Primary appendiceal cancer: gynecologic manifestations and treatment options.

OBJECTIVE: To determine the presenting symptoms, gynecologic manifestations, and optimal intraoperative management of women with primary appendiceal cancer. METHODS: A multi-institutional investigation was performed to identify female patients with primary appendiceal cancer who were treated from 1990 to present. RESULTS: Forty-eight women with primary appendiceal cancer were identified from the tumor registries of participating institutions. The most common symptoms were abdominal pain (40%) and bloating (23%), but only 8% experienced rectal bleeding. Serum CEA was elevated (>2.5 U/ml) in 67% of patients, and serum Ca-125 was elevated (>35 U/ml) in 50% of patients. Thirty-one patients (65%) presented with a right adnexal or right lower quadrant mass and were operated on initially by a gynecologic oncologist. Ovarian involvement by metastatic appendiceal cancer was documented in 18 patients (38%). All of these patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging, but only 8 had a right hemicolectomy at the time of initial surgery. Forty-one patients (85%) presented with advanced stage appendiceal cancer (Stage III or IV) and 19 patients (46%) received postoperative chemotherapy, most commonly with a combination of 5-FU/Leukovorin. Following surgery, 22 patients (46%) experienced disease progression or recurrence, and 14 have died of disease. The most common sites of recurrence were abdominal or pelvic peritoneum (18), colon (2), and ovary (2). Patient survival was 70% at 2 years, and 60% at 5 years. CONCLUSION: Women with primary appendiceal cancer frequently present with ovarian metastases, and initial surgical intervention is often performed by a gynecologic oncologist. All patients with mucinous epithelial ovarian cancer should undergo appendectomy at the time of surgical staging. The appendix should be examined intraoperatively, and if appendiceal carcinoma is identified, a right hemicolectomy and appropriate surgical staging should be considered.

The efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC).

OBJECTIVE: To determine the efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC). METHODS: A retrospective multi-institutional investigation was performed to identify surgically staged patients with Stage I UPSC who were (1) treated after surgery with 3-6 courses of platinum-based chemotherapy without radiation from 1990-2003, and (2) followed for a minimum of 12 months, or until recurrence. RESULTS: Six patients (IA-2, IB-3, IC-1) were treated with carboplatin (AUC 6) or cisplatin (50 mg/m2) alone. One patient recurred to the vagina, was treated with chemo-radiation, and is alive and well at 122 months. One patient recurred to the lung, liver, and brain, and died of disease at 24 months. The remaining 4 patients are alive with no evidence of disease 15-124 months (mean 62 months) after treatment. Two patients (IB-1, IC-1) were treated with cisplatin (50 mg/m2) and cyclophosphamide (1000 mg/m2), and both are alive and well with no evidence of disease 75 and 168 months after treatment. Twenty-one patients (IA-5, IB-13, IC-3) were treated with a combination of carboplatin (AUC 6) and paclitaxel (135 mg/m2-175 mg/m2). One patient recurred to the vagina after 3 cycles of carboplatin/paclitaxel, and was treated with chemo-radiation. She is now without evidence of disease 10 months after treatment. At present, all 21 patients with Stage I UPSC treated following surgical staging with carboplatin/paclitaxel chemotherapy are alive and well with no evidence of disease 10-138 months (mean 41 months) after treatment. CONCLUSION: Combination carboplatin/paclitaxel chemotherapy following surgery is effective in the treatment of Stage I UPSC.

Preoperative differentiation of malignant from benign ovarian tumors: the efficacy of morphology indexing and Doppler flow sonography.

OBJECTIVE: The goal of this study was to determine the efficacy of morphology indexing and Doppler flow sonography as methods to predict risk of malignancy in sonographically confirmed ovarian tumors. METHODS: Risk of malignancy was assessed preoperatively in 442 ovarian tumors using a new morphology index (MI) based on tumor volume and wall structure. Each tumor was assigned a score of 0 to 10 based on increasing volume and morphologic complexity. Doppler flow studies were performed on 371 of these tumors. Following morphologic evaluation, all ovarian tumors were removed surgically. RESULTS: Of 315 tumors with a MI < 5 there was only 1 malignancy (a stage IA granulosa cell tumor <2 cm in diameter) whereas there were 52 malignancies in 127 tumors with a MI > or = 5. Stage of disease was as follows: stage I, 33; stage II, 6; stage III, 14. Risk of malignancy was related directly to MI score, varying from 0.3% in tumors with a MI < 5 to 84% in tumors with a MI > or = 8. A MI value of > or = 5 as indicative of malignancy was associated with the following statistical parameters: sensitivity 0.981, specificity 0.808, PPV 0.409, NPV 0.997. A pulsatility index (PI) < 1.0 as indicative of malignancy was associated with: sensitivity 0.528, specificity 0.776, PPV 0.288, NPV 0.906. A resistive index (RI) < 0.4 as indicative of malignancy was associated with: sensitivity 0.222, specificity 0.867, PPV 0.222, and NPV 0.867. The addition of Doppler flow indices to MI did not improve the accuracy of predicting malignancy. Likewise, the absence or presence of ovarian tumor blood flow was not reliable as a means to differentiate benign from malignant ovarian tumors. CONCLUSIONS: Morphology indexing is an accurate and inexpensive method of differentiating benign from malignant ovarian tumors, and can be a valuable adjunct in treatment planning. The addition of Doppler flow studies did not improve diagnostic accuracy of MI.

Continuing participation supports ultrasound screening for ovarian cancer.

The effect of ovarian cancer screening on survival is enabled by women who continue to actively participate in screening. In this report, factors that affect participation are examined. Participants included 13,963 Kentucky women who received 56,392 screens accounting for a 46,113 screening year experience. Background, health history and reasons for participating in transvaginal sonographic screening were collected via a self-reported questionnaire. Screening participants were characterized as > 50 years old, mostly married, well educated, medically insured, health conscious women, living in the vicinity of the screening centre or 51-150 miles away. Approximately 70% of the participants can be considered active in the study based upon a screening visit during the 1997-1998 2-year period. The probabilities of a return screen at 1, 2, 5 and 7.5 years were 77.8%, 72.0%, 58.7% and 50.6%, respectively. A total of 96% of return visits occurred within 2 years, with 33.7% having intervals of < 1 year. Perceived family history was not observed to affect continuation. However, abnormal findings were associated with a shortened participation. These high levels of continuation in ultrasound screening indicate that women take this disease seriously and demonstrate that this disease is of consequence to them.

The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer.

OBJECTIVE: The purpose of this study was to determine the efficacy of annual transvaginal sonography (TVS) as a screening method for ovarian cancer. METHODS: Annual TVS screening was performed on 14, 469 asymptomatic women from 1987 to 1999. Eligibility criteria included (1) all women >/= 50 years of age and (2) women >/= 25 years of age with a family history of ovarian cancer. Ovarian volume was calculated using the prolate ellipsoid (length x height x width x 0.523). An abnormal sonogram was defined by (1) an ovarian volume >10 cm(3) in postmenopausal women or >20 cm(3) in premenopausal women or (2) a papillary or complex tissue projection into a cystic ovarian tumor. All women with abnormal TVS had a repeat sonogram in 4-6 weeks. Patients with a persistently abnormal second screen had a serum CA-125 determination, tumor morphology indexing, and Doppler flow sonography, and were advised to have surgical tumor removal. RESULTS: One hundred eighty patients with persisting TVS abnormalities underwent exploratory laparoscopy or laparotomy. Seventeen ovarian cancers were detected: 11 Stage I, 3 Stage II, and 3 Stage III. Only three patients with Stage I cancers had a palpable ovarian mass on clinical examination. All patients with Stage I and II ovarian cancer are alive without recurrence 1.8-9.8 years (median, 4.5 years) after diagnosis. Two of the three Stage III patients have died of disease: one at 4.3 years and one at 7.7 years after detection. Four patients developed ovarian cancer within 12 months of a negative scan (FN): 2 Stage II, 2 Stage III. Three of these patients are alive with no evidence of disease 0.4, 1.9, and 5.5 years after diagnosis, and 1 patient has died of disease 0.7 years after diagnosis. Four patients developed ovarian cancer more than 12 months following a normal screen. All 4 presented clinically with Stage III disease. Two of these patients have died of disease and two patients are alive 1.5 and 2.1 years after diagnosis. TVS screening was associated with the following statistical variables: sensitivity, 81%; specificity, 98.9%; positive predictive value (PPV), 9.4%; and negative predictive value (NPV), 99.97%. After 46, 113 screening years, there have been 3 ovarian cancer deaths in the annually screened population and 2 ovarian cancer deaths in women receiving less than annual screening. The survival of ovarian cancer patients in the annually screened population was 95.0 +/- 4.9% at 2 years and 88.2 +/- 8.0% at 5 years. Excluding all cases of nonepithelial or borderline epithelial malignancies, the survival of patients with ovarian cancer in the annually screened population was 92.9 +/- 6.9% at 2 years and 83.6 +/- 10.8% at 5 years. CONCLUSIONS: (1) TVS screening, when performed annually, is associated with a decrease in stage at detection and a decrease in case-specific ovarian cancer mortality. (2) TVS screening does not appear to be effective in detecting ovarian cancer in which ovarian volume is normal.

Ovarian volume related to age.

OBJECTIVE: The goal of this study was to determine the relationship of ovarian volume to age, height, and weight in women undergoing transvaginal sonography. METHODS: Thirteen thousand nine hundred sixty-three women 25-91 years of age undergoing annual transvaginal sonography as part of the University of Kentucky Ovarian Cancer Screening Program were the subjects for this investigation. Each ovary was measured in three dimensions, and ovarian volume was calculated using the prolate ellipsoid formula (L x H x W x 0.523). Mean ovarian volume according to age was calculated for each decade of life. RESULTS: Data were obtained from 58,673 observations of ovarian volume. Mean ovarian volume was 6.6 +/- 0.19 cm(3) in women less than 30 years of age; 6.1 +/- 0.06 cm(3) in women 30-39; 4.8 +/- 0.03 cm(3) in women 40-49; 2.6 +/- 0.01 cm(3) in women 50-59; 2. 1 +/- 0.01 cm(3) in women 60-69; and 1.8 +/- 0.08 cm(3) in women >/=70. Mean ovarian volume was 4.9 +/- 0.03 cm(3) in premenopausal women and 2.2 +/- 0.01 cm(3) in postmenopausal women (P < 0.001). The use of exogenous estrogens was associated with a significant reduction in ovarian volume in women 40-59 years of age, but not in women >/= 60. Ovarian volume was unrelated to patient weight but was greater in tall women (>68 in.) than in short women (<58 in.). CONCLUSION: There is a statistically significant decrease in ovarian volume with each decade of life from age 30 to age 70. Mean ovarian volume in premenopausal women is significantly greater than that in postmenopausal women. The upper limit of normal for ovarian volume is 20 cm(3) in premenopausal women and 10 cm(3) in postmenopausal women.

Transvaginal sonography as a screening method for the detection of early ovarian cancer.

From December 1987 to December 1993, 6470 women underwent screening with transvaginal sonography (TVS) as part of the University of Kentucky Ovarian Cancer Screening Project. Two groups of women were eligible to participate in this investigation: (i) asymptomatic postmenopausal patients or patients >50 years of age, and (ii) asymptomatic women >30 years of age with a family history of ovarian cancer. Ovarian volume was calculated using the prolate ellipsoid formula (length x height x width x 0.523). An abnormal sonogram was defined by (1) an ovarian volume >10 cm3 in postmenopausal women or >20 cm3 in premenopausal women, and (2) a papillary or complex tissue projection into a cystic ovarian tumor. All women with an abnormal TVS had a repeat sonogram in 4-6 weeks. Patients with persistently abnormal scans had a serum CA-125 determination, tumor morphology indexing, and color Doppler sonography. Ninety patients (1.4%) with a persisting abnormality on TVS underwent exploratory laparotomy or laparoscopy for tumor removal. Thirty-seven patients had serous cystadenomas and six had primary ovarian cancers. Five patients had Stage IA ovarian cancer and one patient had Stage IIIB disease. Only one of the ovarian cancer patients had a palpable abnormality on pelvic examination, and none had an elevated (>35 u/ml) serum CA-125. All these patients are presently alive and well 1-5 years after conventional therapy. There was one false negative in this study, a 38-year-old white female who was noted to have a small ovarian cancer at the time of laparoscopic prophylactic oophorectomy 11 months after a normal scan. Over 17,000 screening years have been accrued and there have been no deaths from primary ovarian cancer in the screened population. A cost analysis of TVS screening is presented.

Publication-quality labeling of gels using transparency-mounted photographs and word processing software.

Obtaining a high quality nucleic acid or protein gel may be an easier and less daunting task than labeling the gel for publication. Techniques for adding information and identifiers to gels range from laboriously applying lettering or labels on gel photographs to computerized approaches that work directly with digitized gel images and produce photographic-quality output. The computerized approach may require specialized software and a considerable investment in a photographic-quality output device, like a dye sublimation printer. It can be argued that electronically processed gel images do not actually achieve the quality readily obtained photographically. We describe an approach that uses photographic gel images that are quickly and easily labeled using the drawing-lettering capability of a commercial word processor in widespread use (Microsoft Word for Windows Version 6).

Ovarian cancer screening.

BACKGROUND: The three most extensively evaluated screening methods for ovarian cancer are pelvic examination, serum CA 125, and transvaginal sonography (TVS). The lack of sensitivity of pelvic examination and serum CA 125 has limited their use in ovarian cancer screening. Currently, the most effective screening method for ovarian cancer is TVS. METHODS: Transvaginal sonography was performed with a standard ultrasound unit and a 5.0 MHz vaginal transducer. Each ovary was measured in three dimensions and ovarian volume was calculated using the prolate ellipsoid formula (L x H x W x 0.523). An ovarian volume greater than or equal to 20 cm3 in premenopausal women and greater than or equal to 10 cm3 in postmenopausal women was considered abnormal. Also, any internal papillary projection from the tumor wall was considered abnormal. A patient with an abnormal screen had a repeat TVS in 4-6 weeks. Women with a persisting abnormality on TVS underwent pelvic examination, serum CA 125 determination, Doppler flow sonography, and tumor morphologic indexing before operative tumor removal. RESULTS: Eighty-five hundred asymptomatic women underwent TVS screening. One hundred twenty-one of these women had a persisting abnormality and underwent tumor removal. Fifty-seven patients had serous cystadenomas and eight had primary ovarian cancers. Six patients had Stage IA ovarian cancer, one had Stage IIC ovarian cancer, and one had Stage IIIB ovarian cancer. Only one of these patients had palpable ovarian enlargement on clinical examination and one had an elevated serum CA 125. All patients are alive and well 4-61 months after conventional therapy. The direct cost of TVS screening was highest during the initial years of the program and fell progressively to $30/screen during the 4th year of the study. Worldwide, more than 14,000 women have been screened using ultrasonography, and 19 ovarian cancers have been detected. More than 20,000 patient-screening-years have been accrued, and there have been no deaths from primary ovarian cancer in the screened population. CONCLUSIONS: Transvaginal sonography screening causes a decrease in stage at detection and a decrease in case-specific mortality. Further study is needed to determine if annual TVS screening will significantly reduce ovarian cancer mortality. The cost for TVS screening is reasonable and is well within the range of that reported for other screening tests.

Participation in transvaginal ovarian cancer screening: compliance, correlation factors, and costs.

The objective was to identify factors influencing participation in screening for ovarian cancer using transvaginal sonography in the free experimental program at the University of Kentucky over its 6+ year history. Database records for screenings, performed from 1987 to June 1994, were utilized. Computer sorts, 1990 census information as predictors, and stepwise multiple regression analysis were employed. Participation in the model ovarian screening program took 3-4 years to approach > 300 screens/month, with repeat screenings exceeding new subject participation in this time period. A number of participants traveled > 200 miles for screening on both initial and repeat encounters. Analysis of distance to the screening site, median family income, county physician population, and education levels indicated that distance and then education correlated best with participation. Unit screening cost shrank from $45 to under $25 when maximal participation was achieved. Distance and education correlated with participation. Expenses compare favorably with diagnostic procedures for other diseases.

Images of estrogen-receptor-positive breast tumors produced by estradiol labeled with iodine I 123 at 16 alpha.

OBJECTIVE: To examine the suitability of estradiol labeled with iodine I 123 at 16 alpha for imaging estrogen-receptor-positive breast carcinoma using imaging instrumentation that is widely available. DESIGN: Single-photon emission computed tomographic imaging survey of 29 women with suspected primary or expected recurrent breast carcinoma. SETTING: University-based referral center. PARTICIPANTS: Twenty-nine women undergoing diagnosis for primary or recurrent breast carcinoma. Selection was voluntary. MAIN OUTCOME MEASURE: Qualitative imaging study designed to provide tomographic data of radioligand retention and descriptive data of imaging results. RESULTS: Single-photon emission computed tomographic imaging using 123I-estradiol at 16 alpha was performed for patients with breast carcinoma. Independent readers, without knowledge of receptor status or proven disease, interpreted the films. Scintigraphic detection was most noteworthy in patients with chest wall tumors and inflammatory breast cancer. Agreement between readers was 98% for true-negative readings and 94% for true-positive readings, but only 60% for false-positive and false-negative film readings. CONCLUSIONS: Our results indicated that areas shown on imaging were also found to have estrogen-receptor activity and that radioligand accumulation can occur with low frequency in some surgically explored tissue. Radioligand imaging with 16 alpha-123I-estradiol can locate estrogen-receptor-positive breast tumors, including some that may be difficult to detect using conventional diagnostic imaging.

Ovarian cancer screening in asymptomatic postmenopausal women.

From 1987 to 1992, 3220 asymptomatic postmenopausal women underwent screening with transvaginal sonography (TVS) as part of the University of Kentucky Ovarian Cancer Screening Project. Ovarian volume was calculated using the prolate ellipsoid formula (length x height x width x 0.523). An abnormal sonogram was defined by (1) an ovarian volume > 10cm3 or (2) a papillary projection into a cystic ovarian tumor. All women with an abnormal TVS had a repeat sonogram in 4-6 weeks. If the repeat sonogram was abnormal, a morphology index score was assigned to each tumor, and a serum CA-125 was obtained. The patient then had a pelvic examination and an exploratory laparotomy. Forty-four patients (1.4%) with a persisting abnormality on TVS underwent exploratory laparotomy. Twenty-one patients had serous cystadenomas and 3 had primary ovarian cancers. Two patients with primary ovarian cancer had Stage IA disease and one had Stage IIIB disease. All patients with ovarian cancer had normal pelvic examinations and normal serum CA-125 levels, and are presently alive and well 32, 31, and 8 months after conventional therapy. Over 5000 screening years have been accumulated at this institution, and there have been no ovarian cancer deaths in the screened population. TVS screening has produced a decrease in stage at detection and case-specific mortality from ovarian cancer. A multi-institutional trial to test the efficacy of TVS as a screening method for ovarian cancer is indicated.

A morphology index based on sonographic findings in ovarian cancer.

A morphology index based on morphologic characteristics of ovarian tumors was developed. Specific categories included tumor volume, wall structure, and septal structure. A point scale (0-4) was developed within each category with the total points per evaluation varying from 0-12. Sonograms on 121 patients undergoing exploratory laparotomy for ovarian masses were evaluated using this index. Eighty ovarian tumors had a morphology index score < 5, and all were benign (negative predictive value, 1.000). In postmenopausal patients, a morphology index score > or = 5 had a positive predictive value for malignancy of 0.45. All ovarian malignancies had significant abnormalities in wall structure and all had a total volume in excess of 10 cm3. The findings of the present investigation indicate that the morphology index is a cost effective adjuvant method which significantly increases the specificity and positive predictive value of transvaginal sonography. The routine application of a morphology index to screening sonography should decrease the amount of diagnostic surgery performed in order to detect each case of ovarian cancer.

Immunohistochemical staining for CA-125 in fallopian tube carcinomas.

From 1981-1991, 15 patients with primary fallopian tube carcinomas were treated at the University of Kentucky Medical Center. Immunohistochemical staining for CA-125 was performed on tumor specimens from all cases. Thirteen tumors (87%) stained positively for CA-125. Antigen staining was most intense in the apical portions of carcinoma cells. Serum CA-125 levels were measured in 5 patients and were elevated in 4 (80%). There was a positive correlation between tumor and serum antigen expression in these cases. Serum CA-125 levels accurately reflected disease status in the patients studied. These data suggest that CA-125 is a useful marker in patients with fallopian tube carcinoma. Immunohistochemical localization of CA-125 in tumor tissue should predict which patients will benefit most from serial antigen determinations.

Ovarian cancer screening.

BACKGROUND: Despite advances in evaluation and treatment, ovarian cancer mortality has decreased minimally during the past two decades. Most patients have advanced-stage disease at diagnosis, and the prognosis is poor. As a result, there has been increasing interest in the development of methods for the early detection of ovarian cancer. To benefit from screening, a disease should (1) be a significant cause of mortality, (2) have a high prevalence in the screened population, (3) have a preclinical phase that can be detected by screening, and (4) be amenable to therapy, such that the survival rate of patients with early-stage disease is significantly higher than that of patients with advanced-stage disease. Ovarian cancer fulfils all of these criteria. METHODS: An optimal screening method should be safe, easy to do, time efficient, and acceptable to the patients being screened. Most importantly, it should have a high sensitivity and specificity. RESULTS: Currently, the most effective screening methods for ovarian cancer are serum CA 125 levels and transvaginal sonography (TVS). In screening studies, the serum CA 125 level has had a reasonably high specificity but a low sensitivity. Currently, approximately 8000 asymptomatic women have been screened with TVS. Ten primary ovarian cancers were detected, and all were Stage I lesions. Patients whose tumors were detected by TVS all have been cured by conventional treatment. TVS screening has resulted in a significant reduction in stage at detection and in the case-specific death rate from ovarian cancer. In these studies, TVS has had a high sensitivity but only a moderate specificity. CA 125 level, Doppler flow sonography, and the use of a morphology index are being evaluated as methods to increase the specificity of TVS. CONCLUSIONS: A large multiinstitutional study is indicated to determine if annual TVS screening will cause a significant decrease in site-specific mortality from ovarian cancer.

Resistance to tamoxifen with persisting sensitivity to estrogen: possible mediation by excessive antiestrogen binding site activity.

The growth of a large proportion of estrogen receptor-positive breast tumors is stimulated by estrogen and can often be controlled through antiestrogen therapy. Resistance to antiestrogen (AE) therapy can occur while tumors retain the expression of estrogen receptors (ERc) and remain functionally responsive to estrogens. The ability of specific antiestrogen binding sites (AEBS) to prevent AE from interacting with ERc has been examined as a possible mechanism through which this appropriation of AE could interfere with antiestrogen action. Comparisons were performed between uterine preparations where ERc activity exceeded AEBS binding and liver preparations where AEBS binding predominated. Identical estimates of ERc activity were obtained in uterine preparations using either [3H]estradiol or [3H]-4OH-tamoxifen and radioinert diethylstilbestrol (alpha,alpha'-diethyl-4,4'-stilbenediol) to estimate nonspecific binding. AEBS binding was observed only when [3H]-4OH-tamoxifen was used, while binding to Type II sites was resolved only with [3H]estradiol. When excess AEBS activity predominated, analyses with radiolabeled estrogen and antiestrogen present simultaneously showed that virtually all of the antagonist was bound to AEBS with little of the antagonist available to associate with ERc. In an effort to relate these observations to AE resistance per se, ERc and AEBS were measured in MCF-7 human breast cancer cells (ERc-positive, responsive to estrogens and antiestrogens) and in variant AE-insensitive LY-2 human breast cancer cells (ERc-positive, responsive only to estrogens). In AE-resistant LY-2 cells, the ratio of AEBS:ERc was approximately three times greater than in MCF-7 cells. Examination of 128 human breast carcinomas revealed that AEBS activity was present and could exceed ERc activity. Importantly, the partition of significant AE away from ERc was observed in human specimens. These observations identify a biochemical mechanism for antiestrogen resistance through which AE access to ERc can be totally incapacitated while sensitivity to estrogens continues. These observations indicate that AEBS activity, in addition to ERc activity, may provide helpful information for predicting the response of certain cancers to hormonal therapy.

The growth response of BG-1 ovarian carcinoma cells to estradiol, 4OH-tamoxifen, and tamoxifen: evidence for intrinsic antiestrogen activation.

The influence of estrogen (E) and antiestrogen (AES) on the in vitro growth of BG-1 ovarian carcinoma cells, which express steroid receptors was examined (K. R. Geisinger, T. E. Kute, M. J. Pettenati, C. E. Welander, Y. Dennard, L. A. Collins, and M. E. Berens, Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors, Cancer 63, 280-288, 1989). All determinations were simultaneously referenced under similar conditions to MCF-7 cells, a well-established cell line for modeling hormonal responses in breast cancer. In "complete" media containing fetal calf serum (FCS, 10%), MCF-7 cell numbers increased approximately 7 x in 7 days, remaining at this level Days 8-15. In contrast, BG-1 cells achieved similar numbers by Day 7, but showed apparent exponential growth over Days 8-15 to 15-20 x. Phenol red-free media containing 10% FCS (less than 20 pg estradiol (E2)/ml by RIA) was used to assess responses to E and AES. Growth of both MCF-7 and BG-1 cells slowed in E-free media. E2 (10 nM) stimulated the growth of both cell lines, yet was responsible for exponential increases during Days 8-15 only in BG-1 cell numbers (50-70 x). The metabolically active AES (4OH-tamoxifen, 50 nM) reduced E2-stimulated MCF-7 growth to 3-4 x, while tamoxifen (50 nM) had no effect. Rescue with 10 microM E2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E2 was observed to rescue BG-1 cells from both of these antagonists. We conclude that BG-1 ovarian carcinoma cells respond in vitro to E and AES. Moreover, by virtue of responses to tamoxifen, BG-1 cells may have an intrinsic capacity to hydroxylate tamoxifen to its active metabolite. This property of ovarian carcinoma cells might be worth exploiting in the design of more effective combination chemotherapy regimens.

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography.

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA-125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well-accepted by patients. Currently, there are more than 3000 patient years of follow-up in the screened population, and there have been no deaths due to ovarian cancer. A multi-institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors.

16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers.