage is shown. The total number of deaths from squamous-cell cancer and from adenocarcinoma is also shown. For squamous-cell cancer 177 operations were done; 33 (18.6 per cent) patients had positive nodes. The uncorrected 5 plus to 13 plus year salvage in these 33 patients was 12 (36.3 per cent). Deaths from all causes in the 177 patients numbered 49 (28.6 per cent). The uncorrected salvage was 128 (72.3 per cent). For adenocarcinomas 20 operations were done; 6 (30 per cent) patients had positive nodes. One patient (16.6 per cent) with positive nodes has lived 13 plus years. There were 8 (40 per cent) deaths from all causes in the 20 patients. The uncorrected salvage in the 20 patients operated upon was 12 (60 per cent). If the 33 (18.6 per cent) patients with positive nodes were excluded from the 177 cases of squamous-cell cancer, in the remaining 144 patients there were 28 (19.4 per cent) deaths in the period of 5 plus to 13 plus years. This would give an uncorrected salvage in all patients with negative nodes of 116 (80.6 per cent). If the 6 (30 per cent) patients with positive nodes were excluded from the 20 patients with adenocarcinoma there would be 2 deaths (14 per cent). This would give an uncorrected salvage in all patients with negative nodes of 12 (86 per cent).

THE VAGINAL FUNGI

In the ages of ovarian function the vagina is the normal habitat for saprophytic and potentially pathogenic yeasts and yeastlike fungi.’, Because the same fungi are not found in the vagina of preadolescent and postclimacteric patients, it is probable that the incidence during menstrual life is related to the increased glycogen content of the vaginal mucosa. A higher incidence occurs during pregnancy, and attempts have been made to explain this phenomenon on the basis of higher hormone levels that tend to produce more mucosal glycogen and to increase the average vaginal acidity. Some investigators3 believe that the so-called “renal glycosuria of pregnancy” may be a contributing factor. In citro, the growth of yeasts and yeastlike fungi is stimulated by the addition of glucose. This factor appears to be the logical explanation for the occurrence of vaginal fungi in diabetics of any age group.

Fetal, parental, and environmental factors associated with perinatal mortality in mothers under 20 years of age.

Abstract 1. 1. Excessive parity in young mothers and illegitimacy are associated with higher perinatal mortality rate. 2. 2. This increased perinatal mortality rate involves both fetal and neonatal components with the neonatal component predominant. 3. 3. Prematurity and toxemia of pregnancy are largely responsible for the increased mortality observed among women under 20 years of age. 4. 4. The socioeconomic status of the patient in this age group is extremely poor and probably accounts for the increased incidence of prematurity and toxemia which are observed.

Carcinoma of The Cervical Stump

Abstract 1. 1. An analysis of 183 cases of carcinoma of the cervical stump is presented. Fourteen of these were Stage 0 carcinoma. One hundred and sixty-nine were invasive carcinomas, an incidence of 7.21 per cent of all cervical cancers seen during the 25 year interval of study. 2. 2. Close comparisons are made with recently reported series as to age, race, parity, symptoms, indications, and doctor and patient delay. 3. 3. No standard therapeutic regimen can be outlined because of the variety of therapy which was given. 4. 4. The arguments in favor of radical operation are strengthened by the 5 year plus salvage rate attained with radical trachelectomy and radical pelvic lymphadenectomy.