Diagnosis of superficial endometriosis on transvaginal ultrasound by visualization of peritoneum of pouch of Douglas.

OBJECTIVE: Around 80% of women with endometriosis have superficial endometriosis (SE) rather than ovarian or deep endometriosis (DE). However, to date, advances in non-invasive, imaging-based diagnosis have been limited to DE or ovarian disease. The objective of this study was to determine whether we can detect SE on transvaginal ultrasound scan (TVS) by assessing the peritoneum of the pouch of Douglas (POD). METHODS: This was a retrospective diagnostic test study following a change in practice to include POD peritoneum assessment for SE during TVS at a tertiary London hospital. Eligible patients underwent TVS by a single clinician trained in endometriosis scanning and a subsequent surgical procedure (laparoscopy) between April 2018 and September 2021. Participants formed a consecutive series. The TVS findings were compared with those of laparoscopy as the gold standard. Comparison of TVS findings with intraoperative findings was performed by calculating the diagnostic test performance measures (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive and negative likelihood ratios). RESULTS: The study included a total of 100 patients. We found that 43/100 (43.0%) patients had no endometriosis, 33/100 (33.0%) had SE and 24/100 (24.0%) had DE on laparoscopy. SE was correctly detected on TVS in 17/33 patients, with a sensitivity of 51.5% (95% CI, 33.5-69.2%), specificity of 94.0% (95% CI, 85.4-98.4%), PPV of 81.0% (95% CI, 60.8-92.1%) and NPV of 79.7% (95% CI, 73.4-84.9%). DE was correctly diagnosed in 20/24 cases, including all ovarian cases, with a sensitivity of 83.3% (95% CI, 62.3-95.3%), specificity of 97.4% (95% CI, 90.8-99.7%), PPV of 90.9% (95% CI, 71.6-97.5%) and NPV of 94.9% (95% CI, 88.3-97.8%). The detection of SE on TVS was most accurate in the POD (sensitivity, 50.0%; specificity, 96.4%; PPV, 76.9%; NPV, 88.9%). CONCLUSIONS: This study shows that the detection of SE in the POD is possible using routine TVS. While negative TVS does not reliably confirm the absence of disease or replace diagnostic laparoscopy, positive TVS facilitates non-invasive diagnosis for a much larger group of women than was previously possible. This should help to reduce the time from the onset of symptoms to diagnosis and enable initiation of medical treatment without the risk, cost and delay associated with a surgical diagnosis. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Should a detailed ultrasound examination of the complete urinary tract be routinely performed in women with suspected pelvic endometriosis?

STUDY QUESTION: Is there any benefit to including the routine examination by ultrasound of the bladder, ureters and kidneys of women with endometriosis? SUMMARY ANSWER: The benefit of examination of the complete urinary tract of women with suspected endometriosis is that ureteric endometriosis, with or without hydronephrosis, can be detected which facilitates early intervention to prevent nephropathy. WHAT IS ALREADY KNOWN: Women with endometriosis can get ureteric obstruction but there is no clear consensus on the correct diagnostic technique. Ultrasound is accurate at detecting women with bladder endometriosis but ureteric involvement has not been assessed previously. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study, conducted at a teaching hospital over a period of 14 months. A total of 848 women presenting with chronic pelvic pain were included into the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women with chronic pelvic pain underwent a detailed transvaginal and transabdominal pelvic ultrasound examination to investigate possible causes of their symptoms. This included a systematic assessment of the urinary bladder, pelvic sections of the ureters and kidneys. The ultrasound findings were compared with findings at surgery and the results of targeted urological imaging and interventions. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 848 women presenting with chronic pelvic pain were included into the study. 28/848 women (3.3% 95% CI 2.1-4.5) had evidence of urinary tract abnormalities on initial ultrasound scan. Among these 17/848 (2.0% 95% CI 1.06-2.94) had evidence of urinary tract endometriosis, whilst 11/848 (1.3% 95% CI 0.54-2.06) women had other urinary tract abnormalities. Among women with urinary tract endometriosis 11/17 (65%) had evidence of ureteric involvement, 3/17 (18%) had both ureteric and bladder disease and 3/17 (18%) had bladder disease only. 12/17 (59%) women with urinary tract endometriosis also had evidence of hydronephrosis. The diagnosis of ureteral endometriosis had a sensitivity of 12/13 (92%) (95% CI 63.9-99.8), specificity 151/151 100% (95% CI 97.6-100), PPV 100% (95% CI 73.5-100), NPV 99.3% (95% CI 96.3-99.9%) LR- 0.08 (95% CI 0.01-0.39). LIMITATIONS, REASONS FOR CAUTION: The routine examination of the complete urinary tract including the distal ureters is a novel technique that should be evaluated in different populations. WIDER IMPLICATIONS OF THE FINDINGS: Ultrasound is an accurate test to diagnose urinary tract involvement in women with suspected pelvic endometriosis and examination of the complete urinary tract should become an integral part of ultrasound assessment of women with suspected endometriosis.

Reproducibility of assessment of severity of pelvic endometriosis using transvaginal ultrasound.

OBJECTIVE: To examine the reproducibility of assessment of severity of pelvic endometriosis by transvaginal sonography (TVS). METHODS: This was a prospective observational study conducted from August 2006 to July 2009 in two academic departments of obstetrics and gynecology. Women with clinically suspected or proven pelvic endometriosis were invited to join the study. All patients included underwent TVS performed by two observers and a laparoscopic assessment of pelvic endometriosis. The ultrasound observers were blinded to each other's results. The reproducibility of TVS was examined by evaluation of interobserver agreement for the American Society of Reproductive Medicine (ASRM) score by Bland-Altman analysis and the stage and the diagnosis of deeply infiltrating endometriosis (DIE) by calculation of kappa coefficients. Agreement between the findings on TVS for each observer and those on laparoscopy was also evaluated. RESULTS: Thirty-four patients were recruited to the study, and TVS was performed by two ultrasound observers. Of these patients, one did not undergo laparoscopy and was therefore excluded from the final analysis. No endometriosis was found in 12 (36.4%) patients. One patient (3%) had minimal disease, one (3%) had mild disease, five (15.2%) had moderate disease and 14 (42.4%) had severe disease. Interobserver agreement was very good for disease classification on TVS (Cohen's kappa, 0.931). Agreement between TVS and laparoscopy findings was also very good (Cohen's kappa, 0.955 and 0.966 for the two examiners). For ASRM score on TVS, the interobserver 95% limits of agreement were -16.6 to 12.7, with a mean difference of -1.9 (95% CI, -4.35 to 0.71). CONCLUSION: TVS is a reproducible method for assessment of the severity of pelvic endometriosis and shows good agreement with findings on laparoscopy.

Value of transvaginal ultrasound in assessing severity of pelvic endometriosis.

OBJECTIVE: The objective of this study was to examine the ability of preoperative transvaginal ultrasound (TVS) scanning to assess the severity of pelvic endometriosis. METHODS: Consecutive women with clinically suspected or proven pelvic endometriosis, who were booked for laparoscopy, were invited to join the study. The severity of endometriosis was assessed preoperatively using TVS and the findings were compared with the results obtained by laparoscopy using the American Society for Reproductive Medicine (ASRM) classification. RESULTS: In total, 201 women had preoperative TVS and laparoscopies. Of these, no endometriosis was found at laparoscopy for 62/201 (30.8%; 95% CI, 24.8-37.5), whereas 33/201 (16.4%; 95% CI, 11.9-22.2) had minimal endometriosis, 31/201 (15.4%; 95% CI, 11.1-21.1) had mild endometriosis, 27/201 (13.4%; 95% CI, 9.4-18.8) had moderate endometriosis and 48/201 (23.9%; 95% CI, 18.5-30.2) had severe endometriosis. The sensitivity and specificity of the TVS diagnosis of severe pelvic endometriosis were 0.85 (95% CI, 0.716-0.934) and 0.98 (95% CI, 0.939-0.994), respectively, and the positive and negative likelihood ratios were 43.5 (95% CI, 14.1-134) and 0.15 (95% CI, 0.075-0.295), respectively. Overall, there was a good level of agreement between ultrasound and laparoscopy in identifying absent, minimal, mild, moderate and severe disease (quadratic weighted kappa = 0.786). The mean ASRM score difference between TVS and laparoscopy in assessing severity of endometriosis was -2.398 (95% CI, -4.685 to -0.1112) and the limits of agreement were -34.62 (95% CI, -38.54 to -30.709) to 29.83 (95% CI, 25.91-33.74). CONCLUSIONS: TVS is a good test for assessing the severity of pelvic endometriosis. TVS is particularly accurate in detecting severe disease, which could facilitate more effective triaging of women for appropriate surgical care.

Use of ultrasound pattern recognition by expert operators to identify borderline ovarian tumors: a study of diagnostic performance and interobserver agreement.

OBJECTIVE: To assess the accuracy and reproducibility of ultrasound 'pattern recognition' for the diagnosis of borderline ovarian tumors by asking experienced ultrasound operators to evaluate representative images of different types of adnexal tumor. METHODS: Digitally stored static two-dimensional B-mode images of representative cases of benign, borderline and invasive malignant ovarian tumors were independently assessed by three expert sonologists who had not performed the original real-time ultrasound examination. The outcome measures included diagnostic accuracy and interobserver agreement in the diagnosis of benign, borderline or invasive malignant ovarian tumors. RESULTS: One hundred and sixty-six cases were included in the final data analysis. A correct classification was made by all three experts in 83% of the primary invasive cancers, 76% of the benign masses and in 44% of the borderline malignant tumors (P < 0.01). The experts showed a tendency to misclassify borderline tumors as benign rather than primary invasive (ratio of 8 : 1 for Expert A, 4 : 1 for B and 6 : 1 for C). The interobserver agreement between any two experts was very good when they were tested for their ability to discriminate between invasive and non-invasive (benign and borderline) ovarian tumors (Cohen's kappa 0.85-0.88), but poorer for the discrimination between malignant (invasive and borderline) and benign tumors (kappa 0.70-0.78). CONCLUSIONS: The accuracy of ultrasound diagnosis of borderline tumors is lower in comparison with benign and invasive malignant lesions. The diagnostic performance and interobserver agreement are better when the outcomes are dichotomized into non-invasive and invasive malignant lesions, as opposed to the traditional diagnosis of benign and malignant tumors.

Confidence of expert ultrasound operators in making a diagnosis of adnexal tumor: effect on diagnostic accuracy and interobserver agreement.

OBJECTIVE: To assess the degree of confidence with which expert ultrasound operators make a diagnosis of benign, borderline and invasive malignant ovarian tumors and its effect on diagnostic accuracy and interobserver agreement. METHOD: Digitally stored static two-dimensional B-mode images of representative cases of benign, borderline and invasive malignant ovarian tumors were independently assessed by three expert ultrasound operators who had not performed the original real-time ultrasound examination. The experts classified the tumors as benign, borderline or invasive malignant and they also indicated the degree of confidence with which they made the diagnosis (certain, probable and uncertain). The diagnostic accuracy and interobserver agreement, in differentiating benign, borderline and invasive malignant ovarian tumors, were calculated depending on the level of confidence with which the diagnosis was made. RESULTS: One hundred and sixty-six cases were included in the final data analysis. The diagnostic accuracy of all three experts decreased with decreasing level of confidence. Interobserver agreement between any two experts was very high when they were certain of the diagnosis (rates of agreement 98%, 99% and 100%), but it was significantly lower with a moderate level of confidence (rates of agreement 78%, 71% and 76%) (P < 0.01 for any two experts). The agreement in both diagnosis and confidence was lowest in cases of borderline ovarian tumors compared to benign and primary invasive lesions. CONCLUSIONS: The accuracy of expert ultrasound operators using pattern recognition depends on the degree of certainty with which the diagnosis is made. Interobserver variability is also influenced by the operators' confidence in making the diagnosis. Our findings suggest that the level of confidence with which the diagnosis is made should be included in the ultrasound report.

Ultrasound methods to distinguish between malignant and benign adnexal masses in the hands of examiners with different levels of experience.

OBJECTIVES: To determine the effect of an ultrasound training course on the performance of pattern recognition when used by less experienced examiners and to compare the performance of pattern recognition, a logistic regression model and a scoring system to estimate the risk of malignancy between examiners with different levels of experience. METHODS: Using ultrasound images of selected adnexal masses, two trainees classified the masses as benign or malignant by using pattern recognition both before and after they had attended a theoretical gynecological ultrasound course. They also classified the masses by using a logistic regression model and a scoring system, but only after they had attended the course. The performance of these three methods when they were used by the trainees was then compared with that when they were used by experts. RESULTS: One hundred and sixty-five adnexal masses were included, of which 42% were malignant (21% invasive tumors and 21% borderline tumors). The area under the receiver-operating characteristics curve of pattern recognition when used by the trainees was similar before and after they had attended the course. Training decreased sensitivity (84% vs. 70% for Trainee 1, P = 0.004; 70% vs. 61% for Trainee 2, P = 0.058) and increased specificity (77% vs. 92% for Trainee 1, P = 0.001; 89% vs. 95% for Trainee 2, P = 0.058). The performance of pattern recognition was poorer in the hands of the trainees than in the hands of the experts. The sensitivities of the logistic regression model were 70% and 54% for the trainees vs. 83% for an expert (P = 0.020 and < 0.001, respectively) and the specificities were 84% and 94% vs. 89% (P = 0.25 and 0.59, respectively). The sensitivities of the scoring system were 59% and 54% for the trainees vs. 75% for the expert (P = 0.002 and < 0.001, respectively), and the specificities were 90% and 93% vs. 85% (P = 0.103 and 0.008, respectively). CONCLUSION: Theoretical ultrasound teaching did not seem to improve the performance of pattern recognition in the hands of trainees. A logistic regression model and a scoring system to classify adnexal masses as benign or malignant perform less well when they were used by inexperienced examiners than when used by an expert. Before using a model or a scoring system, experience and/or proper training are likely to be of paramount importance if diagnostic performance is to be optimized.

Real-time ultrasound vs. evaluation of static images in the preoperative assessment of adnexal masses.

OBJECTIVE: To determine if the prediction of the malignancy of an adnexal mass using pattern recognition, i.e. subjective evaluation of gray-scale and Doppler ultrasound findings, is as accurate when based on static images as it is when based on a real-time ultrasound examination. METHODS: The static images of 166 non-consecutive patients with 'difficult' adnexal masses, who all underwent surgery and for whom a histopathological diagnosis was available, were evaluated by three experts in gynecological ultrasound ('image experts'). All ultrasound examinations had been performed and the static images saved by a fourth expert sonologist ('real-time' sonologist). All four sonologists classified the adnexal masses as benign or malignant based on their subjective impression and stated with what degree of confidence their diagnosis was made. The diagnostic performance of the real-time sonologist was compared with that of each of the three image experts and with that of the 'consensus opinion' of the image experts (i.e. the diagnosis suggested by at least two of the latter). RESULTS: The real-time sonologist correctly predicted the diagnosis with an accuracy of 89% (148/166) vs. 85% (141/166) for the consensus opinion of static images (P = 0.0707). Equivalent values for sensitivity and specificity were 80% (56/70) vs. 83% (58/70) (P = 0.4142) and 96% (92/96) vs. 86% (83/96) (P = 0.0027), respectively. CONCLUSIONS: The preoperative diagnosis of an adnexal mass made on the basis of a real-time ultrasound examination is more precise than a diagnosis made on the basis of saved static ultrasound images. Evaluation of static images is associated with lower diagnostic specificity.

Imaging of gynecological disease (3): clinical and ultrasound characteristics of granulosa cell tumors of the ovary.

OBJECTIVES: To describe the clinical and ultrasound characteristics of granulosa cell tumors (GCTs) of the ovary, and to define the ultrasound appearance of GCTs based on pattern recognition. METHODS: Databases of four gynecological ultrasound centers were searched to identify patients with histologically proven GCTs who had undergone a standard preoperative ultrasound examination. RESULTS: A total of 23 women with confirmed GCT were identified. Twelve (52%) women were postmenopausal, nine (39%) were of fertile age and two (9%) were prepubertal. Clinical symptoms were abdominal distension (7/23, 30%), pain (5/23, 22%) and irregular vaginal bleeding (6/23, 26%). Seven patients (30%) were asymptomatic. Endometrial pathology was found in 54% (7/13) of the patients from whom endometrial biopsies were taken. On ultrasound scan 12/23 (52%) masses were multilocular-solid, 9/23 (39%) were purely solid, one mass (4%) was unilocular-solid and one mass was multilocular (4%). Multilocular and multilocular-solid cysts typically contained large numbers of small locules (> 10). The echogenicity of the cyst content was most often mixed (6/16, 38%) or low level (7/16, 44%). Papillary projections were found in only four women (17%). The GCTs were large tumors with a median largest diameter of 102 (range, 37-242) mm and manifested moderate or high color content at color Doppler examination (color score 3 in 13/23 tumors (57%); color score 4 in 8/23 tumors (35%)). CONCLUSIONS: At ultrasound examination, most GCTs are large multilocular-solid masses with a large number of locules, or solid tumors with heterogeneous echogenicity of the solid tissue. Hemorrhagic components are common and increased vascularity is demonstrated at color/power Doppler ultrasound examination. The hyperestrogenic state that is created by the tumor often causes endometrial pathology with bleeding problems as a typical associated symptom.

Ultrasound diagnosis of ectopic pregnancy in the non-communicating horn of a unicornuate uterus (cornual pregnancy).

OBJECTIVE: To prospectively evaluate ultrasound criteria for the diagnosis of pregnancy in the rudimentary horn of a unicornuate uterus (cornual pregnancy). METHODS: This was a prospective observational study over a period of 90 months in a tertiary referral center in a London teaching hospital. A diagnosis of cornual pregnancy was made when all the following ultrasound criteria were met: (1) a single interstitial portion of Fallopian tube in the main uterine body; (2) a gestational sac, mobile and separate from the uterus, surrounded by myometrium; and (3) a vascular pedicle joining the gestational sac to the unicornuate uterus. In cases where the ultrasound criteria were met the pregnancy was followed up and the final outcome was recorded, including operative and histological findings. RESULTS: Over the study period eight cases of cornual pregnancy were diagnosed. Six women had a single case of cornual pregnancy. One woman was managed expectantly in her first cornual pregnancy and subsequently suffered a recurrence. Surgical management varied depending on viability of the pregnancy and gestational age at presentation. In all the women who underwent surgery the diagnosis was eventually confirmed at operation and on histological examination. During the study period there were no false positive or false negative results in our unit using the above criteria. CONCLUSION: The proposed ultrasound criteria appear accurate and may be applied in clinical practice to facilitate preoperative diagnosis of cornual ectopic pregnancy.

Pharmacokinetics, absorption, distribution and disposition of [125I]-oligotide following intravenous or oral administration in the rat.

Oligotide (O) was labelled with 125I. The radiolabelled compound ([125I]-Oligotide ([125I]-O)) retained the biological activity of parent O. Following single intravenous administration the half lives of radioactivity associated with O and/or O related components in plasma were 9-10 min and 9-10 h for alpha and beta phases respectively. Following single oral administration the half life of radioactivity associated with O and/or O related components in plasma was 11.45-12.76 h for beta fase. Following multiple oral administration once daily for 7 days, the half life of radioactivity associated with O and/or O related components following the 7th dose was 10-12 h for beta phase. The areas under plasma total radioactivity versus time curves were dose-dependent. Following single intravenous administration the major proportion of the administered dose was excreted via urine, while following single oral administration excretion via urine and faeces accounted for similar proportions of the administered dose. Following both single and oral administration the levels of radioactive components derived from [125I]-O in organs examined were generally highest in highly perfused organs.

Study on pharmacokinetics of radioactive labelled defibrotide after oral or intravenous administration in rats.

Defibrotide (D) was labelled with 125I or with 32P. The radiolabelled compounds ([125I]-Defibrotide ([125I]-D), [32P]-Defibrotide ([32P]-D) retained the same profibrinolytic activity, in vitro, as the parent drug, suggesting that the labelling procedures had not modified the pharmacological properties of D and hence that its chemical structure was not affected significantly. After single intravenous or oral administration of [125I]-D or [32P]-D the pharmacokinetic parameters for the two labels were generally in good agreement (75%). t 1/2 alpha was in the range of minutes while t 1/2 beta was in the range of hours. Bioavailability, following single oral administration of [125I]-D or [32P]-D, was in the range of 58-70%. These data suggest that D, in spite of its macromolecular nature, is absorbed, after oral administration, fairly well.

Pharmacokinetics, absorption, distribution and disposition of [125I]-defibrotide following intravenous or oral administration in the rat.

Defibrotide (D) was labelled with 125I. The radiolabelled compound ([125I]-Defibrotide ([125I]-D)) retained the same profibrinolytic activity as the parent drug. Following single intravenous administration of [125I]-D the half lives of radioactivity associated with D components in plasma were 9.45 min and 11.27 h for alpha and beta phases respectively. Following single oral administration of [125I]-D the half life of radioactivity associated with D components in plasma was 12.83 h for the elimination phase. Bioavailability was apparently 58%. The areas under plasma total radioactivity versus time curves were dose-dependent following both intravenous and oral administration. No significant accumulation of total radioactivity in plasma was observed following multiple oral administration of [125I]-D. Following single intravenous administration of [125I]-D a larger proportion of administered radioactivity was excreted via urine than faeces while following single oral administration excretion via urine and faeces accounted for similar proportions of administered radioactivity. Following both single and oral administration the levels of total radioactivity in tissues and organs examined were generally highest in highly perfused organs and were very high in the thyroid despite pretreatment with non-radiolabelled potassium iodide. Radioactivity was also found to be associated with the aorta wall.

Evaluation of the effect of cicletanine on genetic atherosclerosis in the rabbit.

This study was designed to evaluate the hypolipidaemic and anti-atherosclerotic potential of cicletanine in a genetic hypercholesterolaemic rabbit model. In a pilot study the effect of 8 weeks oral administration of 2 treatment levels of cicletanine (10, 30 mg.kg-1.day-1) was compared with vehicle alone. In the main study, 8 weeks oral administration of 2 treatment levels of cicletanine (5, 30 mg.kg-1.day-1) was compared with parallel treatment with probucol (15 mg.kg-1.day-1) and with nifedipine (10 mg.kg-1.day-1). At the start of each study and at scheduled points throughout, blood samples were collected for routine biochemical and lipid/lipoprotein analyses. At the end of each test period all animals were examined at post mortem. Aortae were dissected and examined for the presence ans degree of atheroma. Hearts were examined for the presence of lesions. Sections of aortae were stained for lipid, examined histologically and scored for extent of atheroma using an atherosclerotic index. In the pilot study cicletanine had no effect on blood lipid levels. Gross pathology indicated a reduction in the extent of aortic atheroma in cicletanine-treated animals. Histopathological examination of thoracic and abdominal regions of the aortae confirmed these gross findings. The atherosclerotic index was significantly reduced (p less than 0.06) in all drug treated animals. In the main study similar data were achieved. None of the test drug affected plasma lipid/lipoprotein levels. Gross pathology indicated a reduction in the extent of aortic atheroma in all cicletanine-treated animals and also in the nifedipine-treated group. This was confirmed by histopathological examination of thoracic and abdominal regions of the aortae.(ABSTRACT TRUNCATED AT 250 WORDS)

The interrelationship between thromboxane biosynthesis, aggregation and 5-hydroxytryptamine secretion in human platelets in vitro.

Platelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl inidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.