Cancer Antigen 125 Levels are Significantly Associated With Prognostic Parameters in Uterine Papillary Serous Carcinoma.

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a highly aggressive subtype of endometrial carcinoma. Histopathologically, it resembles the pattern of serous papillary carcinoma of the ovary. Cancer antigen 125 (CA-125) is the most widely used biomarker in epithelial ovarian carcinoma. Its use in UPSC evaluation has yet to be determined. The purpose of this study was to investigate the significance of preoperative serum CA-125 as a prognostic factor in patients with UPSC. METHODS: The study cohort included all women with UPSC operated in our institution between January 2002 and June 2016. All patients underwent complete surgical staging. Preoperative CA-125 was reviewed and correlated with clinical and pathological parameters. RESULTS: Sixty-one women met the study criteria. Median preoperative CA-125 was found to be significantly associated with disease stage. Patients with disease stages I to IV had median preoperative CA-125 levels of 12.15, 19.6, 22.6, and 177.5 U/mL (P < 0.0001) respectively. Levels of CA-125 were significantly associated with positive cytology (P < 0.0001), omental disease (P < 0.0001), pelvic or para-aortic lymph node metastasis (P < 0.0001), and adnexal involvement (P < 0.0001). The optimal cutoff that provided the best sensitivity and specificity for omental and parametrial involvement as well as positive cytology was 57.5 U/mL. For adnexal and lymph node involvement, the optimal cutoff value was 41.8 U/mL. CONCLUSIONS: In patients with UPSC, preoperative CA-125 level correlates with known prognostic parameters of endometrial carcinoma and is associated with extrauterine involvement. These data should stimulate the need for further evaluation of the role of CA-125 in predicting recurrence and survival in UPSC.

The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC).

OBJECTIVES: Preoperative hematologic parameters: thrombocytosis, leukocytosis and anemia have been demonstrated to be independent poor prognostic factors in ovarian and endometrial cancers. However, little is known about their relation to uterine serous papillary carcinoma (USPC). We evaluated several preoperative hematologic parameters and their association with clinicopathologic features, disease progression and overall survival in USPC patients. STUDY DESIGN: This was a retrospective cohort study reviewing charts of all patients with a histologic pure USPC at two gynecologic oncology centers from January 2000 through July 2012. All patients had comprehensive hematologic tests prior to primary surgical treatment and were exposed to the same adjuvant treatment protocol. RESULTS: The study included 56 patients, mean age at diagnosis 69.4±15. Six (11%) had platelet count above 400000 10(6)/L, of them four (66%) were dead at the end of follow up (HR=1.4, p=0.48; CI 95% 0.5-4.3). The mean hemoglobin level was 12.3g/dl, fibrinogen 437.5mg/dL and lymphocytes 2013/µL. None of these parameters was significantly associated with 5 year survival. Leukocyte and neutrophil levels were adversely associated with survival. Of 15 patients with leukocytosis >10000/µL, 67% were dead at the end of follow up (HR=3.98, p=0.003; CI 95% 1.6-9.8). Of the 27 with neutrophils above 65%, 14 (52%) were dead at the end of follow up (HR=3.1; p=0.015; CI 95% 1.2-7.8). CONCLUSIONS: In patients with USPC, leukocytosis and neutrophilia are associated with aggressive tumor biology, and may predict a lower 5 year survival.

The clinical relevance of rising CA-125 levels within the normal range in patients with uterine papillary serous cancer.

The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from 1999 to 2008 were included in this analysis. Information was extracted from records to assess the changes in CA-125 values with clinical and/or radiographic detection of recurrence. Of the 56 evaluable patients, 23 (41%) recurred. Of the 23 patients that recurred, 11 had serial CA-125 levels measured in remission. Elevated CA-125 levels at diagnosis were significantly associated with disease recurrence and advanced stage (P = .01, P = .001, respectively). The rise in CA-125 by 10 U/mL in the normal range and ≥ 15 U/mL were associated with disease recurrence (P < .001, P < .001, respectively). In multivariate analysis, only CA-125 level ≥ 15 U/mL was significantly associated with worse progression-free survival. In this small cohort of patients with recurrent UPSC after remission, surveillance of CA-125 levels may have a role in disease surveillance and management.

The prognostic significance of thrombocytosis in uterine papillary serous carcinomas.

OBJECTIVES: We have shown that preoperative thrombocytosis (platelet counts >400 x 10(9)/l) is an independent poor prognostic factor in epithelial ovarian cancers (EOC) and is associated with worse survival. In light of the similarities between uterine papillary serous carcinomas (UPSC) and EOC, we sought to determine the incidence of thrombocytosis in UPSC and examine associations with clinico-pathologic features and survival. METHODS: 68 patients with UPSC were identified between 1996 and 2004 at 3 institutions. After IRB approval, records were retrospectively reviewed and data analyzed using Chi-squared and Cox proportional hazards model; survival was analyzed by the method of Kaplan and Meier. RESULTS: 8/68 (12%) patients had thrombocytosis at primary diagnosis. Patients with thrombocytosis were found to have more advanced stage disease (p=0.002) and ascites >1 L (p<0.0001). Of the 21 patients with stage IV disease, those with normal preoperative platelet counts demonstrated a greater likelihood of optimal tumor resection to less than 1 cm residual disease (13/15 versus 1/6 in patients with thrombocytosis, p<0.002). Patients with thrombocytosis had a shorter disease-free interval (17 months versus median survival not yet reached, p=0.0067) and overall survival (24 versus 45 months, p=0.0026). On multivariate analysis, thrombocytosis retained significance as a poor prognostic indicator in patients after controlling for age and stage (p=0.04). CONCLUSIONS: Thrombocytosis may be a marker of aggressive tumor biology in UPSC. Platelet-secreted growth factors may promote aggressive cancer phenotype through contribution to metastasis, invasion, and primary tumor growth.

The utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer.

The objective of this study was to evaluate the ability of a preoperative serum CA125 to predict whether optimal debulking (OD) could be achieved for patients with stage III and IV epithelial ovarian cancer (EOC). The records of consecutive patients who underwent primary surgery for EOC at Indiana University Hospital between January 1997 and January 2003 were reviewed. Eligibility criteria included FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative CA125, and an operative note clearly defining volume of residual disease. The Medcalc software statistical package was used to generate a receiver-operating characteristic (ROC) curve. Two hundred and eighty-nine cases of stage III/IV EOC were identified, of which 164 met the eligibility criteria. Serum CA125 /=75% of the time. Conversely, OD was achieved in /=4500. The area under the ROC curve for CA125 was .670. The OD rate for those with and without ascites was 49% and 79%, respectively (P < 0.001). In a multivariate analysis using CA125, age, and ascites, the area under the curve was 0.686. We conclude that preoperative serum CA125 did not reliably predict OD in patients with stage III-IV EOC.

Overexpression of kallikrein 10 (hK10) in uterine serous papillary carcinomas.

OBJECTIVE: Kallikrein 10 is a secreted serine protease recently implicated in the growth and invasion of several human tumors. The goal of this study was to investigate the expression and secretion levels in vitro and in vivo of kallikrein 10 in uterine serous papillary carcinoma, a highly aggressive variant of endometrial tumor. STUDY DESIGN: Human kallikrein 10 gene expression levels were evaluated in 11 snap-frozen uterine serous papillary carcinoma biopsies and 6 normal endometrial cell biopsies by real-time polymerase chain reaction. Secretion of kallikrein 10 protein by 10 primary tumor cultures including 3 uterine serous papillary carcinomas, 2 endometrioid carcinomas, and 5 ovarian serous papillary tumors was measured using a sensitive ELISA. Finally, kallikrein 10 concentration in 75 serum and plasma samples from 22 healthy women, 20 women with benign diseases, 21 women with endometrioid carcinomas, and 12 uterine serous papillary carcinoma patients was studied. RESULTS: Kallikrein 10 gene expression levels were significantly higher in uterine serous papillary carcinoma when compared with normal endometrial cell biopsies (mean copy number by real time polymerase chain reaction = 743 versus 1.4; uterine serous papillary carcinoma versus endometrioid carcinoma: P < .02). In vitro kallikrein 10 secretion was detected in all primary uterine serous papillary carcinoma cell lines tested (mean = 2.7 microg/L), and the secretion levels were not significantly different to those found in primary ovarian serous papillary tumor cultures (mean 4.2 microg/L). In contrast, no kallikrein 10 secretion was detectable in primary endometrioid carcinomas. Kallikrein 10 serum and plasma concentrations (microg/L; mean +/- SEM) among normal healthy females (0.6 +/- 0.04), patients with benign diseases (0.6 +/- 0.06), and patients with endometrioid carcinomas (0.7 +/- 0.06) were not significantly different. In contrast, serum and plasma kallikrein 10 values in uterine serous papillary carcinoma patients (1.2 +/- 0.1) were significantly higher than those in the non-cancer group (P = .002), benign group (P = .002), and endometrioid carcinoma patients (P = .005). CONCLUSION: Kallikrein 10 is highly expressed in uterine serous papillary carcinoma, and it is released in the plasma and serum of uterine serous papillary carcinoma patients. Kallikrein 10 may represent a novel biomarker for uterine serous papillary carcinoma.

[Comparison of primary extraovarian peritoneal serous papillary carcinoma with stage III-IV ovarian papillary serous carcinoma].

OBJECTIVE: Extraovarian peritoneal serous papillary carcinoma (EPSPC) is both histologically and clinically similar to stage III-IV ovarian papillary serous carcinoma (OPSC). The purpose of this study is to investigate the clinical findings, treatment, and outcome of EPSPC patients compared with stage III-IV OPSC patients. METHODS: The data of 12 EPSPC patients and 45 stage III-IV OPSC patients were retrospectively reviewed, comparing the characteristics on clinical presentation and treatment, sensitivity to first-line chemotherapy agents and survival. RESULTS: By analysis of patients' characteristics, presenting signs and symptoms, type and extent of surgery, tumor response to first-line chemotherapy, recurrence-free interval, recurrence site and serum CA-125 levels, no significant difference was observed between the EPSPC patients and stage III-IV OPSC controls. The prevailing presenting symptoms were abdominal mass and ascites. The mainstay of treatment was debulking surgery followed by adjuvant platinum-based chemotherapy. The complete clinical response of stage III-IV OPSC was 91.8% compared with 25.0% for women with EPSPC (P < 0.01). CONCLUSION: The clinical and surgical characteristics of EPSPC are similar to those of stage III-IV OPSC. When the same treatment strategy is applied, similar response and survival are expected in either condition.

High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer.

PURPOSE: To evaluate and compare autocrine expression and production of interleukin-6 (IL-6), a pleiotropic cytokine involved in the resistance to cytotoxic agents and inhibition of anti-tumor immune function in endometrial carcinoma in vitro as well as in vivo. PATIENTS AND METHODS: IL-6 gene expression levels were evaluated in twenty-four primary endometrial tumors including 14 endometrioid carcinomas (EC) and 10 uterine serous papillary carcinoma (USPC) as well as in normal control endometrial cells (NEC) by real-time PCR. Secretion of IL-6 protein by 6 primary endometrial tumor cultures including USPC and EC was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in vitro. Finally, IL-6 concentration in 71 serum samples including 20 apparently healthy women, 19 women with benign abdominal diseases, 19 women with primary EC, and 13 USPC patients was studied. RESULTS: IL-6 gene expression levels were significantly higher in USPC when compared to EC (mean copy number by RT-PCR = 313 +/- 55 vs. 53 +/- 11, USPC vs. EC, respectively: P < 0.01). IL-6 serum concentrations between normal healthy females (range 0.01-21.23 pg/ml; mean 3.1 pg/ml) and benign disease patients (range 0.01-95.77 pg/ml; mean 13.07 pg/ml) were not statistically different. In contrast, significantly higher levels of IL-6 were detected in both patients with EC (range 2.86-82.13 pg/ml; mean 20.43 pg/ml) and patients with UPSC (range 16.3-500.1 pg/ml; mean 125.7 pg/ml) when compared to the healthy females (P < 0.01), with a mean serum IL-6 level in USPC patients 6.1-fold higher when compared to EC patients (P < 0.03). Accordingly, higher levels of IL-6 secretion were noted in primary USPC cell lines (mean 3121 pg/ml, range between 1099 and 5017 pg/ml/10(5) cells/48 h) when compared to primary EC (mean 88, range between 19 and 112 pg/ml/10(5) cells/48 h) (P < 0.01) in vitro. CONCLUSIONS: IL-6 is highly expressed in USPC, and it is released in high concentration in the serum of USPC patients. IL-6 may be a novel biomarker for USPC. Drugs used to inhibit the expression of IL-6 or the IL-6 signal transduction pathway may potentially be highly beneficial in USPC.

Human kallikrein 6: a new potential serum biomarker for uterine serous papillary cancer.

PURPOSE: The discovery of novel biomarkers might greatly contribute to improve clinical management and outcomes in uterine serous papillary carcinoma (USPC), a highly aggressive variant of endometrial cancer. EXPERIMENTAL DESIGN: Human kallikrein 6 (hK6) gene expression levels were evaluated in 29 snap-frozen endometrial biopsies, including 13 USPC, 13 endometrioid carcinomas, and 3 normal endometrial cells by real-time PCR. Secretion of hK6 protein by 14 tumor cultures, including 3 USPC, 3 endometrioid carcinoma, 5 ovarian serous papillary carcinoma, and 3 cervical cancers, was measured using a sensitive ELISA. Finally, hK6 concentration in 79 serum and plasma samples from 22 healthy women, 20 women with benign diseases, 20 women with endometrioid carcinoma, and 17 USPC patients was studied. RESULTS: hK6 gene expression levels were significantly higher in USPC when compared with endometrioid carcinoma (mean copy number by real-time PCR, 1,927 versus 239, USPC versus endometrioid carcinoma; P < 0.01). In vitro hK6 secretion was detected in all primary USPC cell lines tested (mean, 11.5 microg/L) and the secretion levels were similar to those found in primary ovarian serous papillary carcinoma cultures (mean, 9.6 microg/L). In contrast, no hK6 secretion was detectable in primary endometrioid carcinoma and cervical cancer cultures. hK6 serum and plasma concentrations (mean +/- SE) among normal healthy females (2.7 +/- 0.2 microg/L), patients with benign diseases (2.4 +/- 0.2 microg/L), and patients with endometrioid carcinoma (2.6 +/- 0.2 microg/L) were not significantly different. In contrast, serum and plasma hK6 values in USPC patients (6.1 +/- 1.1) were significantly higher than those in the noncancer group (P = 0.006), benign group (P = 0.003), and endometrioid carcinoma patients (P = 0.005). CONCLUSIONS: hK6 is highly expressed in USPC and is released in the plasma and serum of USPC patients. hK6 may represent a novel biomarker for USPC for monitoring early disease recurrence and response to therapy.

Phase II study of sequential doublets: topotecan and carboplatin, followed by paclitaxel and carboplatin, in patients with newly diagnosed advanced ovarian cancer.

OBJECTIVE: Incorporating topotecan into standard platinum/taxane chemotherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclitaxel and carboplatin, in newly diagnosed advanced ovarian cancer patients. METHODS: Forty-five patients (median age, 56 years; range, 38-77 years) with stage III/IV disease and GOG performance status <2 were enrolled and received four cycles of topotecan (1.0 mg/m(2)/day on days 1 to 3) and carboplatin (AUC 4 on day 1), followed by four cycles of paclitaxel (175 mg/m(2) via 3-h IV infusion on day 1) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete response (CR) underwent second-look laparotomy for determination of pathologic CR (PCR). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia, and for grade 3/4 nonhematologic toxicity. RESULTS: Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, respectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progression was 14 months and actuarial survival was 23 months. Neutropenia was the primary toxicity and cause of dose adjustments and delays, including two deaths. CONCLUSION: The antitumor activity observed is comparable with other series, although neutropenic complications were increased. Progression-free and actuarial survivals were slightly inferior. A Phase III trial (GOG 182) of sequential doublets in the reverse sequence is ongoing.

Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the significance of preoperative platelet counts in advanced epithelial ovarian cancer with respect to second-look laparotomy results and disease progression. METHODS: We prospectively evaluated 37 consecutive patients with advanced epithelial ovarian cancer who underwent primary surgical treatment. In addition to platelet counts, all patients were evaluated with respect to age, gravida, parity, and stage and grade of tumor. Thirty-six patients had stage III, and 1 patient had stage IV disease. Optimal debulking (diameter of residual tumor, less than 1 cm) was performed in all patients who subsequently received adjuvant chemotherapy (platin-paclitaxel). According to second-look laparotomy and follow-up results patients were divided into 2 groups. The first group had negative second-look laparotomy or no evidence of disease during follow-up (n = 20), and the second group had positive second-look laparotomy or progressive disease (n = 17). Sensitivity and specificity values were calculated for different cutoff values of platelet counts with receiver operating characteristic curve analysis. RESULTS: Age, gravida, and parity were not significantly different compared with controls (P >.05). Mean platelet counts were 371 x 109/L and 446 x 109/L in the first and second groups, respectively (P =.03). Different cutoff values of platelet counts for the diagnosis of thrombocytosis were evaluated. A cutoff value of 380 x 109/L had sensitivity 77% and specificity 60% for recurrence, whereas a cutoff value of 400 x 109/L had sensitivity 59% and specificity 65%. Area under the curve (+/- standard error) was 0.72 +/- 0.08 (P =.026). CONCLUSION: In patients with progressive disease and positive second-look laparotomy, preoperative platelet counts were significantly higher compared with patients with no evidence of disease on follow-up.

Can optimal primary cytoreduction be predicted in advanced stage epithelial ovarian cancer? Role of preoperative serum CA-125 level.

The aim of this study was to determine the ability of preoperative serum CA-125 levels to predict optimal cytoreduction in patients with stage III epithelial ovarian cancer. A retrospective review was made of the records of 40 patients with FIGO stage III ovarian carcinoma who underwent primary cytoreductive surgery. A receiver operating characteristic (ROC) curve was used to determine the most useful CA-125 level in predicting optimal versus suboptimal tumour cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual disease 500 U/ml. At this threshold, preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and negative predictive value of 76%. In the management of patients with advanced epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict optimal primary cytoreduction and to identify candidates for alternative approaches other than traditional primary cytoreductive surgery, such as neoadjuvant chemotherapy.

Comparison of serum vascular endothelial growth levels between patients with and without ovarian malignancies.

The objective of this study was to determine if there was a relationship between serum vascular endothelial growth factor (VEGF) levels and ovarian malignancies by contrasting a population with ovarian malignancies and a population free of gynecological neoplasms. Two hundred forty four serum samples were obtained from the US National Cancer Institute's Prostate, Lung, Colon, and Ovarian Cancer Screening Project. These samples were analyzed by enzyme-linked immunosorbent assays in duplicate, and on completion of the assays, the samples were decoded for age and disease type. Average VEGF values for the nongynecological control group was 4.399 ng/ml; for benign gynecologic cases, 2.515 ng/ml; and for patients with malignancies, 4.287 ng/ml. Specifically, there was no difference between the mean value of VEGF in patients with ovarian malignancies and the patients with benign gynecological tumors (P = 0.8823). Also, there was no difference between the mean value of VEGF in patients with ovarian malignancies and the control patients who did not have gynecological disease (P = 0.3110). Using the Mann-Whitney U-test, no significant differences were found between the three populations of this study. Based on our data, due to the lack of significant difference in mean serum VEGF values between patients with and without ovarian malignancies, we feel that serum VEGF cannot be used as a possible screening tool for ovarian cancer.

Whole-body PET with (fluorine-18)-2-deoxyglucose for detecting recurrent primary serous peritoneal carcinoma: An initial report.

OBJECTIVE: Because of the limited sensitivity and specificity of conventional tools such as computerized tomography (CT) or magnetic resonance imaging (MRI) for detecting persistent or recurrent primary serous peritoneal carcinoma (PSPC), a reliable means of diagnosis remains elusive. Positron emission tomography (PET) scanning may offer another approach to this problem. METHODS: A prospective study of three patients requiring surgical exploration for suspected recurrence of PSPC received a whole-body PET (fluorine-18)-2-deoxyglucose (FDG) scanning in a teaching hospital from July 1995 to December 1998. The suspected recurrence was based upon clinical findings including a detailed physical examination, serum CA-125 marker ultrasound, CT, and MRI. Three patients were enrolled in this study. RESULTS: In all three patients, PET images demonstrated increased FDG uptake in a distribution that correlated with surgical-pathologic findings (100%); on the contrary, CT can detect 33.3% of these patients with malignant diseases and MRI can detect two-thirds of cases. Serum CA-125 was also elevated in all three patients, although one patient showed an equivocal elevation of 25.7 IU/ml. CONCLUSIONS: Conventional imaging studies are neither sensitive nor specific for detecting recurrent PSPC. In contrast, besides CA-125, PET might offer a relatively effective tool for detecting recurrent primary serous peritoneal carcinoma. Due to the very small number of patients available in this study, considerable research must be performed to clarify the impact of PET on detecting recurrence of PSPC.

Serum CA-125 as a marker of disease activity in uterine papillary serous carcinoma.

Papillary serous carcinoma of the endometrium exhibits many clinical features of ovarian cancer, including a high metastatic potential and response to platinum-based chemotherapy. We investigated the clinical utility of the serum CA-125 antigen level, an established marker of response or progression in ovarian cancer, to serve as a indicator of these events in patients with this highly malignant subtype of endometrial cancer. Of 21 individuals with this cancer treated in our program from 11/91 to 6/97, 16 had baseline CA-125 determinations prior to the administration of chemotherapy, of whom 13 were elevated above the normal range. Of these 13 patients, 8 (57%) experienced either a major reduction or normalization of CA-125 levels following therapy, consistent with their clinical course at that point in time. Similarly, of 11 patients who ultimately relapsed, 8 (73%) were found to have a rise in the CA-125 antigen level which closely corresponded to, or proceeded, clinical relapse. A single patient was demonstrated to have disease progression with a declining level of CA-125. We conclude the serum CA-125 antigen level is a useful indicator of disease response or progression in individuals with papillary serous carcinoma of the endometrium.

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.

[Detection of tumor cells in peripheral blood for patients with ovarian epithelial carcinoma].

OBJECTIVE: To detect tumor cell contamination of peripheral blood stem cell (PBSC) and the presence of tumor cells in peripheral circulating blood in patients with primary advanced ovarian cancer. METHODS: To establish limits of sensitivity of the immunocytochemical stainings technique (ABC method) for tumor cell detection, four types of ovarian cancer tumor cell(ovarian cancer cell lines SKOV3, 3AO, primary cancer cell from ascites of serous papillary carcinoma and undifferentiated adenocarcinoma) were added into normal blood to prepare the models with different ratios of tumor cells to mononuclear cells. Monoclonal antibodies(MAB) of COC 183 B2, CK(AE1/AE3) and their cocktail antibody (mixture of them) were used for immunocytochemical stainings. 14 blood specimens were examined (6 stem cell blood specimens, 8 primary advanced ovarian cancer blood spcimens). RESULTS: The sensitivity of detection achieved by cocktail antibodies was superior to either COC183B2 or CK MAb alone. The sensitivity of cocktail antibody was 1:5 x 10(5). According to the established sensitivity, none of the fourteen specimens contained tumor cell. CONCLUSIONS: None of the 6 PBSC specimens obtained from 2 patients and eight peripheral blood specimens obtained from 8 patients with primary ovarian epithelial carcinoma contained tumor cell.

Advanced ovarian carcinoma presenting with a cerebrovascular accident.

Ovarian carcinoma usually presents in an indolent manner, most often nonspecifically with complaints of abdominal pain or swelling, bloating, constipation, anorexia, early satiety, and evidence of ascites. We present a case of ovarian cancer with a cerebrovascular accident (CVA) as the presenting symptom, with minimal classic presenting signs and symptoms. The patient is a 43-year-old female with no cardiovascular risk factors who presented with a left parietal lobe infarct and advanced ovarian carcinoma. The patient underwent an extensive workup for the etiology of her CVA and possible hypercoagulation syndrome and eventually had surgical treatment. Ovarian carcinoma with a thromboembolic event as the initial presenting symptom is extremely rare. Although this patient did not appear to have hypercoagulability, consideration of this diagnosis should be given to patients presenting in this manner.

Borderline ovarian tumours: retrospective analysis of twenty-one cases.

Twenty-one borderline ovarian tumour cases, diagnosed and treated in our oncology section between 1986 and 1996, were retrospectively analysed. Thirty-three percent of the cases had serous tumours and the rest (66.6%) were mucinous, 57.1% of the mucinous tumours were the intestinal type and the remaining 42.9% were the endocervical type. When all the cases were analysed, the average age was 45.4+/-18.6 years, the average follow-up period was 5.5+/-2.6 years. The preoperative average CA125 level was 55.1+/-51.9 U/mL, and for CA19.9 it was 48.2+/-47.8 U/mL. Of the patients 85.7% were stage I and 14.3% state III. There were not any significant differences between the serous, intestinal-type mucinous and endometroid-type mucinous tumours regarding tumour volumes (p>0.05). When serous and mucinous tumours were compared according to the tumour markers, CA125 levels were significantly higher in the serous tumours (p=0.04) and CA19.9 levels were significantly higher in the mucinous tumours (p=0.02). All of the patients are under our follow-up and are in remission, except one, who died in the third year of the treatment because of chronic renal failure unrelated to the ovarian pathology.

PIP: Tumors of low malignant potential represent approximately 15% of epithelial ovarian tumors and tend to occur at a younger age than malignant neoplasia. This paper presents a retrospective analysis of the 21 borderline ovarian tumors diagnosed and treated at Dokuz Eylul University in Izmir, Turkey, in 1986-96. The average age at presentation was 45.4 +or- 18.6 years. The diagnosis was made by exploratory laparotomy and frozen section. 7 tumors (33.3%) were serous and 14 (66.6%) were mucinous. 8 borderline mucinous tumors (57.1%) were intestinal type and 6 (42.9%) were endocervical. The average preoperative cancer marker level was 55.1 +or- 51.9 U/ml for CA125 and 48.2 +or- 47.8 U/ml for CA19.9. CA125 levels were significantly higher in serous tumors (p = 0.04) while CA19.9 measurements were significantly higher in mucinous tumors (p = 0.02). 18 tumors (85.7%) were stage I and 3 (14.3%) were stage III. There were no significant differences in tumor volume between serous, intestinal-type mucinous, and endometroid-type mucinous tumors. Women with stage I tumors who wanted to preserve their fertility underwent unilateral salpingo-oophorectomy; total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed in the remaining cases. Women with stage III tumors received 6 rounds of first-line adjuvant chemotherapy followed by second-look laparotomy. 1 patient died in the third year of treatment as a result of chronic renal failure unrelated to the ovarian pathology; the remaining women, who have been followed an average of 5.5 +or- 2.6 years, are in remission.

Docetaxel and cyclophosphamide induced remission in platinum and paclitaxel refractory ovarian cancer.

Platinum-based chemotherapy is the standard treatment for advanced ovarian cancer, with response rates of 40-60%. In patients who fail platinum treatment, paclitaxel has resulted in response rates of 10-48%. Docetaxel has partial non-cross-resistance with and is twice as potent in vitro as paclitaxel in inhibiting microtubule disaggregation. The combination of docetaxel and cyclophosphamide is synergistic in pre-clinical studies and clinically active in breast cancer. We present the case of a patient with platinum and paclitaxel refractory ovarian cancer who achieved a remission with docetaxel and cyclophosphamide.