Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement.

OBJECTIVES: A panel of 14 physicians practicing medicine in the United States with expertise in radiology, obstetrics and gynecology, gynecologic oncology, hysteroscopy, epidemiology, and pathology was convened by the Society of Radiologists in Ultrasound to discuss the role of sonography in women with postmenopausal bleeding. Broad objectives of this conference were (1) to advance understanding of the utility of different diagnostic techniques for evaluating the endometrium in women with postmenopausal bleeding; (2) to formulate useful and practical guidelines for evaluation of women with postmenopausal bleeding, specifically as it relates to the use of sonography; and (3) to offer suggestions for future research projects. SETTING: October 24 and 25, 2000, Washington, DC, preceding the annual Society of Radiologists in Ultrasound Advances in Sonography conference. PROCEDURE: Specific questions to the panel included the following: (1) What are the relative effectiveness and cost-effectiveness of using transvaginal sonography versus office (nondirected) endometrial biopsy as the initial examination for a woman with postmenopausal bleeding? (2) What are the sonographic standards for evaluating a woman with postmenopausal bleeding? (3) What are the abnormal sonographic findings in a woman with postmenopausal bleeding? (4) When should saline infusion sonohysterography or hysteroscopy be used in the evaluation of postmenopausal bleeding? (5) Should the diagnostic approach be modified for patients taking hormone replacement medications, tamoxifen, or other selective estrogen receptor modulators? CONCLUSIONS: Consensus recommendations were used to create an algorithm for evaluating women with postmenopausal bleeding. All panelists agreed that because postmenopausal bleeding is the most common presenting symptom of endometrial cancer, when postmenopausal bleeding occurs, clinical evaluation is indicated. The panelists also agreed that either transvaginal sonography or endometrial biopsy could be used safely and effectively as the first diagnostic step. Whether sonography or endometrial biopsy is used initially depends on the physician's assessment of patient risk, the nature of the physician's practice, the availability of high-quality sonography, and patient preference. Similar sensitivities for detecting endometrial carcinoma are reported for transvaginal sonography when an endometrial thickness of greater than 5 mm is considered abnormal and for endometrial biopsy when "sufficient" tissue is obtained. Currently, with respect to mortality, morbidity, and quality-of-life end points, there are insufficient data to comment as to which approach is more effective. The conference concluded by identifying several important unanswered questions and suggestions that could be addressed by future research projects.

New developments in the sonographic assessment of ovarian, uterine, and breast vascularity.

Recent developments in ultrasound have presented new opportunities for assessing tissue vascularity and blood flow with ultrasound. These new methods include 3D imaging, power Doppler sonography, a variety of harmonic imaging techniques, ultrasound contrast agents, electronic compounding, and pulse sequencing methods that improve the signal-to-noise relationship as well as structural conspicuity. By using these technological advances, it is now possible to assess macroscopic blood flow in organs and tumors, and to assess changes in flow and vascularity that occur in response to therapeutic efforts. This review article describes and illustrates the concepts and methods used to evaluate vascularity and blood flow in tissues with ultrasound. It describes some of the potential clinical applications of these new techniques in the ovary, uterus, endometrium, adnexal vessels, and breast.

Quantified power Doppler US of tumor blood flow correlates with microscopic quantification of tumor blood vessels.

PURPOSE: To evaluate the ability of a quantified power Doppler ultrasonography (US) system to help quantitate differences in tumor vascularity after radiation therapy and administration of tumor necrosis factor (TNF). MATERIALS AND METHODS: Murine glioblastoma tumors were grown in the thighs of two sets of 25 mice each. Each mouse was assigned to one of four treatment groups: control (no treatment), radiation therapy, TNF therapy, or combination therapy (both radiation and TNF therapies). Mice were then evaluated with quantified power Doppler US, and a vascularity index (color area) was calculated for different tumor regions in each group. The tumors were then excised, and histologic evaluation was performed by using an immunofluorescence-tagged monoclonal antibody against blood vessel endothelium. The number of stained blood vessels per high-power field was correlated with the sonographically determined vascularity index. RESULTS: The color area of the total tumor decreased to 37% of that in the control group in mice treated with radiation therapy alone (P: =.02), 26% of that in the control group in mice treated with TNF alone (P: =.05), and 8% of that in the control group in those treated with both TNF and radiation (P: =.006). These results correlated well with the quantified results from immunofluorescent staining (r = 0.98). CONCLUSION: Quantified power Doppler US is a noninvasive method for the evaluation of tumor vascularity and blood flow.

Sonographic depiction of ovarian vascularity and flow: current improvements and future applications.

The objective of this image presentation is to update the reader with the current clinical applications and future developments concerning the sonographic depiction of ovarian vascularity and flow. This topic is discussed and illustrated using numerous figures that show actual images and their histologic correlation as well as illustrative drawings of central concepts. Color Doppler sonography is an accurate means to depict ovarian vascularity and flow. This information can be used to detect ovarian cancer and adnexal torsion. Future developments include the use of sonographic contrast agents and three-dimensional imaging. This report describes the current state of the art regarding Color Doppler sonography of ovarian vascularity and flow. It also describes areas for future research and development.

An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms.

OBJECTIVE: Our purpose was to evaluate the use of transvaginal ultrasonography for the detection of endometrial disease in a population of postmenopausal women who were without symptoms. STUDY DESIGN: Postmenopausal women were screened for potential inclusion in 2 multicenter, double-blind, placebo-controlled studies of 2 years' duration to evaluate the safety and efficacy of idoxifene in the prevention of osteoporosis. Baseline endometrial evaluation was performed by transvaginal ultrasonography and aspiration biopsy of the endometrium. RESULTS: A total of 1926 women were screened by transvaginal ultrasonography, and 1833 of them had endometrial thickness < or =6 mm. Five cases of endometrial abnormality (adenocarcinoma [n = 1] and atypical hyperplasia [n = 4]) were detected in the 1750 women from this cohort who underwent biopsy. The negative predictive value was >99%. One case of adenocarcinoma was detected in the 42 women who had endometrial thickness >6 mm and underwent biopsy. However, the sampling rate (45%) of women with endometrial thickness >6 mm was too low for confidence in the positive predictive value of 2%. CONCLUSIONS: Despite a high negative predictive value, transvaginal ultrasonography may not be an effective screening procedure for detection of endometrial abnormality in untreated postmenopausal women who are without symptoms.

New insights into transvaginal sonography of endometrial disorders.

This overview provides information regarding the clinical application of transvaginal sonography of the endometrium. The latest information is described and illustrated.

Three-dimensional color Doppler sonography before and after fibroid embolization.

Three-dimensional color Doppler sonography was performed within 1 hour, 1 day, 3 months, and 6 months of fibroid embolization in 20 patients who had a total of 31 fibroids greater than 2 cm in average dimension. The greatest decrease in vascularity occurred 1 day after the procedure, whereas the greatest volume change was found at the 3 month follow-up examination. In about one half of the patients scanned, depiction of fibroid vascularity by color Doppler sonography was found to improve the delineation of the size, location, and extent of myometrial involvement. Hypervascular fibroids (12 of 31) tended to decrease in size after treatment more than isovascular (10 of 31) or hypovascular ones (9 of 31). Additional investigations that are similar to this one will be needed to determine if three-dimensional color Doppler sonography can be used to predict those who will be responders, partial responders, or nonresponders to embolotherapy.

Sonographic depiction of tumor vascularity and flow: from in vivo models to clinical applications.

This review discusses and illustrates the sonographic depiction and quantification of tumor vascularity and flow using three-dimensional color Doppler sonography. The potential clinical applications mentioned here are based on work done with in vivo tumor models and as well as extensive clinical experience with this technique. Three-dimensional color Doppler sonography, as used with contrast agents and novel imaging techniques, has significant current and potential clinical application for detailed depiction of tumor vascularity and flow. This technique can provide important information concerning changes in tumor vascularity and flow related to various biologic, chemical, and radiation therapies as demonstrated in animals and a few human studies. Additional animal and human studies are needed for further refinement and eventual clinical application of this technique.

Sonographic assessment of endometrial disorders.

This overview describes the clinical applications of transvaginal sonography in the evaluation of women with suspected endometrial disorders. The role of sonohysterography is also presented as an additional test when evaluating women for possible endometrial disorders.

Quantified color Doppler sonography of tumor vascularity in an animal model.

This study was designed to evaluate the accuracy of a system to quantitate tumor vascularity with amplitude (power) color Doppler sonography two- and three-dimensionally. The vascularity of 20 transplanted murine tumors was determined with quantitated amplitude color Doppler sonography both two- and three-dimensionally and compared to tumor vascularity estimated by histologic examination. Serial examinations were performed 15, 30, 45, and 60 min after the injection of the exotoxin CM-101 and saline solution to assess changes in tumor vascularity. Three-dimensional amplitude color Doppler sonography best depicted the overall vascularity of tumor when compared to histologic estimation of vessel density. However, neither two- nor three-dimensional amplitude color power angiography correlated well to the microvessel count, probably a reflection of the difference in the method for vessel quantification using sonographic versus histologic techniques. Three-dimensional amplitude Doppler sonography correlated better with counts of large vessels (> 100 microm) as opposed to small vessels (> 15 microm). Time-activity curves showed no difference in tumor flow at the times measured in the experimental group injected with CM-101 or when compared to saline solutions in either the peripheral or central portions of the tumor. This three-dimensional amplitude color Doppler sonographic system affords global quantification of tumor vascularity and flow that may, in turn, be useful in determining the probability of malignancy (by determination of branching patterns and vessel regularity) or tumor response or both to treatment.

Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene.

Idoxifene is a novel selective estrogen receptor modulator that has shown beneficial effects on bone turnover and lipid metabolism in clinical studies. Preclinical studies have demonstrated that idoxifene has estrogen antagonist activities on the endometrium. This paper describes the results of a double-blind, placebo-controlled, and dose ranging study involving 331 osteopenic postmenopausal women who were treated with either placebo or idoxifene (2.5, 5, or 10 mg/day) for 12 weeks. In these women, endometrial assessment was carried out by transvaginal sonography and endometrial biopsy on selected patients at baseline and on all women at the end of treatment. Women with an endometrial thickness greater than 10 mm were excluded from the study. Aspiration endometrial biopsy was performed on women with an endometrial thickness between 6 and 10 mm at baseline and on all women after treatment. Of the 298 biopsies performed in the subjects at the end of treatment, 99% of the women were reported to have either a benign or atrophic endometrium (85%) or insufficient tissue for diagnosis (14%). Proliferative histologic features were reported in two cases (1%) (2.5 mg idoxifene) and atypical hyperplasia in one placebo patient. Even though idoxifene use was associated with a dose related increase in endometrial thickness as evaluated by transvaginal sonography, no relationship was established between endometrial histologic features and change in endometrial thickness. On histologic analysis, the increase in endometrial thickness seen on transvaginal sonography was not associated with proliferative or hyperplastic change in the epithelial (glandular) endometrial tissue. In 48 patients (16% of total) transvaginal sonography showed endometrial thickening of 5 mm or more over the study period. The endometrial histologic features were benign in all these patients. Nineteen percent of women developed intraluminal fluid, even though endometrial thickness was normal and unchanged and histologic features were normal. Our data show that after 3 months of treatment, no significant pathologic changes of the endometrium were observed. Our data indicate that measurements of endometrial thickness by transvaginal sonography may falsely suggest the presence of endometrial pathologic changes in some postmenopausal women treated with idoxifene. Additional testing using saline infusion sonohysterography is an important part of the transvaginal sonography protocol in equivocal or abnormal cases to exclude focal lesions such as polyps. In addition, our data indicate that pathologic changes of the endometrium are extremely rare in the treated group, indicative of its short term safety. Continued investigation such as this will be needed to establish long term safety.

Sonographic features of ovarian remnants.

Ovarian remnants occur after a portion of ovarian tissue is left behind unintentionally after oophorectomy. The ovarian remnant may be functional and cystic, producing pelvic pain and, in some patients, extrinsic compression of the distal ureter. Ovarian remnants frequently are associated with adhesions from previous pelvic surgery for endometriosis or pelvic inflammatory disease. Ovarian remnants also may be included within pelvic peritoneal inclusion cysts. In this retrospective study, the sonographic features of ovarian remnants in 10 patients with surgical proof or clinical follow-up data are described. Most ovarian remnants were simple cysts (seven of 10), three had multiple septations, and six had a rim of presumably ovarian tissue with arterial and venous flow. Three patients with ovarian remnant masses that were aspirated had symptomatic relief without recurrence. In one patient, guided aspiration was unsuccessful, probably owing to the presence of organized hemorrhage within the mass. Extrinsic compression of the distal ureter was observed in one patient, who was treated with gonadotropin releasing hormone agonist (Lupron). The sonographic findings of a completely cystic or multiseptated pelvic mass with a rim of vascularized solid tissue in a postoophorectomy patient, although such cases are rare, suggest the diagnosis of an ovarian remnant. If the diagnosis can be established with a high degree of certainty, sonographically guided aspiration may be attempted in an effort to provide symptomatic relief. Otherwise, sonography is useful in serial assessment of these masses in patients receiving medical treatment.

Diagnosis of ovarian torsion with color Doppler sonography: depiction of twisted vascular pedicle.

The purpose of this study was to assess the diagnostic value of ultrasonography for the detection of twisted vascular pedicle in ovarian torsion and to verify whether the blood flow alterations in the twisted vascular pedicle on color Doppler sonography can predict the viability of adnexal structures. In 28 of 32 patients with surgically proved torsion, the twisted vascular pedicle was detected preoperatively by ultrasonography, which shows a diagnostic accuracy of 87%. Arterial and venous flows were present in the twisted vessels on color Doppler sonography in 16 of 28 patients with a visible twisted vascular pedicle. In 11 patients who underwent adnexectomy, the pathologic findings revealed nonnecrotic ovaries in 10 patients. Untwisting of the twisted vascular pedicle was performed in five patients, and follow-up ultrasonography showed normal follicular development and ovulation. All 12 patients who showed no blood flow within the twisted vascular pedicle had necrotic ovaries. In conclusion, identification of the twisted vascular pedicle through ultrasonography is suggestive of ovarian torsion, and color Doppler sonography could be helpful in predicting the viability of adnexal structures by depicting blood flow within the twisted vascular pedicle.

Sonohysterography combined with sonosalpingography: correlation with endoscopic findings in infertility patients.

The diagnostic accuracy of sonohysterography combined with sonosalpingography or sonohysterosalpingography was evaluated in 100 infertility patients who also underwent endoscopic (hysteroscopy with or without laparoscopy) procedures. In patients with normal endometrial biopsy results, single endometrial layer thickness ranged from 3 to 5 mm and varied up to 2 mm in some areas. Diagnostic accuracy was 98% for submucosal fibroids, 96% for polyps, and 81% for synechiae. Missed lesions, were less than 2 mm in diameter. Tubal patency was successfully assessed in 79% of women with saline solution and in 92% of those who received contrast agent. This study demonstrates the efficacy of the combined use of SHG and SSG in infertility patients with uterine or tubal factor disorders.

Complex adnexal mass in pregnancy: predictive value of color Doppler sonography.

We sought to establish color Doppler sonographic criteria specific to benign and malignant neoplasms in pregnant patients for parameters already reported for complex adnexal masses in nongravid patients. Thirty-four patients with complex adnexal masses were evaluated during the second trimester with transabdominal sonography and transvaginal color Doppler sonography. The lowest pulsatility index obtained was chosen to be indicative of histologic type. A pulsatility index of less than 1.0 in a morphologically suspect area was taken to be suggestive of malignancy. Prospective diagnoses made by color Doppler sonography were compared with actual histologic diagnosis. Three malignant ovarian lesions and five tumors of low malignant potential were identified correctly, with a sensitivity of 0.89 and a mean pulsatility index of 0.71 (range, 0.44 to 1.3). The mean pulsatility index for benign masses was 1.21 (range, 0.4 to 2.8) (P = 0.03). The negative predictive value of a pulsatility index greater than 1.0 was 0.93. The positive predictive value and false-positive rate for a pulsatility index less than 1.0, however, were 0.42 and 0.48, respectively. Low impedance was associated with malignant ovarian masses detected during pregnancy. A considerable overlap in blood flow patterns, however, may cause incorrect assignment of malignant potential to some benign lesions.

Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model: preliminary results.

This study was designed to evaluate a system to quantitate vascularity and tumor blood flow with amplitude (power) color Doppler sonography. The vascularity of nine transplanted murine tumors was determined with quantitated amplitude color Doppler sonography and compared to tumor vascularity estimated by histologic examination. The system used seemed to provide an accurate depiction of the vascularity of tumor vis-àa-vis histologic estimation of vessel density (r = 0.80). Time-activity curves showed greater flow in the experimental group injected with an exotoxin than in the group injected with saline solution. Vascular density quantification with amplitude color Doppler sonography also was more accurate when an intravascular agent (such as an exotoxin) was used than when saline infusions were given. This quantification scheme may allow the development of a system to assess the probability of malignancy and to monitor tumor response to treatment on the basis of the vascularity of the mass.

Color Doppler sonography of tubal torsion.

These case reports illustrate the clinical and color Doppler sonographic findings in two cases of isolated tubal torsion. This condition may be associated with prior tubal ligation. The presence of high impedance or absent flow in a tubular structure in a patient with a history of tubal ligation should make one suspect this condition.