Chapter 35: SONOGRAPHIC TECHNIQUES FOR EARLY DETECTION OF OVARIAN AND ENDOMETRIAL CANCERS

This chapter discusses and illustrates factors that influence the efficacy of screening and early detection schemes for ovarian and endometrial cancers using transvaginal sonography (TVS) and related techniques such as color Doppler sonography (CDS), three-dimensional sonography (3DS), and contrast-enhanced harmonic TVS (CE-TVS). The role of sonography in these 2 common gynecologic cancers is considered together in this chapter, because TVS can be used to evaluate both neoplasms. Sonography is probably best used in a multimodal scheme including certain lab tests for the detection and evaluation of these gynecologic cancers.^{1,2,3,4,5,6,7,8,9,10,11, and 12}

Of these 2 cancers, TVS clearly has a greater potential role for early detection of early-stage ovarian cancer, which is difficult to detect by nonspecific or minimal symptomatology (as compared to advanced-stage disease with diffuse carcinomatosis) when compared to endometrial cancer, which is typically associated with postmenopausal uterine bleeding.

We present the potential role of TVS for the detection of both ovarian and endometrial cancer in this chapter to emphasize differences in their presentation, clinical course, and potential for earlier detection with sonographic techniques. Another reason to include discussion of these 2 common gynecologic cancers is the fact that there are recognizable TVS findings for the early stages of both ovarian and endometrial cancer. In addition, TVS can be used to evaluate both of these entities in the same patient. Admittedly, the potential lethality, prevalence, and clinical presentations of these 2 cancers are quite different.

In this chapter, identification of an appropriate screening population consisting of women at greatest risk for ovarian cancer by clinical history, CA-125, breast/ovarian cancer genetic analysis (BRCA1 and BRCA2), and proteomics is discussed. Women with risk factors for endometrial cancer such as obesity, diabetes, anovulation, polycystic ovarian syndrome, and hypertension are also excellent candidates to benefit from early detection.^1,2 Used for this purpose, TVS has high negative predictive value but is limited by a relatively high false-positive rate.

Additional sonographic imaging using 3D- and/or contrast-enhanced sonographic techniques may improve early detection of ovarian cancer.^{13,14,15, and 16} These will be mentioned as they relate to improving screening efficacy, taking into consideration their incremental cost and requirements for increased technical expertise.

As of 2007 ovarian and endometrial cancers each accounted for over 22,000 deaths of American women yearly—approximately half as many deaths as breast cancer (Table 35-1). However, unlike breast cancer, there are currently no available, effective screening mechanisms in place to prevent mortality from these diseases. In the introductory comments of this chapter, we explore the challenges and possibilities for screening and early detection of these cancers and discuss the role of sonographic techniques in providing early diagnosis of both ovarian and endometrial cancer. The discussion will be divided into separate sections dealing with ovarian and endometrial cancers.

Recent studies have reported that TVS with CDS, 3D, and/or contrast used as a secondary test can effectively detect ovarian and endometrial cancers in their earliest stages. In fact, it has been suggested that combining the evaluation of the endometrium with screening for ovarian cancer with TVS may potentially approximate the chance of detection of breast cancer with mammography (see Table 35-1).^1,2 The actual efficacy of combined testing using laboratory and imaging techniques (multimodality) will be determined after the data from large-scale trials currently being conducted in several countries and regions of the world, including the United States, United Kingdom, Scandinavia, and Japan, is analyzed several (5 to 10) years from now. However, some practicing gynecologists have begun to offer sonographic screenings to their patients in their office, whereas others have are actively screening only for those considered to be at high risk.^3,4

Recent improvements in serum screening as well as sonographic imaging have generated major interest in the potential of combined (multimodal) serum and imaging screening. Serum biomarker assays can involve immunologic assay of certain serum analytes or mass spectroscopy of proteins and gene products (proteomics). Proteomic analysis involving microcapillary high-performance liquid chromatography (HPLC) and mass spectroscopy can detect femtomolar concentrations of serum proteins and is reported to be highly accurate.⁵ One study of 50 women with known ovarian cancer and 66 with non-cancer reported sensitivity of 100%, specificity of 99%, and positive predictive value of 94%.⁵ Another serum assay of 4 analytes including leptin, prolactin, osteopontin, and insulin-like growth factor in 106 controls and 100 women with ovarian cancer reported sensitivity of 95%, specificity of 95%, a positive predictive value of 95%, and a negative predictive value of 94%.⁶ Neither of these tests are currently clinically available, but they have great potential to be part of a multimodal screening scheme including TVS.

Another factor associated with increased risk (30% to 40%) of developing ovarian cancer before the age of 70 is the presence of BRCA1 or BRCA2 gene mutation.⁷ It seems that the gene locus of ovarian and breast cancer are in relative proximity to each other on the long arm of chromosomes 13 and 17.¹⁷

Color Doppler sonography has been shown to be a clinically useful adjunct to TVS for the evaluation of patients with pelvic masses.^2,8,9 Color Doppler sonography can improve the detection of malignancy by showing low-impedance, high-velocity flow in morphologically abnormal areas (Figure 35-1). However, false-positive and false-negative diagnoses can occur with CDS. Occasionally, the CDS features may suggest malignancy in morphologically nonsuspicious masses. This stresses the importance of integration of clinical and laboratory information with the CDS findings. Color Doppler sonography is operator and equipment dependent and is relatively expensive when compared to serum screening. These advantages and limitations must be recognized when considering its optimal integration in screening and/or early detection programs for ovarian cancer.^4,11,12

This chapter discusses and illustrates factors that influence the efficacy of screening and/or early detection schemes involving TVS with CDS. Identification of women at greatest risk for ovarian cancer by clinical history, CA-125, and breast/ovarian cancer genetic analysis (BRCA1 and BRCA2) is mentioned. Women with risk factors for endometrial cancer such as obesity, diabetes, and hypertension are also excellent candidates to benefit from screening. For this purpose, TVS has high negative predictive value but is limited by a relatively high false-positive rate. Additional imaging using 3D and/or contrast sonography may improve early detection of ovarian cancer.^{13,14,15, and 16} These will be mentioned as they relate to improving screening efficacy, taking into account their incremental cost and more demanding technical expertise.

To best understand the applications and limitations of early detection of these 2 cancers, one must first consider some fundamental concepts regarding screening. It is important to distinguish screening tests from diagnostic studies. By definition, a screening test is performed in an asymptomatic population, whereas diagnostic studies are performed on selected subjects when warranted by signs, symptoms, or clinical suspicion. The ideal screening test is one that meets the following criteria:

1. Sensitivity of the test is high, ie, there are few false negatives.

2. Specificity of the test is high, ie, there are few false positives.

3. The test is easily reproducible.

4. The test is available and both cost- and effort-effective.

5. The test does not cause harm to the patient or put the patient at risk (ideally noninvasive, eg, imaging).¹⁷

Other factors that influence the effectiveness of screening are intrinsic to the unique disease biology. Doubling times for all histologic types of ovarian and endometrial carcinomas are influenced by many factors, such as tumor vascularity, oxygenation, and perfusion, making the effect of "length" and "lead time" biases difficult to calculate. Thus, characteristics intrinsic to disease processes also influence the effectiveness of screening. These include the following:

1. The disease must be serious and result in substantial morbidity or mortality.

2. There must be a high preclinical prevalence of the disease in the screening population.

3. Detection of disease by screening should change the natural history of the disease (eg, result in improved outcomes).

4. There should be a low prevalence of pseudodisease (disease found by screening which would not otherwise impact the quality or length of a patient's life).

Finally, one must consider the possibility of introducing "length-time" and "lead-time" bias when determining efficacy of a screening program. Length-time bias describes differences in outcomes between screened and unscreened populations as a result of overrepresentation of less aggressive tumors in the screened population. Length-time bias derives from the concept that a slower-growing tumor will have a longer preclinical period in which it may be detected by screening; however, outcomes for these tumors are intrinsically more favorable than outcomes for more aggressive tumors with shorter preclinical periods. Lead time refers to the period of time between development of a disease and diagnosis. Lead-time bias refers to the artifactual skewing of outcome measures such as length of time from diagnosis to death. If a disease is discovered early in the preclinical phase through screening, it may appear that time from diagnosis to death has been lengthened, although the reality may be that the difference between the screened and unscreened populations is due to a longer lead time.

These factors must all be weighed in any consideration about the efficacy of screening for ovarian and endometrial cancers. The sonographic techniques discussed in this chapter enjoy the advantages of posing minimal harm to the patient and being relatively reproducible, accessible, and affordable. We discuss the accuracy (sensitivity and specificity) of each technique in detail later in this chapter.

Factors intrinsic to ovarian and endometrial cancers themselves, however, pose greater challenges to effective screening. Although both these cancers clearly merit screening on the basis of the seriousness of the diseases (15,000 American deaths yearly from ovarian cancer; 7400 deaths yearly from endometrial cancer), considerable barriers exist to screening. For example, the challenge facing ovarian cancer screening is the necessity of its earliest detection when still confined to the ovary (stage I) or within the pelvis (stage II). Five-year survival statistics show 85% to 90% survival for early-stage disease and much poorer survival (5% to 25%) for more advanced stages. From these data, it is extrapolated that early detection of ovarian cancer will improve long-term survival outcomes. However, as discussed above, length- and lead-time biases are important parameters in evaluating the efficacy of screening, and the impact of these biases in ovarian and endometrial cancers is difficult to calculate. This is due, in part, to the wide range of doubling times for various histologic types of ovarian and endometrial carcinomas.

The efficacy of screening is further limited by the low prevalence of these cancers in the general population. Although the annual incidence of endometrial cancer is higher than that of ovarian cancer (55,000 vs 26,500), endometrial cancer is associated with fewer mortalities (5000 vs 14,000), presumably as a result of early symptomatic bleeding and subsequent diagnosis. It is important to note that although screening may be limited by low prevalence in the general population, it is possible to define a subset of women at higher risk for these diseases. By identifying these risk factors, discussed below, a selective population can be created in which the prevalence of preclinical ovarian and endometrial cancer is high enough to warrant early detection measures (see Table 35-1).

Although the incidence of ovarian cancer is relatively low, it has very few clinical symptoms early in its course. Thus, ovarian cancer is usually discovered late at a metastatic state. Unfortunately, screening the general population may not be efficacious with currently available tests.^18,19 Presently, the lifetime risk for developing ovarian cancer is 1 in 70 (1.4%) for the general American female population, with an average age at diagnosis of 57. However, close evaluation of women who are identified to be "at risk" will improve the efficacy of screening schemes (Table 35-2). More recent estimates indicate that the lifetime risk for developing ovarian cancer is now up to 1 in 55 (1.8%) for the general worldwide population. In comparison, risk factors such as nulliparity, perineal talc exposure, infertility, high-fat diet, and previous breast cancer each confer a 2.0% lifetime risk. A family history of ovarian cancer also increases risk. Ovarian cancer in 1 second-degree relative increases a woman's lifetime risk to 2.9%; 1 first-degree relative increases risk to 4.5%; and history of 2 first-degree relatives with ovarian cancer confers a lifetime risk of 39% (see Table 35-2).¹⁹ Despite the greatly increased risk associated with family history of ovarian cancer, the vast majority (>90%) of ovarian cancers occur in women without a family history or known predisposing factor.

Ovarian cancer syndromes represent fewer than 10% of all ovarian cancers and can be subdivided into 3 general categories: cancer limited to the ovaries, breast–ovarian, and multiple site (Lynch type II: ovarian, proximal colon, and endometrial cancers, Li-Fraumeni syndrome, and Cowden syndrome). Women with one of these syndromes tend to be diagnosed with ovarian cancer at an earlier age (median 47 years, with 20% occurring before age 40) than the general population (median 57 years).

Recently, it has been recognized that genetics play an important role in the identification of women at risk for ovarian cancer.^20,21,22,23 It has been estimated that 40% to 60% of ovarian cancers are associated with malfunction of p53, a protein responsible for tumor growth inhibition.²⁴ As a result of mutations in the p53 gene, tumor suppression pathways malfunction, thus leading to the development of tumors. The most recent advancement in genetic testing to identify women at risk for developing breast and ovarian cancer is analysis of the BReast CAncer (BRCA) gene on the long arm of chromosome 17. The presence of one of 2 gene mutations at this locus (BRCA1 and BRCA2) confers a 30% risk of ovarian cancer by the age of 60.²² Loss of heterogeneity in the BRCA gene has been identified in up to 70% of sporadically occurring ovarian cancers. A high incidence of this gene mutation has been shown to be present in a group of Israeli women (Ashkenazi Jews) with ovarian cancer.²³

Serum tests have also been suggested as a method to identify high-risk women who would benefit from early detection of ovarian cancer. CA-125 is an antigen that can be detected in serum and is associated with malignancies such as ovarian cancer. However, CA-125 has a relatively limited sensitivity and specificity. Only 47% of Federation of Gynecologists and Obstetricians (FIGO) stage I ovarian cancers were positive for CA-125 in one large series. Furthermore, elevated levels of this glycoprotein can be seen in a variety of disorders, especially in the premenopausal age group. CA-125 is, however, an accurate means by which patients may be followed for detection of recurrent disease.²⁵

There have been several recent developments in serum biomarker tests, including the use of proteomics and multianalyte screening. Proteomic assays involve mass spectroscopy of certain serum proteins and gene products and is reported to be highly accurate.⁵ One study of 50 women with known ovarian cancer and 66 women with nonovarian cancer pathology reported a sensitivity of 100% and specificity of 99% for the proteomic assay (positive predictive value 94%).⁵ Another serum assay for a panel of 4 analytes (leptin, prolactin, osteopontin, and insulin-like growth factor) in 106 controls and 100 women with ovarian cancer reported a sensitivity of 95%, specificity of 95%, positive predictive value of 95%, and negative predictive value of 94%.⁶ Although neither of these tests is currently clinically available, there is great potential for the combination of serum analysis with sonographic imaging in the formulation of a multimodal screening scheme.

Risk factors for endometrial cancers include obesity, low parity, diabetes, and hypertension. Endometrial cancer differs from ovarian cancer, however, in that most endometrial cancers become symptomatic before significant intramyometrial spread occurs. In one study of mass screening for endometrial cancers in asymptomatic women, a high incidence (6.3%) of pre-invasive cancers was found in diabetic women. In comparison, the incidence of preclinical endometrial cancer in a population of hypertensive women was 1.3%.²¹ Although many women with endometrial cancer will present with postmenopausal bleeding, the corollary is not true; only 10% to 15% of women with postmenopausal bleeding are eventually found to have endometrial cancer. Transvaginal sonography therefore plays a pivotal diagnostic role in distinguishing those patients needing biopsy from those who would be best observed or treated medically.

Through analysis of risk factors, genetics, serum analyses, and proteomics, it may be possible to define a population of women at high risk for ovarian or endometrial cancers who would likely benefit from early detection.^8,10,26,27 When used in a screening capacity, TVS can detect morphologic findings such as wall thickening and/or papillary excrescences within ovarian masses—findings suggestive of malignancy. The role of TVS in ovarian cancer screening has been investigated in several large series.^{28,29, and 30} Differences in long-term outcome (defined as longer than 5 years from initial diagnosis) between screened and non-screened patients is now being published.

The University of Kentucky group has recently reported a significant reduction in stage of ovarian cancers at diagnosis and a reduced mortality in over 23,000 women screened.²⁸ Similar data have been reported from a large Japanese screening program that included 122,000 women.³⁰ Additionally, a British study of over 6000 women compared screened and nonscreened populations and confirmed the efficacy of TVS for ovarian cancer screening.²⁹ Some groups in the United States, however, have emphasized that TVS alone may not be an effective means of screening; they stress the need for an accurate serum test to initially identify appropriate candidates for early detection with TVS.

Occasionally, the accuracy of TVS in evaluating the endometrium is limited by the presence of fibroids or by the patient's body habitus. If the endometrium is difficult to assess on the initial visit, sonohysterography should be performed for enhanced delineation of the endometrium.²⁸

Inadvertent reflux of cancer cells is a theoretic concern, but is, in practice, very unlikely. Retrograde passage of cancer cells with subsequent peritoneal implantation has, to our knowledge, not been observed or reported.³¹ Endometrial cell dissemination during diagnostic hysteroscopy has been documented in about one-quarter of patients undergoing this procedure.³² However, one group reports a small but real risk of malignant cell dissemination in patients with endometrial carcinoma who undergo saline infusion sonohysterography (SIS).³³ Cytologic analysis showed the presence of malignant cells in the spilled fluid in 7% of subjects. This has led some to discourage the performance of sonohysterography in women in whom there is suspicion of endometrial carcinoma.³⁴ Some have suggested that transtubal fluid leakage does not occur during hysteroscopy when intrauterine pressure is less than 40 mm Hg.³⁵ Thus, the chance that malignant cells could reflux during SIS and survive to establish metastatic peritoneal disease is very unlikely.

Although the above-mentioned morphologic features may be subtle and nonspecific, use of TVS in combination with CDS can help to distinguish benign from malignant masses (Figures 35-2,35-3,35-4,35-5,35-6, and 35-7). CDS has been shown to be a clinically useful adjunct to TVS for the evaluation of patients with pelvic masses.^2,8,9 Fortunately, the high degree of vascularity of most early-stage tumors improves their detection with CDS. The extent of vascularity may differ according to the stage of tumor growth, but even so, a number of investigators have reported detection of early-stage tumors with CDS, some of which were detected in ovaries that were only slightly enlarged on morphologic evaluation.^{8,9, and 10}

CDS can improve the detection of malignancy by showing low-impedance, high-velocity flow in morphologically abnormal areas (see Figure 35-1). Those CDS features that suggest malignancy include the following:

1. Morphologic abnormalities, ie, papillary excrescences or an irregularly thickened wall

2. Low impedance (pulsatility index ≤1.0; resistance index ≤0.4)

3. High velocity (maximum systolic velocity >15 cm/s)

4. Clustered vessels or high vessel density

There have been several studies describing the range of impedance values and the sensitivity and specificity of TV-CDS for the detection of ovarian tumors. These data are presented in tabular form in Chapter 32 (Color Doppler Sonography of Pelvic Masses).

As with all tests, false-positive and false-negative diagnoses can occur with CDS. Occasionally, CDS features may suggest malignancy in morphologically nonsuspicious masses. This illustrates the importance of integration of clinical and laboratory information with TV-CDS findings. Furthermore, CDS is operator and equipment dependent and is relatively expensive when compared to serum screening. These advantages and limitations must be considered when considering the optimal integration of TV-CDS in screening and early detection programs for ovarian cancer.^4,11,12

TV-CDS has shown promise in screening efficacy in several groups of high-risk women. In one study examining women with a history of breast cancer, CDS improved the positive predictive value from 25% to 60% for the detection of ovarian cancer when compared with TVS alone.²⁸ In another study, the combined use of TVS and CDS improved the odds ratio of finding an ovarian cancer at surgery from 1:9 to 2:5 in women with a familial history of ovarian cancer.¹⁰ A further study of 1600 women with a family history of ovarian cancer detected 6 ovarian cancers, 5 of which were stage I.⁶ Other studies using CA-125 levels as a screening threshold detected ovarian cancer, but more frequently at later stages.²¹

In addition to having a role in screening for ovarian cancer, recent studies have reported that TVS combined with CDS can also effectively detect endometrial cancers in their earliest stages. In fact, it has been suggested that combining the evaluation of the endometrium with screening for ovarian cancer may potentially approximate the chance of detection of breast cancer with mammography (see Table 35-1).^1,2 In 2 studies using TVS and CDS as a means to detect ovarian cancer in the general population, a detection rate of 2 per 1000 was reported.^1,2 When TVS was offered to a general population, one gynecologist found 1 case of ovarian cancer and 1 of endometrial cancer in 478 women examined.³ He also found 9 benign ovarian masses and 3 benign endometrial disorders.

The actual efficacy of combined testing will be determined several years from now, after data from ongoing large-scale trials are analyzed from several countries and regions of the world (United States, United Kingdom, Scandinavia, and Japan). However, some practicing gynecologists have already begun to offer sonographic screenings to all patients in their practice, whereas others are actively screening only those considered to be at high risk.^3,4 We are hopeful that long-term data will eventually support the efficacy of multimodal screening.

The assessment of the vascularity of ovarian masses by basic TV-CDS allows classification of tumors into hyper-, iso-, or hypovascular categories. Tumors typically contain central vascularity, clustered vessels, and vessels that are of varying caliber. Three-dimensional-CDS provides a visual depiction of vessel arrangement and density. While some investigators have reported improved accuracy in diagnosing ovarian masses with 3D-CDS, others remain skeptical of its incremental value and have elected to rely on two-dimensional (2D) ultrasound (US) imaging.¹³

Some investigators have used a 5-mm cubic volume to subjectively assess the vascularity for its relative density, branching pattern, and vessel caliber. Additional refinement is needed to make this subjective assessment.

Although areas of abnormal endometrial vascularity may be seen in either hyperplasia or cancer, 3D-CDS has shown to be helpful in differentiating these 2 entities. TV-CDS has also proven beneficial in providing guidance regarding which potential abnormalities should be biopsied (Figure 35-8). Of note, it is important to realize that the vessels depicted by CDS are macrovessels such as arterioles and venules, not capillaries (Figures 35-9,35-10,35-11,35-12,35-13,35-14,35-15, and 35-16). Contrast-enhanced sonography, however, can depict flow within capillaries growing in tumors—a more representative picture of tumor neovascularity (Figures 35-17,35-18,35-19,35-20, and 35-21).

Quantification of vascularity has been shown to improve discrimination between benign and malignant ovarian masses, particularly with 3D sonography.^{13,36,37,38, and 39} Software programs can quantitate vascularity using a variety of parameters such as vascularity index (VI; defined as the number of pixels with color divided by total number of pixels), power-weighted pixel density (PWPD), or vascular flow index (VFI), which takes into account the relative vascularity within an area. New parameters that reflect vascular density and vessel arrangement may objectify the TV-CDS exam. Vessel density can be estimated by calculating the percentage of a mass that contains color Doppler signal as depicted on a 3D-CDS representation of a volume of tissue.

Preliminary reports studying contrast-enhanced TVS (CE-TVS) have indicated that sonography may have even greater promise in the evaluation of ovarian masses than previously thought. Contrasted sonography with the use of harmonics and microbubbles is capable of depicting the capillaries and microvasculature present in a mass, which cannot otherwise be visualized. In addition, enhancement kinetics provides an objective method to determine peak enhancement, wash-out time, and perfusion. Due to the uniqueness of tumor microvasculature, malignancies tend to exhibit relatively fast wash-in and high temporal peaks, followed by longer wash-out times and greater perfusion.¹⁵

The improvement in detection of ovarian cancers with contrast has been reported in several recent studies, including those from Finland, France, and Italy.^{14,15, and 16} Some investigators have used CDS and contrast, while one investigator^14,15 reported the use of tuned or harmonic detection of microbubbles.¹⁶ Some centers in the United States, including ours, are actively investigating the use of contrast for early detection of ovarian cancer. Initial results have been encouraging; a statistically significant difference between benign and malignant masses has been reported in parameters such as peak enhancement, wash-out time, and perfusion (see Figures 35-10 and Figures 35-19,35-20, and 35-21).¹⁷ Results from studies with larger cohorts of women will be available in the near future.

Transvaginal sonography offers a complete assessment of the thickness and texture of the endometrium and provides a means to differentiate those patients who should undergo biopsy from those who may forgo this procedure. In general, endometria that measure 5 mm or less are usually atrophic, whereas those thicker than 5 mm may be proliferative, hyperplastic, or cancerous (see Figure 35-11).⁴⁰ Although the false-negative rate of TVS for the detection of clinically significant abnormal endometrial pathology is low (~2%), false-positive results can occur in up to 30% of patients.⁴¹ Apparent thickening of the endometrium is frequently seen in women taking tamoxifen, possibly due to cystic atrophy or stromal edema, resulting in the production of multiple interfaces depicted sonographically.⁴² A large series of women undergoing hormone replacement therapy showed overlap in the thicknesses of various endometrial abnormalities.⁴³ There may be concern that cancer may be found with a thin endometrium; however, the thinnest endometrium found to be an endometrial cancer was reported to be 9 mm in one large series.⁴⁴ There has been only one published report of an endometrial cancer whose endometrial bilayer measured 4 mm.⁴⁴

Transvaginal sonography offers complete assessment of the thickness and texture of the endometrium. Occasionally, its accuracy is limited by the presence of fibroids or by the patient's body habitus. Any patient who experiences postmenopausal bleeding is suspect for harboring endometrial cancer, even though only 10% to 15% of women with unexplained bleeding have this disease. Liberal use of sonohysterography in patients with a thickened or irregular endometrium is encouraged for the clear delineation of polyps that may contain cancer. Inadvertent reflux of cancer cells is a theoretic concern but is very unlikely and of unknown clinical significance.³¹ Retrograde passage of cancer cells with subsequent peritoneal implantation has, to our knowledge, not been observed or reported.

The efficacy of screening for ovarian and endometrial cancer with sonography in an unselected general population of women is inherently limited due to the low prevalence of these cancers. However, in women who are identified to have increased risk, TVS with CDS and/or contrast enhancement can lead to early detection of these gynecologic cancers. Recent improvements in serum biomarker screening for ovarian cancer risk, combined with refinements in sonographic assessment of vascularity, have provided an important stimulus to continued investigation for optimal screening strategies for these 2 common gynecologic cancers.

Highlighted References