Diagnostic Workup Of Women Research Articles

Premature ovarian insufficiency

Key content: Premature ovarian insufficiency (POI) is a clinical syndrome involving ovarian follicle depletion and defined by loss of ovarian function before 40 years of age. The diagnostic workup in women with suspected POI is in two steps: confirming the diagnosis and establishing its cause; it is important to understand the rationale for performing each diagnostic test, how to interpret results and appropriate multidisciplinary team involvement. Treatment options include various regimens and preparations of hormone replacement therapy (HRT), monitoring and surveillance, induction of puberty in those with very early POI, complimentary treatment and fertility treatment. Management of POI requires a comprehensive and personalised strategy that addresses not only the physical symptoms and disease risks, but also the psychosocial and reproductive health aspects, and it is important that women receive adequate counselling. Learning objectives: To raise awareness of early diagnosis of POI. To be able to discuss the implications of POI for the health of women affected and their families, as well as for different hormonal and non‐hormonal treatment options. To understand various fertility treatment options for POI. Ethical issues: It is important to consider the reproductive and diagnostic implications for women with chromosomal or genetic problems (e.g. Turner syndrome, Fragile X mutation carriers) and for their family members. A diagnosis of POI may have differing implications based on social and cultural factors, and healthcare providers should consider a patient's values, beliefs, cultural background and preferences.

Endometrial Pipelle Biopsy Computer-Aided Diagnosis: A Feasibility Study

Endometrial biopsies are important in the diagnostic workup of women who present with abnormal uterine bleeding or hereditary risk of endometrial cancer. In general, approximately 10% of all endometrial biopsies demonstrate endometrial (pre)malignancy that requires specific treatment. As the diagnostic evaluation of mostly benign cases results in a substantial workload for pathologists, artificial intelligence (AI)-assisted preselection of biopsies could optimize the workflow. This study aimed to assess the feasibility of AI-assisted diagnosis for endometrial biopsies (endometrial Pipelle biopsy computer-aided diagnosis), trained on daily-practice whole-slide images instead of highly selected images. Endometrial biopsies were classified into 6 clinically relevant categories defined as follows: nonrepresentative, normal, nonneoplastic, hyperplasia without atypia, hyperplasia with atypia, and malignant. The agreement among 15 pathologists, within these classifications, was evaluated in 91 endometrial biopsies. Next, an algorithm (trained on a total of 2819 endometrial biopsies) rated the same 91 cases, and we compared its performance using the pathologist’s classification as the reference standard. The interrater reliability among pathologists was moderate with a mean Cohen’s kappa of 0.51, whereas for a binary classification into benign vs (pre)malignant, the agreement was substantial with a mean Cohen’s kappa of 0.66. The AI algorithm performed slightly worse for the 6 categories with a moderate Cohen’s kappa of 0.43 but was comparable for the binary classification with a substantial Cohen’s kappa of 0.65. AI-assisted diagnosis of endometrial biopsies was demonstrated to be feasible in discriminating between benign and (pre)malignant endometrial tissues, even when trained on unselected cases. Endometrial premalignancies remain challenging for both pathologists and AI algorithms. Future steps to improve reliability of the diagnosis are needed to achieve a more refined AI-assisted diagnostic solution for endometrial biopsies that covers both premalignant and malignant diagnoses.

Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment

BackgroundOvarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30–50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass.MethodsProtein concentrations of 11 proteins were characterized in plasma from 1120 clinical samples with a custom version of the proximity extension assay. The performance of the assay was evaluated in terms of prediction accuracy based on receiver operating characteristics (ROC) and multiple hypothesis adjusted Fisher’s Exact tests on achieved sensitivity and specificity.ResultsThe assay’s performance is validated in two independent clinical cohorts with a sensitivity of 0.83/0.91 and specificity of 0.88/0.92. We also show that the risk score follows the clinical development and is reduced upon treatment, and increased with relapse and cancer progression. Data-driven modeling of the risk score patterns during a 2-year follow-up after diagnosis identifies four separate risk score trajectories linked to clinical development and survival. A Cox proportional hazard regression analysis of 5-year survival shows that at time of diagnosis the risk score is the second-strongest predictive variable for survival after tumor stage, whereas MUCIN-16 (CA-125) alone is not significantly predictive.ConclusionThe robust performance of the biomarker assay across clinical cohorts and the correlation with clinical development indicates its usefulness both in the diagnostic work-up of women with adnexal ovarian mass and for predicting their clinical course.

Integrating mammography screening programmes into specialist breast centres in Italy: insights from a national survey of Senonetwork breast centres

BackgroundDespite recommendations, mammography screening is often insufficiently integrated into specialist breast centres. A national, cross-sectional, voluntary, online survey on this issue was carried out among the Italian breast centres associated with Senonetwork, the Italian network of breast cancer services.MethodsA 73-item questionnaire was created, pre-tested and piloted. Centres integrating and not integrating a screening programme were compared using the unified theory of acceptance and use of technology (UTAUT) model. Centres’ clustering was performed using the Gower’s distance metric. Groups and clusters were compared with the equality-of-means test.ResultsThe response rate was 82/128 (65%). Overall, 84% (69/82) breast centres reported a collaboration with a screening programme in performing and/or reading mammograms and in the diagnostic work-up of women with abnormal screening results. The same proportion was observed among those centres responding to all questions (62/74). Performance expectancies (or the perceived usefulness of integration in terms of clinical quality, patient convenience, ease of job, and professional growth), satisfaction and motivation were higher in those centres collaborating with the screening programme. Effort expectancy indicators (or the degree to which the respondents believe that the integration is easy to implement) and those concerning the existence of facilitating conditions were lower both in centres collaborating and not collaborating with the screening programme. Among the former, six clusters of centres, distributed from ‘no integration’ to ‘high’, were identified. In cluster analysis, the highest level of integration was associated with higher agreement that integration eases the job, offers better opportunities for professional growth, and makes the working environment more satisfactory. The least integrated cluster assigned the lowest score to the statement that local health authority made available the resources needed.ConclusionsWhile confirming the positive effects of integrating screening programmes into breast centres, this survey has brought to light specific difficulties that must be faced. The results provide insights into the importance of integration focusing on the perspectives of professional career and motivation. The deficiency of facilitating conditions to integration is modifiable. Screening professionals’ societies may have a role as initiators of the integration. Other supporting actions may be included in health laws at the national and regional level.

Derangements of vaginal and cervical canal microbiota determined with real-time PCR in women with recurrent miscarriages

Balanced vaginal microbiota and, as a continuum, cervical canal microbiota help prevent reproductive disorders, including recurrent miscarriage (RM). In a significant proportion of couples with RM, routine diagnostic workup cannot find any manageable cause, leading to a requirement for new diagnostic tools. In the present study, we determined the quantitative composition of the microbiota of the vagina and cervical canal, assessed by real-time polymerase chain reaction, in women with RM. It also evaluated their derangements related to the pathogenesis of RM, and thus the suitability of this test as a diagnostic tool for managing RM. Vaginal and cervical canal specimens of 25 women with RM and 25 healthy volunteers were collected. The test results revealed information about the total vaginal bacterial biomass by measuring the abundance of Lactobacillus spp.; other bacteria; and pathogens, including Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma (urealyticum + parvum), and Candida spp. Overall, the findings of this study implied the abundance of Lactobacillus spp. decreased in women with RM with an increase in the abundance of other microorganisms in accordance with the reduction in the abundance of Lactobacillus spp. due to aerobic vaginitis and bacterial vaginosis. Vaginal and cervical canal microbiota need to be considered during the diagnostic workup of women with RM. IMPACT STATEMENT What is already known on this subject? Recurrent miscarriage (RM) is a well-known reproductive disorder. Its diagnostic workup is not successful in determining the underlying problem in many cases. Hence, novel diagnostic tools based on real-time polymerase chain reaction (PCR) are needed for evaluating reproductive microbiota, which are considerably reliable, to satisfy the expectations of women with RM. What do the results of this study add? Overall, the decrease in the abundance of Lactobacillus spp. was found to be related to RM, and the patterns of the presence of other microorganisms were in accordance with the reduction in the abundance of Lactobacillus spp. These findings suggested an important role of vaginal and cervical canal microbiota in the pathogenesis of RM. What are the implications of these findings for clinical practice and/or further research? Additional research is warranted to elucidate the functional impact of altered components of the microbiota of vaginal and cervical canals on the physiology of the local cervical canal and its participation in the microbiota of the endometrial cavity, especially regarding unsuccessful pregnancies as a result of the disturbed physiology of the local endometrial microenvironment. However, possible applications of real-time PCR-based tests for the screening of subclinical infections in clinical practice require the performance of further investigations in patients with RM.

Endometrial sampling before or after saline contrast sonohysterography in women with postmenopausal bleeding (ESPRESSO trial): A multicenter randomized controlled trial.

IntroductionThe aim of this study is to evaluate the quality of the endometrial sample obtained by office endometrial aspiration when performed before or after saline contrast sonohysterography (SCSH) in women with postmenopausal bleeding and a thickened endometrium. To conduct a complete, minimally invasive and cost‐effective diagnostic workup in women with postmenopausal bleeding and a thickened endometrium, ideally both the office endometrial sampling and SCSH are performed. However, it is not known whether both tests affect each other when performed one after another.Material and methodsWomen with postmenopausal bleeding and an endometrial thickness >4 mm were eligible. Women were randomized into two groups: one group received endometrial aspiration before SCSH, the other group received SCSH before endometrial aspiration. The primary outcome was the proportion of sufficient endometrial samples. Reliability of the SCSH images and pain during procedures were secondary outcomes.ResultsDuring the inclusion period, 513 eligible women with postmenopausal bleeding visited the participating hospitals, 293 of whom received information about the study. Of these women, 232 (79%) agreed to participate. In the SCSH‐aspiration group, 65 women (59%) had a sufficient endometrial sample compared with 70 (67%) in the aspiration‐SCSH group (odds ratio 1.46, 95% CI 0.83‐2.54, P = .19). The proportion of reliable sonographic images was significantly higher in the SCSH‐aspiration group (n = 88, 87%) compared with the aspiration‐SCSH group (n = 71, 74%) (OR 2.38, 95% CI 1.38‐4.99, P = .02) in the per protocol analysis.ConclusionsThis study shows that the quality of an endometrial sample in women with postmenopausal bleeding is not affected by SCSH. Both procedures can be performed in one outpatient visit to perform an optimal diagnostic workup.

Risk of Injuries around Diagnosis of Cervical Cancer and Its Precursor Lesions: A Nationwide Cohort Study in Sweden

Abstract Background: Highly increased risk of injuries has been noted around the time of cancer diagnosis. Whether there is a similar increase in risk around the diagnosis of cervical cancer and its precursor lesions was unknown. Methods: We performed a cohort study including 3,016,307 Swedish women that participated in cervical screening during 2001 to 2012. We calculated the incidence rates (IR) of hospitalized iatrogenic or noniatrogenic injuries during the diagnostic workup, and the time interval from smear or punch biopsy until surgical treatment or 2 months after the last smear or biopsy, among women with invasive cervical cancer (ICC) or its precursor lesions. We calculated the IRs of injuries during the 2 months after a normal smear among the other women as reference. IR ratios (IRR) and 95% confidence intervals (CI) were calculated using Poisson regression. Results: Compared with other women, there was an increased rate of iatrogenic injuries during the diagnostic workup of women with ICC (IR, 0.58 per 1,000 person-months; IRR, 8.55; 95% CI, 3.69–19.80) as well as of women with cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ (IR, 0.09 per 1,000 person-months; IRR, 3.04; 95% CI, 1.73–5.34). We also found an increased rate of noniatrogenic injuries during the diagnostic workup of women with invasive cancer (IR, 0.65 per 1,000 person-months; IRR, 2.48; 95% CI, 1.30–4.47). Conclusions: Although rare, there was an increased risk of inpatient care for iatrogenic and noniatrogenic injuries during the diagnostic workup of women with ICC. Impact: Women experienced burden of medical complications and psychologic distress around diagnosis of a potential cervical cancer.

344 Poster - Diagnostic work-up in women suspect for breast cancer in the Netherlands

344 Poster - Diagnostic work-up in women suspect for breast cancer in the Netherlands

Gender Differences in Patients Admitted to a Certified German Chest Pain Unit: Results from the German Chest Pain Unit Registry

Introduction: Gender-specific atypical clinical presentation in acute coronary syndrome and sex-specific outcomes in cardiovascular disease in women are well known. The aim of this study is to analyze possible differences between men and women presenting to certified German chest pain units (CPUs). Methods: Data from 13,900 patients derived from the German CPU registry were analyzed for gender differences in patient characteristics, cardiovascular disease manifestation, critical time intervals, treatment and prognosis. Results: A total of 37.8% of patients were female. Typical chest pain occurred more frequently in men, while atypical symptoms occurred more frequently in women. Female gender was associated with longer pre- and in-hospital time delays. Women were more often diagnosed with a nonischemic origin of pain. In a 3-month follow-up, there was no gender-specific difference in combined major adverse coronary and cerebrovascular events. Discussion/Conclusion: This study points out gender-specific differences in prehospital time intervals and a significantly higher percentage of atypical symptoms in suspected myocardial ischemia as well as more noncoronary diagnoses in women. Symptom awareness and a broader diagnostic workup in women are essential.

Role of laparoscopy in initial tumour staging in advanced epithelial ovarian cancer: A systematic review.

BackgroundThe aim of this systematic review was to investigate the accuracy of additional staging laparoscopy (SL) in advanced epithelial ovarian cancer (AEOC) to predict futile laparotomy (FL).MethodsSystematic review according to preferred reporting items for systematic reviews and meta-analyses statement (PRISMA) criteria. Clinical studies investigating the role of SL in selecting women with AEOC for primary debulking surgery (PDS) were included. Index test: SL. Reference test: laparotomy. Target condition: incomplete cytoreduction (CR) with remaining disease<1 cm.ResultsNine prospective and retrospective studies reporting on eight cohorts totalizing 778 LS were included. Reference test was completed in 76 % cases. PPV for FL was between 0.69 and 1.0. In three studies examining the value of a predictive index value (PIV) for predicting FL, sensitivity of the index test (LS with PIV ≥8) was between 46% and 70 %, and specificity between 89 % and 100 %. The proportion of patients that received CR during PDS differed widely between studies (from 50 to 91). Using a PIV did not increase the sensitivity and might result in more patients receiving FL. In the only randomized trial, FL occurred in 10 (10 %) of 102 patients in the LS group versus 39 (39 %) of 99 patients in the primary PDS group (relative risk, 0.25; 95 % CI, 0.13–0.47; p<0.001). Port-site recurrences occurred in 2%–6 % patients. Overall costs of with or without SL were comparable.ConclusionsThe evidence available from this systematic review supports the inclusion of an additional LS to the conventional initial diagnostic workup in women with AEOC.

A predictive model combining human epididymal protein 4 and radiologic features for the diagnosis of ovarian cancer

ObjectiveOvarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovarian Malignancy Algorithm (ROMA) score, which is suggested to further increase the diagnostic accuracy than either marker alone. However, information from ultrasound and CT-scan is not included in this algorithm. This study evaluated the diagnostic accuracy of HE4 in the pre-operative diagnosis of ovarian cancer and the predictive values of biomarkers, ultrasound and CT-scan and combinations hereof. MethodsHE4 and CA125 were measured in 361 subjects (34 benign, 147 ovarian cancer and 180 controls). Sensitivity, specificity and area under the curve (AUC) for CA125, HE4, ROMA and RMI scores were calculated using the receiver operating characteristic (ROC) methodology. The additional predictive value of ultrasound or CT-scan to the individual markers was analyzed using logistic regression. ResultsThe sensitivity in predicting ovarian cancer of CA125 was 91% and of HE4 90%. The specificity was 65% and 97% respectively. HE4 demonstrated the highest discrimination (ROC-AUC=0.96), compared to ROMA, RMI and CA125 (AUC=0.95, 0.89 and 0.90 respectively). ROMA did not improve when it was combined with different ultrasound factors. The presence of intra-abdominal metastasis on CT-scan improved the discriminative potential of HE4 (p=0.0004). ConclusionHE4 in combination with CT-scan may be incorporated in the diagnostic work-up in women with a pelvic mass.

Value of One-View Breast Tomosynthesis Versus Two-View Mammography in Diagnostic Workup of Women With Clinical Signs and Symptoms and in Women Recalled From Screening

The purpose of this study is to compare the diagnostic value of one-view digital breast tomosynthesis versus two-view full-field digital mammography (FFDM) alone, and versus a combined reading of both modalities. The datasets of one-view digital breast tomosynthesis and two-view FFDM of abnormal mammograms in 144 consecutive women admitted for diagnostic workup with clinical signs and symptoms (n = 78) or recalled from screening (n = 66) were read alone and in a combined setting. The malignant or benign nature of the lesions was established by histologic analysis of biopsied lesions or by 12-16-month follow-up. Eighty-six of the 144 patients were found to have breast cancer. The BI-RADS categories for one-view digital breast tomosynthesis were significantly better than those for two-view FFDM (p < 0.001) and were equal to those of the combined reading in both women admitted for diagnostic workup and women recalled from screening. The sensitivity and negative predictive values of digital breast tomosynthesis were superior to those of FFDM in fatty and dense breasts overall and in women admitted for diagnostic workup and in women recalled from screening. Only 11% of digital breast tomosynthesis examinations required additional imaging, compared with 23% of FFDMs. In patients with abnormal mammograms, one-view digital breast tomosynthesis had better sensitivity and negative predictive value than did FFDM in patients with fatty and dense breasts. They also suggest that digital breast tomosynthesis would likely increase the predictive values if incorporated in routine screening.

Prevalence and qualitative properties of circulating anti–human leukocyte antigen alloantibodies after pregnancy: No association with unexplained recurrent miscarriage

In pregnant women, circulating alloantibodies, triggered by exposure to paternal HLA antigens, are frequently detectable. The finding of lower alloantibody levels in women who experience spontaneous abortion (miscarriage) has led to the speculation that antipaternal antibodies could favor maintenance of pregnancy, whereas their lack poses a risk of miscarriage. Postulating a role of alloantibodies in the pathogenesis of unexplained abortion, we examined whether different categories of recurrent miscarriage (RM) can be distinguished according to prevalence or distinct qualitative properties of anti–human leukocyte antigen (HLA) antibody patterns. Sera obtained from 167 women with RM were assessed for complement- and non–complement-fixing anti-HLA alloreactivity using Luminex-based bead array technology. Women with RM had less often detectable anti-HLA class I and/or II reactivity (19%) compared with a control group of 96 multiparous women without a history of miscarriage (49%). However, analysis of different categories of RM (unknown [ n = 112] versus known cause [ n = 55]; primary [ n = 125] versus secondary RM [ n = 42]) did not reveal any differences regarding antibody prevalence, number of targeted HLA single antigens, antigen specificity, binding density, or complement-fixing ability of detected alloantibodies. Our results do not support a link between anti-HLA antibody formation and RM, and argue against a diagnostic value of alloantibody detection in the diagnostic work-up of women with RM.

Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease

BackgroundRecent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.MethodsThe study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.ResultsWomen with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.ConclusionThese findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

Should endometrial polyps be removed in patients with postmenopausal bleeding?—an assessment of study designs and report of a failed randomised controlled trial (ISRCTN73825127)

We describe the design of a randomised controlled trial to evaluate the efficacy of endometrial polyp removal in women with postmenopausal bleeding. We designed a trial in which patients with postmenopausal bleeding and endometrial thickness >4 mm undergo hysteroscopy. If during hysteroscopy an endometrial polyp was diagnosed, patients were asked to participate in this trial and after informed consent allocated to immediate removal of the polyp or expectant management. This trial suffered from lack of recruitment related both to doctors seeking for informed consent as well as to patients' unwillingness to participate in this trial. However, a randomised controlled trial on this subject is still necessary to evaluate the efficacy of uterine cavity evaluation in the diagnostic work-up of women with postmenopausal bleeding, focussing on benign pathology. Therefore, we propose an alternative design, which might be more feasible.

Cone-Beam Computed Tomography for Breast Imaging

This article reviews the many modalities used today in the screening and diagnostic work-up of breast cancer, the second most common cause of cancer (after skin cancer) and the second most common cause of cancer death (after lung cancer) in women in the United States today. Newer technologies in breast imaging are also described, in particular the Cone Beam Computed Tomography (CBCT) as developed at the University of Rochester Medical Center. CBCT is a three-dimensional imaging modality which has potential in the screening and diagnostic work-up of women who may have breast cancer. Pilot studies show good coverage of the breast with adequate visualization of parenchymal detail and acceptable radiation dose in comparison with the gold standard of mammography.

The relation between age, time since menopause, and endometrial cancer in women with postmenopausal bleeding

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1-3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00-1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.

Cost-effectiveness of transvaginal sonography and saline infused sonography in the evaluation of menorrhagia

Objectives: To assess the cost-effectiveness of transvaginal sonography (TVS) and saline infused sonography (SIS) in the diagnostic work-up of women with menorrhagia. Methods: We performed a decision analysis in which we compared the percentage of patients treated successfully and cost of six strategies for the evaluation of menorrhagia: (0) hormonal treatment, (I) treatment of all patients with balloon ablation, (II) TVS and therapeutic hysteroscopy, (III) TVS, SIS and therapeutic hysteroscopy, (IV) SIS and therapeutic hysteroscopy, and (V) diagnostic hysteroscopy and therapeutic hysteroscopy. Hormonal treatment was considered to be the reference strategy to which the five strategies were compared. Data were obtained from the published literature. In order to evaluate the robustness of our results, we performed extensive sensitivity analyses, in which we varied sensitivity and specificity of TVS and hysteroscopy, the prevalence of intracavitary abnormalities, as well as costs of TVS and SIS. Results: We found that the strategy starting with SIS (IV) and the strategy with diagnostic hysteroscopy (V) revealed the highest number of patients treated successfully for menorrhagia. In terms of cost-effectiveness, SIS for all patients was superior over immediate diagnostic hysteroscopy for all patients. Strategies starting with TVS were less effective than the strategy starting with SIS. Conclusions: We recommend SIS as the procedure of first choice in the work-up for women with menorrhagia.

Cost-effectiveness of the use of transvaginal sonography in the evaluation of postmenopausal bleeding

Objectives: To assess the cost-effectiveness of transvaginal sonography (TVS) in the diagnostic work-up of women with postmenopausal bleeding. Methods: We performed a decision analysis in which we estimated life expectancy and cost of four strategies for the evaluation of postmenopausal bleeding: TVS (I), TVS and office endometrial biopsy (II), TVS and hysteroscopy (III), and endometrial biopsy (IV). In strategies incorporating TVS, calculations were performed for three different cut-off values between 3 and 9 mm double layer. Expectant management, i.e. no diagnosis or treatment was considered to be the reference strategy to which the other four strategies were compared. Data were obtained from the published literature. In extensive sensitivity analyses, we varied patient's age, discount rate, prevalence of endometrial carcinoma and atypical hyperplasia, and costs. Results: The strategy with endometrial biopsy and the strategy with TVS followed by endometrial biopsy in case of an increased endometrial thickness were the most cost-effective strategies. The strategy starting with endometrial biopsy was the most cost-effective when the prevalence of endometrial carcinoma was ≥15.3%, whereas the strategy with TVS and endometrial biopsy was the most cost-effective for women in which the prevalence of endometrial carcinoma was lower. In these strategies, a cut-off level for abnormality of 9 mm resulted in lowest cost per life-year gained. Conclusions: TVS is of use in women with postmenopausal bleeding and a probability of endometrial carcinoma below 15%.

Application of magnetic resonance imaging to early detection of breast cancer.

Since its first introduction approximately 10 years ago, there has been extensive progress in the application of magnetic resonance imaging (MRI) to the detection and diagnosis of breast cancer. Contrast-enhanced MRI has been shown to have value in the diagnostic work-up of women who present with mammogram or clinical abnormalities. In addition, it has been demonstrated that MRI can detect mammogram occult multifocal cancer in patients who present with unifocal disease. Advances in risk stratification and limitations in mammography have stimulated interest in the use of MRI to screen high-risk women for cancer. Several studies of MRI high-risk screening are ongoing. Preliminary results are encouraging.