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Biomedical subjects

D Timmerman

Publications and source records attributed to D Timmerman.

At least 19 recordsLinked to original sources
PubMed2007

Body mass index and HER-2 overexpression in breast cancer patients over 50 years of age.

PURPOSE: In breast cancer, in vitro as well as in vivo experiments have shown an inverse relationship between HER-2 and steroid hormone receptors. It is unknown whether circulating estrogens affect HER-2 expression. We hypothesize that the postmenopausal body mass index (BMI) as a surrogate marker for bio-available estrogens, is inversely associated with HER-2 over-expression. PATIENTS AND METHODS: A total of 535 women over age 50 or with known postmenopausal status, with a unilateral, not previously treated, operable breast cancer were evaluated the evening prior to surgery for body weight, height, abdominal and hip circumference over a 3 years period. Waist-to-hip ratio (WHR) and BMI were calculated. HER-2, estrogen receptor and progesterone receptor staining was done by immunohistochemistry. All tumours with DAKO 2+ staining were submitted for HER-2 detection by FISH analysis. HER-2 was defined as positive if DAKO 3+ or FISH positive. We assessed the frequency of HER-2 positivity in each of 6 quantiles for all parameters of body composition and tested for a trend in HER-2 expression across the 6 quantiles. Furthermore, we investigated whether BMI contributed, together with other known predictors for HER-2, in a standard multivariate logistic regression model that predicts HER-2 over-expression. RESULTS: There is a decrease in HER-2 over-expression per increasing quantile of BMI. In a multivariate model-including both steroid receptors-BMI remains an independent predictor for HER-2 over-expression. CONCLUSION: In women over age 50 or with known postmenopausal status with an operable breast cancer, there is an inverse association between BMI and HER-2 over-expression.

Age Factors↗
PubMed2006

Prospective cross-validation of three methods of predicting failing pregnancies of unknown location.

BACKGROUND: We compared the performance of each of three tests for predicting pregnancy failure in the pregnancy of unknown (PUL) population. METHODS: In a prospective observational study, we compared the performance of three models for the prediction of pregnancy failure in women with a PUL: (i) logistic-regression model incorporating vaginal bleeding, endometrial thickness (ET), initial serum progesterone and hCG levels; (ii) serum progesterone at 0 h; and (3) the hCG ratio. RESULTS: A total of 5942 consecutive pregnant women attending the Early Pregnancy Unit were scanned and 439 (7.4%) were classified as PULs. Of these women, 420 had complete data for serum hCG at 0 and 48 h, the hCG ratio, serum progesterone at 0 h, vaginal bleeding and ET. The final outcomes were 219 (52.1%) failing PULs, 167 (39.8%) intra-uterine pregnancies and 34 (8.1%) ectopic pregnancies. For the prediction of pregnancy failure in the PUL population, the area under the receiver operating characteristic (ROC) curve (AUC) for the logistic-regression model was 0.907 (Standard error (SE) 0.015), the AUC for serum progesterone was 0.952 (SE 0.010) and the AUC for the hCG ratio was 0.980 (SE 0.004). This improved performance of the hCG ratio was significant when compared with that of initial serum progesterone (P = 0.0076) and the logistic-regression model (P < 0.0001). Using the hCG ratio cut-offs of < 0.87 and 70% for the prediction of failing PUL, sensitivities were 86.3 and 82.2% (S), 87.2% (NS) and 78.1% (S), specificities were 97.0 and 98.0% (NS), 89.6% (S) and 88.6% (S), positive-likelihood ratios were 28.91, 41.30, 8.34 and 6.82 and negative-likelihood ratios were 0.14, 0.18, 0.14 and 0.25, respectively. CONCLUSION: The hCG ratio seems to be an optimal test for the prediction of pregnancy failure in a PUL population. The hCG ratio cut-off of 0.79 is recommended on the basis of minimizing risk to those PULs discharged at 48 h. Most importantly, when the hCG ratio is below a particular cut-off, these women can be discharged at 48 h without intervention and need for further follow-up.

Adolescent↗
PubMed2006

A validation of the most commonly used protocol to predict the success of single-dose methotrexate in the treatment of ectopic pregnancy.

BACKGROUND: Currently, the likely success of single-dose methotrexate (MTX) (50 mg/m(2)) for the treatment of ectopic pregnancy is indicated by a >15% decrease in hCG from days 4-7 after administration. The aim of this study was to assess this protocol and to develop new rules that could be used to predict the outcome at an earlier stage. METHODS: Data were collected prospectively. Women receiving MTX for an ectopic pregnancy had serum hCG and progesterone levels checked on days 1, 3, 4, 5 and 7. Other factors including age, gestational age, previous obstetric history and ultrasound findings were recorded. The women were followed up until the outcome of medical management was known. Univariate analysis was performed to determine the benefit of the '15% day 4-7 rule', as well as to develop new rules, which potentially could be used to predict the likelihood of success before 7 days. Historical and ultrasound variables were also analysed to identify the significant variables associated with successful conservative management. RESULTS: The success rate of single-dose MTX was 68.1% (47/69). A second dose was required in 18.8% (13/69) of cases, and it was successful in 84.6% (11/13). The 15% day 4-7 rule correctly predicted the outcome in 90.3% of cases [sensitivity 93.0%, specificity 84.2%, positive predictive value (PPV) 93.0% and negative predictive value (NPV) 84.2%, Fisher exact test P-value < 0.0001]. New rules were developed based on the percentage change day 4-5 and logistic regression models incorporating day 5 hCG levels and ultrasound findings. These new rules did not outperform the current 15% day 4-7 rule. CONCLUSIONS: We have confirmed that a 15% decrease in serum hCG between day 4 and day 7 is a very good indicator of the likely success of MTX. The development of new rules did not significantly improve our ability to predict a successful outcome at an earlier stage.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

Ovarian torsion in a premenarcheal girl: MRI findings.

Adnexal torsion is an uncommon cause of severe lower abdominal pain in women and is often difficult to distinguish from other acute abdominal conditions. However, adnexal torsion should be considered in premenarcheal girls admitted with acute abdominal pain and evidence of an ovarian mass. Accurate and early radiological diagnosis is mandatory immediately after onset of clinical symptoms in order to preserve the viability of the ovary. Ultrasound (US) is usually the first line examination performed in an emergency setting, but computed tomography (CT) and magnetic resonance imaging (MRI) can be useful in case of ambiguous US findings, especially in patients with sub-acute symptoms and a suspected adnexal mass. This case report describes the additional value of MRI in a premenarcheal girl with sub-acute right fossa pain.

Abdomen, Acute↗
PubMed2006

There is no role for uterine curettage in the contemporary diagnostic workup of women with a pregnancy of unknown location.

BACKGROUND: The aim of this study was to generate and evaluate a new protocol that defined non-viability in the pregnancy of unknown location (PUL) population and therefore ensured no viable intra-uterine pregnancy (IUP) would be interrupted if uterine curettage was performed. A secondary aim was to evaluate published biochemical criteria that define non-viability in a PUL population to establish if these criteria could result in inadvertent termination of pregnancy (TOP) if uterine curettage was performed. METHODS: All clinically stable women classified as having a PUL were included in this study. Protocol 1 was developed retrospectively based on data from 500 consecutive PULs. Using this protocol, no cases of viable IUPs would undergo uterine curettage and the potential for TOP was eliminated. This protocol was then validated prospectively on the data from a further 503 consecutive PULs. Results were then compared with three established criteria (Protocols 2-4) for the use of uterine curettage as a diagnostic tool to classify the location of PULs. Protocol 2 defined non-viability when the hCG ratio (hCG at 48 h/hCG at 0 h) was or=2000 U/l or when the initial serum hCG was <2000 U/l with a serum hCG rise of <35% over 48 h (hCG ratio<1.35); Protocol 4 advised uterine curettage with a serum hCG rise of <50% over 48 h (hCG ratio<1.50). The number of uterine curettages performed and viable IUPs that would have undergone an unplanned TOP were recorded for all protocols. RESULTS: A total of 12 572 consecutive women were scanned: 1003 (8.0%) women were classified as PULs. Training set consisted of 500 PULs: 278 (55.6%) failing PULs, 176 (35.2%) IUPs and 46 (9.2%) ectopic pregnancies (EPs). Test set consisted of 503 PULs: 255 (50.7%) failing PULs, 203 (40.4%) IUPs and 45 (9.0%) EPs. Protocol 1 when developed retrospectively on the training set would have resulted in 293 uterine curettages and no potential TOP. Protocol 1 tested prospectively on 503 PULs would have resulted in 272 uterine curettages and no potential TOP. Three established criteria were tested on the entire data set (n=1003). Protocol 2 would have resulted in 114 uterine curettages and 14 (12.3%) potential TOPs; Protocol 3 would have led to 611 uterine curettages and seven (1.2%) potential TOPs; Protocol 4 would have resulted in 617 uterine curettages and three (0.5%) potential TOPs. No harm came to the women whose EP diagnosis was delayed. CONCLUSIONS: Established criteria for the use of uterine curettage in the management of PULs, including those advocated by the American Society for Reproductive Medicine (ASRM), can theoretically result in an inadvertent TOPs. On the basis of these data, a change in contemporary clinical practice should be considered to avoid further damage to wanted pregnancies. We conclude that uterine curettage should not be used in the routine diagnostic workup of women with a PUL.

Abortion, Spontaneous↗
PubMed2006

Predicting the outcome of pregnancies of unknown location: Bayesian networks with expert prior information compared to logistic regression.

BACKGROUND: As women present at earlier gestations to early pregnancy units (EPUs), the number of women diagnosed with a pregnancy of unknown location (PUL) increases. Some of these women will have an ectopic pregnancy (EP), and it is this group in the PUL population that poses the greatest concern. The aim of this study was to develop Bayesian networks to predict EPs in the PUL population. METHODS: Data were gathered in a single EPU from all women with a PUL. This data set was divided into a model-building (599 women with 44 EPs) and a validation (257 women with 22 EPs) data set and consisted of the following variables: vaginal bleeding, fluid in the pouch of Douglas, midline echo, lower abdominal pain, age, endometrial thickness, gestation days, the ratio of HCG at 48 and 0 h, progesterone levels (0 and 48 h) and the clinical outcome of the PUL. We developed Bayesian networks with expert information using this data set to predict EPs. RESULTS: The best Bayesian network used the gestational age, HCG ratio and the progesterone level at 48 h and had an area under the receiver operator characteristic curve (AUC) of 0.88 for predicting EPs when tested prospectively. CONCLUSIONS: Discrete-valued Bayesian networks are more complex to build than, for example, logistic regression. Nevertheless, we have demonstrated that such models can be used to predict EPs in a PUL population. Prospective interventional multicentre studies are needed to validate the use of such models in clinical practice.

Adolescent↗
PubMed2006

Acoustic streaming in two endometriomas: the exception to the rule?

The presence of acoustic streaming in ovarian cysts can be determined by ultrasound imaging and provides an indication of the viscosity of the cyst content. It has previously been demonstrated that the absence of acoustic streaming in endometriomas could be a pathognomonic feature of endometriomas. In this report we demonstrate the presence of acoustic streaming in two endometriomas.

Adult↗
PubMed2006

The practical application of a mathematical model to predict the outcome of pregnancies of unknown location.

OBJECTIVE: A logistic regression model has been developed previously to predict which pregnancies of unknown location (PULs) become ectopics. This model was based on the human chorionic gonadotropin (hCG) ratio (hCG 48 h/hCG 0 h). The aim of this study was to evaluate the model in an early pregnancy clinical setting. METHODS: This was a prospective non-interventional observational study. Women classified as having a PUL had serum hCG and progesterone levels taken at presentation and 48 h later. At 48 h, nurse practitioners in the early pregnancy unit gave their subjective assessment of the likely pregnancy outcome based upon existing strategies to predict the outcome of PULs and their own previous experience. This was used as the basis for the clinical management of the women. The hormonal data were then entered into the model, which was available on the clinic computer in the form of a Microsoft Excel package, and the predicted outcome according to this model was recorded for each case. The model was weighted in favor of detecting an ectopic pregnancy at the expense of failing PULs and intrauterine pregnancies. All women were followed up until the final true diagnosis was established: a failing PUL, an intrauterine pregnancy or an ectopic pregnancy. The predicted outcome according to the model was compared with that of the subjective assessment of the expert operator and the true outcome after follow-up. RESULTS: Data were obtained from 357 women classified as having PULs. The final clinical outcomes were: 162 (45.4%) failing PULs, 166 (46.5%) intrauterine pregnancies and 29 (8.1%) ectopic pregnancies. Subjective assessment utilizing current strategies gave sensitivities of 79.3%, 92.8% and 87.0% for the detection of ectopic pregnancy, intrauterine pregnancy and failing PUL, respectively. The model detected ectopic pregnancy, intrauterine pregnancy and failing PUL with sensitivities of 82.8%, 86.8% and 73.5%, respectively. There were no adverse outcomes. CONCLUSION: This logistic regression model, based on the hCG ratio, can be used to predict the outcome of PULs, especially the ectopic pregnancies, with a high degree of certainty. It compares favorably with subjective assessment by experienced operators using current strategies to predict the outcome of PULs. The model can be used by those with limited knowledge or understanding of the behavior of serum biochemistry in the first trimester and in turn aid in the classification of PULs into those at low and those at high risk of ectopic pregnancy at 48 h.

Chorionic Gonadotropin↗
PubMed2006

Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings and is there a way of making a correct diagnosis?

OBJECTIVES: To determine which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings, and to determine if the use of logistic regression models for calculation of individual risk of malignancy would improve the diagnostic accuracy in difficult tumors. METHODS: In a prospective, international, European multicenter study involving nine centers, 1066 women with a pelvic mass judged to be of extrauterine origin underwent transvaginal ultrasound examination by an experienced ultrasound examiner before surgery. A standardized examination technique and predefined definitions of ultrasound characteristics were used. On the basis of subjective evaluation of ultrasound findings, the examiner classified each mass as being certainly benign, probably benign, unclassifiable, probably malignant or certainly malignant. Even when the examiner found the mass unclassifiable (i.e. difficult mass) he or she was obliged to state whether the mass was more likely to be benign or malignant. Borderline tumors were classified as malignant. RESULTS: There were 90 (8%) unclassifiable masses. Multiple logistic regression analysis showed papillary projections, >10 locules in a cyst without solid components, low-level echogenicity of cyst fluid, and moderate vascularization as assessed subjectively at color Doppler examination to be ultrasound variables independently associated with unclassifiable mass. Borderline malignant tumors (n = 55) proved to be most difficult to assess with only 47% being correctly classified (i.e. classified as malignant), 29% being incorrectly classified (i.e. classified as benign) and 24% being unclassifiable vs. 90% of non-borderline tumors being correctly classified, 3% being incorrectly classified and 8% being unclassifiable (P < 0.0001). Papillary cystadeno(fibro)mas, myomas and cases of struma ovarii were also more common among the unclassifiable masses than among the classifiable ones (5.6% vs. 1.1%, P = 0.008; 4.4% vs. 0.9%, P = 0.02; 4.4% vs. 0.2%, P = 0.0006). No ultrasound variable or clinical variable (including CA 125) entered a logistic regression model to predict malignancy in difficult masses. A model could be constructed for difficult masses containing papillary projections but this model performed no better than subjective evaluation of the ultrasound image. Sensitivity and specificity of subjective evaluation with regard to malignancy in the group of unclassifiable masses were 56% (14/25) and 77% (50/65) vs. 91% (220/241) and 97% (712/735) in the classifiable masses. CONCLUSIONS: Borderline tumors cause great diagnostic difficulties, but so do papillary cystadeno(fibro)mas, struma ovarii and some myomas. Logistic regression models do not solve the diagnostic problem in difficult pelvic masses.

Adnexa Uteri↗
PubMed2006

Impact of the availability of sonography in the acute gynecology unit.

OBJECTIVE: The initial assessment of acute gynecology patients is usually based on history and clinical examination and does not involve ultrasound. The aim of this study was to investigate the impact of the availability of transvaginal sonography at the time of initial assessment of the emergency gynecology patient. METHODS: This was a prospective observational study carried out over a 5-month period in the acute gynecology unit of an inner London teaching hospital. Women were assessed in the routine manner by history-taking and clinical examination and questionnaires were completed by the doctors, including details of the intention to treat. Transvaginal ultrasound examinations were then performed and a second diagnosis and management plan were made utilizing the extra information from the scan. The plans for clinical management before and after the ultrasound examination were compared. RESULTS: We originally recruited 1000 consecutive women to the study. The mean age was 31.1 (SD, 9.81) years. Complete data were available for 920 (92%). 84 (9.1%) women did not require a scan. Of the 521 women with a positive pregnancy test, 75.6% were reassured immediately that their pregnancy was intrauterine. 143 women (27.4%) were given the diagnosis of a suspected ectopic pregnancy before sonography, compared with 29 (5.6%) after. Following the ultrasound examination there was a change in clinical management in 54.1% of the women with a positive pregnancy test and a reduction in admissions (including inpatient theater admissions) (from 40.3% to 17.1%) and outpatient follow-up examinations (from 41.1% to 35.5%). In 90 (23.8%) non-pregnant women a significant ovarian cyst (> 5 cm) was suspected clinically; 28/90 (31.1%) were confirmed on sonography. Following the ultrasound examination there was a change in clinical management for 38.1% of non-pregnant women and a reduction in admissions (from 37.1% to 19.4%) and outpatient follow-up examinations (from 25.7% to 18.1%). CONCLUSION: It appears that the availability of transvaginal sonography at the time of initial assessment of emergency gynecology patients improves diagnostic accuracy and reduces unnecessary admissions and follow-up examinations.

Adolescent↗
PubMed2006

New models to predict depth of infiltration in endometrial carcinoma based on transvaginal sonography.

OBJECTIVES: Preoperative knowledge of the depth of myometrial infiltration is important in patients with endometrial carcinoma. This study aimed at assessing the value of histopathological parameters obtained from an endometrial biopsy (Pipelle de Cornier; results available preoperatively) and ultrasound measurements obtained after transvaginal sonography with color Doppler imaging in the preoperative prediction of the depth of myometrial invasion, as determined by the final histopathological examination of the hysterectomy specimen (the gold standard). METHODS: We first collected ultrasound and histopathological data from 97 consecutive women with endometrial carcinoma and divided them into two groups according to surgical stage (Stages Ia and Ib vs. Stages Ic and higher). The areas (AUC) under the receiver-operating characteristics curves of the subjective assessment of depth of invasion by an experienced gynecologist and of the individual ultrasound parameters were calculated. Subsequently, we used these variables to train a logistic regression model and least squares support vector machines (LS-SVM) with linear and RBF (radial basis function) kernels. Finally, these models were validated prospectively on data from 76 new patients in order to make a preoperative prediction of the depth of invasion. RESULTS: Of all ultrasound parameters, the ratio of the endometrial and uterine volumes had the largest AUC (78%), while that of the subjective assessment was 79%. The AUCs of the blood flow indices were low (range, 51-64%). Stepwise logistic regression selected the degree of differentiation, the number of fibroids, the endometrial thickness and the volume of the tumor. Compared with the AUC of the subjective assessment (72%), prospective evaluation of the mathematical models resulted in a higher AUC for the LS-SVM model with an RBF kernel (77%), but this difference was not significant. CONCLUSIONS: Single morphological parameters do not improve the predictive power when compared with the subjective assessment of depth of myometrial invasion of endometrial cancer, and blood flow indices do not contribute to the prediction of stage. In this study an LS-SVM model with an RBF kernel gave the best prediction; while this might be more reliable than subjective assessment, confirmation by larger prospective studies is required.

Aged↗
PubMed2006

The use of ultrasound-based 'soft markers' for the prediction of pelvic pathology in women with chronic pelvic pain--can we reduce the need for laparoscopy?

OBJECTIVE: To assess the accuracy of new transvaginal ultrasound-scan-based markers and to compare them to conventional ultrasound methods used in the detection of common pelvic pathology in women with chronic pelvic pain (CPP). DESIGN: A prospective observational study. SETTING: Teaching hospital. POPULATION: A total of 120 consecutive women with CPP undergoing transvaginal ultrasonography before either diagnostic or operative laparoscopy. METHODS: Anatomical abnormalities, e.g. endometrioma or hydrosalpinx (hard markers), were documented. The woman was then assessed for the presence or absence of 'soft markers' (reduced ovarian mobility and site-specific pelvic tenderness). MAIN OUTCOME MEASURE: Presence or absence of pelvic pathology noted during laparoscopy. RESULTS: Seventy women had pelvic pathology, of whom 51 had endometriosis alone, 7 both endometriosis and pelvic adhesions, 6 pelvic adhesions, 1 hydrosalpinx with endometriosis and 5 hydrosalpinx and pelvic adhesions. The likelihood ratio for the hard markers was infinity (specificity was 100%), for the soft makers 1.9 (95% CI 1.2-3.1) and for a 'normal' ultrasound 0.18 (0.09-0.34). The pre-test probability of pelvic disease in our population of women with CPP was 58%, and this probability of disease was raised to 100% with the presence of hard markers and to 73% with the presence of soft markers. The pre-test probability of 58% fell to 20% when ultrasound finding was found to be normal. CONCLUSION: This new approach improves the detection and exclusion of significant pathology in women with CPP and may lead to a reduction in the number of unnecessary laparoscopies carried out on women with CPP.

Adult↗
PubMed2006

Failing pregnancies of unknown location: a prospective evaluation of the human chorionic gonadotrophin ratio.

OBJECTIVE: To assess the performance of the human chorionic gonadotrophin (hCG) ratio (hCG 48 hours/hCG 0 hour) to predict spontaneous resolution of pregnancies of unknown location (PUL). DESIGN: Prospective cohort study. SETTING: Teaching Hospital Early Pregnancy Unit. POPULATION: Women classified as having a PUL. METHODS: The optimal cutoff value for hCG ratio (serum hCG at 48 hours/serum hCG at 0 hours) was calculated from data on 189 consecutive PULs (the 'training set'). This cutoff was tested prospectively on a further 200 consecutive PULs (the 'test set'). The hCG ratio was also compared to absolute levels of serum hCG at 0 and 48 hour for the prediction of failing PULs. MAIN OUTCOME MEASURES: hCG ratio in spontaneously resolving ('failing') PUL compared with those requiring intervention. Optimum cutoff determined and tested to predict spontaneously resolving PUL. Comparison of hCG ratio with absolute levels of serum hCG. RESULTS: A total of 3996 consecutive women were scanned, of which 438 (11.0%) were classified as PULs. Complete data were available for 389 women: 189 in the training set and 200 in the test set. In the training set, there were 102 (54%) failing PUL, while 109 (55%) in the test set. hCG ratio of <0.87 predicted failing PUL, with a sensitivity of 93.1% (95% CI 85.9-97.0) and a specificity of 90.8% (95% CI 82.2-95.7) in the training set. In the test set, sensitivity was 92.7% (95% CI 85.6-96.5) and specificity was 96.7% (95% CI 90.0-99.1). The hCG ratio outperformed absolute serum hCG levels at 0 and 48 hours. CONCLUSIONS: We have defined the optimal hCG ratio for the prediction of failing PUL. Using this cutoff, clinicians can safely adopt a noninterventional approach in women with PUL.

Biomarkers↗
PubMed2006

Endometrial safety of third generation aromatase inhibitors versus tamoxifen in breast cancer patients.

The estrogenic activity of tamoxifen on the uterus increases the risk of developing benign and malignant uterine pathologies in breast cancer patients receiving this drug. This has led to gynecological interventions specifically in symptomatic women to exclude malignant disease. Given this known side effect associated with tamoxifen therapy, newer endocrine therapies such as the third-generation aromatase inhibitors have been compared to tamoxifen also in terms of their uterine effects. To date, studies that have directly compared the uterine effects of tamoxifen with that of aromatase inhibitors generally show that aromatase inhibitors such as anastrozole, letrozole, and exemestane are associated with less uterine pathologies compared to tamoxifen. Furthermore, aromatase inhibitors may even reverse uterine abnormalities induced by tamoxifen. This implies that the absence of a stimulatory effect on the uterus would be one of the benefits gained with aromatase inhibitor therapy and may decrease or even obviate the need for gynecological interventions.

Antineoplastic Agents, Hormonal↗
PubMed2005

Do levels of serum cancer antigen 125 and creatine kinase predict the outcome in pregnancies of unknown location?

BACKGROUND: The aim of this study was to evaluate the role of maternal serum cancer antigen 125 (CA 125) and creatine kinase (CK) levels in predicting the outcome of pregnancies of unknown location (PUL). METHODS: Prospective observational study. Women classified as PUL were recruited. Final outcome of each PUL was established: failing PUL, intrauterine pregnancy (IUP), ectopic pregnancy (EP) or persisting PUL. The persisting PUL group almost certainly represent ultrasonically missed EP and were included in EP group. Serum CK and CA 125 were measured at 0 and 48 h. The values at presentation and the change in levels after 2 days were used in the analysis. We incorporated the most significant of variables into a multinomial logistic regression model to predict all outcomes. The performance of this model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In all, 4698 consecutive women were scanned; 403 were classified as PUL, 27 were lost to follow-up. Of the 376 women eligible, 297 had complete data and therefore were recruited. Mean age and mean gestation were 30.0 years and 43.3 days respectively. Final outcomes: 153 failing PUL (51.5%), 116 IUP (39.1%) and 28 EP (9.4%). Mean serum CK levels at 0 and 48 h were 88.5 and 86.8 IU/l respectively. Mean serum CA 125 levels at 0 and 48 h were 43.8 and 40.1 kIU/l respectively. 81.1% of women had CK and CA 125 ratios (CK 48 h/CK 0 h, CA 125 48 h/CA125 0 h) between 0.7 and 1.3. CA 125 ratio was the only significant variable in the three outcome groups (P < 0.0001). Logistic regression analysis incorporating CA 125 ratio gave an area under ROC curve of 0.782 (SE = 0.041) for failing PUL, 0.768 (SE = 0.043) for IUP and 0.560 (SE = 0.078) for EP. This model was capable of distinguishing failing PUL from IUP, but was not able to detect EP. CONCLUSIONS: Absolute levels of serum CK and CA 125 at the defined times cannot be used to predict the outcome of PUL. Although the CA 125 ratio when incorporated into logistic regression model can distinguish failing PUL from IUP, its inability to detect the high risk PUL, i.e. the developing EP, renders it inappropriate for use in the clinical setting.

Age Factors↗
PubMed2005

The accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery.

BACKGROUND: To evaluate the accuracy of transvaginal ultrasonography (TVS) for the detection of ectopic pregnancies (EPs) in women undergoing surgery for presumed ectopic pregnancy. METHODS: A prospective, observational study. Women were diagnosed with an EP using TVS if any of the following were noted in the adnexal region: (i) an inhomogeneous mass or blob sign adjacent to the ovary and moving separately from the ovary; or (ii) a mass with a hyper-echoic ring around the gestational sac or bagel sign; or (iii) a gestational sac with a fetal pole with or without cardiac activity. The final diagnosis was based on the findings at surgery and subsequent histology of removed tissues. RESULTS: 6621 consecutive women underwent TVS during the study; 200/6621 (3.0%) women were diagnosed as having an EP using TVS. Forty-eight non-surgically managed women were excluded from the analysis. 85.5% of women presented with symptoms and 14.5% were asymptomatic. In 88 (57.9%) cases an inhomogeneous mass or blob sign was visualized and in 20 cases (13.2%) an embryo +/- cardiac activity. Thirty-one (20.4%) had a hyper-echoic ring in the adnexa. In 11 (7.2%) cases there was no evidence of either an intra-uterine (IUP) or EP on ultrasound. Two (1.3%) IUPs were subsequently diagnosed as heterotopic pregnancies. There was no association between the presenting complaints and TVS findings. 152 surgical procedures were performed. In 5.9% (9/152) of these cases no EPs were confirmed in fallopian tube or pelvis at laparoscopy. In 9.1% (13/143) of cases an EP was visualized at surgery when not seen on the index ultrasound scan. The sensitivity and specificity of TVS to detect EP were 90.9% and 99.9%, respectively, with positive and negative predictive values of 93.5% and 99.8%, respectively. CONCLUSIONS: 90.9% of ectopic pregnancies in this study population can be accurately diagnosed using TVS prior to surgery. The diagnosis of an ectopic pregnancy should be based on the positive visualization of an adnexal mass using TVS. This should in turn result in a decrease in the number of false positive laparoscopies.

Adult↗