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ROLE OF GONADOTROPINS IN THE EXPRESSION OF NERVE GROWTH FACTOR AND ITS HIGH-AFFINITY RECEPTOR TRKA IN EPITHELIAL OVARIAN CANCER
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
380
382
TREATMENT OUTCOME OF PATIENTS WITH STAGE I CLEAR CELL CARCINOMA OF THE OVARY
EPITHELIAL OVARIAN CANCER: ANY DIFFERENCE ACCORDING TO MENOPAUSAL STATUS?
T. Goto, R. Ohishi, N. Iwasa, K. Hasegawa, M. Shimizu, S. Nagao, K. Fujiwara. Saitama Medical University International Medical Centre Comprehensive Cancer Centre, Department of Gynaecologic Oncology, Hidaka, Japan
H. Lopes, S. Custódio, M. Figueiredo Dias, C. Freire de Oliveira. Coimbra University Hospital, Gynecology department, Coimbra, Portugal
Objectives: Clear cell carcinomas of the ovary (CCCO) are frequently diagnosed at stage I. Adjuvant chemotherapy for such patients without postoperative residual disease is not always easy to accept for patients as well as physicians since it is relatively chemoresistant disease. We investigated treatment outcome of stage I CCCO patients in our institute. Methods: Twenty-six stage I CCCO patients treated in our institute from 2003 to 2007 were retrospectively analyzed. Results: Five patients (19%) were stage Ia and 21 were stage Ic, of whom, 2 (8%) had positive washing cytology, 1 (4%) had spontaneous capsular rupture, and 18 (69%) had capsular rupture due to operative procedure. Postoparative platinum-based chemotherapy following radical surgery was performed in 19 patients, of whom, only 2 patients who had positive washing cytology recurred after 11 months and 4 years and both didn’t respond to chemotherapy after recurrence. Of the other 7 patients who did not receive postoparative chemotherapy, 5 patients who had radical surgery were alive without recurrence. Two patients who underwent fertility-sparing surgery and no adjuvant chemotherapy developed recurrence after 21 and 28 months, respectively. Recurrence was observed not only in contralateral ovaries, but also para-aortic nodes or pelvic peritoneum. Both patients received debulking surgery followed by adjuvant chemotherapy and were alive with no evidence of disease. Conclusions: Patients with positive washing cytology were considered to be high risk for recurrence in spite of radical surgery and adjuvant chemotherapy. Fertility-sparing operation might not be applicable for CCCO, even by a strong request from the patient.
S97
Introduction: Ovarian cancer is the second most common cancer of the female reproductive system and the leading cause of death from gynaecologic malignancies. Although posmenopausal ovary is not exposed to mitotic stimuli at follicle rupture, ovarian cancer is more common among postmenopausal women. Some authors believe that different histological types develop from different ethiopathogenic ways. Objectives: To evaluate ovarian cancer in pre and pos menopausal women in order differences of risk factors and histological types. Material/methods:Retrospective assessment of clinical data of epithelial ovarian cancer patients diagnosed and treated in our department since Jan2000 to Dec2007. Results: Out of 161 ovarian cancer, 29 (18,1%) were pre menopausal at time of diagnosis with a mean age of 42,1, whereas 132 (81,9%) were post menopausal with a mean age of 67,9. Only 5,3% of post menopausal women reported use of HRT. Nulliparity was more frequent among pre menopausal women. Use of oral contraceptives did not differ considering both groups. Post menopausal women were more frequently obese (9vs3,4%; p=0,044); association of endometriosis was more frequent before menopause (20,6vs5,3%; p=0,021). Early stages were respectively 34 vs 25% in pre and post menopausal. Serous adenocarcinoma was the more frequent histological type in both groups. Mucinous (12vs6,8%) and endometrioid (10 vs 6,8%) were more common after menopause; clear cell tumor were more frequent before ovarian failure (10,3vs2,3%). Conclusions: Results that ovarian cancer in post menopausal women usually is diagnosed at advanced stages and less associated endometriosis. No statistical significance was reported mucinous and endometrioid histological types were more frequent after menopause.
381 STEREOTACTIC BODY RADIOSURGERY FOR RECURRENT CHEMOREFRACTORY ENDOMETRIAL AND OVARIAN CANCER
383
C. Kunos 1 , R. DeBernardo 2 . 1 Case Comprehensive Cancer Center, Radiation Oncology, Cleveland, United States; 2 Case Comprehensive Cancer Center, Gynecologic Oncology, Cleveland, United States
M. Milivojevic. Clinical Centre of Serbia, Institute of Medical Biochemistry, Belgrade, Serbia
Objectives: Limited options exist for women experiencing recurrent ovarian and endometrial cancer after surgery and multi-agent chemotherapy. Stereotactic body radiosurgery, using a linear accelerator mounted on an industrial robotic arm for radiation therapy delivery with sub-millimeter precision, offers a new treatment option. This study describes the first reported use of radiosurgery for treatment of recurrent ovarian and endometrial cancer in seven women. Methods: Five women with ovarian and two women with endometrial cancers refractory to chemotherapy underwent body radiosurgery for inoperable histologically-confirmed recurrent disease. All seven patients had undergone multi-agent chemotherapy. Radiosurgery doses ranged from 500cGy to 1200cGy per fraction for three fractions. Cross-plane radiographic images of gold seed fiducials marking targeted lesion confirmed tumor positioning during stereotactic radiation. Retrospective reviews of treatment-related toxicity and clinical outcome were done. Results: For all seven women, median age was 47 years and median follow-up was 10 months. Median volume for radiosurgical targets was 75.6cm3 (range 20-160cm3 ). All seven women tolerated radiosurgery without significant constitutional, gastrointestinal, and genitourinary toxicities. Through four weeks of clinical observation, six of seven women experienced grade 1 or less toxicity. One patient had grade 3 esophagitis requiring hospital-based intravenous hydration. Radiosurgical targeted lesions were sterilized, with all seven women achieving stable or reduced volume of disease by three-month follow-up. Conclusions: Stereotactic body radiosurgery sterilizes targeted lesions without significant during treatment or acute treatment-related toxicity in women with recurrent chemorefractory ovarian and endometrial cancer. A phase II toxicity and clinical efficacy study is planned. Keywords: Stereotactic body radiosurgery.
SERUM PROTEIN MARKERS FOR EARLY DETECTION OF OVARIAN CANCER
Objectives: Early diagnosis of epithelial ovarian cancer (EOC) would significantly decrease the morbidity and mortality from this disease but it is difficult in the absence of physical symptoms.The most commonly used biomarker is CA-125, but, sensitivity and specifity for early stage disease remains questionable. Methods: In this ELISA cross-validation study were collected 90 plasma samples for examining the level of two serum proteins: osteopontin (OPN) and prolaktin (PRL).In the first group were 40 samples from healthy womens, and in the second were other 50 newly diagnosed with EOC. Results: The mean osteopontin level in the category of healthy control was 147,1 ng/mL, but in the group of the patient it was 230,9 ng/mL.(p< 0,001). The result of PRL in the healthy group was 25,8-628,5 miU/L (mediana 183,54 mIU/l) and in the group of patient was 968-2843 mIU/l.The final result of the test have shown a sensitivity of 95% and specificity of 95%. Conclusions: Evaluation of proteins showed significant diffrences in expression between controls and cancer patients.So these markers may be specific markers for EOC. Keywords: Osteopontin, prolaktin, ovarian cancer.
384 ROLE OF GONADOTROPINS IN THE EXPRESSION OF NERVE GROWTH FACTOR AND ITS HIGH-AFFINITY RECEPTOR TRKA IN EPITHELIAL OVARIAN CANCER C. Romero 1 , M. Munoz 2 , X. Campos 2 , F. Gabler 3 , L. Moyano 3 , A. Selman 2 , M. Vega 2 . 1 University of Chile, Obstetric and Gynecology, Santiago, Chile; 2 Hospital Clinico Universidad de Chile, Obstetric and Gynecology, Santiago, Chile; 3 Hospital Clinico Universidad de Chile, Pathology, Santiago, Chile Objectives: To evaluate the role of gonadotropins in trkA and NGF expression in explants of EOC and to examine whether the changes in NGF and trkA expression are related to ovarian carcinogenesis progression.
S98
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
Methods: Seven EOC explants were incubated with FSH and LH (10mUI/L and 100mUI/L) and also with LH+FSH (50mUI/L and 500 mUI/L). NGF produced by explants was detected by ELISA in culture media. trkA expression was detected by immunohistochemistry. During carcinogenesis progression, NGF and trkA expression was evaluated by immunohistochemistry in 42 samples of ovarian tissues (n= 5 for each group: Inactive ovary, benign tumor, borderline tumor and EOC (grade I, II, III). Results: In EOC explants, FSH (10 mIU/L) and FSH+LH (500 mIU/L) stimulated NGF levels (p<0.05), whereas, trkA protein expression augmented with FSH (10 mIU/L), LH (100 mIU/L) and FSH+LH (500 mIU/L) (p<0.05). During ovarian carcinogenesis progression, a gradual increased of NGF and trkA expression was observed (p<0.001: EOC vs inactive ovary). Conclusions: Based on the high gonadotropin levels during menopause, the data of this study suggest a role for gonadotropins in ovarian carcinogenesis progression. Keywords: LH, FSH, trkA, NGF, Ovarian Cancer.
385 EXPERIENCE OF COMBINATION THERAPY WITH BEVACIZUMAB FOR RECURRENT/REFRACTORY CLEAR CELL CARCINOMA OF THE OVARY M. Takano 1 , Y. Kikuchi 2 , T. Kita 3 , K. Kudoh 4 , M. Kato 1 , T. Yoshikawa 1 , M. Miyamoto 1 , A. Watanabe 1 , N. Sasaki 1 , K. Furuya 1 , T. Goto 5 , H. Inoue 6 , M. Ohbayashi 6 . 1 National Defense Medical College, Department of Obstetrics and Gynecology, Tokorozawa, Japan; 2 Ohki Memorial Kikuchi Cancer Clinic for Women, Department of Gynecology, Tokorozawa, Japan; 3 Teikyo University School of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan; 4 National Hospital Organization Nishi Saitama Chuo Hospital, Department of Obstetrics and Gynecology, Tokorozawa, Japan; 5 Saitama Medical University International Cancer Center, Department of Gynecologic Oncology, Hidaka, Japan; 6 Shonan General Hospital, Department of Obstetrics and Gynecology, Kamakura, Japan Objectives: Recent reports confirmed extremely low response rate of second-line chemotherapy for recurrent or refractory clear cell carcinoma of the ovary (CCC). We report five case series of recurrent and refractory CCC treated with combination therapy with Bevacizumab. Methods: From August, 2007 to July, 2008, cases with recurrent or refractory CCC were treated with bevacizmab-containing chemotherapy after obtaining informed consent in Japanese cancer clinic. Response and toxicities were analyzed. Results: Median age of the patients was 54 years (range; 45-61). FIGO stage was stage IIc in 3 cases, and stage IIIc in 2 cases. Previous chemotherapy regimens were 2 regimens in 2 cases, and 3 in 3 cases. Bevacizumab was administered weekly at a dose of 2mg/kg/week in combination with cytotoxic agents. Among three response-assessable cases, PR was observed in two cases, and PD in one case. Although there were no hematological toxicities more than grade3 in 5 cases, one case with massive ascites and peritonitis carcinomastosis developed gastrointestinal perforation on the 28th day of the therapy. Conclusions: Combination therapy with bevacizumab showed a promising effect for recurrent/refractory clear cell carcinoma of the ovary. Our preliminary experience would facilitate the further investigation of bevacizumab-based regimen for CCC. Keywords: Ovarian cancer, clear cell carcinoma, bevacizumab, refractory, recurrence.
(BMI 28). She presented with minimal breast development sparse axillary and pubic hairs and normal female external genitalia. Medical history comprised bipolar depression with two severe suicidal attempts. Endocrinological evaluation demonstrated hypogonadotropic hypogonadism. Abdominal imaging revealed hypoplastic uterus and streak gonads. A genetic testing was performed and 46 X Y karyorype was proven. The patient underwent diagnostic laparoscopy which confirmed the ultrasonographic diagnosis and bilateral gonadectomy was performed. Results: The histopathologic examination revealed dysgerminoma in the left gonad and Retiform Sertoli -Leydig cells tumor in the right gonad. Surgical staging was performed, consisted of bilateral pelvic lymphadenectomy, omentectomy and random peritoneal biopsies. Histology did not reveal additional metastatic disease. Two sessions of carboplatin chemotherapy followed and treatment with estrogens was prescribed. Three months later the patient presented with deterioration of her psychiatric condition with frequent episodes of mania despite of medical therapy. Conclusion: Because the occurrence of malignancy in dysgenetic gonads is high, early diagnosis and prophylactic removal of the dysgenetic gonads is essential. Hormonal replacement with estrogens must be given with caution in patients with underlying bipolar disease because of the possible destabilizing effects of estrogens. Keywords: Swyer syndrome, double primary, ovarian CA.
387 SIGNIFICANT CA125 DECREASE AFTER REMOVAL OF THE OVARIES IN PREMENOPAUSAL WOMEN; THE NECESSITY OF A NEW REFERENCE LEVEL A. van Altena 1 , H. Holtsema 1 , J. Hendriks 2 , L. Massuger 1 , J. de Hullu 1 . 1 Radboud University Nijmegen Medical Centre, Department of Obstetrics & Gynaecology, Nijmegen, Netherlands; 2 Radboud University Nijmegen Medical Centre, Department of Epidemiology and Biostatistics, Nijmegen, Netherlands Objectives: CA125 is the only biomarker available for follow-up after treatment for ovarian cancer. However, the same reference level is used before and after treatment involving a bilateral salpingo-oophorectomy (BSO). We investigated the contribution of the ovaries on the CA125 level by measuring the effect of a BSO on CA125. Methods: All BRCA mutation carriers in the Nijmegen screening program who underwent prophylactic BSO were included. Information was obtained on menopausal state, age, smoking, previous hysterectomy and breast cancer, histopathological examination of the adnexa, HRT and CA125. The logarithmic transformed CA125 levels were used in a linear mixed model to study the relative change in CA125 and possible confounding or interaction. Results: In 60 identified women a relative decrease of 18% in CA125 after BSO was found (p=0.004). The median serum CA125 level was 10.15 U/ml before and 8.36 U/ml after BSO. The only factor interacting with CA125 was menopausal state (p=0.0017). The premenopausal group showed a relative decrease of 25% after BSO. Additionally, the ovarian volume did not explain the difference in CA125 after BSO (p=0.94). Conclusions: After BSO a relative decrease in CA125 level is shown. Menopausal state is the only factor interacting with CA125. Ovarian volume was excluded as confounding factor. The hormonal effect of ovaries might play a role in CA125. Our study suggests that not the reference level of 35 U/ml but a lower level, as suggested for postmenopausal women, should apply to women after a BSO. Keywords: CA125, ovarian cancer, menopausal state.
386 DOUBLE PRIMARY OVARIAN MALIGNANCIES IN A GIRL WITH BIPOLAR DEPRESSION COMPLICATING SWYER SYNDROME N. Thomakos 1 , A. Rodolakis 1 , E. Zapanti 2 , A. Giakoumi 2 , A. Manoli 1 , P. Grigori 3 , A. Antsaklis 1 . 1 University of Athens, ’Alexandra’ Hospital, 1st Department of Obstetrics & Gynecology, Athens, Greece; 2 ’Alexandra’ Hospital, Department of Endocrinology, Athens, Greece; 3 ’Alexandra’ Hospital, Department of Genetics, Athens, Greece Objectives: Swyer Syndrome is a type of pure gonadal dysgenesis 46 XY caryotype in phenotypically female patients. A rare case of Swyer syndrome complicated by dysgerminoma and Retiform Sertoli-Leydig cell’s tumor is reported. Methods: A 20 year -old phenotypically female patient referred to our department wit primary amenorrhea. She measured 1.68 meters and 82 kg
Preventive Medicine
388 EFFECT OF AQUEOUS GLYCYRYHZA GLOBRA EXTRACT ON MENOPAUSAL SYMPTOMS F. Abdollahy. Mazandaran University of Medical Sciences, Public Health, Sari, Iran, Islamic Republic of Objectives: There are many side effects of hormone therapy for menopausal symptoms. In different regions with various diet regimens, menopausal symptoms are different Glycyhrhza glabra has constituents with estrogen
380
382
TREATMENT OUTCOME OF PATIENTS WITH STAGE I CLEAR CELL CARCINOMA OF THE OVARY
EPITHELIAL OVARIAN CANCER: ANY DIFFERENCE ACCORDING TO MENOPAUSAL STATUS?
T. Goto, R. Ohishi, N. Iwasa, K. Hasegawa, M. Shimizu, S. Nagao, K. Fujiwara. Saitama Medical University International Medical Centre Comprehensive Cancer Centre, Department of Gynaecologic Oncology, Hidaka, Japan
H. Lopes, S. Custódio, M. Figueiredo Dias, C. Freire de Oliveira. Coimbra University Hospital, Gynecology department, Coimbra, Portugal
Objectives: Clear cell carcinomas of the ovary (CCCO) are frequently diagnosed at stage I. Adjuvant chemotherapy for such patients without postoperative residual disease is not always easy to accept for patients as well as physicians since it is relatively chemoresistant disease. We investigated treatment outcome of stage I CCCO patients in our institute. Methods: Twenty-six stage I CCCO patients treated in our institute from 2003 to 2007 were retrospectively analyzed. Results: Five patients (19%) were stage Ia and 21 were stage Ic, of whom, 2 (8%) had positive washing cytology, 1 (4%) had spontaneous capsular rupture, and 18 (69%) had capsular rupture due to operative procedure. Postoparative platinum-based chemotherapy following radical surgery was performed in 19 patients, of whom, only 2 patients who had positive washing cytology recurred after 11 months and 4 years and both didn’t respond to chemotherapy after recurrence. Of the other 7 patients who did not receive postoparative chemotherapy, 5 patients who had radical surgery were alive without recurrence. Two patients who underwent fertility-sparing surgery and no adjuvant chemotherapy developed recurrence after 21 and 28 months, respectively. Recurrence was observed not only in contralateral ovaries, but also para-aortic nodes or pelvic peritoneum. Both patients received debulking surgery followed by adjuvant chemotherapy and were alive with no evidence of disease. Conclusions: Patients with positive washing cytology were considered to be high risk for recurrence in spite of radical surgery and adjuvant chemotherapy. Fertility-sparing operation might not be applicable for CCCO, even by a strong request from the patient.
S97
Introduction: Ovarian cancer is the second most common cancer of the female reproductive system and the leading cause of death from gynaecologic malignancies. Although posmenopausal ovary is not exposed to mitotic stimuli at follicle rupture, ovarian cancer is more common among postmenopausal women. Some authors believe that different histological types develop from different ethiopathogenic ways. Objectives: To evaluate ovarian cancer in pre and pos menopausal women in order differences of risk factors and histological types. Material/methods:Retrospective assessment of clinical data of epithelial ovarian cancer patients diagnosed and treated in our department since Jan2000 to Dec2007. Results: Out of 161 ovarian cancer, 29 (18,1%) were pre menopausal at time of diagnosis with a mean age of 42,1, whereas 132 (81,9%) were post menopausal with a mean age of 67,9. Only 5,3% of post menopausal women reported use of HRT. Nulliparity was more frequent among pre menopausal women. Use of oral contraceptives did not differ considering both groups. Post menopausal women were more frequently obese (9vs3,4%; p=0,044); association of endometriosis was more frequent before menopause (20,6vs5,3%; p=0,021). Early stages were respectively 34 vs 25% in pre and post menopausal. Serous adenocarcinoma was the more frequent histological type in both groups. Mucinous (12vs6,8%) and endometrioid (10 vs 6,8%) were more common after menopause; clear cell tumor were more frequent before ovarian failure (10,3vs2,3%). Conclusions: Results that ovarian cancer in post menopausal women usually is diagnosed at advanced stages and less associated endometriosis. No statistical significance was reported mucinous and endometrioid histological types were more frequent after menopause.
381 STEREOTACTIC BODY RADIOSURGERY FOR RECURRENT CHEMOREFRACTORY ENDOMETRIAL AND OVARIAN CANCER
383
C. Kunos 1 , R. DeBernardo 2 . 1 Case Comprehensive Cancer Center, Radiation Oncology, Cleveland, United States; 2 Case Comprehensive Cancer Center, Gynecologic Oncology, Cleveland, United States
M. Milivojevic. Clinical Centre of Serbia, Institute of Medical Biochemistry, Belgrade, Serbia
Objectives: Limited options exist for women experiencing recurrent ovarian and endometrial cancer after surgery and multi-agent chemotherapy. Stereotactic body radiosurgery, using a linear accelerator mounted on an industrial robotic arm for radiation therapy delivery with sub-millimeter precision, offers a new treatment option. This study describes the first reported use of radiosurgery for treatment of recurrent ovarian and endometrial cancer in seven women. Methods: Five women with ovarian and two women with endometrial cancers refractory to chemotherapy underwent body radiosurgery for inoperable histologically-confirmed recurrent disease. All seven patients had undergone multi-agent chemotherapy. Radiosurgery doses ranged from 500cGy to 1200cGy per fraction for three fractions. Cross-plane radiographic images of gold seed fiducials marking targeted lesion confirmed tumor positioning during stereotactic radiation. Retrospective reviews of treatment-related toxicity and clinical outcome were done. Results: For all seven women, median age was 47 years and median follow-up was 10 months. Median volume for radiosurgical targets was 75.6cm3 (range 20-160cm3 ). All seven women tolerated radiosurgery without significant constitutional, gastrointestinal, and genitourinary toxicities. Through four weeks of clinical observation, six of seven women experienced grade 1 or less toxicity. One patient had grade 3 esophagitis requiring hospital-based intravenous hydration. Radiosurgical targeted lesions were sterilized, with all seven women achieving stable or reduced volume of disease by three-month follow-up. Conclusions: Stereotactic body radiosurgery sterilizes targeted lesions without significant during treatment or acute treatment-related toxicity in women with recurrent chemorefractory ovarian and endometrial cancer. A phase II toxicity and clinical efficacy study is planned. Keywords: Stereotactic body radiosurgery.
SERUM PROTEIN MARKERS FOR EARLY DETECTION OF OVARIAN CANCER
Objectives: Early diagnosis of epithelial ovarian cancer (EOC) would significantly decrease the morbidity and mortality from this disease but it is difficult in the absence of physical symptoms.The most commonly used biomarker is CA-125, but, sensitivity and specifity for early stage disease remains questionable. Methods: In this ELISA cross-validation study were collected 90 plasma samples for examining the level of two serum proteins: osteopontin (OPN) and prolaktin (PRL).In the first group were 40 samples from healthy womens, and in the second were other 50 newly diagnosed with EOC. Results: The mean osteopontin level in the category of healthy control was 147,1 ng/mL, but in the group of the patient it was 230,9 ng/mL.(p< 0,001). The result of PRL in the healthy group was 25,8-628,5 miU/L (mediana 183,54 mIU/l) and in the group of patient was 968-2843 mIU/l.The final result of the test have shown a sensitivity of 95% and specificity of 95%. Conclusions: Evaluation of proteins showed significant diffrences in expression between controls and cancer patients.So these markers may be specific markers for EOC. Keywords: Osteopontin, prolaktin, ovarian cancer.
384 ROLE OF GONADOTROPINS IN THE EXPRESSION OF NERVE GROWTH FACTOR AND ITS HIGH-AFFINITY RECEPTOR TRKA IN EPITHELIAL OVARIAN CANCER C. Romero 1 , M. Munoz 2 , X. Campos 2 , F. Gabler 3 , L. Moyano 3 , A. Selman 2 , M. Vega 2 . 1 University of Chile, Obstetric and Gynecology, Santiago, Chile; 2 Hospital Clinico Universidad de Chile, Obstetric and Gynecology, Santiago, Chile; 3 Hospital Clinico Universidad de Chile, Pathology, Santiago, Chile Objectives: To evaluate the role of gonadotropins in trkA and NGF expression in explants of EOC and to examine whether the changes in NGF and trkA expression are related to ovarian carcinogenesis progression.
S98
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
Methods: Seven EOC explants were incubated with FSH and LH (10mUI/L and 100mUI/L) and also with LH+FSH (50mUI/L and 500 mUI/L). NGF produced by explants was detected by ELISA in culture media. trkA expression was detected by immunohistochemistry. During carcinogenesis progression, NGF and trkA expression was evaluated by immunohistochemistry in 42 samples of ovarian tissues (n= 5 for each group: Inactive ovary, benign tumor, borderline tumor and EOC (grade I, II, III). Results: In EOC explants, FSH (10 mIU/L) and FSH+LH (500 mIU/L) stimulated NGF levels (p<0.05), whereas, trkA protein expression augmented with FSH (10 mIU/L), LH (100 mIU/L) and FSH+LH (500 mIU/L) (p<0.05). During ovarian carcinogenesis progression, a gradual increased of NGF and trkA expression was observed (p<0.001: EOC vs inactive ovary). Conclusions: Based on the high gonadotropin levels during menopause, the data of this study suggest a role for gonadotropins in ovarian carcinogenesis progression. Keywords: LH, FSH, trkA, NGF, Ovarian Cancer.
385 EXPERIENCE OF COMBINATION THERAPY WITH BEVACIZUMAB FOR RECURRENT/REFRACTORY CLEAR CELL CARCINOMA OF THE OVARY M. Takano 1 , Y. Kikuchi 2 , T. Kita 3 , K. Kudoh 4 , M. Kato 1 , T. Yoshikawa 1 , M. Miyamoto 1 , A. Watanabe 1 , N. Sasaki 1 , K. Furuya 1 , T. Goto 5 , H. Inoue 6 , M. Ohbayashi 6 . 1 National Defense Medical College, Department of Obstetrics and Gynecology, Tokorozawa, Japan; 2 Ohki Memorial Kikuchi Cancer Clinic for Women, Department of Gynecology, Tokorozawa, Japan; 3 Teikyo University School of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan; 4 National Hospital Organization Nishi Saitama Chuo Hospital, Department of Obstetrics and Gynecology, Tokorozawa, Japan; 5 Saitama Medical University International Cancer Center, Department of Gynecologic Oncology, Hidaka, Japan; 6 Shonan General Hospital, Department of Obstetrics and Gynecology, Kamakura, Japan Objectives: Recent reports confirmed extremely low response rate of second-line chemotherapy for recurrent or refractory clear cell carcinoma of the ovary (CCC). We report five case series of recurrent and refractory CCC treated with combination therapy with Bevacizumab. Methods: From August, 2007 to July, 2008, cases with recurrent or refractory CCC were treated with bevacizmab-containing chemotherapy after obtaining informed consent in Japanese cancer clinic. Response and toxicities were analyzed. Results: Median age of the patients was 54 years (range; 45-61). FIGO stage was stage IIc in 3 cases, and stage IIIc in 2 cases. Previous chemotherapy regimens were 2 regimens in 2 cases, and 3 in 3 cases. Bevacizumab was administered weekly at a dose of 2mg/kg/week in combination with cytotoxic agents. Among three response-assessable cases, PR was observed in two cases, and PD in one case. Although there were no hematological toxicities more than grade3 in 5 cases, one case with massive ascites and peritonitis carcinomastosis developed gastrointestinal perforation on the 28th day of the therapy. Conclusions: Combination therapy with bevacizumab showed a promising effect for recurrent/refractory clear cell carcinoma of the ovary. Our preliminary experience would facilitate the further investigation of bevacizumab-based regimen for CCC. Keywords: Ovarian cancer, clear cell carcinoma, bevacizumab, refractory, recurrence.
(BMI 28). She presented with minimal breast development sparse axillary and pubic hairs and normal female external genitalia. Medical history comprised bipolar depression with two severe suicidal attempts. Endocrinological evaluation demonstrated hypogonadotropic hypogonadism. Abdominal imaging revealed hypoplastic uterus and streak gonads. A genetic testing was performed and 46 X Y karyorype was proven. The patient underwent diagnostic laparoscopy which confirmed the ultrasonographic diagnosis and bilateral gonadectomy was performed. Results: The histopathologic examination revealed dysgerminoma in the left gonad and Retiform Sertoli -Leydig cells tumor in the right gonad. Surgical staging was performed, consisted of bilateral pelvic lymphadenectomy, omentectomy and random peritoneal biopsies. Histology did not reveal additional metastatic disease. Two sessions of carboplatin chemotherapy followed and treatment with estrogens was prescribed. Three months later the patient presented with deterioration of her psychiatric condition with frequent episodes of mania despite of medical therapy. Conclusion: Because the occurrence of malignancy in dysgenetic gonads is high, early diagnosis and prophylactic removal of the dysgenetic gonads is essential. Hormonal replacement with estrogens must be given with caution in patients with underlying bipolar disease because of the possible destabilizing effects of estrogens. Keywords: Swyer syndrome, double primary, ovarian CA.
387 SIGNIFICANT CA125 DECREASE AFTER REMOVAL OF THE OVARIES IN PREMENOPAUSAL WOMEN; THE NECESSITY OF A NEW REFERENCE LEVEL A. van Altena 1 , H. Holtsema 1 , J. Hendriks 2 , L. Massuger 1 , J. de Hullu 1 . 1 Radboud University Nijmegen Medical Centre, Department of Obstetrics & Gynaecology, Nijmegen, Netherlands; 2 Radboud University Nijmegen Medical Centre, Department of Epidemiology and Biostatistics, Nijmegen, Netherlands Objectives: CA125 is the only biomarker available for follow-up after treatment for ovarian cancer. However, the same reference level is used before and after treatment involving a bilateral salpingo-oophorectomy (BSO). We investigated the contribution of the ovaries on the CA125 level by measuring the effect of a BSO on CA125. Methods: All BRCA mutation carriers in the Nijmegen screening program who underwent prophylactic BSO were included. Information was obtained on menopausal state, age, smoking, previous hysterectomy and breast cancer, histopathological examination of the adnexa, HRT and CA125. The logarithmic transformed CA125 levels were used in a linear mixed model to study the relative change in CA125 and possible confounding or interaction. Results: In 60 identified women a relative decrease of 18% in CA125 after BSO was found (p=0.004). The median serum CA125 level was 10.15 U/ml before and 8.36 U/ml after BSO. The only factor interacting with CA125 was menopausal state (p=0.0017). The premenopausal group showed a relative decrease of 25% after BSO. Additionally, the ovarian volume did not explain the difference in CA125 after BSO (p=0.94). Conclusions: After BSO a relative decrease in CA125 level is shown. Menopausal state is the only factor interacting with CA125. Ovarian volume was excluded as confounding factor. The hormonal effect of ovaries might play a role in CA125. Our study suggests that not the reference level of 35 U/ml but a lower level, as suggested for postmenopausal women, should apply to women after a BSO. Keywords: CA125, ovarian cancer, menopausal state.
386 DOUBLE PRIMARY OVARIAN MALIGNANCIES IN A GIRL WITH BIPOLAR DEPRESSION COMPLICATING SWYER SYNDROME N. Thomakos 1 , A. Rodolakis 1 , E. Zapanti 2 , A. Giakoumi 2 , A. Manoli 1 , P. Grigori 3 , A. Antsaklis 1 . 1 University of Athens, ’Alexandra’ Hospital, 1st Department of Obstetrics & Gynecology, Athens, Greece; 2 ’Alexandra’ Hospital, Department of Endocrinology, Athens, Greece; 3 ’Alexandra’ Hospital, Department of Genetics, Athens, Greece Objectives: Swyer Syndrome is a type of pure gonadal dysgenesis 46 XY caryotype in phenotypically female patients. A rare case of Swyer syndrome complicated by dysgerminoma and Retiform Sertoli-Leydig cell’s tumor is reported. Methods: A 20 year -old phenotypically female patient referred to our department wit primary amenorrhea. She measured 1.68 meters and 82 kg
Preventive Medicine
388 EFFECT OF AQUEOUS GLYCYRYHZA GLOBRA EXTRACT ON MENOPAUSAL SYMPTOMS F. Abdollahy. Mazandaran University of Medical Sciences, Public Health, Sari, Iran, Islamic Republic of Objectives: There are many side effects of hormone therapy for menopausal symptoms. In different regions with various diet regimens, menopausal symptoms are different Glycyhrhza glabra has constituents with estrogen