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Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Endometrial stromal tumors are rare uterine tumors (

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

CA125 levels were measured in the sera of 54 women with normal menstrual cycle and without infectious, benign and malignant gynecologic disorders. In 54 subjects studied, 13 (24%) had no significant variations in serum CA125 levels throughout the menstrual cycle. In contrast, there 41 (76%) had significant variations in serum CA125 with peak levels (51.8 +/- 6.5 U/ml, mean +/- SEM) during menstruation. The concentration reached a normal value (17.7 +/- 1.6 U/ml, mean +/- SEM) at proliferative phase, and remained low throughout the rest phases of the cycle. The mean peak level was significantly higher than that at proliferative phase (P0.001), where as no significant difference in mean concentration was detected between sequential phases from proliferative phase to premenstrual phase (P0.1). Among 41 with variable CA125 levels in the menstrual cycle, more than half of them, namely 39% of the total (21/54), had the levels of the upper limit or normal values.

Sixty-one postmenopausal women were randomized into 3 groups. Two groups of women were treated with estrogen replacement therapy (ERT) by percutaneous administration of estradiol gel at a dosage of 1.25 g and 2.5 g, respectively. The third group of women, receiving no treatment except placebo, was studied concurrently as a control group. Bone mineral density (BMD) was measured by quantitative computed tomography (QCT) in the vertebrae from T12-L3 and hormones (E1, E2, FSH, LH and testosterone) were determined by radioimmunoassay at baseline, then at 6 monthly intervals thereafter. One year of the study has been completed thus far. The results of this study indicate that: (1) loss of BMD in the control group was observed significantly only in surgical menopausal women and no significant loss of BMD was observed in women receiving ERT treatment regimens; (2) decrease of E1 in control group and increase of E1 in the treatment group were both significant. These data suggest that percutaneous ERT may be used in prevention of postmenopausal bone loss, particularly in surgical menopausal women and the increased E1 may play a beneficial role in inhibiting loss of bone mass and relieving menopausal syndrome. Different dosages of estradiol gel which did not create any significant difference between the 2 treatment groups, need a longer period of follow-up.

During embryo implantation in species with hemochorial placentation, such as the mouse and human, trophoblast cells of the attached blastocyst penetrate the luminal epithelium of the endometrium before invasion into the endometrial stroma. Signs of apoptosis were demonstrated in luminal endometrial epithelial cells (EEC) adjacent to the trophoblast cells; however, the signaling mechanisms leading to apoptosis in EEC remain unclear. Because mitogen-activated protein kinases (MAPK) were shown to mediate apoptosis in several model systems and found to be activated in the uterus during decidualization, the possible involvement of MAPK during trophoblast-EEC interactions was studied. By coculturing BeWo human trophoblast spheroids with RL95-2 human EEC monolayers to mimic the blastocyst-endometrial interaction, we found that most spheroids rapidly attached to EEC monolayers and then progressively expanded, with marked dislodgment of EEC adjacent to the spreading trophoblast cells. Immunoblotting analysis showed that both p38 MAPK and extracellular signal-regulated kinase (ERK) were activated in EEC after coculture. However, only SB203580 (a p38 MAPK inhibitor), but not PD98059 (an ERK inhibitor), inhibited trophoblast outgrowth on EEC monolayers through the suppression of p38 MAPK activation in EEC. Furthermore, trophoblast expansion caused prominent EEC apoptosis at the spheroid-EEC interface, as detected by annexin V labeling and valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (which binds activated caspases) staining, and SB203580 significantly decreased the percentage of apoptotic cells. Our results, based on a model of human trophoblast-EEC interactions, establish that trophoblast cells cause activation of p38 MAPK in EEC and, consequently, induce apoptosis and displacement of EEC, a process that may facilitate implantation.

Objectives: To evaluate tumor-spreading patterns in the parametrium. Methods: We conducted a prospective clinical trial between January 1998 and December 2000 to define a new method for parametrium evaluation. The parametrium was divided into three areas, paracorpus, paracervix, and paravagina. A total of 284 consecutive patients with FIGO stage IB to IIA cervical cancer who had undergone radical hysterectomy were considered for the study. Results: Of the 262 patients who were found eligible for evaluation, 135 had histopathologic analysis performed according to the new method and 127 with the traditional method. The detection of rate of parametrial invasion was 36 (26.7%) with the new and 13 (10.2%) with the traditional method (P=0.0014). The frequency of pelvic lymph node metastasis was 66.7% in patients who had tested positive for invasion of the paracorpus, 57.7% in those who had tested positive for invasion of the paracervix, and 71.4% in those who had tested positive for invasion of the paravagina. The frequency of pelvic lymph node metastasis in patients who had tested negative for invasion of the paracorpus, paracervix, or paravagina was 4.0%. Tumor cells tend to spread laterally and inferiorly in the parametrium. Conclusions: Using our classification of three parametrium areas for histologic examination can increase the detection rates of parametrial tumor invasion and help prevent failure of local treatment by allowing to implement appropriate adjuvant therapy.

Degenerative changes occur relatively frequently in uterine leiomyomas. Morphologic changes such as necrosis, hyalinization, and alterations in cellularity are described after uterine artery embolization. A modified method to interrupt the uterine blood supply is laparoscopic bipolar coagulation of uterine vessels (LBCUV). Although the success rate is good, occasional patients require hysterectomy because of complications or continuing symptoms. A woman with symptomatic myomas underwent LBCUV, but required hysterectomy due to rapid enlargement of myomas and intractable symptoms including pelvic pain and pressure, and acute urinary retention. The combination of degenerative and iatrogenic changes resulted in a histologic appearance resembling diffuse hyalinization and hydropic degeneration of the leiomyomas.

To assess the effectiveness of laparoscopic uterine nerve ablation (LUNA) in women with dysmenorrhea caused by uterine myomas treated by laparoscopic bipolar coagulation of uterine vessels (LBCUV).Prospective, randomized, longitudinal study (Canadian Task Force classification II-1).Private practice, university-affiliated hospital.Eighty-five women with uterine leiomyomas and associated dysmenorrhea.Laparoscopic bipolar coagulation of uterine vessels with or without LUNA.Of 85 patients who entered the study, 41 were assigned to undergo LBCUV-LUNA (group A), which was successful in 40 (97.6%). In 44 women assigned to have LBCUV only (group B), 43 (97.7%) underwent successful surgery. Eighty women completed 1-, 3-, and 6-month follow-up (38 group A, 42 group B). The groups did not differ significantly in age, history of abdominopelvic surgery, intraperitoneal adhesions, endometriosis, concomitant surgery, and operating time. Seven (18.4%) of 38 women in group A and 12 (28.6%) of 42 in group B experienced lower abdominal pain postoperatively. Acceptable pain was defined as a score of zero or 1: 31 and 30 women in groups A and B reported scores of zero; 3 and 2 reported scores of 1; 4 and 8 reported scores of 2; zero and 2 reported scores of 3; and no patients reported scores of 4. The frequency and severity of postoperative pain were less in group A than in group B (both p0.05). The efficacy of both methods was almost equal in shrinking the uterus and dominant myoma, and in improving menorrhagia and bulk-related symptoms. Dysmenorrhea improvement was 84.2% and 61.9% in groups A and B at 3 months and 92.1% and 73.8% at 6 months, respectively. This was more significant in group A than in group B (p0.05).Our results suggest that LUNA may decrease postoperative ischemic pain and improve dysmenorrhea associated with uterine myomas treated by LBCUV.

Study Objective To assess laparoscopic bipolar coagulation of uterine vessels (LBCUV) for symptomatic myomas in women with elevated CA 125 (>35 U/ml). Design Prospective, longitudinal study (Canadian Task Force classification II–1). Setting Private practice, university-affiliated hospital. Patients Forty-six women (age 30–50 yrs) with symptomatic myomas and elevated CA 125 level. Intervention Laparoscopic bipolar coagulation of uterine vessels performed over 10 months. Measurements and Main Results All patients underwent successful LBCUV and coagulation of anastomotic site of uterine arteries with ovarian arteries without intraoperative complication. One, 3, and 6 months after treatment, respectively, 52.2%, 65.2%, and 71.7% of women reported improvement in menorrhagia, 19.6%, 45.7%, and 56.5% noted improvement in dysmenorrhea, and 6.5%, 16.1%, and 38.7% had improvement in bulk-related symptoms. Average reduction in uterine volume was 9.1%, 16.9%, and 38.3% and average reduction in dominant myoma was 12.1%, 23.9%, and 59.1% at those times; the average reduction of CA 125 in all patients was 39.8, 75.4, and 126.1U/ml. Conclusion Symptoms were improved and uterine volume and dominant myoma were reduced by LBCUV. The CA 125 level fell during follow-up in 40 patients (87.0%). Improvement in symptoms, especially menorrhagia, and shrinkage of uterine volume and dominant myoma seemed to be more pronounced in women with decreased than in those without decreased CA 125 after treatment (p = 0.045). The CA 125 level may be a valuable indicator for monitoring the efficacy of LBCUV.

Study Objective To determine the safety and side effects that may be caused by laparoscopic-assisted uterine depletion (LAUD) of submucous myomas. Design Retrospective chart review and follow-up (Canadian Task Force classification II-2). Setting University-affiliated tertiary referral center. Patients Five hundred twenty women with symptomatic myomas warranting surgical treatment, who wished to retain their uteri. Intervention Laparoscopic bipolar coagulation of uterine arteries and anastomotic sites of uterine arteries with ovarian arteries. Measurements and Main Results Postoperative sonographs showed submucous myomas in 53 (10.2%) women. During follow-up for a mean of 8.6 months very few complications occurred; however, nine women (1.7%) experienced vaginal expulsion of myomas from 2 weeks to 5 months postoperatively. Four of them were readmitted within 43 days with high fever and fetid discharge, and cervical cultures revealed heavy growth of Escherichia coli in three. Vaginal myomectomy was performed in six patients, and one woman passed the myoma spontaneously. Histopathologic studies of these nine specimens showed that two had infarction, three had coagulative necrosis, and four had degeneration. After treatment, all nine women had normal menstruation and their symptoms resolved during follow-up of at least 3 months. Conclusion In our experience LAUD led to satisfactory symptomatic improvement and reduction in myoma volume and few complications. If vaginal expulsion of submucous fibroids can be viewed as a side effect, we should pay close attention to women with submucous myomas, especially within 2 months of LAUD. Otherwise, more dangerous complications could occur.

Objective: To evaluate the effects of laparoscopic bipolar coagulation of uterine vessels in treating symptomatic fibroids. Design: Prospective clinical study. Setting: University-affiliated tertiary referral center. Patient(s): Eighty-seven women with symptomatic fibroids warranting surgical treatment and wanting to retain their uteri. Intervention(s): Laparoscopic bipolar coagulation of uterine arteries and anastomotic sites of uterine arteries with ovarian arteries. Main Outcome Measure(s): Percentage reduction in the dominant fibroid size and clinical response evaluation. Result(s): Eighty-five (97.7%) of 87 patients underwent technically successful laparoscopic coagulation of uterine vessels without intraoperative complications. The mean follow-up time was 10.2 months. Symptomatic improvement was reported in 76 (89.4%) of 85 patients, including 18 (21.2%) with complete resolution of symptoms. Significant reductions in the dominant fibroid size (average, 76%) and the uterine volume (average, 46%) were sonographically demonstrated. Two patients conceived 4 and 9 months, respectively, after treatment. Three (3.5%) premenopausal women became postmenopausal postoperatively. Conclusion(s): Laparoscopic bipolar coagulation of uterine vessels appears to be a promising new method for treating fibroid-related menorrhagia and pelvic pain.

The aim of this study was to investigate the effectiveness of transvaginal power Doppler angiography in predicting cervical malignancy by detecting intratumoral blood flow and to understand the relationship between squamous cell carcinoma (SCC) serum levels and intratumoral blood flow analysis of invasive cervical carcinoma before treatment.Thirty-eight patients with cervical carcinoma (35 with stages Ia to IVb invasive carcinoma, 3 with cervical carcinoma in situ) were enrolled for the evaluation of tumor flow using transvaginal ultrasound accompanied with power Doppler angiography before surgery. The pulsatility, resistance index, and vascular index of tumor flow were measured. Thirty patients with proven healthy cervices were used as the control group. Pretreatment SCC serum levels were obtained in 34 women with cervical carcinoma.The pulsatility index and resistance index were significantly lower in the study group than in the control group (P0.0001). The vascular index was also significantly lower in the study group than in the control group (P0.0001). There were no significant differences among patients with SCC type and non-SCC type cervical carcinoma (P0.05) among the six parameters. There was no significant correlation between the pretreatment SCC serum levels with any of the six parameters obtained from the intratumoral blood flow analysis in the SCC group.Transvaginal ultrasound with power Doppler angiography is a valuable diagnostic tool for differentiating benign tumors of the cervix from malignant ones. Intratumoral blood flow of the cervix supplied us with practical diagnostic information before surgery and may aid in early prediction and management of cervical carcinoma. The use of transvaginal ultrasound with power Doppler angiography in the grading of vascularity ratio within cervical masses provided more sonographic characteristics among the different subclassifications of cervical cancer and is more useful than color Doppler imaging in the visualization of sonographic morphology.

Many clinicopathological factors of cervical cancer are still controversial in their prognostic significance. The case records of 1,115 patients who received radical hysterectomy at the Veterans General Hospital, Taipei, from 1980 to 1989 were collected to evaluate prognosis-related factors by univariate and multivariate analyses. The pathology was reviewed retrospectively by one pathologist. Ten parameters known to be prognostic in the literature were included for analysis. Univariate analysis showed that patients with all these factors had higher recurrence rates. However, when the effects of parametrial invasion, progressive stage and stromal invasion were weighed against the presence of lymph node metastasis, their influence on recurrence became unimportant. Nevertheless, these factors still influenced prognosis when there was no lymph node metastasis. Multivariate analysis of both recurrence and survival time in the patients with squamous cell carcinoma shared a consensus that pelvic lymph node metastasis and deep stromal invasion were significant risk factors. We conclude that these simplified and consistent results obtained by multivariate analysis provide a basis for subclassification of patients to predict prognosis and change therapy.

A heterotopic pregnancy is in effect a multiple pregnancy with one or more intrauterine pregnancies coexisting with an ectopic pregnancy and is rarely spontaneous. With the increasing popularity of ovulation induction performed during assisted reproductive techniques, it will not be surprising to observe that this phenomenon has increased significantly. However, diagnosis is often delayed because of its rarity and difficulty. We report a case of a woman with a viable intrauterine pregnancy who had a complication of ovarian hyper-stimulation syndrome secondary to ovulation induction following in vitro fertilization and embryo transfer, but who, during hospitalization, presented with clinically progressive abdominal pain. An unruptured ectopic pregnancy of the right fallopian tube was diagnosed accidentally by laparoscopy and laparoscopic salpingectomy was immediately performed. Post-operative follow-up revealed that the intrauterine pregnancy continued normally. She delivered a normal female baby at 38 weeks of gestation. The promising neonatal outcome might suggest that laparoscopy might be safely performed to aid differential diagnosis in an uncertain condition during pregnancy: therefore, laparoscopic surgery might be an appropriate method to manage some carefully selected patients with HP. A brief review of the published literature on the role of laparoscopy in the diagnosis and management of heterotopic pregnancy is given.

Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors. They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS). The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature. This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.

The tumor-suppressor gene p53 acts as "the guardian of the genome", sensing DNA damage and initiating protective responses. To examine the hypothesis that p53 abnormality leads to increased genomic alterations in primary tumor cells, our study utilized 51 primary tumors of cervical carcinoma and 10 microsatellite markers. These markers were mapped to the short arms of chromosomes 3 and 5, covering the regions 3p13-25 and 5p15.1-15.3. Genomic deletion on 3p and 5p was correlated with genetic or epigenetic p53 inactivation pathways, including p53 mutation, genetic deletion of p53 and cervical infection with human papillomavirus. The proportion of abnormal p53 was found to be significantly higher in the cases exhibiting loss of heterozygosity (LOH) on 5p (p < 0.001), supporting the hypothesis of the presence of a p53-dependent pathway to cervical tumorigenesis. In contrast, however, LOH on 3p was found to be independent of p53 inactivation. A common deletion region, 3p22-24, was identified in 44% of informative cases, and genomic loss at this specific region was correlated with early tumorigenic onset and poor grade of tumor differentiation. Diversity within the patterns of genomic alteration in the same form of cancer suggests different sets of risk/tumorigenic profiles, molecular pathogenesis, as well as prognosis and outcome.

Objective: To study the prognosis and metastatic route of cervical carcinoma with ovarian metastasis. Method: From 1980 to 1993, 10 of the 1507 patients with cervical carcinoma operated and who had ovarian metastasis were analyzed. Results: Six patients had squamous cell carcinomas and 4 patients had adenocarcinomas. Their mean age was 45 years. Six of 9 patients undergoing pelvic lymphadenectomy had nodal metastasis. One patient did not have nodal dissection in the treatment course. Five of 10 patients had involvement of corpus: 3 were accompanied with nodal metastasis, 1 was not and 1 other was unknown. None of our cases survived more than 5 years. Their mean survival time was 20.8 months for squamous cell carcinomas and 29 months for adenocarcinomas. Conclusions: (1) Ovarian metastasis is histologically one of the ominous signs of cervical carcinomas regardless of stage. The prognosis of patients with ovarian metastasis from cervical squamous cell carcinoma from our data is not different from those from cervical adenocarcinoma. (2) Lymphatic spread and transtubal implantation are possible pathways of cervical cancer metastasizing to ovary, and involvement of the corpus may potentiate this mechanism.

Objective: The nomogram of blood velocity flow resistance of the spiral arteries was built at 13–25 gestational weeks. Thereafter, by using the nomogram we tried to assess the results of the color Doppler examination of the uteroplacental circulation at the second trimester to predict pregnancy-induced hypertension (PIH) and small-for-gestational-age (SGA). Methods: Two groups of patients were studied. Group 1, for the establishment of the nomogram, included 175 uncomplicated pregnancies with gestational ages ranging from 13–25 weeks. The Doppler flow waveforms of the spiral arteries were measured once for each pregnancy in the studies. Group 2 consisted of 305 singletons selected consecutively for prospective study to confirm the occurrence of PIH or SGA. They were scanned twice for the measurements of the spiral artery waveforms at 13–19 and 20–25 weeks, respectively to test which gestational weeks interval in the nomogram is most sensitive in predicting PIH and SGA. Results: The 5th, 50th and 95th percentiles of the pulsatility index (PI) values of the nomogram at the second trimester were used as the cut-off points to predict pregnancies complicated with SGA or PIH at delivery. Using the receiver operator curve, the 50th percentiles of the PI values of the nomograms were chosen as predictives for the development of PIH and SGA. At 13–19 gestational weeks, the specificities in predicting PIH and SGA were 50.71% and 49.82%, respectively, and the sensitivities were 52.00% and 50.00%, respectively. The calculated Cohen's Kappa statistics were 0.008 and 0.001, respectively in predicting PIH and SGA. At 20–25 gestational weeks, the specificities in predicting PIH and SGA were 49.64% and 49.46%, respectively, and the sensitivities were 56.00% and 57.14%, respectively. The calculated Cohen's Kappa statistics were 0.017 and 0.022, respectively in predicting PIH and SGA. Conclusion: The measurements of uteroplacental blood flow velocity waveforms at the second trimester are not sensitive enough to be an early screening tool for PIH and SGA in the low risk, non-selected pregnancy population. The fact suggests that in most gravidas complicated with PIH and SGA, the physiological process of trophoblastic invasion in the spiral artery was not prevented before the 25th gestational week.

The aim of this study is to understand the current status of bone mineral density (BMD) among Taiwanese women and to determine the relationship between bone mass, weight, height and body mass index (BMI), and the proportion of osteoporosis sufferers, based on World Health Organization standards, in each age group. A total of 4689 women underwent lumbar vertebrae (L2-L4) BMD measurements, and 3529 women underwent femoral neck bone mineral density measurements. BMD was measured using dual-energy X-ray absorptiometry. Standards were based on the BMD of the 20- to 40-year-old age group, as were relationships between height, weight, BMI, and BMD. Pearson correlation revealed a positive relationship between body weight, BMI, and BMD in the femoral neck; other correlations were insignificant. The defined BMD value for a diagnosis of osteoporosis was 0.827 g/cm(2) for lumbar vertebrae and 0.605 g/cm(2) for the femoral neck. The proportion of osteoporosis calculated for each age group in the lumbar vertebrae group was: 40-49 years old, 8.25%; 50-59 years old, 8.62%; 60-69 years old, 14.14%; 70-79 years old, 14.25%;80 years old, 16.07%. For the femoral neck group, the values were: 40-49 years old, 5.24%; 50-59 years old, 5.28%; 60-69 years old, 11.17%; 70-79 years old, 17.30%;80 years old, 24%. The total proportion of osteoporosis in the lumbar vertebrae was 10.08%, and in the femoral neck, 7.45%. The BMD of Taiwanese women shows a positive relationship to body weight and BMI in the femoral neck group but not in the lumbar vertebrae group. The proportion of osteoporosis by age group in this cohort was lower than that among Western women.

In the present study, we report the establishment of a monoclonal antibody (Mab) designated F10 that recognized an antigen commonly shared by human trophoblasts and leucocytes. F10 MAb was obtained using cell membrane components from a trophoblast cell line HT as immunogen. Based on immunochemical studies, the F10 reactive antigen (F10-Ag) could be located on both villous and nonvillous trophoblasts from early and term placental tissues and on all trophoblastic cell lines. In addition, flow cytometry revealed that most (95%) peripheral blood lymphocytes, monocytes, as well as polymorphonuclear leukocytes (PMN) were positively stained with F10 MAb. Immunoblotting with F10 MAb identified two protein bands with apparent molecular mass of 62 and 56 kDa. Furthermore, the antigens were glycoproteins and were glycosylated via the O-linkage. Scatchard plot analyses of the binding data between 125I-labeled MAb F10 IgG and HT cells revealed a single class of F10 binding sites with an apparent dissociation constant (Kd) of 10.54 +/- 2.03 pM and maximum binding-site (Bmax) value of 2.1 +/- 0.11 x 10(6) sites per cell. We suggest that F10 may be useful for the identification of a novel epitope that is commonly shared by all trophoblasts and leukocytes and such an epitope may be potentially active in maternal-fetal interactions.

Objective. In the testosterone-secreting ovarian tumor (TSOT), the role of whole-body positron emission tomography (WBPET) with (fluorine-18)-2-deoxyglucose scanning (FDG) and/or [ 11 C]acetate is unclear, although it presents a rationale that these functional tumors would be more active and have increased use of glucose and oxygen consumption than normal tissues. Case. A 52-year-old woman had a history of steroid cell tumors of the right ovary (IIA) and she received staging surgery including total hysterectomy, salpingo-oophorectomy, and lymph node sampling. Reelevated serum levels of T (5.24 ng/ml) were noted 52 months later. The patient received serial preoperative examinations including WBPET with FDG and acetate, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) to evaluate her recurrence. A suspicious mass on the liver was found on ultrasound, CT, and MRI. The ultrasound-guided biopsy was performed three times, and each of them failed to provide any pathological confirmation. Functional imaging studies showed an abnormal uptake in WBPET using [ 11 C]acetate but were negative using FDG. Because of the size of the tumor, the patient's hesitatancy toward an operation, and good previous response to gonadotropin-releasing hormone (GnRH) agonist treatment, the patient received a six-cycle GnRH agonist treatment. Serum T levels returned to normal limits after administration of the first dose of GnRH agonist. At follow-up, serum hormone levels were all within the normal ranges consistent with menopause, but the size of the metastatic tumor was constant. The tumor was then completely excised pathologically proven to be a metastatic TSOT. Conclusions. Recurrent TSOT might be successfully detected using WBPET with [ 11 C]acetate. In addition, GnRH agonist could be tried in patients with TSOT if initial responses were excellent and surgical intervention could not be performed.

A pelvic abscess occurred in an infertile woman with an endocervical gonococcal infection after hysterosalpingographical examination. The pelvic abscess was not cured despite rigorous antimicrobial chemotherapy until two intra-abscess ceftriaxone injections were administered. This shows that antibiotics administered systemically may not reach therapeutic concentration in an abscess and an intra-abscess antibiotic injection may help to cure it.

Ž . Gestational trophoblastic disease GTD is a highly chemo-sensitive and curable disease; however, a significant portion of the patients still die from the disease, mostly due to drug resistance and initial advanced disease. Brain metastases andror liver metastases are a leading cause of death. Although Small et al. demonstrated that treatment with multi-agent chemotherapy and Ž concurrent whole-brain irradiation 3000 cGy in . 200-cGy fractions cures many patients with maw x lignant GTD metastatic to the brain 1 , and Wong et al. demonstrated that the survival of GTD patients with hepatic metastases has imw x proved during the recent decades 2 , our previous report demonstrated that the patients with GTD associated with brain andror metastases

The presence of human cytomegalovirus (HCMV) was tested in 388 cervicovaginal cells specimens obtained from the same number of pregnant women. HCMV was detected in 5·41%, 11·6% and 13·9% of these specimens by conventional culture, in situ DNA hybridization and polymerase chain reaction (PCR) methods, respectively. The sensitivities of detecting HCMV by in situ hybridization and PCR methods were 76·2% and 90·5% and the specificities were 92·1% and 90·5%, respectively, when compared with conventional culture method. The PCR compared favourably with both conventional culture and in situ hybridization methods and it may become a valuable and useful tool for the early and rapid detection of HCMV in clinical specimens.

During embryo implantation in species with hemochorial placentation, such as the mouse and human, trophoblast cells of the attached blastocyst penetrate the luminal epithelium of the endometrium before invasion into the endometrial stroma. Signs of apoptosis were demonstrated in luminal endometrial epithelial cells (EEC) adjacent to the trophoblast cells; however, the signaling mechanisms leading to apoptosis in EEC remain unclear. Because mitogen-activated protein kinases (MAPK) were shown to mediate apoptosis in several model systems and found to be activated in the uterus during decidualization, the possible involvement of MAPK during trophoblast-EEC interactions was studied. By coculturing BeWo human trophoblast spheroids with RL95-2 human EEC monolayers to mimic the blastocyst-endometrial interaction, we found that most spheroids rapidly attached to EEC monolayers and then progressively expanded, with marked dislodgment of EEC adjacent to the spreading trophoblast cells. Immunoblotting analysis showed that both p38 MAPK and extracellular signal-regulated kinase (ERK) were activated in EEC after coculture. However, only SB203580 (a p38 MAPK inhibitor), but not PD98059 (an ERK inhibitor), inhibited trophoblast outgrowth on EEC monolayers through the suppression of p38 MAPK activation in EEC. Furthermore, trophoblast expansion caused prominent EEC apoptosis at the spheroid-EEC interface, as detected by annexin V labeling and valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (which binds activated caspases) staining, and SB203580 significantly decreased the percentage of apoptotic cells. Our results, based on a model of human trophoblast-EEC interactions, establish that trophoblast cells cause activation of p38 MAPK in EEC and, consequently, induce apoptosis and displacement of EEC, a process that may facilitate implantation.

BACKGROUND: Laparoscopic bipolar coagulation of uterine vessels (LBCUV) has been employed for women with symptomatic uterine myomas but its effect on subsequent pregnancy has not been characterized. METHODS: Four-hundred and twenty-three women entered the study between March 1999 and December 2001. Of these 142 women (33.6%) were under the age of 40 years at the time of LBCUV 36 of whom (36/142 25.3%) were sexually active without contraception. In a prospective study of 142 patients (

Wound endometriosis is still a rare phenomenon. In this study, we tried to identify its risk factors and presented our experience in managing such disease.We studied twenty-three women with pathologically confirmed wound endometriosis after surgery between January 1990 and June 1999 retrospectively.Patients were classified to three groups according to the types of operations including obstetric surgery (n = 6186), gynecologic surgery (n = 3231) and laparoscopic procedures (n = 2184), which made a significant difference in the occurrence rate of endometriosis (p = 0.04): 2.7 per 1000 obstetric surgeries, 1.5 per 1000 cases of gynecologic surgeries, and 0.5 per 1000 laparoscopic procedures. Obstetric surgery showed the relative risk of occurrence of wound endometriosis 7.71 (95%: 1.03-57.92) compared with laparoscopic procedures. The median time for occurrence of wound endometriosis in patients with normal preoperative CA-125 (15 mIU/ml), 760 days, was significantly longer than that in patients with abnormal preoperative CA-125 (15 mIU/ml) of 496 days (p = 0.03). Preoperative CA-125 level, patient's age, preoperative extent of endometriosis, or operative time made no significant contributions to the occurrence of wound endometriosis. Combination therapy of surgical excision and postoperative adjuvant therapy of GnRH-agonist or Danazol showed the better prognosis because it could decrease the recurrence of wound endometriosis (42.9% versus 11%, p = 0.01).Obstetric surgery may be an important risk factor in contributing to wound endometriosis, and the aggressive behavior of endometriosis itself might also be a possible risk factor because it shortens the time of occurrence of wound endometriosis after surgery. Therapy might be dependent on individuals. Surgical excision with postoperative adjuvant therapy of either GnRH-agonist or Danazol might be valid, although its effectiveness needed proven in the future.

Objective. Altered messenger ribonucleic acid (mRNA) expression of the four sialyltransferases (STs including ST3Gal I, ST3Gal III, ST3Gal IV, and ST6Gal I) is important in squamous cell carcinoma of the cervix. This study further investigates their changes in mRNA expression of the four STs in FIGO stage IB1 squamous cell carcinoma to assess the extent of sialylation associated with lymph node metastases. Methods. Alterations in ST mRNA expression in FIGO IB1 cervical squamous cell carcinomas ( n = 79) were examined by semiquantitative reverse transcription–polymerase chain reaction. Results. Both ST6Gal I mRNA and ST3Gal III mRNA expressions were significantly increased in patients with lymph node metastases compared to those without lymph node metastases ( P = 0.002 and P = 0.001, respectively, Mann–Whitney U test). Using receiver operating characteristic curves of ST ratio index for accuracy comparison of lymph node metastases, ST3Gal III and ST6Gal I were observed to be fairly interchangeable (area under the curve (AUC) of 3Gal I=0.810; AUC of 6Gal I=0.786, significance of difference between AUC=0.810). High ST6Gal I expression was associated with other invasive properties of cervical cancer, such as deep stromal invasion and presence of lymph–vascular space involvement. ST6Gal I expression seemed to be more enhanced in bigger tumors. Conclusions. Our results suggested that ST3Gal III and ST6Gal I were of importance for the lymph node metastases in FIGO IB1 cervical cancer patients; more specifically, overexpression of ST6Gal I was of crucial relevance for the presence of poor prognostic factors, such as deep stromal invasion and lymph–vascular space involvement and lymph node metastases.

Objective. The aim of this study was to study the presence of cytokeratin 19 (CK19)-expressing cancer cells in the blood of preoperative patients with FIGO stage Ib and IIb cervical cancers who received radical hysterectomy and to investigate the cells' clinical significance. Methods. CK19 mRNA in the blood cells of the patients was detected preoperatively by a newly designed nested reverse transcriptase–polymerase chain reaction, which excluded pseudogenes a and b, performed on 84 patients with stage Ib and IIb cervical carcinoma. Possible correlations between clinicopathological factors were then analyzed. Results. The sensitivity of this assay was 1 CK19-mRNA-positive cell per 10 6 peripheral blood mononuclear cells. Results showed that 21.4% of the 84 patients with cervical carcinoma had CK19-mRNA-positive cells in the blood, in comparison with 5.7% of the 35 patients with benign gynecological tumors and 0% of the 28 healthy controls ( P = 0.037 and 0.006, respectively). The positive tests in the cervical cancer patients were not associated with prognostic factors including stage, pelvic lymph node metastasis, pathological types, bulky tumor size (≥4 cm), differentiation, parametrial extension, lymphovascular space involvement, deep stromal invasion, or age. Conclusions. This study revealed the presence of circulating CK19-expressing cancer cells in the blood of patients with untreated early-stage cervical carcinomas, indicating that cervical cancer disseminated early. The survival effect of this phenomenon must be clarified. This detection assay provides an early checkpoint in the multistep process for developing metastasis in cervical cancer patients.

Carcinoma of the cervix is still common female cancer in Taiwan. A large portion of patients die of the disease in spite of various kinds of therapies and even the combination of multi-modality treatment.The current review includes a comprehensive review of the literature. Many new strategies and advanced in the management of cervical carcinoma have been the subject of this intense study and include assisted systems to improve sensitivity and specificity of Pap smear, human papillomavirus (HPV), and its vaccination, operation, radiation, chemotherapy, and combination of these strategies. Because of the constant failure rate, a systemic and critical review of the disease and management should be considered.With improvement of detection rate of pre-invasive cancer and popularity of screening protocol, the prevalence rate of cervical carcinoma decreases progressively. However, although new strategies in managing cervical carcinoma focus on combination therapy, the life quality and survival rate of these patients with cervical carcinoma only show beneficial in certain group patients.As to the complexity of both disease nature and various combinations in the diagnosis and treatment of cervical cancer, comprehensive quality control programs and large prospective multicenter trials are mandatory for establishing the "standard of care" adhered to the principles of evidence-based medicine.

To evaluate whether laparoscopic bipolar coagulation of uterine vessels (LBCUV) and supracervical amputation improve laparoscopic-assisted vaginal hysterectomy (LAVH).Prospective, randomized, longitudinal study (Canadian Task Force classification II-1).Private practice, university-affiliated hospital.Sixty-four women (age 31-52 yrs) with symptomatic myomatous uteri larger than 12 weeks on bimanual examination.LAVH with or without LBCUV and laparoscopic supracervical amputation followed by trachelectomy.LBCUV and laparoscopic supracervical amputation followed by trachelectomy and removal of the specimen vaginally were performed successfully in 29 women (group A). Hysterectomy was performed successfully in 32 comparable patients (group B) with severing of the round ligament, ovarian ligament, or infundibulopelvic ligament, and preparation of the bladder flap in the laparoscopic phase, and severing of uterine vessels and cardinal-uterosacral ligament complex through the vagina. Average blood loss was 169.8 and 308.7 ml in groups A and B, respectively (p0.05); average operating time was 126.4 and 152.8 minutes, respectively (p0.05); hemoglobin decreased on average 0.9 and 1.7 g/100 ml, respectively (p0.05). Conclusion. LBCUV and laparoscopic supracervical amputation followed by trachelectomy reduce operating time and blood loss in LAVH, and allow conversion of many abdominal procedures to laparoscopy.

Objective: To report a case of symptomatic arteriovenous malformation (AVM) of the uterus that was successfully treated with laparoscopic bipolar coagulation of uterine vessels. Design: Case report. Setting: University-affiliated tertiary referral center. Patient(s): A 66-year-old woman with symptomatic AVM of the uterus. Intervention(s): Laparoscopic bipolar coagulation of uterine vessels. Main Outcome Measure(s): Clinical symptoms, color Doppler sonographic examination, and pelvic magnetic resonance imaging. Result(s): Remarkable shrinkage of the lesion size, obvious decrease in all of the impedance measurements (pulsatility, resistance, velocity indexes [systolic/diastolic]), and freedom from symptoms. Conclusion(s): This modality is a new alternative method for the management of patients with symptomatic AVM of the uterus who do not respond to conservative treatment.

OBJECTIVE: To establish a cell line from a woman with malignant mixed mullerian tumor of the uterus and to examine the biologic properties of this cell line (MT-213-VGH). STUDY DESIGN: Cells were cloned by the limiting dilution method. Histologic staining of mixed mullerian (mesodermal) tumor (MMMT) cells was performed with May-Grunwald-Giemsa and hematoxylin and eosin stain. After more than 20 passages, cells were used to estimate the population-doubling time and colony-forming efficiency of MMMT cells, The cell line exhibited considerable variation in the degree of sensitivity to diverse chemotherapy drugs in vitro. RESULTS: MMMT cells containing antigens for vimentin and myoglobin were detected, but those for CA-125, carcinoembryonic anti-gen, cytoskeleton, desmin, epithelial membrane antigen and fibronectin were not found. In addition, MT-213-VGH cells contained a mucinous substance; its chromosome model number is 45. This cell line showed differential sensitivities to chemotherapeutic agents, such as bleomycin, cisplatin, 5-fluorouracil and vinblastine. CONCLUSION: The establishment and availability of the number cell line MT-213-VGH for a malignant mixed mullerian tumor of the uterus should assist in research on new methods of managing this type of gynecologic cancer.

During trophoblast invasion, luminal and glandular endometrial epithelial cells (EEC) have been found to undergo apoptosis through undetermined mechanisms. We postulate that nitric oxide (NO) and progesterone may mediate apoptosis in EEC because they are produced by trophoblasts at concentrations that can cause apoptosis in non-uterine cells. Using a cultured EEC line, RL95-2, we found that sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP), two commonly used NO-releasing agents, caused the death of EEC in a dose-dependent manner and progesterone markedly enhanced NO-induced cytotoxicity. Cells treated with NO/progesterone showed a significant increase in the percentage of condensed nuclei, as detected by DAPI staining, and in caspase-3 activity, indicating that these cells underwent apoptosis. Immunoblot analysis revealed that SNP/NO could activate extracellular signal-regulated kinase (ERK) and, to a lesser extent, p38 mitogen-activated protein kinase (MAPK). While pretreatment with PD98059 (an ERK inhibitor) did not prevent cell death, the addition of SB203580 (a p38 MAPK inhibitor) effectively rescued the cells from NO/progesterone treatment. Moreover, SNP/NO-induced p38 MAPK activation was significantly up-regulated by progesterone. Our results demonstrate that NO and progesterone may synergistically activate p38 MAPK to induce apoptosis in EEC, a process that may facilitate implantation.

With increasing use of assisted reproductive technologies (ART) and its related issues, the Ethics Committee of the Asia-Oceania Federation of Obstetrics and Gynecology (AOFOG), after discussion at its council meeting, took up the mission to understand the current legal and ethical aspects of this special subject in Asia-Oceania area before making proper recommendations. This Committee drafted a questionnaire to all 22 country member societies in 1995, and again conducted the same survey in 2000 to track changes in each country/region's laws and regulations. The results show that the current attitude and status of country member societies vary in a wide range and do not have formal legal codes in majority regulating the ethical aspects of ART. The use of ART and surrogacy is obviously affected by local traditions, popularity in the use of such techniques and cultural/religious concerns. The changes in 5 years are not major. Three countries do not as yet practice such techniques. However, liberalization of surrogate motherhood has become a trend. Five countries, compared with two only in 1995, are now available for surrogate motherhood, though regulated by strict criteria. Based on the data collected and issues discussed, a detailed guideline may not be generally applicable as each region has its own rules, reflecting differences in the management of ART, especially in the surrogate motherhood. This Committee therefore recommends that ART must be performed by a board certified gynecologist in a certification laboratory and surrogate motherhood must be used only for medical reasons and not be commercialized. The patients of this special group must be treated individually, based on this recommendation and the regulations of their own country/region.

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.

Objective. The aim of this study was to determine the potential clinical utility of tumor markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) in patients with FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix with low-risk clinicopathologic factors (negative lymph node metastasis, no lymphovascular space involvement, no bulky tumor size, no parametrial invasion, no deep stromal invasion, and well-differentiated cellular histology). Methods. A retrospective study was performed on 558 patients with FIGO stage IB–IIA and pathology-proven invasive squamous cell carcinoma of the uterine cervix, treated at the Veterans General Hospital, Taipei, between December 1986 and November 1990. Serum specimens were drawn before operation. A total of 140 assessable patients were enrolled into the study (including 109 stage IB patients and 31 stage IIA patients; all patients had no clinicopathologic risk factors and had at least one tumor marker datum). Survival curves were constructed according to the Kaplan–Meier method and survival curves were compared using the log-rank test. Results. In univariate analysis of survival, CEA, TPA, and SCC-Ag all have roles in the prediction of prognosis. In Cox proportional hazards model using CEA, TPA, and SCC-Ag as covariates, TPA demonstrated the most significant risk factor ( P = 0.031). Conclusions. We concluded that preoperative evaluation of serum TPA might be of great value in the prediction of survival of patients without any clinicopathologic risk factors and this special group of patients should be paid much attention in the follow-up period. From this study, preoperative elevation of TPA defines a group of otherwise low-risk invasive cervical cancer patients who are at high risk for recurrence. Adjuvant therapy might be necessary for this special subset of patients. A prospective study with a larger sample should be conducted to prove this particular finding.

Granulocyte colony-stimulating factor (GCSF) is a member of a family of glycoprotein hormones that stimulates the proliferation and differentiation of hematopoietic cells in vivo and in vitro. In ovarian cancer chemotherapy, GCSF is used clinically to build up bone marrow function after severe cytotoxicity to granulocytes by chemotherapy. Little is known about the effects of these cytokines on the growth of cancer cells. To study the influence of GCSF on the proliferation of ovarian cancer cells in vitro, five established ovarian cancer cell lines (OC-89-VGH, OC-117-VGH, OCPC-2-VGH, NIH-OVCAR-3, and NIH-SK-OV-3) were treated with the concentration ranging from 0.1 pg to 10 ng GCSF for 5 days and compared with vehicle control. In addition, we also examined the effect of GCSF (0.01–1.0 ng) on eight primary cultures of fresh ovarian cancer tissues. Cell viability after treatment was measured by Cell Titer AQueous assay and expressed as a percentage of untreated control cultures. A decrease in cell growth (75–85%) was observed in OC-89-VGH, OC-117-VGH and OCPC-2-VGH cell lines while NIH-OVCAR-3 and NIH-SK-OV-3 cells showed minimal growth stimulation. However, all dose-response curves were nonsignificant, suggesting indirect effects. In the eight fresh tumor primary cultures treated with GCSF, no statistical significant difference in growth was observed. In conclusion, our data suggest that GCSF has little or no growth-modulatory effect on human ovarian carcinoma in vitro. Therefore, the clinical use of GCSF is unlikely to have a direct effect on tumor growth.

The role of hyperbaric oxygenation in the treatment of radiation-induced sequelae and chronic ulcer is well established. On the contrary, a possible cancer-causing or growth-enhancing effect by hyperbaric oxygenation was highly controversial. Herein, we present a 55-year-old Chinese woman with recurrent squamous cell carcinoma of the cervix on her left inguinal area. She received concurrent chemoradiation therapy followed by radical inguinal lymphadenectomy due to persistent tumor mass. The patient was complicated with severe radiation fibrosis and unhealed wounds, so she was treated with hyperbaric oxygenation (HBO). However, the patient died of complications of the disease after completing HBO therapy 1 month later and autopsy of the patient showed carcinomatosis of the abdominal cavity and lower abdominal wall. Because previous studies have been inconclusive regarding the effect of HBO on tumor cells, we reviewed the possible relation between the HBO and tumor cells.

The objective of this study was to investigate and determine fitted percentiles of blood flow resistance of cervical internal carotid arteries in normal pregnancies from gestational weeks 20 to 42 and to compare the resistance indices and mean velocities of the these arteries in normotensive and preeclamptic gravidas. A duplex color apparatus with pulsed Doppler ultrasound scanner (7.5 MHz) was used to determine the resistance index and mean velocity values of maternal cervical internal carotid arteries in 310 healthy singleton gravidas (group 1) and 74 singleton preeclamptic gravidas (group 2). The resistance index and mean velocity values of the maternal cervical internal carotid arteries decrease as the gestational age increases in normal gravidas, whereas in preeclamptic pregnancies these values are no different from those in normal gravidas during the second half of the gestational period.