Isolation of type C virions from a normal human fibroblast strain.

Type C virions were spontaneously released from cultures of a diploid human cell strain. The varions have properties of known type C RNA tumor viruses and share antigenic determinants with the major interspecies-specific antigen (p30) of simian sarcoma virus. Antiserum to reverse transcriptase of gibbon ape leukemia virus inhibits the reverse transcriptase of the putative human virions and that of simian sarcoma virus, but has no effect on the corresponding enzymes of avian or murine RNA tumor viruses.

Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model.

Human malignant mesothelioma of the pleura was successfully transplanted s.c. into athymic nude mice and grew as a solid neoplastic mass. Tumor growth resulted in death of the animals between 98 and 161 days after implantation. Minced samples of the growing tumor were propagated as a malignant peritoneal effusion. Animals with malignant ascites died predictably at 32 to 33 days. Light and electron microscopy, and immunocytochemistry demonstrated a similarity of the transplanted solid and fluid malignancies with the human primary mesothelioma. Cytogenetic analysis demonstrated a predominance of cells with a triploid number of identifiable but abnormal human chromosomes. This model, which mimics the clinical behavior of malignant mesothelioma in the human, may be of value in animal trials of chemotherapy and immunotherapy.

Primary radiation therapy for endometrial carcinoma: a case controlled study.

PURPOSE: Primary radiation therapy is generally considered inferior to a surgical approach for patients with endometrial carcinoma and is reserved for patients with a high operative risk. These patients are usually elderly, have multiple medical problems and frequently die of intercurrent disease. To evaluate the efficacy of primary radiation therapy a case controlled analysis comparing corrected survival of patients treated with primary radiation to patients treated with surgical therapy with or without radiation therapy was performed. METHODS AND MATERIALS: Sixty-four patients treated with primary radiation therapy were retrospectively studied. A Kaplan-Meier product limit survival analysis was used to estimate survival among patients treated with primary radiation therapy. A case control study matched by clinical stage, tumor grade, and time of diagnosis was performed. The Mantel-Cox statistic was used to evaluated the equality of the survival curves. RESULTS: Primary radiation therapy was used to treat 9.0% of the patients with endometrial carcinoma during the study period. Cardiovascular disease, diabetes, age greater than 80 and morbid obesity were the most common indications. Ninety percent of patients had either Stage I or II disease. Forty-eight of the 64 patients (75%) completed treatment which included both teletherapy and brachytherapy. Ten patients received brachytherapy only. Twelve complications, both acute and chronic, occurred in eleven patients (17%). Intercurrent disease accounted for 13 of the 36 (36%) of the deaths. Clinical stage of disease and histologic grade of the tumor were significant predictors of survival, p = 0.0001 and p = 0.013, respectively. The case controlled study of Stage I and II patients treated by primary radiation therapy matched to surgically treated controls showed no statistical difference in survival. Dilatation and curettage after the completion of radiation therapy was predictive of local control, p = 0.003. CONCLUSION: Although surgery followed by tailored radiation therapy has become widely accepted therapy for Stage I and II endometrial carcinoma, even in patients who are a poor operative risk, the survival with primary radiation therapy is not statistically different.

Differentiation by TICAS analysis of cell populations of tracheal aspirates from hamsters with squamous-cell carcinoma.

Individual cells from the tracheal aspirates of hamsters exposed to benzo-a-pyrene were scanned at .5 mum in three colors. Features relating to size, shape, and color were extracted and calculated by computer. The single cells were then classified by these features into separate populations with varying degrees of atypia, extending up to frank cancer cells. A high degree of accuracy was attained in classification by these methods.

Papillary serous carcinoma of the peritoneum following endometrial cancer.

Two cases of advanced papillary serous carcinoma of the peritoneum occurred after hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. Careful resectioning of the original ovarian specimens failed to demonstrate a previously undiagnosed ovarian malignancy. In both cases, CA 125 levels, which were being followed routinely because of the previous endometrial cancer, rose before the diagnosis of peritoneal carcinoma and corresponded closely to patient response to therapy.

Prognostic significance of estrogen and progesterone receptors in epithelial ovarian cancer.

Estrogen and progesterone receptor assays were analyzed from epithelial ovarian cancer in 123 patients to determine the prognostic significance of receptor results. In 110 (89%), assays were performed at diagnosis and in 13, assays were performed after previous therapy. Estrogen receptor determinations were positive (above 10 fmol/mg) in 75 cases (61%), progesterone receptor determinations were positive (above 3 fmol/mg) in 35 (28%), and both were positive in 20 (16%). Progesterone receptors were more frequently positive (53%) in tumors of endometrioid histology than with other histologic types (P = .01). Thirty-one subjects had a second assay; estrogen receptors were positive in 16 cases (52%), progesterone receptors were positive in five (17%), and both were positive in five (17%). Synchronous and metachronous assays were in agreement in 60-79% of the cases. By multivariate analysis, positive estrogen receptor, progesterone receptor, or both did not predict response to chemotherapy, negative second-look findings, or survival. Thirty-one women received hormonal therapy; one of 26 evaluable subjects had a partial response and four (13%) maintained stable disease for at least 6 months (6-21 months). Positive receptors did not predict hormonal response or disease stabilization.

Appendectomy in primary and secondary staging operations for ovarian malignancy.

Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures.

Primary adenocarcinoma of the breast arising in the vulva.

Primary adenocarcinoma of ectopic breast tissue in the vulva has been reported in only four instances. A fifth case, in which estrogen and progesterone receptors were present, is described. Estrogen and progesterone receptor studies may be helpful in identifying adenocarcinoma of uncertain origin.

Profile of women 45 years of age and younger with endometrial cancer.

OBJECTIVE: The clinical characteristics and outcomes of endometrial cancer patients 45 years of age and younger were compared with those of patients older than 45 years of age. METHODS: We performed a cross-sectional study of 301 consecutive endometrial cancer patients referred to our center from 1989 to 1994. Of the 289 patients eligible for study, 40 were 45 years of age or younger (group A) and 249 were older than 45 years of age (group B). RESULTS: The majority of patients in both groups presented with stage I disease. Of the women with stage I disease, patients in group A were more likely than those in group B to have low-grade disease localized to the endometrium (P < .001; relative prevalence 3.39; confidence interval [CI] 1.88, 6.12). However, the distribution of stages I to IV overall was the same for the two groups (P = .269). Although univariate analysis revealed that 11% of the patients in group A and 2% in group B had synchronous ovarian malignancies (P = .007; relative prevalence 5.42; CI 1.39, 21.14), multivariate logistic regression found that nulliparity, not age, was an independent risk factor for synchronous ovarian malignancy (P = .017; relative prevalence 6.15; CI 1.52, 25.61). There were no statistically significant differences by age in the prevalence of high-risk endometrial histology (serous and clear cell carcinoma) or in survival. CONCLUSION: The overall distribution of tumor stage and survival were the same for the younger and older women; this finding contradicts previous reports that suggest that young women with endometrial cancer are at lower risk. Additionally, nulliparity, which occurs with a higher prevalence in younger women who develop endometrial cancer, is associated statistically with the development of synchronous ovarian malignancies.

Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma.

OBJECTIVE: To evaluate the usefulness of serum assays for CA 125 to detect recurrent endometrial carcinoma. METHODS: Two hundred sixty-six patients were studied with 1101 post-treatment assays. Patients were categorized as low, medium, or high risk based on surgical-pathologic findings. CA 125 values were analyzed with respect to each patient's disease status. RESULTS: Serial CA 125 levels were elevated (greater than 35 U/mL) in 19 of 33 patients (58%) with recurrent disease. Among 236 surgically treated patients, 97 (41.1%), 42 (17.8%), and 97 (41.1%) were considered low, medium, and high risk, respectively. None of the low-risk and only two (4.7%) of the medium-risk patients developed recurrent disease. One of the latter patients was detected based on an elevated CA 125 level alone. Twenty-seven (27.8%) of the high-risk patients developed recurrent disease, 23 of whom had elevated pre-treatment CA 125. Fifteen of 16 (94%) with recurrent disease had an elevated CA 125 level. Nine of 12 patients with papillary serous carcinoma experienced recurrence; eight of these nine had elevated CA 125 levels at diagnosis and recurrence, in contrast to only one patient with a normal pre-treatment level (P = .018). False elevations were noted in 13 patients, 12 of whom had received radiation therapy. CONCLUSIONS: CA 125, if elevated at diagnosis of endometrial carcinoma, is an important marker for recurrent disease. The use of serial CA 125 assays is most beneficial in diagnosing recurrence in a high-risk population, including patients with papillary serous carcinomas. False elevations may occur following radiation therapy.

Preoperative CA-125 levels predict poor prognostic pathologic features in early stage, FIGO grade 1 and 2 endometrial adenocarcinoma.

Preoperative CA-125 levels were studied in patients with favorable histology and early clinical stage endometrial adenocarcinoma to determine its ability to predict the presence of poor pathologic prognostic features on final pathology. One hundred and one patients with clinical stage I (N = 65) or II (N = 19) or diagnosed by endometrial curettage (EMC) only (N-17) with grade 1 or 2 endometrial adenocarcinoma without gross cervical involvement underwent preoperative CA-125 levels. Final pathology was reviewed for five poor prognostic pathologic features: FIGO grade 3 histology, unfavorable histologic type (sarcoma, clear cell, or papillary serous), invasion into the outer third of the myometrium, extension to the cervix, and extra-uterine metastases. Fifteen patients (14.9%) had CA-125 levels greater than 30 IU ml-1. Of these 15 patients, 12 had one or more of the five poor prognostic pathologic features (positive predictive value 80.0%, specificity 95.8%, P < 0.0001). However, since 30 of the 101 patients were found to have one or more of these poor prognostic pathologic features the sensitivity was only 40.0%. When clinical stage I patients were analyzed separately three patients (4.6%) had CA-125 levels greater than 30 IU ml -1 (positive predictive value 100%, specificity of 100%, sensitivity of 21.4%, P = 0.008). For patients with clinical stage II carcinoma, CA-125 was not predictive of pathologic findings except as a negative predictor of disease in a subgroup of patients whose endocervical curettage (ECC) demonstrated carcinoma unattached to endocervical tissue. In patients diagnosed by EMC only, an elevated CA-125 level was associated with poor prognostic pathologic features (P = 0.001). An elevated preoperative CA-125 reliably predicts advanced disease even in patients with apparently favorable histology and clinical stage, however the sensitivity of this method remains low.

Brachytherapy for early endometrial carcinoma: a comparative study with long-term follow-up.

The current study was undertaken to evaluate the effect of preoperative uterine or postoperative vaginal brachytherapy compared to no adjuvant therapy on the disease-free interval, sites of recurrence, and survival in favorable stage IB endometrial carcinoma. One hundred and forty-six patients with FIGO grade 1 and 2 endometrial carcinoma and 1-33% myometrial invasion treated between 1974 and 1992 were retrospectively studied. The use of brachytherapy varied among the treating physicians during the study period. A Kaplan-Meier survival analysis was used to estimate disease-free survival and differences between treatment groups were evaluated with the Mantel-Cox statistic. Recurrent disease occurred in 7 patients (5.3%). Vaginal recurrences accounted for 6 of the 7 sites of recurrences. Recurrences occurred in 1.3% of grade 1 vs. 8.7% of grade 2 tumors (P = 0.04). Among 69 grade 2 tumors, recurrences occurred in 7.5% of those treated with brachytherapy vs. 10.3% of those not treated (P = 0.68). Brachytherapy did not affect the disease-free or overall survival. No serious complications directly related to therapy occurred. Vaginal recurrences occur even in early endometrial carcinoma. This study demonstrates no apparent benefit to brachytherapy. A larger study would be required to see a recurrence or survival difference.

Torsion of the uterine adnexa: A clinicopathologic correlation.

Although uterine adnexal torsion is a rare phenomenon and an infrequent diagnosis, there have been several reported cases. Two cases that occurred in our practice in the past year are presented to illustrate the acute and chronic phases of the disease. This paper discusses the intrinsic and extrinsic concepts of etiologic factors of adnexal torsion and reviews the common presenting symptoms and the physical, laboratory and pathologic findings of this syndrome. An increased index of suspicion of intermittent adnexal torsion may lead to laparoscopic diagnosis and conservative therapy.

Cytodiagnosis of Hodgkin's disease in sputum specimens.

In patients with histologically proven Hodgkin's disease, knowledge of the extent of involvement of lymph nodes and other organs has proven valuable in the determination of treatment and prognosis. One of the most common sites of involvement outside the hematopoietic system has been shown to be the lung parenchyma; in this study, six patients with a tissue-proven diagnosis of Hogdkin's disease and positive cytologic findings in the sputum were reviewed. Three cell types not found in normal sputum specimens were identified in these patients and were correlated with the histologic patterns of the tumors as seen in lung biopsies. Our results suggest the usefulness of sputum examination as an adjunctive or possibly a substitute diagnostic procedure in the evaluation of patients with Hodgkin's disease and possible lung involvement. They also suggest that in some cases the cytologic diagnosis can be quite specific in the identification of neoplastic cells as consistent with a diagnosis of Hodgkin's disease.

An automated device for the production of cell preparations suitable for automatic assessment.

A set of preparatory steps has been developed for the processing of clinical samples from the female genital tract onto microscopic slides suitable both for machine assessment and for regular microscopic evaluation. These steps involve the depositing of the cell sample in a collection fluid, the semi-automatic adjustment of cell concentration to about 30,000 cells per milliliter through a combination of transmittance and light scatter measurements, the dispersion of the sample by syringing, and the deposition of the cellular content onto microscope slides by centrifugation. These steps were designed so as not to allow loss of cells--except the lysis of erythrocytes--with the understanding that this condition entails the presence of 4--10 per cent cell aggregates in the final preparation.

Serous papillary carcinoma of the cervix.

Two cases of serous papillary carcinoma of the cervix are reported. Both patients had clinical stage IB disease. One patient underwent radical hysterectomy and bilateral pelvic lymphadenectomy. The second patient was treated with pelvic radiation therapy after exploration demonstrated uterosacral ligament metastasis. Both patients are alive at 35 months after treatment with local therapy alone. In contrast to ovarian, tubal, and endometrial serous carcinomas, local therapy appears to be effective treatment for serous carcinomas of the cervix.

Isolated parenchymal splenic metastasis in epithelial ovarian cancer.

Metastatic parenchymal splenic disease in patients with ovarian cancer is unusual. It is most commonly seen in the presence of large-volume upper abdominal disease when parenchymal involvement occurs by surface extension. A patient with isolated parenchymal splenic metastasis and no peritoneal disease in the abdomen at primary surgery is described.

Squamous cell carcinoma arising in a mature cystic teratoma with metastasis to the paraaortic nodes.

Accurate surgical staging is critical to the management of early ovarian cancers. A patient with squamous cell carcinoma arising from a mature cystic teratoma was found to have paraaortic nodal metastasis as her only evidence of extraovarian disease. Extended field radiation therapy to the pelvis and paraaortic nodes with concomitant cisplatin and adjuvant chemotherapy failed to control her disease. Inadequate surgical staging may explain the recurrences in apparent stage I disease.