Walter L. Thomas

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.

Genital cytology in obstetric and gynecologic patients. A four-year study☆☆☆

Abstract 1. 1. Cytologic interpretations were made on 51,022 smears from 15,217 obstetric and gynecologic patients in a four-year study. 2. 2. Technical procedures and classification of cytology are substantially those of Papanicolaou and colleagues. Classification of cervical cytologic atypicalities as studied in smears from pregnant women is recommended. 3. 3. Only 12.3 per cent of the women studied had what were judged to be normal elements in smear preparations whereas some degree of benign abnormalities was encountered in 80.4 per cent. 4. 4. False-negative and false-positive percentages of error are given. Various methods of calculating the false-positive error are illustrated and criticized. 5. 5. A total of 594 genital cancers was studied by smear preparations, of which 447, or 75.2 per cent, consisted of squamous-cell carcinoma of the cervix. Adenocarcinoma of the uterus comprised 80, or 13.4 per cent of the total number. Thirty-two (29 squamous-cell and 3 adenocarcinomas), or 6.8 per cent of the cervical cancers, occurred in cervical stumps. 6. 6. Ninety-five intraepithelial carcinomas of the cervix were studied. These represent 0.62 per cent of all patients studied, 0.65 per cent of the patients who did not have malignancy, and 17.5 per cent of the neoplastic squamous lesions of the cervix. The ratio of intraepithelial carcinoma to squamous-cell carcinoma of the cervix was 1:4.7. 7. 7. Cold-knife conization of the cervix is considered to be the method of choice to provide adequate material for the diagnosis of intraepithelial and early invasive carcinoma of the cervix. The punch biopsy method missed 18.5 per cent of the lesions. 8. 8. The number of patients who had intraepithelial and squamous-cell carcinoma of the cervix are presented graphically according to age groups. 9. 9. The importance of correlating smear interpretations with corresponding pathologic studies is emphasized. 10. 10. The cost of cytologic studies is estimated to be as follows:

Adenocarcinoma of the cervix and of the cervical stump

0.90 per smear;

Vulvovaginal mycoses in pregnancy

3.00 per new patient;

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

2.00 per visit;

A clinical study of granuloma inguinale with a routine for the diagnosis of lesions of the vulva

75.00 per malignancy studied. 11. 11. It is suggested that many intraepithelial carcinomas of the cervix will not be detected unless women as young as 20 years of age have routine cytologic studies made. 12. 12. It is strongly suggested that efforts be made to standardize reports of cytologic interpretations, the staining procedure, classification, and the statistical methods employed. 13. 13. The method is of value for broad screening purposes, providing the interpretations are properly controlled. The detection of early cervical neoplasms is, perhaps, its greatest value. The identification for future study of the cervices which exfoliate benign but definite atypicalities of the epithelium is important.

Nonspore-forming anaerobic bacteria of the vagina.

Abstract 1. 1. The incidence of adenocarcinoma of the cervix or of the cervical stump was 3.4 per cent in a series of 1,441 patients with carcinomas of the cervices or of the cervical stumps who were registered in the ten years, 1938 to 1947. 2. 2. Forty-two of the adenocarcinomas, when first seen, were Stage II, III, or IV. Histologic grading was, in all probability, inaccurate but the incidence of undifferentiated carcinomas was high. 3. 3. The average duration of symptoms before the patients were seen was nine months; the average delay in diagnosis and the starting of treatment was ten months. 4. 4. There were eleven (22 per cent) patients in this series of 50 who had adenocarcinomas of the cervical stumps. This incidence, with our high incidence of squamous-celled carcinomas in cervical stumps, strengthens our conviction that panhysterectomies are preferable to supravaginal hysterectomies. 5. 5. “Adequate” x-ray and radium therapy, as the only method of treatment, was given 18 patients. Two (11.1 per cent) are living; one has lived 36 months and one 96 months with no evidence of disease. The other 16 patients are either in the terminal stages of the disease, are dead, or are lost and counted as dead of cancer. 6. 6. Five patients had radical hysterectomies or radical removals of the cervical stumps and radical pelvic lymphadenectomies. Cancer was found in the cervices of four patients, in the uterus and vagina in one, and in the pelvic lymph nodes in four. All of these patients died of cancer. 7. 7. Seven patients had radical hysterectomies and radical pelvic lymphadenectomies. In one the left iliac nodes showed cancer; in the other six there were no positive nodes. This patient with positive nodes has lived 60 months and two other patients have lived 64 and 72 months, respectively, without evidence of cancer. The four other patients have lived 24, 8, 8, and 7 months, respectively, without evidence of cancer. 8. 8. There were no deaths in this series from either irradiation therapy or from operations. 9. 9. Of the thirteen (26 per cent) patients living at present without evidence of disease, only six (12 per cent) have reached or passed the five-year limit at which we list the patients as “presumptive” cures.

The diagnosis of genital malignancy by vaginal smears

Abstract 1.1. Cultures of yeastlike fungi from the vaginas and vulvas of 200 pregnant women were positive in 86 (or 43 per cent) of the patients. These fungi belonged to the genera Monilia, Saccharomyces, or Cryptococcus. Sixty-six (33 per cent) of the patients showed positive vaginal cultures; 20 (10 per cent) showed positive labial cultures with negative vaginal cultures. 2.2. A total of 151 strains of yeastlike fungi were classified according to the method previously described by Jones and Martin. Each strain identified as M. albicans was pathogenic for rabbits. Each strain identified as M. stellatoidea was nonpathogenic for rabbits. 3.3. In patients in whom the fungi were identified as belonging to the genera Saccharomyces or Cryptococcus, no symptoms referable to a mycotic infection were described. Symptoms in patients with positive cultures for yeastlike fungi, belonging to the genus Monilia, were found only in those in whom the 3 species, albicans, stellatoidea and (candida) tropicalis were isolated. Although the incidence of trichomonads was higher in the patients from whom M. stellatoidea was cultured, more patients complained of pruritus in the group from which M. albicans was cultured. 4.4. Intradermal skin test with antigens from the 5 species of Monilia showed no correlation between positive cultures and positive intradermal tests. The incidence of Monilia was higher in the group with negative skin tests. 5.5. The presence or absence of agglutinins in the patients serum could not be used as an index of vaginal or labial infection with Monilia. 6.6. Vaginal smear typing showed that monilia were found more frequently in patients with Type 2 smears; that trichomonads were found more frequently in patients with Type 3 smears. 7.7. Additional work must be done on the mycologic flora of the vulva and vagina in normal patients and in patients with mycotic vulvovaginitis, before we may understand the relative pathogenicity of the different genera and species of yeastlike fungi and may evaluate methods of diagnosis and treatment.

Metro-nidazole in the Treatment of Vaginal Tricho-moniasis: Heinatologic, Neurologic, and Long-Term Clinical Evaluations.

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).