Use of intraperitoneal chemotherapy for treatment of ovarian cancer.

Second line chemotherapeutic therapy following failure with Cis-platinum combined regimens for treatment of cancer of the ovary is discouraging. Similarly, results with the use of Cis-platinum combined regimens for patients with less than well debulked primary surgery are also discouraging. In an attempt to improve these results, a series of 57 patients were subjected to high dose Cis-platinum and AraC given intraperitoneally. 44 of these patients were those that had been subjected to a second look procedure after 8-12 months of Cis-platinum therapy and were found to have residual disease in the form of positive cytology or microscopic disease up to nodules of 1.5 cm in diameter. 13 of the patients, because of less than well-debulked surgical procedures, were also accepted for therapy. In all patients, a subcutaneously implanted catheter was introduced into the patient and the tube was tunneled through the subcutaneous tissue into the peritoneal cavity. Cis-platinum and AraC were introduced into the peritoneal cavity through this cutaneous line. Concurrently, with the administration of the intraperitoneal therapy, Sodium Thiosulfate was given intravenously for systemic protection from Cis-platinum toxicity. Treatments were given every three to four weeks and the number of courses varied from 3 to 8 for a total of 184 injections for the entire group. In seven of these patients distribution studies were carried out using radioactive sulfur colloids which were injected peritoneally prior to the first treatment and preceding each subsequent treatment in order to evaluate the anticipated distribution of the chemotherapeutic agents. Only 4 of the 44 patients in group 1 and 3 of the 13 patients in group 2 are alive without evidence of disease at the present time. The low success rate is believed due to the poor distribution of the chemotherapeutic agents after the first two or three injections. In most of the patients, by the third or fourth treatment, they were found to have developed loculated restricted areas with minimal distribution of the agents. This was also demonstrated by the distribution studies carried out with the sulfur colloid.

CO2 laser for suppurative hidradenitis of the vulva.

Chronic suppurative hidradenitis is a disease of the apocrine glands occurring predominantly in the axillae of the anogenital region. Treatment, to date, has been frustrating. Prolonged antibiotic therapy and multiple incisions and drainage have been the usual form of therapy, but those surgical procedures leave patients with ugly scars; retracted, hypertrophic skin edges; and pitted, indurated and disfiguring abscesses. The only successful treatment to date has been wide excision of the entire apocrine gland-bearing tissues, such as radical vulvectomy, which often necessitates grafts to cover the surgically exposed areas. That has left patients with unsatisfactorily functioning vaginas and a mutilated appearance. Recently we instituted the use of the CO2 laser to treat these patients with the goal of eradicating the suppurative sinus tracts and the infected apocrine glands without removing large volumes of adjacent, unaffected tissue. Over the past eight years we treated 11 patients who had extensive, chronic hidradenitis of the anogenital area with the CO2 laser. The use of laser therapy for these patients has produced effective and less-mutilating results. Such treatment has been a successful option for treating this debilitating disease.

Laser therapy for vaginal intraepithelial neoplasia after hysterectomy.

In recent years there has been a marked increase in the number of reported cases of vaginal intraepithelial neoplasia (VAIN) after hysterectomy. Until about 10 years ago radiation or surgery had been the therapeutic modality mostly used for this disease. More recently, topical drugs, such as bleomycin and 5-fluorouracil cream, have been used, but they are often ineffective and poorly tolerated. For the last 14 years we have used the CO2 laser for the treatment of VAIN and have treated a total of 143 patients. Our use of a combination of wire sutures through the vaginal mucosa and the introduction of fluids into the underlying submucosal areas allows retraction and ballooning of the recesses and scars and permits us to place the vaginal mucosa at right angles to the laser beam to allow complete treatment.

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.

The role of prostaglandins in obstetrics/gynecology.

After a lag between the recognition of the biologic activity of material derived from seminal vesicles and the actual isolation and identification of prostaglandins, information on the structure, biosynthesis, physiology, and biomedical relevance of this family of substances has expanded explosively in recent years. Their ubiquitous presence in mammalian tissues has contributed to the intense interest in and investigation of their role in normal physiology and a variety of pathologic states. The availability of pure compounds of known chemistry, as well as of numerous agents that interfere with their production or metabolism, continues to allow unravelling of their regulatory influences, mechanism of action, and participation in disease processes. Understanding of the role of prostaglandins in reproductive physiology has led to widespread and effective applications in clinical obstetrics and gynecology, including menstrual disorders, therapeutic abortion, and labor. Their implication in the pathogenesis of toxemia of pregnancy, coupled with expanding information on the general role of prostaglandins in the regulation of hemostasis, has advanced understanding of hemorrhagic and thromboembolic disorders and opened innovative avenues for potential therapeutic intervention.

The precursors of endometrial carcinoma.

For many years, a variety of abnormal endometrial lesions have been linked to endometrial cancer but have been designated as hyperplasia and classified by modifying adjectives such as cystic, adenomatous, atypical, moderate, and severe. Though descriptively distinctive, there are enough consistent histologic transitions between them to designate the entire group as belonging to a continuous spectrum from benign to malignant. Furthermore, because these epithelial lesions demonstrate not just hyperplasia but significant disorderly growth patterns, it has been suggested that they be referred to as dysplasias. In order to evaluate the association of these types of dysplasia to cancer, two groups of patients were studied. In one group, the histologic states of the endometrium of patients with endometrial cancer were retrospectively analyzed. In the second group of patients, who were selected for study because the endometria were diagnosed as belonging to the dysplastic groups, the subsequent endometrial histology was prospectively studied. The findings suggest that there is a recognizable group of endometrial lesions with an association to endometrial cancer strong enought to label and treat them as neoplastic.

Anterior segment metastases from an ovarian choriocarcinoma.

A 28-year old woman with ovarian choriocarcinoma developed a uveitis in her left eye. Subsequently, a mass was observed in the anterior segment of that eye together with a subconjunctival mass that appeared to extend from it. Biopsy of the subconjunctival nodule showed two different cell types consistent with the cytotrophoblastic and syncytiotrophoblastic elements typical and choriocarcinoma. No abnormalities of the posterior segment were found on careful examination. Treatment consisted of systemic chemotherapy with a variety of therapeutic agents, argon laser photocoagulation of tumor seedings in the anterior chamber angle, radiation to the eye, and finally, subconjunctival injections of methotrexate. The eye became blind and painful and was enucleated. Histopathologic examination revealed residual tumor cells in the anterior segment indicating treatment changes, but there were no abnormalities posteriorly. Choriocarcinoma metastatic to the eye has been reported infrequently, and this is the first case in which anterior segment metastases have been observed and the effects of treatment thoroughly documented.

Comparison of cancer cell surfaces of the lower reproductive tract by scanning electron microscopy.

The squamous cells of the cervix simulate those of the vagina and vulva both histologically and by scanning electron microscopy. However, in areas of the cervix undergoing active metaplasia, there are cells which share some of the characteristics demonstrated by scanning electron microscopy of both squamous and columnar epithelium. In these cells there is a wide range of characteristics of each cell type, suggesting a possible gradual transition from columnar to squamous epithelium. Furthermore, the cells of severe dysplasia and of intraepithelial and invasive squamous cancers of the cervix, though histologically similar to those of vaginal and vulvar cancers, are distinctly different when examined by scanning electron microscopy. These findings suggest that both metaplastic and neoplastic squamous cells are derived from the same progenitor columnar cells of the cervix, by orderly transition in the former and by atypical transformation in the latter. Second, the distinctiveness from the vaginal and vulvar cells indicates different embryonic stem cell lines.

Symposium on scanning electron microscopy of fertility and infertility, Eighth Congress of Fertility and Sterility, Buenos Aires, Argentina, November 1974. Human vaginal adenosis and adenocarcinoma.

PIP: Samples of vaginal tissue were obtained from patients with a recorded history of exposure to nonsteroidal estrogens such as diethylstilbestrol (DES) in utero as well as from patients not exposed to DES but undergoing vaginal operations for other reasons. The tissue was removed from various sites within the vagina and divided into 2 segments, 1 fixed in 10% formalin and the other in 3.5% glutaraldehyde. The formalin series received routine histological analysis. The glutaraldehyde series was further prepared for scanning electron microscopy. As a result of exposure to DES several cervico-vaginal aberrations were noted, the most striking of which were those seen histologically. These have been classified into 5 groups: 1) complete epidermidization - complete replacement by metaplasia; 2) surface epidermidization - residual glands beneath and surface; 3) incomplete epidermidization - mixture of columnar epithelium on surface including crypts and glandlike elements; in-situ or invasive: and 5) squamous cell dysplasia. The differentiation of the early embryonic vaginal epithelium to that of the mature squamous epithelium of the newborn seems to be interfered with by the in utero exposure to nonsteroidal estrogens. It is not known whether this is due to inhibition with steroid estrogens or to some other enzymatic process. As a result of this exposure, vaginal adenosis develops. There is a natural tendency of the body to convert this adenosis to normal squamous epithelium through the process of metaplasia and the 5 states observed represent all phases of this process. In the group of patients in which the metaplastic process is incomplete or in a state of transition both columnar cells and squamous cells exist adjacent to each other and between them cells with variable degrees of metaplastic change. In a few patients these abnormal embryonic cell nests lead to the development of a malignancy, usually a mesonephromal clear-cell adenocarcinoma. Furthermore, within the areas of metaplastically converted squamous epithelium, anaplastic and dysplastic cellular changes also occur, with the potential danger of developing intraepithelial and possibly invasive squamous cell carcinomas of athe vagina.^ieng

Cervical-vaginal adenosis after in utero exposure to synthetic estrogens.

PIP: A study to determine the incidence of adenosis and/or adenocarcinoma of the vagina in 528 females between 13 and 25 years who were exposed to diethlstilbesterol in utero and to define the clinical and microscopic changes in their vaginas was undertaken, using primary physicians records as a source for patient identification. Lugol's staining was evaluated and was found to be a simple technique for identifying the lesion of adenosis. Of the young women with documented exposure to diethylstilbesterol or dienestrol, over 90% had adenosis of the vagina. In almost all cases the drug treatment began before the twelfth gestational week. In some patients, the appearance of the cervix was unusual. Of the 188 patients who underwent excisional biopsy, 2 showed a small focus of clear cell adenocarcinoma which was not detected clinically. A causal relationship between in utero exposure to diethylstilbesterol or dienestrol is suggested. It is also suggested that the lesion is developmental since it has been found in prepubertal girls.^ieng