Intralymphatic injection of BCG into rhesus monkeys.

Since the route of administration of BCG may have an important function in immunotherapy, we investigated intralymphatic administration to direct BCG to the lymph nodes. Multiple injections of high doses of BCG were administered to 6 rhesus monkeys via the dorsal lymphatics of the lower limb. A suppurative lymphadenitis was observed along the lower limb and in the inguinal area in 5 of the 6 monkeys. However, many of the complications reported with other routes of administration were not observed. Granulomatous reactions and histiocytic responses developed in lymph nodes on the injected sides of the pelvis and distant nodes as well as in the liver. The intralymphatic route is the method by which high doses of nonspecific immunostimulants were delivered to regional lymph nodes. The efficacy of this approach remains to be established in tumor-bearing animals and humans.

Mutations of the BRCA2 gene in ovarian carcinomas.

Inherited mutations in the recently discovered BRCA2 gene are believed to be responsible for a significant fraction of early-onset hereditary breast cancers. Unlike BRCA1, however, which confers a high risk to both breast and ovarian cancer, the incidence of ovarian cancer appears to be much lower In BRCA2-linked families, causing uncertainty as to the relevance of BRCA2 to hereditary ovarian cancer. Numerous allelotype studies indicate that allelic deletions Including the BRCA2 locus on chromosome 13q are common in ovarian cancers in general, suggesting that somatic mutations of this gene may be involved in sporadic ovarian tumorigenesis. The purpose of this study was to test the hypothesis that germline or somatic mutations of BRCA2 are associated with hereditary and/or sporadic ovarian cancers, respectively. The entire 10.2-kb coding region of BRCA2 was screened for mutations in 130 consecutive ovarian tumors, the only selection criterion being a pathological diagnosis of epithelial ovarian carcinoma. Loss of heterozygosity at markers flanking BRCA2 was observed in 56% of the tumors. Four germline mutations and two somatic mutations were identified; two of the germline mutations are recurrent, having been previously described. Remarkably, the patients with germline mutations were late-onset cases with no medical or family histories suggestive of hereditary cancer. These data suggest that mutations of BRCA2 are rare in sporadic ovarian cancers, and that the proportion of ovarian cancers resulting from hereditary predisposition may be higher than previously suspected based on estimates derived from studies of highly penetrant genetic loci.

Malignant leiomyomatosis peritonealis disseminata.

The first known case of malignant change occurring in leiomyomatosis peritonealis disseminata is reported. Six months after leiomyomatosis peritonealis disseminata was found at cesarean section, the patient experienced rapid growth of the pelvic tumor and diffuse bony metastases. The most cellular areas of the pelvic lesions and the bony metastases were very similar histologically. No other primary site was identified. Despite combination chemotherapy and hormonal manipulations, the patient experienced a rapidly declining course and died within two years.

A formula for predicting the risk of a positive second-look laparotomy in epithelial ovarian cancer: implications for a randomized trial.

OBJECTIVE: To develop a formula to predict the risk of a positive second-look laparotomy. METHODS: A retrospective review was performed on 89 patients who underwent second-look surgery following a complete clinical remission after cis-platin- or carboplatin-based chemotherapy. Logistic regression was used to develop a formula to predict the probability of a positive second look based on age, stage, grade of tumor, residual disease after initial surgery, and histologic type. RESULTS: We identified three groups based on estimated probabilities: low probability (0.25 or less), intermediate probability (0.26-0.74), and high probability (0.75 or more). The low-probability group had an 8% chance of a positive second look, the high-probability group had an 82% chance of a positive second look, and the intermediate-probability group had the correct outcome predicted only 61% of the time. Survival curves paralleled these results and were significantly different for each group. CONCLUSIONS: Using known prognostic factors, a formula can aid in implementation of a randomized clinical trial to test the efficacy of second-look laparotomy. This formula could exclude patients not suitable for randomization and give the investigator a better idea of the expected survival of various subgroups.

Cytologic smears of peritoneal surfaces as a sampling technique in epithelial ovarian carcinoma.

Ovarian carcinoma disseminates primarily through the shedding of cells into the peritoneal cavity and subsequent implantation onto peritoneal surfaces. Accurate evaluation of the extent of disease is important both at initial surgical evaluation for staging and at second-look operations to determine the necessity of further therapy. Techniques used for such assessment include node sampling, peritoneal washings, and random biopsies of peritoneal surfaces. Although random biopsies are used by some, others have found them to be of negligible value in the absence of gross disease. The use of cytologic smears of peritoneal surfaces offers a simple method by which cells from a large surface area may be evaluated, and uses equipment readily available to the gynecologist. We compared results of 125 cytologic smears with washings and biopsy specimens obtained during 33 laparotomies for ovarian carcinoma. Cytologic smears identified disease in 48 of 125 sites, whereas biopsy identified only 29 areas of disease. Thirteen of the positive Papanicolaou smears were obtained from clinically disease-free areas. Although the cytologic evaluation of the parietal peritoneal surfaces was more frequently positive than were biopsy specimens, each method identified disease in 16 patients when paired with standard techniques of examination and washing. We conclude that the peritoneal cytologic smear offers an alternative method of further evaluating the extent of disease, particularly when no gross evidence of extraovarian disease is detected.

Androgenic function of a granulosa cell tumor.

Virilizing granulosa cell tumors are uncommon and have not been well studied hormonally. A hirsute woman with a cystic granulosa cell tumor of the ovary is presented. Plasma hormone levles obtained before and after surgery indicate testosterone production by the tumor with LH and FSH suppression. Plasma testosterone (T) and T-index returned to normal after tumor removal, and ovulation resumed.

Single application treatment of human papillomavirus infection of the cervix and vagina with trichloroacetic acid: a randomized trial.

Treatment of human papillomavirus (HPV) infection of the lower genital tract with trichloroacetic acid was evaluated in a randomized, double-blind fashion at the Hospital of the University of Pennsylvania. Thirty-four patients who had colposcopic and histologic evidence of HPV without dysplasia were entered into the study and randomly placed into either a treatment or placebo group. The treatment group received a single topical application of 50% trichloroacetic acid to the vagina and cervix on day 1. The placebo group was treated in the same manner using saline. The patients were evaluated at 4 and 16 weeks post-treatment for cytologic and histologic evidence of HPV. No differences between the treatment and placebo groups were found. Only one of 16 patients in the treatment group and three of 18 in the placebo group were free of HPV infection at the 4- and 16-week evaluations. Our data suggest that treatment of subclinical HPV infection with trichloroacetic acid is ineffective at this concentration.

Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings.

The reproductive capability and labor complications of 98 women exposed to diethylstilbestrol (DES) in utero were compared with those of 3 separate control groups. The controls consisted of 167 age-matched, normal women, 20 siblings not exposed to DES who had achieved pregnancy, and their mothers. Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls. The controls also achieved a higher percentage of desired pregnancies overall; this was statistically significant (89.6 versus 75.0%, P less than .001). When compared with their mothers, however, the DES-exposed population achieved a greater percentage of desired, viable pregnancies (75.6 versus 67.0%, P less than .001). The unexposed siblings of the DES women achieved a higher percentage of desired, viable pregnancies than did their exposed sisters (86.9 versus 73.6%, P = .274), but less than the normal population (86.9 versus 89.6%).

Levels of urinary cathepsin B-like substance in patients with gynecologic malignancy.

Because certain proteolytic enzymes are thought to be released by malignant cells, we have measured the activity of cathepsin B in the urine samples of 57 patients with gynecologic malignancies and 60 disease-free controls. A unit (U) of enzyme activity is the release of one n-mol of 7-amino-4-fluoromethylcoumarin (AFC) from BZ-val-lys-lys-arg-MNA min-1 ml-1. Units of activity in the malignant group (10.6 +/- 9.8) differed significantly (p less than 0.0001) from controls (2.8 +/- 3.3). Although enzyme activity in both groups correlated with increasing age, the difference between those subjects with malignancies and those with none remained significant (p = 0.049) by analysis of covariance after adjusting for age. There was no correlation between titers and the race or weight of the subjects in either group. Enzyme activity of subjects with malignant disease correlated (p = 0.003) with the clinical stage of disease. Optimum sensitivity and specificity as determined by Receiver Operator Characteristic Analysis with an upper normal level of 5 U were 84.2% and 86.7%, respectively. Our findings suggest that measurement of urinary cathepsin B might be useful in detecting and managing patients with gynecologic tumors.

Endometriosis and tamoxifen therapy.

Tamoxifen is an estrogen antagonist/agonist often associated with antiestrogenic effects such as hot flushes and vaginal dryness in premenopausal women. Estrogenic side-effects, such as thromboembolic phenomena and endometrial proliferation has been reported in postmenopausal women. Paradoxically, tamoxifen has also been shown to be capable of increasing estrogen levels in premenopausal women. Since tamoxifen is being used more frequently in this group of women, potential adverse effects are only now being recognized. Two cases of premenopausal women who developed symptomatic endometriomas while on tamoxifen for breast cancer, are reported. Stimulation of endometriosis should be considered when pain and an ovarian mass develops in a woman on tamoxifen. The unique effects of tamoxifen in premenopausal women may contribute to this even in the presence of regular ovulation.

Recurrent squamous cell carcinoma of the cervix with pulmonary lymphangitic metastasis.

A case report and review of the world literature are presented to examine all the reported cases of cervical carcinoma manifesting as pulmonary lymphangitic carcinomatosis in order to better understand this rare condition. The clinical and pathologic features of this disease process are reviewed, as are potential treatment options. We present the first reported case of an immunocompromised patient with cervical carcinoma and pulmonary lymphangitic metastasis with a prospective diagnosis made by transbronchial biopsy. Given that this condition carries a uniformly fatal prognosis, unwanted therapy may result from a missed diagnosis. A prospective pathologic diagnosis by transbronchial biopsy may guide appropriate therapy in these patients.

Preoperative evaluation and staging of endometrial cancer.

Preoperative examination of a patient for whom a diagnosis of endometrial cancer has been made by office biopsy or dilatation and curettage includes careful history taking and physical examination, with emphasis on the pelvic examination, blood tests, and imaging evaluations of the pelvis, abdomen and chest, and other specific studies related to medical operability. The primary approach to endometrial cancer is surgery, which has been used for staging and treatment since the adoption of the Federation of Obstetrics and Gynecology system in 1988. Pilot studies and the Gynecologic Oncology Group have researched this system extensively and have emphasized the findings that could be defined only by pathologic study of the uterus, adnexa, retroperitoneal lymph nodes, and peritoneal cytologic findings. Preoperative endocervical evaluation is no longer necessary unless gross invasion of the cervix is suspected. However, initial histologic findings can identify patients at high risk, that is, those with high grade adenocarcinomas, clear cell carcinomas, adenosquamous carcinomas, and papillary serous adenocarcinomas. Intraoperative pathologic evaluation of the uterus by frozen section, which reveals depth of invasion into the myometrium and correlation with tumor grade, can identify patients for whom lymph node sampling should be performed.

International Federation of Gynecology and Obstetrics staging of endometrial cancer 1988.

In 1988, the International Federation of Gynecology and Obstetrics (FIGO) Cancer Committee changed the staging of endometrial carcinoma from a clinical one to a surgicopathologic one. The emphasis in the new FIGO system was changed to the pathologic findings in the uterus, cervix, adnexa, and pelvic and/or periaortic nodes, and peritoneal cytologic findings. The major changes in this staging system were (1) the use of the depth of myometrial invasion and (2) the identification of tumor cells in peritoneal cytologic examination and of invasion in the retroperitoneal lymph nodes. Preoperative endocervical curettage was no longer necessary. Currently, the high level of operability of patients with endometrial carcinoma makes this staging system a viable one, which will provide information about the need for additional treatment. The use of the grading system for the tumor also was refined to upgrade nuclear changes that were inappropriate for the architectural grade. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading took precedence. Adenocarcinomas with squamous differentiation were graded according to the nuclear grade of the glandular component.