Elucidation of Racemization Process of Azaspirene Skeleton in Neutral Aqueous Media.

Azaspirene and related congeners, which possess various biological activities, have a unique spirocyclic core structure. However, there are few studies on the chemical properties of (-)-azaspirene, despite the fact that it may provide important insights into unveiling the biosynthetic pathway. Here, we report a nine-step chemical synthesis of an azaspirene analogue with a new finding that the natural (-)-azaspirene skeleton easily racemizes in neutral aqueous media.

Advanced Chemoembolization by Anti-angiogenic Calcium-Phosphate Ceramic Microspheres Targeting the Vascular Heterogeneity of Cancer Xenografts.

The purpose of the present study was to develop an advanced method of anti-angiogenic chemoembolization to target morphological vascular heterogeneity in tumors and further the therapeutic efficacy of cancer treatment. This new chemoembolization approach was designed using resorbable calcium-phosphate ceramic microspheres (CPMs), in a mixture of three different sizes, which were loaded with an anti-angiogenic agent to target the tumor vasculature in highly angiogenic solid tumors in humans in vivo. The human uterine carcinosarcoma cell line, FU-MMT-3, was used in this study because the tumor is highly aggressive and exhibits a poor response to radiotherapy and chemotherapeutic agents that are in current use. CPMs loaded with TNP-470, an anti-angiogenic agent, were injected into FU-MMT-3 xenografts in nude mice three times per week for 8 weeks. The treatment with TNP-470-loaded CPMs of three different diameters achieved a greater suppression of tumor growth in comparison to treatment with single-size TNP-470-loaded CPMs alone, and the control. Severe loss of body weight was not observed in any mice treated with any size of TNP-470-loaded CPMs. These results suggest that treatment with a mixture of differently-sized anti-angiogenic CPMs might be more effective than treatment with CPMs of a single size. This advanced chemoembolization method, which incorporated an anti-angiogenic agent to target the morphological vascular heterogeneity of tumors may contribute to effective treatment of locally advanced or recurrent solid tumors.

Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo.

Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Recent studies have shown high angiogenic activities of this tumor, hence anti-angiogenic approaches are expected to provide new treatment strategies for this tumor. In previous work, azaspirene was isolated from Neosartorya sp. fungi, and in vitro anti-angiogenic activities were shown. In the present study, the anti-angiogenic effects of azaspirene analogs, synthetic molecules with a shorter ethyl group replacing a hexadienyl side-chain of the natural compound, were assessed in vitro using human umbilical vein endothelial cells (HUVECs) co-cultured with FU-MMT-3 human uterine carcinosarcoma cells. The anti-tumor and anti-angiogenic effects of these analogs were also evaluated in vivo using FU-MMT-3 xenografted tumors in nude mice. The azaspirene analogs inhibited the tube formation of HUVECs induced by FU-MMT-3 cells in vitro and significantly suppressed tumor growth in vivo compared to the untreated group (control). A significant reduction of the microvessel density in tumors was observed, in comparison to the control. No apparent toxicity, including body loss, was observed in any mice treated in this study. These azaspirene analogs may be effective against uterine carcinosarcoma, possibly acting via potent anti-angiogenic effects.

Development of a Cancer Treatment with the Concomitant Use of Low-Intensity Ultrasound: Entering the Age of Simultaneous Diagnosis and Treatment.

In recent years, studies using ultrasound energy for cancer treatment have advanced, thus revealing the enhancement of drug effects by employing low-intensity ultrasound. Furthermore, anti-angiogenesis against tumors is now attracting attention as a new cancer treatment. Therefore, we focused on the biological effects and the enhancement of drug effects brought by this low-intensity ultrasound energy and reported on the efficacy against a uterine sarcoma model, by implementing the basic studies, for the first time, including the concomitant use of low-intensity ultrasound irradiation, as an expected new antiangiogenic therapy for cancer treatment. Furthermore, we have succeeded in simultaneously utilizing low-intensity ultrasound in both diagnosis and treatment, upon real time evaluation of the anti-tumor effects and anti-angiogenesis effects using color Doppler ultrasound imaging. Although the biological effects of ultrasound have not yet been completely clarified, transient stomas were formed (Sonoporation) in cancer cells irradiated by low-intensity ultrasound and it is believed that the penetration effect of drugs is enhanced due to the drug being more charged inside the cell through these stomas. Furthermore, it has become clear that the concomitant therapy of anti-angiogenesis drugs and low-intensity ultrasound blocks the angiogenic factor VEGF produced by cancer cells, inhibits the induction of circulating endothelial progenitor cells in the bone marrow, and expedites angiogenic inhibitor TSP-1. Based on research achievements in recent years, we predict that the current diagnostic device for color Doppler ultrasound imaging will be improved in the near future, bringing with it the arrival of an age of "low-intensity ultrasound treatment that simultaneously enables diagnosis and treatment of cancer in real time."

AG73-modified Bubble liposomes for targeted ultrasound imaging of tumor neovasculature.

Ultrasound imaging is a widely used imaging technique. The use of contrast agents has become an indispensible part of clinical ultrasound imaging, and molecular imaging via ultrasound has recently attracted significant attention. We recently reported that "Bubble liposomes" (BLs) encapsulating US imaging gas liposomes were suitable for ultrasound imaging and gene delivery. The 12 amino acid AG73 peptide derived from the laminin α1 chain is a ligand for syndecans, and syndecan-2 is highly expressed in blood vessels. In this study, we prepared AG73 peptide-modified BLs (AG73-BLs) and assessed their specific attachment and ultrasound imaging ability for blood vessels in vitro and in vivo. First, we assessed the specific attachment of AG73-BLs in vitro, using flow cytometry and microscopy. AG73-BLs showed specific attachment compared with non-labeled or control peptide-modified BLs. Next, we examined ultrasound imaging in tumor-bearing mice. When BLs were administered, contrast imaging of AG73-BLs was sustainable for up to 4 min, while contrast imaging of non-labeled BLs was not observed. Thus, it is suggested that AG73-BLs may become useful ultrasound contrast agents in the clinic for diagnosis based on ultrasound imaging.

CD133+ cancer stem cell-like cells derived from uterine carcinosarcoma (malignant mixed Müllerian tumor).

Cancer stem cells (CSCs) that display tumor-initiating properties have recently been identified. CD133, a surface glycoprotein linked to organ-specific stem cells, has been described as a marker of CSCs in different tumor types. We herein identify and characterize CSCs in human uterine carcinosarcoma (malignant mixed Müllerian tumor), which is one of the most aggressive and therapy-resistant gynecological malignancies and is considered to be of mesodermal origin. The CD133(+) population was increased in uterine carcinosarcoma, and this population showed biphasic properties in the primary tumor. CD133(+) cells predominantly formed spheres in culture and were able to differentiate into mesenchymal lineages. CD133(+) cells were more resistant to cisplatin/paclitaxel-induced cytotoxicity in comparison with CD133(-) cells. A real-time polymerase chain reaction analysis of the genes implicated in stem cell maintenance revealed that CD133(+) cells express significantly higher levels of Oct4, Nanog, Sox2, and Bmi1 than CD133(-) cells. Moreover, CD133(+) cells showed a high expression level of Pax2 and Wnt4, which are genes essential for Müllerian duct formation. These CD133(+) cells form serially transplantable tumors in vivo and the resulting CD133(+) tumors replicated the EpCAM, vimentin, and estrogen and progesterone receptor expression of the parent tumor, indicating that CSCs likely differentiated into cells comprising the uterine carcinosarcoma tissue. Moreover, strong CD133 expression in both epithelial and mesenchymal elements in primary tumor demonstrated significant prognostic value. These findings suggest that CD133(+) cells have the characteristics of CSCs and Müllerian mesenchymal progenitors.

Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts.

Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Metronomic chemotherapy is accepted as a new approach for cancer treatment, and its underlying mechanism seems to involve the suppression of angiogenesis. However, the efficacy of metronomic and anti-angiogenic therapies against uterine carcinosarcoma is unknown. The anti-angiogenic effect of doxifluridine was assessed in vitro using human umbilical vein endothelial cells (HUVEC) co-cultured with FU-MMT-1 human uterine carcinosarcoma cells. The antitumor and anti-angiogenic effects of metronomic doxifluridine (delivered via oral gavage) in combination with TNP-470 were evaluated in vivo. Tumor vascularity was assessed by contrast-enhanced color Doppler ultrasound, laser Doppler and microvessel density staining. Doxifluridine suppressed tube formation of HUVEC and vascular endothelial growth factor production by FU-MMT-1 cells. Metronomic doxifluridine alone significantly suppressed tumor growth compared with the untreated (control) group, while metronomic doxifluridine in combination with TNP-470 significantly inhibited tumor growth compared with each treatment alone. A significant reduction of intratumoral vascularity was observed in FU-MMT-1 xenografts following treatment with metronomic doxifluridine in combination with TNP-470, as compared with each treatment alone. Intestinal bleeding was only observed when the maximum tolerated dose of doxifluridine was administered in combination with TNP-470. Metronomic doxifluridine chemotherapy in combination with TNP-470 might be effective for uterine carcinosarcoma without marked toxicity, possibly acting via its potent anti-angiogenic effects. Clinical studies are needed to evaluate the safety and efficacy of this treatment in humans.

Clinical usefulness of contrast-enhanced color Doppler ultrasonography in invasive and noninvasive gestational trophoblastic diseases: a preliminary study.

OBJECTIVE: To examine the usefulness of contrast-enhanced color Doppler ultrasonography (CDU) in differentiating between invasive and noninvasive gestational trophoblastic disease (GTD). STUDY DESIGN: In 23 patients with findings suggestive of GTD by transvaginal gray-scale ultrasonography, the presence or absence of blood flow within uterine lesions was assessed by contrast-enhanced CDU using Levovist (Schering, Berlin, Germany) microbubble contrast agent. Intratumoral blood flow waveforms were analyzed using resistance indices. Tumor size in each invasive or malignant GTD was assessed by magnetic resonance imaging. RESULTS: Intratumoral blood flow was detected in all invasive or malignant GTDs (7/7: 5 invasive moles, 1 choriocarcinoma and 1 placental site trophoblastic tumor), whereas it was not seen in any noninvasive GTD (0/16:10 complete moles, 5 partial moles and 1 exaggerated placental site) (p <0.0001). A marked increase in uterine vascularity was thus shown in all invasive or malignant GTDs following enhancement. In small invasive moles (<2 cm) in the uterine myometrium, color flow was remarkably increased by contrast-enhanced CDU. Intratumoral blood flow waveforms showed low resistance indices in all invasive and malignant GTDs. CONCLUSION: Contrast-enhanced CDU may be useful in differentiating invasive or malignant GTDs from noninvasive GTDs. By enhancing color flow, this minimally invasive approach may be helpful for detecting small invasive GTD lesions within the uterine myometrium.

Metronomic irinotecan chemotherapy combined with ultrasound irradiation for a human uterine sarcoma xenograft.

Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic irinotecan combined with low-intensity ultrasound (US) in human uterine sarcoma and evaluated its antiangiogenesis mechanism by measuring the circulating endothelial progenitor cells (CEP), a surrogate marker of angiogenesis. A human uterine sarcoma cell line, FU-MMT-3, was used in the present study because this tumor is one of the most malignant neoplasms of human solid tumors and it also has a high angiogenesis property. The combination of low-dose irinotecan and US irradiation significantly inhibited the tube formation of HUVEC and vascular endothelial growth factor expression of tumor cells in vitro. The FU-MMT-3 xenografts in nude mice were treated using US at a low intensity (2.0 w/cm(2), 1 MHz) for 4 min three times per week each after the intraperitoneal administration of irinotecan; this treatment was continued for 5 weeks. The tumor vascularity was assessed by contrast-enhanced color Doppler US in real time. The combination treatment significantly inhibited the mobilization of CEP and intratumoral vascularity compared with the control. This combination therapy showed a significant reduction in tumor volume, resulting in a significant prolongation of survival, in comparison with each treatment alone. These results suggest that the effect of metronomic chemotherapy for human uterine sarcoma was accelerated by US irradiation in vivo and this combination might therefore be potentially effective for new cancer therapy.

Evidence-based guidelines for treatment of uterine body neoplasm in Japan: Japan Society of Gynecologic Oncology (JSGO) 2009 edition.

Endometrial carcinoma is one of the most common gynecologic malignancies in Japan and its incidence has increased recently. Although surgery is the cornerstone of the management of patients with endometrial cancer, there is significant variation in Japan with regard to the type of hysterectomy employed. Additionally, it remains controversial whether full nodal staging is required in all patients. Furthermore, adjuvant therapy differs between Japan and Western countries. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006 and revised in 2009. The 2009 edition included topics not addressed in the previous edition including the treatment of mesenchymal tumors, for example leiomyosarcoma, and sections covering the treatment of serous and clear-cell adenocarcinoma. These guidelines are composed of nine chapters and include nine algorithms. The guidelines also contain fifty-one clinical questions (CQs) and each CQ consists of recommendations, background, explanations, and references. The treatment recommendations herein are tailored to reflect current Japanese clinical practice and ensure equitable care for all Japanese women diagnosed with endometrial cancer.

Primary leiomyosarcoma of the fallopian tube.

Primary sarcoma of the fallopian tube is a very rare neoplasm. We report the case of a 69-year-old woman affected with leiomyosarcoma of the left fallopian tube. Her chief complaint was lower abdominal pain. The preoperative diagnosis was a left adnexal malignant tumor based on pelvic examination, abdominal computed tomography, and magnetic resonance imaging. Following a laparotomy, she was ultimately diagnosed with a FIGO IIc fallopian tube leiomyosarcoma. She was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, partial omentectomy, and low anterior resection for rectal invasion. The patient subsequently received adjuvant chemotherapy with pirarubicin and ifosfamide. Thirty months after the first therapy, a computed tomography scan revealed metastasis of the liver, lung, and supraclavicular lymph node. The patient died of the disease 39 months after the initial treatment.

Novel chemoembolization using calcium-phosphate ceramic microsphere incorporating TNP-470, an anti-angiogenic agent.

The purpose of the present study was to develop a new method of chemoembolization to improve the therapeutic effectiveness and safety profile of cancer treatment. A chemoembolization approach was designed for human solid tumors using resorbable calcium-phosphate ceramic microspheres loaded with an agent anti-angiogenic to tumor vasculature in vivo. The human uterine sarcoma cell line FU-MMT-3 was used in this study because this tumor is aggressive and also exhibits a poor response to radiotherapy or any chemotherapy currently used. The calcium-phosphate ceramic microspheres loaded with TNP-470, an anti-angiogenic agent, were injected into FU-MMT-3 xenografts in nude mice three times per week for 8 weeks. The treatment using TNP-470-loaded microspheres suppressed tumor growth, compared to treatment with TNP-470 alone, microspheres alone, and the control. The mean tumor weight after treatment using TNP-470-loaded microspheres was significantly lower than that after treatment with microspheres alone. These ceramic microspheres were remarkably embolized in tumor microvessels as well as in the feeding arteries and a significant reduction of intratumoral vascularity was also demonstrated following treatment with TNP-470-loaded microspheres. Severe loss of body weight was not observed in any mice treated with the TNP-470-loaded microspheres, compared to treatment with TNP-470 alone. These results suggest that targeting tumor vasculature in human uterine sarcoma using calcium-phosphate microspheres might be more effective and safer than the treatment that employs anti-angiogenic agent alone. This new chemoembolization method incorporating an anti-angiogenic agent may contribute to the effective treatment of locally advanced or recurrent solid tumors.

Monitoring of endometrial K-ras mutation in tamoxifen-treated patients with breast cancer.

INTRODUCTION: A high incidence of endometrial K-ras mutations has been reported in tamoxifen (TAM)-treated patients with breast cancer. We examined the changes in the frequency of the endometrial K-ras mutations after the cessation of TAM treatment. METHODS: DNA was extracted from fresh cytological or polypectomy samples of the endometrium in 28 patients who had undergone TAM treatment of breast cancer. Mutations were detected by an enriched polymerase chain reaction-enzyme-linked minisequence assay (Sumitomo Metal Industry, Inc, Tokyo, Japan). K-ras codon 12 mutations were monitored in these 28 patients. RESULTS: An initial examination detected endometrial K-ras mutations in 13 of the 28 patients. However, repeated examinations performed after cessation of TAM treatment did not detect endometrial K-ras mutations in any of these 13 patients. No endometrial K-ras mutation has been detected in the repeated examinations performed for these patients for more than 2 years since the cessation of TAM treatment. In addition, the 15 patients who did not have endometrial K-ras mutations in the initial examination did not demonstrate them in repeat examinations. CONCLUSIONS: The cessation of TAM treatment may reduce the risk of developing endometrial cancers through K-ras mutations.

The efficacy of preoperative hormonal therapy before laparoscopic cystectomy of ovarian endometriomas.

AIM: The aim of this study was to investigate the influence of preoperative hormonal therapy before laparoscopic cystectomy of ovarian endometriomas. We identified differences in follicle loss and surgical difficulties with or without preoperative hormonal therapy. METHODS: Ninety-six patients with ovarian endometrioma underwent a laparoscopic cystectomy. Patients were divided into three groups: control group A (53 patients, 57 cysts) with no preoperative hormonal therapy; group B (34 patients, 40 cysts) who received gonadotropin-releasing hormone agonist therapy; and group C (9 patients, 11 cysts) who received danazol therapy before surgery. The medical and videotape records of all patients were retrospectively reviewed. The specimens of endometriomas were histologically evaluated. RESULTS: Mean diameters of endometriomas before hormonal therapy in groups B and C were significantly greater than those in the control group. There were no significant differences in the following: the mean diameter of removed cysts, the revised-American Society of Reproductive Medicine scores, the number of capsules containing follicle(s), and the mean number of follicles attached to a cyst. However, the number of capsules showing fibrosis significantly increased in the preoperative hormonal therapy groups (P < 0.001). Furthermore, the mean operation time of the preoperative hormonal groups was significantly longer than that of the control group (P < 0.01, P < 0.001). CONCLUSION: Our data suggested that preoperative hormonal therapy reduced the size of endometriomas. However, with similar revised-American Society of Reproductive Medicine scores, preoperative hormonal therapy did not contribute to the reduction of the loss of ovarian follicles. Fibrosis resulting from hormonal therapy appears to be responsible for these observations.

Endometrial cytologic findings in tamoxifen-treated breast cancer patients.

OBJECTIVE: To describe the endometrial cytologic findings in tamoxifen (TAM)-treated patients and evaluate the clinical significance of these findings. STUDY DESIGN: A total of 1,739 endometrial cytologic samples were obtained from 203 breast cancer patients with TAM treatment using an endocyte device. Histologic examinations were recommended for the 23 endometrial cytologic samples (18 initial and 5 follow-up endometrial cytologic samples). These 23 samples were cytopathologically reviewed. RESULTS: A large nuclear dimension and anisokaryosis of the endometrial glandular cells were found in the 23 endometrial cytologic samples. All patients were amenorrheic and postmenopausal except for 3 premenopausal women with endometrial cancer. The subsequent histologic examinations showed 3 atrophic endometria, 3 cystic atrophies, 11 endometrial polyps and 6 endometrial cancers. The tumor diathesis and atypical features of cell aggregates, such as a loss of polarity and severe piling up of nuclei, were seen in the cytologic samples of the endometrial cancers but were not found in those with benign conditions. CONCLUSION: A large nuclear dimension and anisokaryosis of the glandular cells were sometimes found in endometrial cytologic samples from the TAM-treated patients. The atypical characteristics of the cell aggregates with these types of cellular atypia are useful for the cytologic assessment of malignancy.

[The efficacy and safety of indisetron hydrochloride for the management of nausea/vomiting caused by chemotherapy for gynecologic cancer].

This clinical trial was designed to evaluate the efficacy and safety of indisetron hydrochloride an oral 5-HT3 receptor antagonist, for the management of nausea/vomiting caused by chemotherapy for gynecologic cancer with paclitaxel/ carboplatin or docetaxel/carboplatin. Indisetron hydrochloride(8 mg)was administered orally to 46 gynecologic cancer patients at 0.5 hours before administration of the above chemotherapy agents. Number of patients who showed nausea or vomiting for 24 hours was counted. The complete vomiting inhibition rate at 24 hours after chemotherapy was 89.1%(41/46), and nausea inhibition rate was 71.7%(33/46). No serious adverse events were observed. These findings indicate that prophylactic administration of indisetron hydrochloride is safe and useful for inhibition of nausea/vomiting caused by cancer chemotherapy.

The sonohysterographic difference in submucosal uterine fibroids and endometrial polyps treated by hysteroscopic surgery.

OBJECTIVE: The purpose of this study was to clarify the differences in sonohysterographic (SHG) findings between submucosal uterine fibroids and endometrial polyps treated by surgical hysteroscopy. METHODS: Eighty patients with intrauterine benign masses without any endometrial cytologic atypia were examined by SHG before undergoing surgical hysteroscopy. The SHG images in these masses were assessed for the following characteristics: size, number, location, echogenicity, and degree of projection into the uterine cavity. The SHG findings were then compared with their hysteroscopic findings. The feeding vessels into these masses were also assessed by transvaginal color Doppler sonography in 26 of the 80 patients. RESULTS: In all 80 patients, 47 histopathologically had submucosal fibroids, whereas the remaining 33 had endometrial polyps. Masses measuring greater than 20 mm were significantly more frequently fibroids than polyps (P < .01). Homogeneous hyperechoic masses were significantly seen in polyps (93.9% [31/33]; P < .01) but not in any fibroids except for 1 case. Multiple feeding vessels were significantly found in fibroids (12/15; P < .01), whereas they were not found in any of the 11 polyps examined. The location and degree of projection into the uterine cavity of these masses as assessed by SHG were consistent with their hysteroscopic findings in 78 (97.5%) of 80 patients. The foci of endometrial hyperplasia were significantly found in 5 (15.2%) of 33 polyps (P < .01), whereas no such tissues were obtained in any fibroids. CONCLUSIONS: Intracavitary fibroids tend to be larger than the polyps, and homogeneous hyperechoic masses in the uterine cavity observed by SHG are highly suggestive of endometrial polyps.

Antitumor effect of TNP-470, an angiogenesis inhibitor, combined with ultrasound irradiation for human uterine sarcoma xenografts evaluated using contrast color Doppler ultrasound.

Microvascular endothelial cells, which are recruited by tumors, have become an important target in cancer therapy. This study firstly examined the antitumor effect of angiogenesis inhibitor combined with ultrasound (US) irradiation for human cancer in vivo and evaluated its vascularity using color Doppler US in real time with a microbubble US contrast agent. A human uterine sarcoma cell line, FU-MMT-1, was used in vivo because this tumor is one of the most malignant neoplasms of the human solid tumors and it also has a poor response to any of the chemotherapeutic agents currently used, as well as to radiotherapy. In angiogenic inhibitors, TNP-470 was selected to use in an in vivo study, because this agent showed a higher inhibitory effect in tube formation assay in vitro, than that of FR118487, or thalidomide. The FU-MMT-1 xenografts in nude mice were treated using US at a low-intensity (2.0 w/cm(2), 1MHZ) for 4 min three times per week each after the subcutaneous injection of TNP-470 (30 mg/kg), an angiogenesis inhibitor, and this treatment was continued for 8 weeks. Either treatment of US alone or TNP-470 alone showed a suppression of tumor growth, in comparison to the non-treatment group (control), and a significantly enhanced effect was obtained using the combined treatment. A reduction in the intratumoral vascularity, which was evaluated using both color Doppler and immunohistochemistry, was significantly demonstrated using the combined treatment, in comparison to each treatment alone, and the control. No side-effect was observed in any mice in the combined treatment group. These results suggest that the antitumor effect of TNP-470 for uterine sarcoma was accelerated by US irradiation in vivo and this combination might be a potentially effective for new cancer therapy.

Sonographic findings of transvaginal color Doppler ultrasound in ectopic pregnancy.

PURPOSE: The objective of this study was to retrospectively assess whether the sonographic findings from transvaginal color Doppler ultrasound (TV-CDU) are helpful in the diagnosis of ectopic pregnancy. METHODS: Thirty-four patients who received surgery for ectopic tubal pregnancies were preoperatively evaluated using TV-CDU. The presence or absence of color vascularity within the ectopic masses was examined. The relationship between the presence or absence of blood flow in the tubal mass and the corpus luteum cyst, or the serum ß-hCG values, was evaluated. RESULTS: Color vascularity within the adnexal mass was detected in 27 of 34 (79.4%) patients with ectopic pregnancies by TV-CDU. Color vascularity within the mass was observed in 18 of 24 (75.0%) patients with a questionable adnexal mass that had no obvious gestational sac in B-mode images. Moreover, color vascularity was seen in all four patients with a serum ß-human chorionic gonadotropin (ß-hCG) value of less than 500 mIU/ml. However, it was difficult to identify the blood flow of the adnexal mass in six of the nine (66.7%) patients with a corpus luteum cyst in the ipsilateral ovary. No relationship was observed between the serum ß-hCG concentrations and the resistance indices, or the peak systolic velocity. CONCLUSIONS: The detection of color vascularity by TV-CDU in patients with an ectopic pregnancy is helpful for diagnosis, especially for patients with either a questionable adnexal mass in B-mode images or lower serum ß-hCG concentrations.