Doppler ultrasonography of the uterine artery and the response to chemotherapy in patients with gestational trophoblastic tumors.

PURPOSE: Increasing new blood vessel formation (neoangiogenesis) within tumors is an adverse prognostic factor for survival in several cancers. Neoangiogenesis is usually determined histopathologically and not in vivo. To assess neoangiogenesis in vivo, we have used Doppler ultrasonography (US) to measure the uterine artery pulsatility index (UAPI) in patients with gestational trophoblastic tumors (GTTs). Here, we assess whether the UAPI can provide independent prognostic information predictive of methotrexate resistance (MTX-R), a drug central to the management of GTT. EXPERIMENTAL DESIGN: All patients treated for GTTs between March 1994 and January 1999 had their records reviewed to determine their pretreatment Charing Cross Hospital (CXH) prognostic score, uterine volume, the lowest UAPI of either uterine artery, number of metastases, and human chorionic gonadotropin (hCG) concentration. Of the 164 patients for whom all data were available, 47 subsequently developed MTX-R, defined as a plateaued or rising hCG in two consecutive samples. RESULTS: UAPI, hCG, uterine volume, presence of metastases, and the overall CXH prognostic score were all predictive of MTX-R on univariate analysis. Moreover, the UAPI remained a significant independent predictor of MTX-R on multiple logistic regression analysis. After adjustment for the CXH prognostic score, the odds ratio for the risk of MTX-R in patients with a UAPI < or =1 compared with those with a UAPI >1 was 2.68 (95% confidence interval, 1.25-5.74; P = 0.01). The unadjusted odds ratio for the above comparison was 2.32 (95% confidence interval, 1.14-4.7; P = 0.02). CONCLUSIONS: The UAPI, as an indirect in vivo measure of functional tumor vascularity, independently predicts the response to chemotherapy in GTTs.

The role of Doppler sonography in assessment of malignant trophoblastic disease.

An observational study on the role of Doppler sonography in the assessment of patients with malignant trophoblastic disease was performed in an Oncology Unit of a University teaching hospital. A total of 32 consecutive patients referred for chemotherapy were recruited. Twenty-three non-pregnant and 18 women in the first trimester of pregnancy acted as controls. The patients were prospectively followed-up for 2 years. It was found that the uterine arterial resistance index and pulsatility index in patients who required chemotherapy were significantly lower when compared with the non-pregnant and pregnant controls; (Student t-test; P < 0.001 and P < 0.01, respectively). Stepwise regression analysis of beta-hCG titres on uterine artery resistance index showed significant correlation, after controlling for uterine volume (adjusted multiple R = 0.71, P < 0.00001). There were, however, no significant independent associations between the initial uterine artery resistance index and the need for chemotherapy, number of courses of chemotherapy required, duration required for the beta-hCG titre to return to normal, presence of metastatic disease, or the subsequent development of drug resistance or relapse. It was concluded that uterine arterial Doppler indices are significantly correlated with trophoblastic activity (beta-hCG titres) in malignant trophoblastic disease. However, their role in the prediction of subsequent tumour behaviour need to be assessed in larger series.

Vascular patterns of gestational trophoblastic tumors by color Doppler ultrasound.

BACKGROUND: Destruction of uterine vasculature is a common phenomenon in gestational trophoblastic tumors. The authors categorized such uterine vasculature by color Doppler ultrasound and studied its clinical significance. METHODS: Color Doppler ultrasound was performed in 28 patients with gestational trophoblastic tumors. The vascular morphologic manifestations were recorded, and the peak systolic velocity and resistance index of uterine artery were calculated. Serum beta-human chorionic gonadotropin (hCG) levels were measured periodically to monitor chemotherapy response. Seventeen uneventful postmole uteri were used as controls. Two-tailed Student's t-test and Fisher's exact test were used for statistical analysis. RESULTS: The gestational trophoblastic tumors were categorized as diffuse type (N = 7), lacunar type (N = 16), and compact type (n = 5) according to their vascular patterns. The mean serum beta-hCG level at diagnosis in diffuse type lesions (6608 +/- 6320 mIU/mL) was significantly lower than in the lacunar type (40462 +/- 39735 mIU/mL; P = 0.04) and compact type (212114 +/- 205126 mIU/mL; P = 0.02), whereas the level in compact type lesions was significantly higher than in the lacunar type (P = 0.003). Lacunar type lesions exhibited a significantly lower uterine artery resistance index (0.51 +/- 0.13) than diffuse type (0.66 +/- 0.10; P = 0.03) or compact type lesions (0.70 +/- 0.06; P = 0.02). All lesions exhibited significantly higher peak systolic velocity than control subjects (P < 0.001); however, no significant difference was observed among them. Brief courses (< 5 cycles) of chemotherapy cured more diffuse type (6 of 7) than lacunar type (3 of 15, P = 0.006) or compact type lesions (0 of 5, P = 0.008). Histopathologic diagnosis was available for 11 lesions. They were invasive mole in seven lacunar type lesions and choriocarcinoma in four compact type lesions. CONCLUSION: Vascular morphologic patterns of gestational trophoblastic tumors by color Doppler ultrasound correlated well with beta-hCG levels, uterine hemodynamics, chemotherapy response, and possibly the histopathologic diagnosis.

The utilization of Doppler ultrasonography with color flow mapping in the diagnosis and evaluation of malignant trophoblastic tumors.

The Doppler ultrasound with color flow mapping image has been recently applied for the evaluation of gynecologic diseases, in particular, malignant trophoblastic tumors with the characteristic abundant blood flow. Doppler color flow mapping of uterine artery and intratumoral blood vessels was performed at a regular interval in all 26 patients including 3 cases of lost for follow up. Systolic/diastolic (S/D) ratio representing blood flow was measured in 19 cases of malignant trophoblastic tumors and 7 cases of hydatidiform mole diagnosed at the department of Obstetrics and Gynecology, Yonsei University, College of Medicine. The initial mean S/D ratio and standard deviation(SD) of uterine artery in 11 remitted and 5 non-remitted patients were 2.72 +/- 1.31 and 2.69 +/- 1.80, respectively. No significant difference was noted between two groups. However, the final S/D ratio of uterine artery in remitted group showed significantly higher values than non-remitted group, of which values were 6.23 +/- 2.38 and 3.08 +/- 1.54, respectively (P < 0.05). In aspect of blood flow changes in malignant trophoblastic tumors after chemotherapy, remitted group showed entirely disappeared blood flow, while non-remitted group had persistent blood flow. The mean S/D ratio and SD measured in hydatidiform mole patients were 5.43 +/- 1.65, of which value reflects higher resistance than malignant trophoblastic tumors. Also blood flow was not detected in all cases. This study suggests that color flow mapping Doppler ultrasound can be a useful method in diagnosing and monitoring the treatment in malignant trophoblastic tumors along with the conventional serum beta-hCG titration.

The utilization of Doppler ultrasonography with color flow mapping in the diagnosis and evaluation of malignant trophoblastic tumors

The Doppler ultrasound with color flow mapping image has been recently applied for the evaluation of gynecologic diseases, in particular, malignant trophoblastic tumors with the characteristic abundant blood flow. Doppler color flow mapping of uterine artery and intratumoral blood vessels was performed at a regular interval in all 26 patients including 3 cases of lost for follow up. Systolic/diastolic (S/D) ratio representing blood flow was measured in 19 cases of malignant trophoblastic tumors and 7 cases of hydatidiform mole diagnosed at the department of Obstetrics and Gynecology, Yonsei University, College of Medicine. The initial mean S/D ratio and standard deviation(SD) of uterine artery in 11 remitted and 5 non-remitted patients were 2.72 +/- 1.31 and 2.69 +/- 1.80, respectively. No significant difference was noted between two groups. However, the final S/D ratio of uterine artery in remitted group showed significantly higher values than non-remitted group, of which values were 6.23 +/- 2.38 and 3.08 +/- 1.54, respectively (p< 0.05). In aspect of blood flow changes in malignant trophoblastic tumors after chemotherapy, remitted group showed entirely disappeared blood flow, while non-remitted group had persistent blood flow. The mean S/D ratio and SD measured in hydatidiform mole patients were 5.43 +/- 1.65, of which value reflects higher resistance than malignant trophoblastic tumors. Also blood flow was not detected in all cases. This study suggests that color flow mapping Doppler ultrasound can be a useful method in diagnosing and monitoring the treatment in malignant trophoblastic tumors along with the conventional serum beta-hCG titration.

Transvaginal color flow Doppler sonography in the assessment of gestational trophoblastic disease.

The aim of this study was to evaluate the blood flow characteristics of the uterine artery and intratumoral vessels in patients with GTD. Twelve patients with GTD were evaluated with TVS, and 11 also had CFD sonography performed. Spectral analysis of both uterine artery and samples intratumoral and intramyometrial vessels revealed systolic frequencies and PI that were significantly higher in the uterine artery than in sampled intratumoral vessels (P < 0.05). Uterine artery PI correlated significantly with age (P = 0.043), uterine size (P = 0.003), and beta-HCG titer (P = 0.03). Intratumoral PI correlated significantly with uterine size (P = 0.05). Intratumoral PI did not correlate with patient age, the shape or orientation of the uterus, presence or absence of subendometrial halo, endometrial thickness or echogenicity, or impression of myometrial invasion. Regression analysis of beta-HCG titers on uterine artery and intratumoral PI revealed a linear association. TVS and color flow Doppler sonography are useful in the assessment of patients with GTD. The PI is strongly associated with prognosis and correlates with beta-HCG titers.

Doppler assessment of the uterine circulation and the clinical behaviour of gestational trophoblastic tumours requiring chemotherapy.

The haemodynamics of the uterine arteries and myometrium were assessed using Doppler ultrasound in forty consecutive patients requiring treatment for invasive mole and choriocarcinoma. The investigations were performed prior to the commencement of chemotherapy and the subjects followed prospectively. The Doppler waveforms from the uterine arteries were analysed using the pulsatility index. It was found that patients with a pulsatility index of 1.1 or less were significantly more likely to develop drug resistance than those with a higher value (P < 0.04). There was no significant association between the pulsatility index and metastatic disease or uterine bleeding. Five out of eight patients who developed drug resistance could have avoided initial inadequate treatment if the Doppler findings were included in the scoring system for selecting chemotherapy for these tumours. It can be concluded that assessment of the uterine arteries using the pulsatility index prior to the treatment of patients with invasive mole and choriocarcinoma is of help in predicting those who will develop drug resistance.

Digital subtraction angiography for the evaluation of persistent uterine trophoblastic disease.

In three patients with persistent uterine trophoblastic disease, follow-up after primary chemotherapy was undertaken by digital subtraction angiography. It was found that the angiographic appearance of the intramural uterine lesions was comparable with that obtained by conventional pelvic angiography. Digital subtraction angiography may be applicable as an easy, safe, and valuable diagnostic method for gestational trophoblastic disease in place of conventional pelvic angiography because it is a relatively noninvasive procedure that can be performed on outpatients.

Spontaneous regression in choriocarcinoma and related gestational trophobalstic neoplasms.

Gestational trophoblastic neoplasia represents a biologic spectrum of tumors progressing from the hydatid mole, to invasive mole, and to choriocarcinoma. This progression is reflected in increasing degrees of aneuploidy in the respective lesions. Just as there is a natural tendency for the rejection of the trophoblast of a normal pregnancy culminating either in parturition or in spontaneous abortion, rejection of tumors of trophoblast occurs at any point in the progression of the disease spectrum. The unusual effectiveness of chemotherapy in trophoblastic disease may be related to this natural tendency to rejection. This tendency, in turn, is thought to derive from the genetic disparity between the maternal host and the tumor tissue of fetal origin, since the fetus possesses both maternal and fetal antigens.

[The angiographic diagnosis of trophoblastic tumours (author's transl)]. / Angiographische Diagnose der Trophoblasttumoren

Pelvic angiograms were performed on ten patients with trophoblastic tumours. Together with a history and HCG determinations the diagnosis can be made with certainty. It is not possible to differentiate between invasive moles and chorion carcinomas. The results of chemotherapy can be clearly evaluated. A normal pelvic angiogram does not exclude a trophoblastic tumour with complete certainty, since this can be localised to other organs. It has the advantage over curettage of being able to show very small tumours, as well as tumours not situated in the uterine cavity.