Richard F. Mattingly

Laser treatment of cervical and vaginal neoplasia.

The conservative management of cervical intraepithelial neoplasia (with electrodiathermocautery and cryosurgery) is unsuitable for the treatment of similar vaginal lesions because of complications of scarring, stenosis, and fistulas. A new modality of treatment with the use of a carbon dioxide laser beam was evaluated for the treatment of cervical and vaginal intraepithelial neoplasia. Histopathologic examination of cervical tissue after laser beam therapy showed that most of the tissue destruction resulted from evaporation of tissue and that the zone of tissue necrosis was much less than after cryosurgery or electrocautery. Laser therapy was used in 50 patients, 46 of whom had varying degrees of cervical and vaginal intraepithelial neoplasia. Treatment failures occurred in five patients (10 per cent). The experience of this study suggests that the major value of laser treatment of the lower genital tract will be in the management of vaginal intraepithelial lesions, while similar results in the treatment of cervical neoplasia may be achieved by much simpler methods.

Vaginal adenosis: A precancerous lesion?

Abstract The prenatal administration of diethylstilbestrol (DES) during the period of vaginal organogenesis alters the embryologic localization of the original squamocolumnar junction which may be established anywhere in the vagina rather than on the cervix. Exposure of the columnar epithelium to the vaginal environment and to the low pH of the vagina stimulates the development of squamous metaplasia. Colposcopically, this squamous metaplasia is part of a large transformation zone which, in some cases, involves the entire vagina. The major clinical significance of this entity concerns the fact that in DES-exposed girls, abnormal colposcopic findings (white epithelium, mosaic pattern, punctation) are present within the transformation zone in 97 per cent of cases, as compared to only 8 per cent in unexposed girls. This highly significant difference suggests that the major clinical risk in DES-exposed girls is the potential development of squamous neoplasia rather than the rare associated case of clear-cell adenocarcinoma. In a colposcopic and histologic study of 131 cases of vaginal adenosis in DES-exposed girls, two cases of squamous carcinoma in situ, two cases of severe dysplasia, and three cases of moderate dysplasia were diagnosed.

THE HORMONE‐SYNTHESIZING TROPHOBLASTIC CELL IN VITRO: A MODEL FOR CANCER RESEARCH AND PLACENTAL HORMONE SYNTHESIS

The human trophoblast, the hormonally functional cell of the placenta, differentiates in the first-order cleavage of the fertilized human ovum immediately following conception.1 Hormonal function from the placental trophoblast can be detected in maternal serum by human chorionic gonadotropin (HCG)2 and human placental lactogen (HPL) assays shortly following the 58-cell stage of the human ovum. Thus, trophoblastic cellular differentiation and placental hormone synthesis are among the earliest morphological and biochemical differentiations to occur in the human. This cell type has not been established in vitro. Choriocarcinoma is a unique malignancy of trophoblastic cells which follows normal pregnancy, spontaneous abortion, or hydatiform mole. This tumor closely parallels the normal placenta in hormone function and cellular metabolism, with the exception that the limited invasiveness of the normal placenta during its implantation is far exceeded by that of the malignant tumor, which, proceeding unrestricted, culminates in the death of the patient within a period of less than 1 year.4 A morphological similarity can be observed among the trophoblastic cells of the human blastocyst less than 92 hours after conception (FIGURE l ) , the invading normal placenta of the first trimester (FIGURE 2), and the rapidly proliferating choriocarcinoma (FIGURE 3 ) .

CONTROL MECHANISMS FOR GONADOTROPHIC HORMONE PRODUCTION IN VITRO

SummaryAn internal control mechanism capable of controlling gonadotrophic hormone secretion in the human trophoblast has been identified by incubation of an established cell line with a precursor of progesterone.Biological, biochemical, and electron microscopic findings verify inhibition of gonadotrophic hormone synthesis, depletion of glycogen, activation of phosphorylase, the glycogen-metabolizing enzyme, and ultrastructural appearance of liquid-containing cytoplasmic granules in single cells, indicative of steroid synthesis.

Bacteriologic study of suprapubic bladder drainage.

Abstract One hundred and sixty patients with apparently normal functioning bladders underwent urethro-supportive procedures and suprapubic drainage. A similar group of patients undergoing the same surgical procedures but with postoperative urethral drainage provided comparative information on the recovery of normal bladder function. Detailed bacteriologic studies revealed that 24 per cent of the suprapubic group of patients developed significant bacteriuria and pyuria following operation. Of the patients with postoperative bacetriuria, 62 were examined and catheterized 6 weeks to 48 months after operation, and only 5 were found to have significant bacteriuria with or without pyuria for a recurrent infection rate of 8.1 per cent. All 5 were treated successfully with antibiotic therapy. The data from this study support the concept that induced bacteriuria as a sequela of temporary bladder drainage in a healthy female bladder is not a significant hazard toward the development of chronic urinary tract infection.

Electron microscopic and biochemical patterns of the normal and malignant trophoblast.

Abstract The malignant trophoblast in cell culture (BeWo line) known to produce human chorionic gonadtropin (HCG) consists of single cells with cytoplasmic ultrastructures similar to that of the placental cytotrophoblast. One of the striking features of the trophoblastic cells is the excessive accumulation of cytoplasmic glycogen, which may be depleted by epinephrine, and, to a lesser extent, by glucose “starvation.” Glycogenolysis is accompanied by a concomitant increase of endoplasmic reticulum. Hence, the development of this cytoplasmic organelle may reflect at least two different phases of functional activity in trophoblastic cells: (1) hormone synthesis and (2) carbohydrate metabolism. It is cocluded that the cytotrophoblast, in addition to its role as progenitor of syncytium, also actively synthesizes HCG. Hormone synthesis may be reflected by the development of endoplasmic reticulum but is not determined by the phase of differentiation of trophoblastic cells at which syncytium is formed. The enzyme pattern of the BeWo cells resembles that of other malignant tumors. A mucoprotein layer surrounding the BeWo cells is revealed by colloidal iron stain, and its significance is discussed. Present studies indicate that the placenta at term is still an actively functioning organ.

Isoantigens ABO in cervical neoplasia

Abstract Some human tissues contain antigens identical to blood group A or B isoantigens which can be detected by the mixed-cell agglutination reaction in paraffin sections even if the sections are several years old. This technique was utilized in this study to identify A or B isoantigens in 74 cases of normal cervical epithelium, 46 cases of cervical dysplasia, 32 cases of carcinoma in situ, and 16 cases of invasive cervical carcinoma. The isoantigens were uniformly demonstrated by indicator erythrocytes in normal squamous epithelium and the vessels in the stroma. Isoantigens were found to be significantly decreased in carcinoma in situ , while in cervical dysplasia the decrease in activity of isoantigens was proportional to the dedifferentiation of the epithelium. Isoantigens were absent in invasive carcinomas. These findings offer additional clinical information concerning the cell biology of premalignant and of malignant lesions of the uterine cervix.

Immunodiagnosis in ovarian cancer: Blocking factor activity☆☆☆

Tumor immunology studies have been utilized for development of a blocking factor assay for therapy monitoring in ovarian cancer. The blocking factor index was defined as the arithmetic difference between assays conducted in the presence and absence of the patients serum compared to incubations with normal control lymphocytes. Eighteen advanced ovarian epithelial malignancies have shown blocking factor activity during treatment. Blocking factor has abated in eight patients whose clinical disease completely regressed. Chemotherapy was discontinued after 18 to 24 months. In 10 patients, blocking factor persisted and chemotherapy has been continued. Some of these patients showed decreasing blocking factor; others have shown increases, which led to death due to disseminated disease in four cases. Blocking factor activity was found to correlate with tumor growth.

Prognostic significance of interval from preoperative irradiation to hysterectomy for endometrial carcinoma

From 1965 through 1980, 193 patients with histologically proven endometrial carcinoma, FIGO‐AJC Stage I‐III, received preoperative radiation therapy. One hundred forty‐two patients had Stage I (Gl:41, G2:68, G3:33), 47 Stage II, and 4 Stage III endometrial carcinoma. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo‐oophorectomy (TAH‐BSO). They were followed from 3 to 18 years (median, 6.2 years) after the completion of the treatment and none was lost to follow‐up. Overall 5‐year actuarial disease‐free survival was 85%. The interval between the completion of radiation therapy and TAH‐BSO ranged from 3 days to 123 days (median, 40 days). Five‐year and 10‐year survivals were 95% among 65 patients who did not have residual cancer in the hysterectomy specimen compared to 75% and 70%, respectively, among 128 patients who had positive hysterectomy specimens (P < 0.01). The presence or absence of residual carcinoma in the surgical specimen after preoperative irradiation was the only important prognostic variable. The most significant factors associated with residual cancer cells were the interval from the completion of radiation therapy to TAH‐BSO (P < 0.001) and the method of preoperative irradiation in patients with Stage I Grade 3 and Stage II external pelvic irradiation was less frequently associated with residual cancer than intracavitary applications (P = 0.043). With one exception, all patients who failed had residual cancer in the hysterectomy specimen. The depth of myometrial invasion of residual tumor in the hysterectomy specimen after preoperative irradiation was correlated to the frequency of failures (P = <0.05). Failures were distributed equally among the pelvis, para‐aortic nodes, and distant sites. Complications of treatment were infrequent (7%) and were mild; no fatal complications were seen. The data suggest an optimal interval for hysterectomy is 29 to 42 days after completion of radiation therapy in unfavorable carcinomas of the endometrium. These patients also benefit from external pelvic irradiation with or without intracavitary applications as this therapy provides the highest probability there will be no residual cancer cells in the surgical specimen.

Absence of prostaglandin synthesis in the malignant human trophoblast in culture

Abstract Established glycoprotein, steroid, and lactogenic hormone-secreting trophoblastic cell lines derived from placental tumors have been studied for evidence of prostaglandin biosynthesis. Although over 50 per cent incorporation of isotopically labeled arachidonic acid, a prostaglandin precursor, occurred in the phospholipasesensitive chromatographic peak, the presence of PGE or PGF 2α or their biosynthesis could not be demonstrated. It was concluded that a high degree of arachidonic acid incorporation in the neoplastic trophoblast in culture is directed into phospholipid.