Alfred I. Sherman

Sexually transmitted papillomaviral infections: I. The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types☆☆☆

Multiple colposcopic biopsy specimens were collected from 160 women, with sampling of principal cervical and vulvar lesions as well as secondary areas of either minor acetowhitening or normal epithelium. Papillomaviral deoxyribonucleic acid was detected by Southern blot hybridization in 197 (90%) of the 218 principal biopsy specimens and 93 (46%) of 198 secondary biopsy specimens. Although different papillomaviruses were found at different sites in 31 women, only six of 416 specimens contained multiple types within the same sample. Specific viral types were associated with specific disease patterns. Only one of 80 type 6 or 11 infections had a diagnosis greater than cervical intraepithelial neoplasia, grade 2. In contrast, 42 of 48 (90%) biopsy specimens of cervical intraepithelial neoplasia, grade 3, or invasive cancer contained type 16, 18, or 31. Nonetheless, 12 of 124 (10%) cases of condyloma and cervical intraepithelial neoplasia, grade 1, were associated with types 16, 18, and 31 infections. Of 58 women with multicentric disease, 46 had positive hybridizations for both cervical and vulvar lesions (32 showing the same type in both samples and 14 showing different viruses). Differing patterns of papillomavirus-induced disease arise partly from the predilection of specific viral types for certain anatomic sites and partly through variations in host response. Detection of viral deoxyribonucleic acid in 46% of the secondary biopsy specimens suggests that disease expression may represent focal breakdown of host surveillance within a field of latent papillomaviral infection.

Office hysteroscopy and suction curettage: Can we eliminate the hospital diagnostic dilatation and curettage?

The hospital diagnostic dilatation and curettage is the most widely used method in investigating abnormal uterine bleeding. This procedure is expensive and inconvenient and poses some surgical and anesthetic risks. As an alternative to hospital dilatation and curettage, the procedure of office hysteroscopy and suction curettage was evaluated in 406 patients. The indications for the procedure are similar to the classic indications for a diagnostic dilatation and curettage. The method is convenient, safe, and relatively inexpensive. The diagnostic accuracy of office hysteroscopy and suction curettage surpasses prior reports of the accuracy of diagnostic dilatation and curettage. Office hysteroscopy and suction curettage should be the method of choice in the evaluation of abnormal uterine bleeding.

An endocrine basis for endometrial carcinoma

In 165 endometrial cancer cases in which ovariectomy was performed i n the course of the surgical treatment hilar regions were not included in the tissue sections of 1 or both ovaries in 32 cases. For controls ovarian sections from 86 postmenopausal women were studied including 52 cases of postmenopausal endometrial hyperplasia. The hilar or Leydig cells were suspected of being of major significance in the etiology of endometrial carcinoma. Since Leydig cells are hormonally dependent upon the pituitary gonadotropin LH or ICSH a corollary study of the urinary excretion of LH was done in selected patients using the ventral prostate weight technique described by MacArthur. In this study urine was assayed in 31 patients with primary adenocarcinoma of the endometrium 37 patients with other conditions 19 patients who had previously been treated for endometrial carcinoma and 4 cases in which LH determinations were repeated after administration of Delalutin (17-hydroxyprogesterone caproate). 133 cases of primary endometrial carcinoma had ovarian hilar tissue available for study in at least 1 section of 1 ovary. Leydig cell hyperplasia was present in 109 cases (81.9%). In the 29 cases of primary adenocarcinoma of the uterus studied since 1957 hilar-cell hyperplasia has been present in 100%. In the controls 14 of 86 cases contained hilar cells. In the 34 controls without evidence of postmenopausal endometrial hyperplasia the incidence of hilar cell clumps was 2 (5.88%). The 52 control patients with such hyperplasia had hilar cell components in 12 cases (23%). The number of hilar or Leydig cells was much lower in cases not associated with endometrial cancer. The urine assays for LH showed that the patients with primary adenocarcinoma of the endometrium had elevated LH levels in all 31 cases. Following bilateral oophorectomy the level of LH fell to normal in all the cases. According to the authors concept at birth a female destined to develop adenocarcinoma of the endometrium is endowed with an abnormal complement of hilar Leydig or theca cells which are LH responsive. During reproductive years these cells are mini mally functioning because of other hormonal activity. However they may cause increased sterilit y. After menopause this restraining activity is less the pituitary is stimulated to excrete excessive LH endometrial hyperplasia results and finally carcinoma of the endometrium.

Carcinoma of the cervix: results obtained from the irradiation of the parametrium with radioactive colloidal gold.

Abstract During the four-year period of 1950 to 1953, inclusive, 324 patients with cancer of the cervix, League of Nations Stages I, II, and III, have been treated by two quite different methods. One group was treated with x-rays and radium. This group is subdivided into clinic and private patients. In the other group the parametrium was treated with radiogold injected transvaginally, and the cervix was treated either by radium or by Wertheim hysterectomy, or by both radium and hysterectomy. In all patients operated upon a fairly extensive pelvic lymphadenectomy was done at the time of the hysterectomy. The two to four and one-half year survival rate of patients with Stage I lesions was 91.4 per cent in the series treated with radiogold, 78.1 per cent in the series of private patients treated with x-ray and radium, and 72 per cent in the clinic patients treated with x-ray and radium. The one-half to four and one-half year survivals were 92.1 per cent, 80.4 per cent, and 68.8 per cent, respectively. Not many patients with Stage II lesions were treated with radiogold in the first two years of the study. Eight out of nine patients (88.8 per cent), however, with Stage II lesions more than two years ago are alive and well. The one-half to four and one-half year survival rate for patients with Stage II lesions was 89.3 per cent in the series treated with radiogold, 56.5 per cent in the series of private patients treated with x-ray and radium, and 48.1 per cent in the series of clinic patients treated with x-ray and radium. There were 11 patients among the 70 subjected to radical operation in whom the lymph nodes were positive. Nine of these patients are alive and apparently free of disease. The incidence of positive nodes in Stage I cases operated upon was 9.8 per cent and in Stage II cases, 31.5 per cent. In the group of 70 patients subjected to operation, one patient developed a ureterovaginal fistula, one a ureterorectovaginal fistula, and one a vesicovaginal fistula. The study also has shown that a dosage of 8,000 to 10,000 r is necessary to destroy epidermoid cancer in the cervix itself.

Sclerosing lipogranuloma of the vulva

placenta covering the almost fully dilated cervix interference became necessary because of onset of hemorrhage (Table I). Spontaneous vaginal delivery occurred in all cases in which the uterus was large, both in the series with quinine drip and in the series with Pitocin or Syntocinon drip. All the 7 mothers with living fetuses were delivered spontaneously of mature infants, 6 of whom cried at birth. One infant was slightly asphyxiated. Although meconium was noted in the liquor amnii after rupture of the membranes, there was no evidence of fetal distress, as indicated by alteration of fetal heart rate or rhythm. Four infants have been followed for periods of between 6 months and 1% years and normal development has been demonstrated. External tocographic tracings showed almost identical curves when quinine was given as with Pitocin and Syntocinon. From the study of this small series it is difficult to escape the conclusion that the clinical effects of quinine bihydrochloride intravenous infusion for induction of labor or abortion are not inferior to Pitocin or Syntocinon, at least in cases of intrauterine deaths in the later months of pregnancy. In regard to its effect in the cases of living fetuses, our small experience indicates further study is necessary.

A review of diagnosis, treatment, and complications for carcinoma of the cervix uteri

Abstract The diagnostic errors, therapeutic complications, and results of treatment for 963 women with carcinoma of the cervix uteri are presented. 1. The diagnosis was not confirmed by re-examination of the tissue from 73 cases which had been diagnosed as invasive carcinoma (Table I). None of these patients are known to have subsequently developed cervical cancer to date. 2. Six hundred and thirty-seven women had initial treatment for invasive cervical cancer at the Washington University Medical Center from Jan. 1, 1950, to Jan. 1, 1957. One hundred and fifty-three others had persistent cervical cancer. These subjects completed their initial treatment at another hospital 6 weeks or more before being examined at the Center. One hundred and seventeen women had carcinoma in situ of the cervix. 3. In Stages I, II, and III the patients treated by intracavitary radium, injections of radioactive colloidal gold into the parametria, and Wertheim hysterectomy with pelvic lymphadenectomy (Method C), survived longer than did those treated by either intracavitary radium and external pelvic roentgen therapy (Method A) or by intracavitary radium and parametrial radioactive gold (Method B). Similarly, those treated by either B or C methods show an absolute 5 to 10 year cure rate, which is statistically higher in all stages and consistently higher for each year. Calculations reveal that these differences are statistically significant. 4. This analysis demonstrated that the incidences of complications for the three principal treatment methods (A, B, and C) were of the same order (Table XVI). However, the severity of the complications for the treatment which combined radiation and operation (Method C) were definitely greater (Table XIX). 5. Women treated by exenteration of the pelvic organs for persistent postradiation cervical carcinoma survived significantly longer than did the women in a comparable group treated by other means. The exenteration procedure is the treatment of choice for women in whom cervical carcinoma persists after radiation therapy and which remains confined to the pelvis.

Radiogold in the treatment of cancer of the cervix.

The main objective in the use of radioactive colloidal gold for the treatment of cancer of the cervix is safe, adequate, and convenient irradiation of the pelvic lymph nodes. This is in no way different from the motive behind the use of conventional x-rays, supervoltage x-rays, or the gamma rays of radium or cobalt. The treatment of the primary lesion is no problem. Supplemental therapy is necessary, however, because some patients undoubtedly have cancer in the pelvic lymph nodes which would not be destroyed by direct irradiation of the cervix or by hysterectomy. Radiogold is only an agent for providing supplemental therapy. The properties of radiogold are nearly ideal for this purpose. The short half-life of 2.8 days limits the duration of irradiation. The radioactivity is primarily beta, so that the majority of the effect is restricted to the immediate vicinity of the interstitial injection. Radiogold, however, is especially valuable because of the manner in which the tissues absorb and “fix” the gold. ...

The use of blood serum in the male frog test for pregnancy

Abstract A modification of the male frog test for pregnancy was described. The modification consists of the intraperitoneal injection of blood serum rather than the injection of urine into the ventral lymph sac of the frog. A review of 800 frog tests performed in this manner was presented. The accuracy of the test was 97 per cent. It was concluded that the use of serum as the testing agent in the male frog test for pregnancy does not compromise the accuracy of the test as originally described.

Radioactive gold for the intracavitary treatment of carcinoma of the cervix.

The purpose of this paper is to describe an attempt to increase the dose of radiation delivered to the parametria for the treatment of carcinoma of the cervix. The generally accepted method of radiation therapy for carcinoma of the cervix consists in combining the radiation from a series of intrauterine and vaginal radium sources with external irradiation of the lateral pelvis. While this method delivers an adequate dose of radiation to the local lesion, the dose to the parametrial tissues is frequently insufficient to control cancer in that area. In the attempt to raise the parametrial dose of radiation to a cancerocidal level, excessive irradiation and injury to the rectum, the bladder, and the paracervical triangles may occur. The vast amount of accumulated clinical experience places the tolerance of the rectum and the bladder in the neighborhood of 6,000 r and that of the paracervical triangles at approximately 9,000 r, when the irradiation is protracted over a period of about four weeks. The radiatio...

Prolongation of the survival time of the corpus luteum

An interesting finding of prolongation of corpora lutea after radiation is described. By histologic appearance the corpora lutea were noted to be more active and in a state of preservation much earlier than would be expected from their expected date of formation. The possible reason for this finding is discussed and seems related to the timing of the radiation. Prolongation of corpora lutea in general in both animals and women is discussed.