The level of urokinase-type plasminogen activator receptor is increased in serum of ovarian cancer patients

Ascites and serum of patients with ovarian carcinoma contain a soluble form of urokinase-type plasminogen activator receptor (uPAR). We now report that pro-uPA-Sepharose-purified uPAR from ascites of patients with ovarian carcinoma is the full-length molecule missing the glycosyl-phosphatidylinositol anchor, as determined by its amino acid composition. We next examined the significance of determining serum soluble uPAR (suPAR) levels in ovarian cancer patients using a specific ELISA and compared the results with serum concentrations of CA-125, an established diagnostic marker. Serum from pre- and postoperative ovarian cancer patients was assayed for suPAR and CA-125. The majority of the patients with ovarian cancer had enhanced preoperative serum levels of suPAR compared with healthy controls, but suPAR concentrations decreased after operation. Although uPAR was associated with most ovarian carcinomas, it appeared to be a less specific indicator for ovarian cancer than CA-125. On the other hand, suPAR was more specific for other types of solid tumors. Moreover, we have observed some cases of ovarian cancer that showed increase of suPAR but not of CA-125. The prognostic significance of serum suPAR assay for survival of ovarian carcinoma patients was evaluated using Cox's proportional hazards analysis. Our preliminary data show that high preoperative levels of suPAR were associated with worse survival of the patients, whereas CA-125 had no prognostic implications. This is the first report evaluating the assay of serum suPAR levels in ovarian cancer and analyzing its value as a tumor or prognostic marker.     

CA-125 and carcinoembryonic antigen assay vs. cytodiagnostic experience in the classification of benign ovarian cysts

OBJECTIVE: To compare the relative strengths of two factors involved in making an accurate differentiation between functional and epithelial ovarian cysts, along with their combination: (1) the cytologist's level of experience in interpreting ovarian cytology, (2) the use of the tumor markers carcinoembryonic antigen (CEA) and CA-125 in cyst fluid, and (3) a combination of (1) and (2). STUDY DESIGN: Papanicolaou-stained sediments from fluid aspirated from 31 resected ovarian cysts (6 functional and 25 epithelial) were blindly and independently evaluated by five pathologists with varying experience in ovarian cytology. Cyst fluid supernatant was used for CEA, enzyme-linked immunosorbent assay, and CA-125 radioimmunoassay; CEA levels > 5 ng/mL or CA-125 > 5,000 U/mL were considered elevated. Cysts were categorized cytologically and histologically as functional or epithelial and by tumor markers as "neither elevated" or "either or both elevated" (EBE). RESULTS: The agreement of histologic diagnosis with each pathologist's cytologic diagnosis ranged from 53% to 84% (53%, 71%, 83%, 82%, 84%), corresponding to increasing level of experience. The percentage of agreement with EBE was 77%, whereas combined experienced pathologist's diagnosis and EBE was 87%. Kappa equaled .45 for experienced cytopathologist's diagnosis or EBE alone. Kappa equaled .53 when the pathologist or EBE diagnosed an epithelial cyst, indicating results unlikely to occur by chance. CONCLUSION: The distinction of functional from epithelial ovarian cysts is best achieved by combining measurement of the tumor markers CEA and CA-125 with a high level of cytopathology experience.     

Evaluation on non invasive diagnostic tests for the second look in epithelial ovarian cancer

OBJECTIVE: To determine the usefulness of diagnostic tests performed before a second look laparotomy in patients with epithelial ovarian cancer. STUDY DESIGN: Thirty-three patients with epithelial ovarian cancer attended at Fundación Jiménez Díaz from 1984 to 1995 were studied. All patients initially underwent cyto-reducing surgery, followed by at least six platinum-based chemotherapy cycles. Prior to second look laparotomy all patients were evaluated by computerized tomography (CT) of the pelvis and abdomen, CA-125, pelvic-abdominal echography and gynecologic examination. To evaluate sensitivity, specificity, positive predictive value and negative predictive value for each test contingency tables were used. RESULTS: Eleven out of the 33 second look patients (33%) had histologic or cytologic evidence of disease. Six out of the eleven positive second look had a positive CT prior to second look (sensitivity of 55%). CT showed lack of disease in 21 out of the 22 negative second look cases (specificity 95%). Positive and negative predictive values of the test were 86% and 81%, respectively. Nine cases out of the 28 who had a CA-125 obtained had a positive second look. Four out of these nine patients had an increased CA-125 value (sensitivity 44%, specificity 95%, positive predictive value 80% and negative predictive value 78%). Sensitivity, specificity, positive predictive value and negative predictive value of physical examination and echography were 36%, 100%, 100%, 76% and 27%, 95%, 75%, 72%, respectively. On the other hand, sensitivity, specificity, positive predictive value and negative predictive value of all tests taken together were 64%, 91%, 78% and 83%, with a rate of false-negative results of 17% and a rate of false-positive results of 22%. CONCLUSION: Pelvic-abdominal computerized tomography, CA-125, pelvic-abdominal echography and gynecologic examination can be an alternative to second look laparotomy for the diagnosis of persistence or recurrence of the disease in patients with epithelial ovarian cancer.     

A risk model for ovarian carcinoma patients using CA 125: time to normalization renders second-look laparotomy redundant

BACKGROUND: We evaluated the incorporation of CA 125 normalization times into a prognostic model based on pretreatment variables in patients with ovarian carcinoma to determine if they could render second-look laparotomy (SLL) redundant. METHODS: A total of 54 consecutive patients with ovarian carcinoma who underwent SLL between 1985 and 1990 were included in this analysis. At diagnosis, all of the patients had abnormal CA-125 serum levels, which fell to within the normal range during chemotherapy. Cox's model was used to select pretreatment variables relevant for prognosis. The influence of the time to normalization of CA 125 (< or = vs. > 1 months) and the capability of SLL results to modify prognostic prediction, were also evaluated. RESULTS: The size of the residual tumor at the beginning of therapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently predictive of survival. The time to normalization of CA 125 serum levels (analyzed either as -a continuous or as a two-category variable) also had an independent prognostic role when included in the model. When we examined the inclusion of both CA 125 parameter and SLL into the model together, we found that only CA 125 continued to have an independent prognostic relevance. On the basis of the two pretreatment parameters (PS and tumor size) and of this response parameter (time to normalization of CA 125 values) we selected six subgroups of patients having different outcomes (log rank test of equality over-strata < 0.001). Patients with good prognostic pretreatment variables, and those with intermediate prognosis at the beginning of therapy who showed a quick normalization of CA 125, had an 80% 5-year survival, compared with 16% 5-year survival in the remaining patients. (P < 0.0001). CONCLUSIONS: Our data suggest that the survival of patients with advanced ovarian carcinoma could be accurately predicted by considering some pretreatment variables and time to CA 125 normalization together, without performing SLL. Our risk model, however, needs to be validated by larger prospective trials, to draw any definitive conclusions about the abandonment of surgically defined response.     

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer

OBJECTIVE: To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free beta human chorionic gonadotrophin (hCG) and cancer-associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma. DESIGN: A two year follow up study of survival. SETTING: A tertiary care gynaecological oncology unit. PARTICIPANTS: One hundred and eleven women with histologically confirmed epithelial ovarian cancer. MAIN OUTCOME MEASURES: Survival over a two year period. RESULTS: Stage corrected log-rank chi 2 tests demonstrated a significant effect on survival for all four tumour markers (CA125 P = 0.0142; PLAP P < 0.0001; CASA P = 0.0098; hCG P = 0.0002). This was confirmed when each variable was fitted together with disease stage in Cox proportional hazard models. When fitted as multiple variables in a Cox proportional hazard model, the addition of free beta-hCG and CASA to disease stage, PLAP concentrations and CA125 levels did not demonstrate further prognostic value. CONCLUSIONS: Levels of all four markers correlate with survival in patients with epithelial ovarian cancer. The combination of PLAP and CA125 concentrations together with disease stage may be used to predict survival but the addition of hCG and CASA levels do not give additional prognostic information.     

Physiologic, biochemical and genetic aspects of malignant hyperthermia

The value of the TAG-72 (CA 72-4) serum marker in primary diagnosis was investigated in 110 patients with histologically diagnosed ovarian cancer. A reference group consisted of 103 patients with benign pelvic masses. Compared to the well-established CA-125, TAG-72 showed a low sensitivity of 42% in the detection of ovarian cancer. By contrast, when the cut-off level for TAG-72 was set at 6 U/ml, it showed a very high specificity of 99%. When the measurement of TAG-72 was combined to that of CA-125, improvements in both the specificity (as compared to a single CA-125 determination) and the sensitivity (as compared to a single TAG-72 assay) were observed. In such a combined assay, our results suggest that the best predictive value (positive and negative) was obtained if CA-125 is assigned a relatively high cut-off value (65 U/ml) in conjunction with a low cut-off level (3.2 U/ml or 4 U/ml) for TAG-72. In the present study, at threshold values of 65 U/ml respectively, a sensitivity of 86%, a specificity of 83% and a positive and negative predictive value of 85% were obtained. In mucinous carcinomas of the ovary, however, the additional TAG-72 determination did not lead to a better predictive power than did CA-125 measurement alone.     

Novel bombesin-like peptide binding proteins from lung

Our first year of experience in the use of PET scanning in the management of nine patients with ovarian cancer leads us to conclude that this promising new technique may be more sensitive than either serum CA-125 determinations or computed tomography for the detection and demonstration of residual or recurrent abdominal and pelvic tumor. Seven of these patients underwent second-look laparotomy which confirmed our impressions from preoperative PET scans in six patients, and the one other scan showed a focus of metabolic uptake coinciding with residual tumor in our retrospective review. The clinical courses of two other patients who did not undergo laparotomy confirmed the impressions gained from PET scans.     

Effect of Saccharomyces boulardii against experimental oral infection with Salmonella typhimurium and Shigella flexneri in conventional and gnotobiotic mice

OBJECTIVE: To compare serum CA 125 assays with computed tomography (CT) and transvaginal ultrasound (TVUS) for early detection of disease recurrence in patients with ovarian cancer. METHODS: Sixty-two patients with non-mucinous epithelial ovarian cancer who had positive CA 125 levels (> 35 U/ml) were studied. We performed a retrospective review to determine the usefulness of serum CA 125 measurements. Setting the cut-off limit at either 35 U/ml or 16 U/ml, the accuracy of CA 125 measurements was compared with that of CT scanning, TVUS and operative findings at second-look laparotomy (SLL) in the early detection of recurrent tumors. RESULTS: Compared with SLL, both the specificity and the positive predictive value of CA 125 measurements were 100% at 16 and 35 U/ml. The sensitivity and the negative predictive value were 30.8 and 71.9%, respectively, below 35 U/ml and 53.8 and 79.3%, respectively, below 16 U/ml. The false-negative rate of CT was 36.1%. When the cut-off limit was reduced from 35 to 16 U/ml, 57.1% of patients considered to be in remission were reclassified as having persistent disease. A complete response confirmed by CT did not represent remission: CA 125 levels were 7.5-fold higher at the time of re-evaluation by CT. TVUS also lagged behind CA 125 assays in detecting disease recurrence. The sensitivity of ultrasound appeared to be lower than that of CT because it failed to detect extrapelvic lesions. CONCLUSION: A screening threshold (cut-off level) of 16 U/ml for CA 125 should be used to detect recurrent serous ovarian adenocarcinoma. Although ultrasound is a convenient method of detecting intrapelvic lesions, and has cost benefit, CT is necessary to detect extrapelvic recurrence. Neither CT nor ultrasound are more accurate than serial CA 125 assays in detecting disease recurrence.     

Ovarian serous papillary cystadenocarcinoma stage IIIC in a 19-year-old

In mature women, the most common histological cell type of ovarian cancer is of epithelial origin. In children and adolescents, germ cell tumors are the most frequent. We report a case of a serous papillary cystadenocarcinoma FIGO stage IIIC in a 19-year-old female. She presented with a 6-month history of vague lower abdominal pain. Preoperative CA-125 was elevated at 296 kU/liter. At laparotomy, she was found to have stage IIIC disease. A debulking procedure including total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node sampling was performed. The immediate postoperative course was complicated by fulminant disseminated intravascular coagulopathy. She was subsequently treated with six courses of cyclophosphamide and carboplatin. Twenty-four months after surgery, the patient has no evidence of disease despite an increased CA-125 of 51 kU/liter.     

Plasma insulin-like growth factor-I, CA-125, estrogen, and progesterone in women with leiomyomas

OBJECTIVE: To determine plasma levels of insulin-like growth factor-I (IGF-I), CA-125, estrone (E1), E2, and P in women with uterine leiomyomas compared with normal women. DESIGN: Women with leiomyomas were compared with normal women (control). SETTING: University Department of Obstetrics and Gynecology. PATIENTS: Fifty-one premenopausal women with uterine myomas > 14 weeks gestation and 30 normal fertile women (controls) were studied. Peripheral blood samples were obtained before myomectomy or hysterectomy and during the nonmenstruating phase in the controls. MAIN OUTCOME MEASURES: Plasma levels of E1, E2, P, CA-125, and IGF-I were determined by specific and sensitive RIAs and immunoradiometric assays. RESULTS: Plasma IGF-I levels were 2,006 +/- 185 mU/mL (mean +/- SEM, n = 35) and 2,335 +/- 287 mU/mL (n = 16) in women with leiomyomas during the follicular and luteal phases, respectively, whereas the corresponding values for normal women were 1,702 +/- 120 (n = 30) and 1,774 +/- 239 mU/mL (n = 30). Similarly, plasma CA-125 levels were unchanged in women with leiomyomas (myomas: 18.8 +/- 2.4, 21.5 +/- 3.7 U/mL; normal: 15.9 +/- 1.5, 15.8 +/- 1.3 U/mL during follicular and luteal phases, respectively). Women with leiomyomas had plasma E1, E2, and P levels during the follicular phase (91.9 +/- 11.5 pg/mL; conversion factor to SI unit, 3.699; 94.6 +/- 19.0 pg/mL; conversion factor to SI unit, 3.671; and 1.5 +/- 0.4 ng/mL; conversion factor to SI unit, 3.180, respectively) and the luteal phase (105.8 +/- 11.2 pg/mL; conversion factor to SI unit, 3.699; 128.7 +/- 24.8 pg/mL; conversion factor to SI unit, 3.671; and 9.6 +/- 1.6 ng/mL; conversion factor to SI unit, 3.180) similar to normal women. CONCLUSION: Plasma levels of IGF-I, CA-125, E1, E2, and P are normal in women with leiomyomas.     

Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma

Activin induces proliferation in epithelial ovarian carcinoma cell lines, whereas follistatin (FS), an activin binding protein, inhibits this action. To test the hypothesis that activin production, in excess of inhibin and FS, results in cell proliferation in epithelial ovarian tumors, messenger RNA (mRNA) expression of the activin family of proteins, FS, and activin type I and II receptors was examined in 25 primary epithelial ovarian tumors and tumor epithelium in culture (n = 7) using RT-PCR. Activin A was measured in the serum of ovarian cancer patients, and activin A, total inhibin, and FS protein secretion was measured from primary epithelial tumors in vitro. The effect of activin and FS on cell proliferation was assessed by measuring [3H]thymidine incorporation. All results were compared with normal ovarian epithelium. All epithelial ovarian tumors expressed mRNA for the alpha, beta A, and beta B subunits; FS 288 and 315; and the activin type IA, IB, II, and IIB receptors. beta A mRNA expression, as assessed using semiquantitative RT-PCR, was 3-fold greater in cultured tumor epithelium than in primary tumors (band density 0.86 +/- 0.17 vs. 0.28 +/- 0.09; P < 0.01). In addition, beta A mRNA was abundantly expressed in normal epithelium in culture (n = 2), whereas only trace amounts were seen in 2/9 primary epithelial samples. Activin protein was secreted by 24/25 primary epithelial ovarian tumors (range 0.2-155.8 ng/mL). In contrast, total inhibin was secreted by only 2/25 (range 0.01-0.92 ng/mL), whereas free FS was not detectable in the medium of any tumor (< 0.5 ng/mL). Treatment with activin or FS did not consistently affect cell growth. Measurement of serum activin A in a subset of subjects and in 27 additional subjects with epithelial ovarian carcinoma (n = 33) revealed preoperative activin A levels > 3 SD above the mean for pre- and postmenopausal women in 13/33 (39%) subjects. We conclude that in epithelial ovarian cancer: 1) beta A subunit mRNA is expressed, 2) activin protein is secreted more frequently than inhibin and in greater quantities than FS, 3) beta A subunit mRNA expression is greater in neoplastic and normal epithelium in culture than in the primary tissue, 4) the majority of tumors in culture do not respond to activin or FS treatment with proliferation, and 5) serum activin levels may reflect tumor secretion in some patients. Thus, activin A appears to be available as an autocrine/paracrine factor in epithelial ovarian tumors and may contribute to circulating levels, but its role in tumorigenesis has yet to be defined.     

Perioperative coagulopathy in patients undergoing primary cytoreduction

BACKGROUND: This study was performed to determine the frequency of a perioperative coagulopathy in patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum and to identify variables that might predict this phenomenon. METHODS: A retrospective review of 90 patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum was performed at Cedars Sinai Medical Center. Univariate analysis was performed to test the relationship between 15 variables and coagulopathy status. RESULTS: Six patients (6.7%) developed a perioperative coagulopathy that was unrelated to preoperative subcutaneous heparin or dilution. Coagulation disturbances developed intraoperatively before packed erythrocyte replacement equivalent to one blood volume. Four patients (4.4%) required a repeat laparotomy due to continued postoperative bleeding unresponsive to blood component replacement. Vascular pedicles were not the cause of bleeding in any patient. Univariate analysis demonstrated a significant association between perioperative coagulopathy and the following variables: ascites volume (P = 0.009), estimated blood loss (P = 0.002), preoperative serum albumin less than 3.5 g/dl (P < 0.0001), and metastasis greater than 10 cm (P = 0.033). CONCLUSIONS: Patients undergoing primary cytoreduction who have ascites, preoperative serum albumin less than 3.5 g/dl, or metastases greater than 10 cm may be at increased risk for development of a perioperative coagulopathy.     

Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant

BACKGROUND: To estimate the value of CA-125 for the diagnosis of endometriosis in women with dysmenorrhea, as well as its significance in monitoring therapy and follow-up. METHODS: One hundred and fifty-seven women undergoing laparoscopy for dysmenorrhea were prospectively studied for serum CA-125 concentration. For those with advanced endometriosis receiving danazol treatment after conservative surgery, CA-125 was also determined every month during medication and once every 12 months after treatment. RESULTS: The sensitivity and specificity of serum CA-125 for the diagnosis of endometriosis were 61.1% and 87.5% respectively. Elevated CA-125 (>35 U/ml) was noted in 65/75 cases (86.70%) with advanced endometriosis, but in only 15/56 patients (26.8%) with minimal and mild endometriosis. Although there were significantly higher CA-125 levels in unmarried women, and a negative correlation (r=-0.1970, p=0.0284) between CA-125 and parity, there was no statistical difference in incidence of endometriosis by the status of marriage or parity. Ten women with advanced endometriosis were found with persistent endometriosis by laparoscopy during danazol treatment, even though they tested with normal CA-125 levels (<35 U/ml) at that time. Fifteen patients had elevated CA-125 levels before and one year after therapy, and were confirmed with recurrence of endometriosis by laparoscopy. Nine women with elevated CA-125 levels before treatment, were found without recurrence of endometriosis and had normal CA-125 levels one year after therapy. CONCLUSION: For endometriosis, CA-125 is a valuable adjuvant in the follow-up of recurrence in patients with advanced endometriosis and initially elevated CA-125 levels. It is not an effective screening tool for patients with dysmenorrhea, or for monitoring therapy. There was no significant correlation between the development of endometriosis and reproductive factors.     

Analysis of telomeric length in epithelial carcinoma of the ovary

BACKGROUND: As a consequence of the high cell division rate, telomeric repeat reduction in human tumor cells, giving rise to genetic instability, has recently been described. The aim of this study was to analyze by Southern blot telomeric length alterations in a retrospective group of patients with ovarian epithelial carcinoma. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated from paraffin-embedded tissue of 16 patients with ovarian epithelial carcinoma. Telomeric Restriction Fragments (TRF) were studied by Southern blot and densitometric analysis. RESULTS: No telomere alterations were detected in 37.5% of patients (6/16). Of the remaining ten, 5 were found to have telomere reduction and five telomere elongation. No significant correlation was found between clinicopathological variables, response to chemotherapy, survival rate or time to progression, and telomere length alterations. CONCLUSIONS: In ovarian epithelial carcinoma telomere elongation may be a marker of the presence of immortal cells within the tumor, but telomere or the absence of telomeric alterations do not rule out the presence of these cells. Although TRF analysis can be performed in paraffin-embedded tissues, it is not the best indicator of telomerase activity and thus of tumor aggressiveness in early stages of this carcinoma.     

Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome

The concentrations of endometrial proteins PP14 and CA-125 were measured in uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile women and 49 women who suffered recurrent miscarriage. The concentration of PP14 was significantly lower in the flushings from the recurrent miscarriage patients than in those from fertile controls on both day LH+10 (median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40 404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly concentrations of CA-125 were significantly lower in flushings from recurrent miscarriage women compared to controls on both day LH + 10 (median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731 U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there was no significant difference in the concentration of PP14 in plasma samples taken on the same days as the flushings from recurrent miscarriage patients and fertile controls. The concentrations of PP14 in uterine flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage women during a pre-pregnancy investigative cycle were significantly lower (P < 0.05) in patients who went on to miscarry (median: 1000, range: 9-2900 ng/ml) than those who went on to have a live birth (median: 1440, range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was no significant difference in uterine CA-125 or plasma PP14 concentrations between these two groups of recurrent miscarriage patients. The results suggest that measurements of uterine PP14 and CA-125 may be useful in the assessment of endometrial development in recurrent miscarriage patients and suggest the importance of PP14 in preparing the endometrium for embryo implantation. In addition pre-pregnancy uterine PP14 measurements may be useful in predicting subsequent pregnancy outcome.     

Lack of improved survival plus increase in thromboembolic complications in patients with clear cell carcinoma of the ovary treated with platinum versus nonplatinum-based chemotherapy

BACKGROUND: This study was conducted to evaluate survival rates for patients with clear cell ovarian carcinoma who had platinum-based chemotherapy versus nonplatinum-based chemotherapy and the risk of thromboembolic complications. METHODS: One hundred and eleven evaluable patients with clear cell ovarian carcinoma who underwent primary surgery and postoperative therapy were retrospectively evaluated. Median follow-up was 21.3 months (range, 3-280 months). Patients treated with platinum-based chemotherapy and nonplatinum-based chemotherapy were evaluated according to stage, age, grade, extent of surgery, and development of thromboembolic complications. Patient populations were compared using the chi-square test. Estimated 5- and 10-year survivals for each group were calculated using the method of Kaplan and Meier. Differences in survival rates were calculated using the log rank test. The frequency of thromboembolic complications in the clear cell ovarian carcinoma group was compared with its frequency in a matched-control group of 109 patients with epithelial nonclear cell ovarian carcinoma. RESULTS: Seventy-one patients were treated with nonplatinum-based chemotherapy and 40 patients were treated with platinum-based chemotherapy. There was no statistically significant difference in the characteristics of patient populations treated with platinum-based chemotherapy or nonplatinum-based chemotherapy. The estimated 5-year survival for clear cell ovarian carcinoma patients treated with platinum-based chemotherapy did not differ significantly from the estimated 5-year survival for patients with clear cell ovarian carcinoma treated with nonplatinum-based chemotherapy (36% vs. 32%; P = 0.23). Twelve patients with clear cell ovarian carcinoma developed thromboembolic complications remote from primary surgery, whereas in a matched-control group of patients with nonclear cell ovarian carcinoma treated with platinum-based chemotherapy, no patients developed a thromboembolic complications (P = 0.0004). Eight of 40 patients (20%) with clear cell ovarian carcinoma treated with platinum-based chemotherapy developed thromboembolic complications, whereas 4 of 71 patients (6%) treated with nonplatinum-based chemotherapy developed thromboembolic complications (P = 0.03). Multivariate logistic regression analysis demonstrated that the development of a thromboembolic complication was significantly related to clear cell ovarian carcinoma and platinum-based chemotherapy and had a significant (P = 0.009) negative impact on survival. CONCLUSIONS: Platinum-based chemotherapy did not appear to improve survival compared with nonplatinum-based chemotherapy of patients with clear cell ovarian carcinoma. The combination of platinum-based chemotherapy and clear cell ovarian carcinoma significantly increases the risk for thromboembolic complications and has a significant negative impact on survival.     

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma

BACKGROUND: The authors report observed 10-year brachytherapy results in the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. METHODS: One hundred and fifty-two consecutive patients with T1-T3, low to high Gleason grade, prostate carcinoma were treated between January 1987 and June 1988 at Northwest Hospital in Seattle, Washington. Their median age was 70 years (range, 53-92 years). Of these 152 patients, 98 (64%) received an iodine-125 implant alone (Group 1), and the remaining 54 patients (36%), who were judged to have a higher risk of extraprostatic extension, also were treated with 45 gray (Gy) of external beam irradiation to the pelvis (Group 2). No patient underwent lymph node sampling, and none received androgen ablation therapy. Multivariate regression and the Mann-Whitney rank sum test were used for statistical analysis. Preoperative patient data with associated success or failure outcomes at 10 years after treatment were used for training and validating a back-propagation neural network prediction program. RESULTS: The average preoperative prostate specific antigen (PSA) value, clinical stage, and Gleason grade were 11.0 ng/mL, T2, and 5, respectively. The median posttreatment follow-up was 119 months (range, 3-134 months). Overall survival 10 years after treatment was 65%. At last follow-up only 3 of the 152 patients (2%) had died of prostate carcinoma. Ninety-seven patients (64%) remained clinically and biochemically free of disease at 10 years of follow-up and had an average PSA value of 0.18 ng/mL (range, 0.01-0.5 ng/mL). In these patients a period of 42 months was required to reach the average PSA (0.5 ng/mL). The median to last PSA follow-up was 95 months (range, 3-134 months). Postoperative needle biopsies were negative in 56% of patients, positive in 15% of patients, and not available in 29% of patients. Only 6% of patients developed bone metastasis. At 10 years there was no statistically significant difference in treatment outcome between patients who received iodine-125 alone, and those who received iodine-125 with 45-Gy external beam irradiation (P = 0.08). Nevertheless, in these two groups preoperative PSA, stage, and Gleason grade were significantly different (P < 0.01). In the artificial neural network analysis, pretreatment serum PSA was the most accurate predictor of disease-free survival. CONCLUSIONS: Percutaneous prostate brachytherapy is a valid and efficient option for treating patients with clinically organ-confined, low to high Gleason grade, prostate carcinoma. Observed 10-year follow-up documents serum PSA levels superior to those reported in several published external beam irradiation series, and comparable to those published in a number of published radical prostatectomy series.     

Physical and genetic localization of the gene encoding the AP-2 transcription factor to mouse chromosome 13

This retrospective study assessed 46 patients with advanced ovarian cancer who had elevated preoperative serum CA 125 (>35 U/ml) and who had another serum CA 125 assay 6-9 days after surgery. Preoperative CA 125 levels were similar in patients with residual disease below 20 mm and in those with larger residuum. The postoperative decline of serum CA 125 was significantly higher in patients with small residual disease at any preoperative serum CA 125 value. By taking 60% as the cutoff of CA 125 decline, the diagnostic accuracy of this parameter in discriminating between patients with residual disease below or above 20 mm improved progressively when we considered patients with increasing preoperative antigen values. However, even in the subset of patients with preoperative serum CA 125 above 400 U/ml, 2 of the 20 patients with less than 20 mm residual disease had a percentage reduction of antigen levels lower than 60%, whereas 5 of the 10 patients with larger than 20 mm residuum had a CA 125 decline higher than 60%. Therefore, we believe that the perioperative changes of CA 125 levels have a limited clinical relevance in the management of patients with ovarian cancer.     

Antibodies to cardiolipin and tumor-associated antigens CA-125 and CA-19-9 in patients with ovarian tumors]

Antibodies to cardiolipin (ACL) were detected in 12 (35%) of 34 patients with tumors of the ovaries. 8 of 12 patients exhibited clinical signs of antiphospholipid syndrome, 9 (75%), 2 and 1 patients demonstrated isolated hyperproduction of IgG ACL, combined rise of IgG ACL and IgM ACL, IgM ACL, respectively. Most frequently ACL occurred in endometriosis of the ovaries and serous cystadenomas (50 and 60%, respectively). In 5 (42%) of 12 patients CA-125 antigen concentration was above the upper norm (35 U/ml), in 3 (25%) cases the level of CA 19-9 antigen was elevated. There were parallel changes of ACL concentration and tumor marker CA-125 before and after operation. Autoimmune origin of ovarian endometriosis is suggested.     

An expression system for mammalian amino acid transporters using a stably maintained episomal vector

Aggressive tumor reduction surgery has been widely used in patients with advanced stage epithelial ovarian carcinoma before initiation of cytotoxic chemotherapy. No randomized controlled trial has been carried out to confirm the benefits of such procedures. To examine the role of cytoreductive surgery in the management of stage 2 and 3 patients with epithelial ovarian carcinoma treated with postoperative adjuvant platinum-based chemotherapy, survival analysis was carried out on patients with initial microscopic disease documented on staging laparotomies, patients with large volume of disease at time of exploration and tumor reduced to microscopic residuals, and patients who were suboptimally debulked with more than 2-cm residual disease. Twenty-four, 81, and 191 patients were identified from a computerized data base, respectively. Kaplan-Meier survival estimates showed that 62% with initial microscopic residual are alive with no evidence of disease at 5 years and 56% of patients left with microscopic residuals after tumor reduction are alive and well at 5 years. There was no statistical significant difference between these two groups. The groups are equivalent with respect to known adverse prognostic factors. In contrast, 5-year survival in the suboptimal debulked group was significantly lower at 15%. Debulking surgery to achieve microscopic residual disease improved the prognosis in patients with initial large volume of disease. Survival was similar to survival in patients with microscopic disease at time of exploration. The beneficial effect may be attributed to the removal of chemoresistant clones in bulky tumors. Tumor reduction surgery remains important in the management of advanced stage epithelial ovarian carcinoma.