Gian Benedetto Melis

Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group

Objectives To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result. Design Prospective temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses. The rules comprised five ultrasonic features (including shape, size, solidity, and results of colour Doppler examination) to predict a malignant tumour (M features) and five to predict a benign tumour (B features). If one or more M features were present in the absence of a B feature, the mass was classified as malignant. If one or more B features were present in the absence of an M feature, it was classified as benign. If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive. Setting 19 ultrasound centres in eight countries. Participants 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a standardised research protocol. Reference standard Histological classification of the excised adnexal mass as benign or malignant. Main outcome measures Diagnostic sensitivity and specificity. Results Of the 1938 patients with an adnexal mass, 1396 (72%) had benign tumours, 373 (19.2%) had primary invasive tumours, 111 (5.7%) had borderline malignant tumours, and 58 (3%) had metastatic tumours in the ovary. The simple rules yielded a conclusive result in 1501 (77%) masses, for which they resulted in a sensitivity of 92% (95% confidence interval 89% to 94%) and a specificity of 96% (94% to 97%). The corresponding sensitivity and specificity of subjective assessment were 91% (88% to 94%) and 96% (94% to 97%). In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements, the sensitivities were 89% (83% to 93%) for subjective assessment, 50% (42% to 58%) for the risk of malignancy index, 89% (83% to 93%) for logistic regression model 1, and 82% (75% to 87%) for logistic regression model 2; the corresponding specificities were 78% (72% to 83%), 84% (78% to 88%), 44% (38% to 51%), and 48% (42% to 55%). Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91% (88% to 93%) and a specificity of 93% (91% to 94%), compared with a sensitivity of 90% (88% to 93%) and a specificity of 93% (91% to 94%) when subjective assessment was used in all masses. Conclusions The use of the simple rules has the potential to improve the management of women with adnexal masses. In adnexal masses for which the rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test; the risk of malignancy index and the two regression models were not useful.

Diagnostic value of transvaginal ‘tenderness-guided’ ultrasonography for the prediction of location of deep endometriosis

BACKGROUND The aim was to evaluate the diagnostic accuracy of transvaginal tenderness-guided ultrasonography in the identification of location of deep endometriosis. METHODS Consecutive women scheduled for surgery in our Department for clinically suspected endometriosis were included in this prospective study. All women underwent modified transvaginal ultrasonography using a stand-off in the week before surgery, which also evaluated the painful sites evocated by a gentle pressure of the probe. Five locations of deep endometriosis were considered: vaginal walls, rectovaginal septum, rectosigmoid involvement, uterosacral ligaments and anterior compartment (anterior pouch and/or bladder). Sensitivity, specificity and likelihood ratios (LR+/-) were calculated with 95% confidence intervals (CIs). RESULTS We included 88 women; surgery associated with histopathological evaluation revealed deep endometriosis in different pelvic locations in 72 patients. With respect to the vaginal walls, transvaginal ultrasonography had a sensitivity of 91% (95% CI, 79-97%), specificity of 89% (95% CI, 81-93%), an LR+ of 8.2 and an LR- of 0.09. For endometriosis of rectovaginal septum, transvaginal ultrasonography had a sensitivity of 74% (95% CI, 64-80%), specificity of 88% (95% CI, 4-8%), an LR+ of 6.2 and an LR- of 0.3. For other locations, the sensitivity was lower (ranging from 67% to 33%) with a comparable specificity. CONCLUSIONS This technique shows a high specificity and sensitivity in the detection of vaginal and rectovaginal endometriosis. Good specificity associated with a lower sensitivity was obtained in the diagnosis of deep endometriosis of uterosacral ligaments, rectosigmoid involvement or anterior deep endometriosis.

Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients.

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.

Estradiol-17β reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension

After menopause, both systolic (SBP) and diastolic (DBP) blood pressure (BP) become higher in women than in men of the same age, suggesting that estrogen deficiency may influence the age-related increase in BP. We studied 30 postmenopausal women (mean age, 55 +/- 5.7 years; time from menopause, 2-5 years) affected by mild hypertension with no target-organ complications by means of 24-h BP monitoring. None of the group were undergoing estrogen replacement therapy or taking antihypertensive drugs. According to a randomized, double-blind protocol, subjects received patches of transdermal estradiol-17beta (E2) or a matched placebo, with crossover after a 7-day washout period. In 12 patients the 24-h peak-to-trough variation in SBP and DBP amounted to less than 10% (nondippers). Administration of E2 significantly decreased 24-h SBP and DBP in the whole cohort (P < .05). Furthermore, E2 restored the expected reduction in BP during nighttime in the nondipper subgroup. It is well known that estrogen replacement therapy protects against the development of both cardiovascular diseases and stroke. Our data suggest that this activity could be attributed, at least in part, to the activity of E2 in preserving physiologic circadian fluctuation of BP.

Influences of melatonin administration on the circulation of women

The cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared with those of placebo in 17 young, healthy, early follicular-phase women. Compared with placebo, the administration of melatonin modified, within 90 min, the pulsatility index (PI), evaluated by color Doppler ultrasound, of the internal carotid artery, abdominal aorta, and axillary artery. The effect was linearly related to baseline PI, higher baseline PI being associated with greater PI declines. Melatonin administration significantly decreased mean PI of internal carotid artery ( P < 0.02), systolic and diastolic blood pressure ( P < 0.01), and norepinephrine levels evaluated after 5 min of standing position ( P < 0.02). Heart rate and supine catecholamine levels were not modified. These data indicate that in young, healthy women the administration of 1 mg of melatonin greatly influences artery blood flow, decreases blood pressure, and blunts noradrenergic activation. Clinical implications of present data are worthy to be fully explored.

Complex pelvic mass as a target of evaluation of vessel distribution by color Doppler sonography for the diagnosis of adnexal malignancies: results of a multicenter European study.

Objective. To compare the diagnostic accuracy of gray scale sonography and color Doppler imaging in the differential diagnosis of adnexal malignancies from benign complex pelvic masses in a multicenter prospective study. Methods. The study was performed as a collaborative work at 3 European university departments of obstetrics and gynecology. A total of 826 complex pelvic masses on which transvaginal sonography and evaluation of cancer antigen 125 plasma concentrations were performed before surgical exploration were included in the study. The scanning procedure was the same in the 3 institutions. An adnexal mass was first studied in gray scale sonography, and a probable histologic type was predicted. Second, solid excrescences or solid portions of the tumor were evaluated for vascular flow with color Doppler sonography (conventional or power). A mass was graded malignant if flow was shown within the excrescences or solid areas and benign if there was no flow. The overall agreement between the test result and the actual outcome was calculated by κ statistics. Results. Color Doppler evaluation was more accurate in the diagnosis of adnexal malignancies in comparison with gray scale sonography (κ = 0.82 and 0.65, respectively) because of significantly higher specificity (0.94 versus 0.84; P < .001). The evaluation of the cancer antigen 125 plasma concentration did not seem to increase the accuracy of either method. Conclusions. The evaluation of vessel distribution by color Doppler sonography in complex adnexal cysts seems to increase the diagnostic accuracy of gray scale sonography in the detection of adnexal malignancies in a large study population.

Transvaginal ultrasonography in the diagnosis of cystic teratoma

Objective To assess prospectively the role of transvaginal ultrasonography in screening for cystic teratoma and in differentiating cystic teratoma from other ovarian masses. Methods Three hundred seventy-six premenopausal non-pregnant women underwent transvaginal ultrasonography 1 week before undergoing laparotomy or laparoscopy. The visualization of localized or diffuse echogenicity was chosen as the characteristic ultrasonographic finding of cystic teratoma. Endosonographic diagnosis was compared with surgical and pathologic findings. Results Sensitivity and specificity for the ultrasonographic screening were 57.9 and 99.7%, respectively, calculated for each visualized overy (n = 659), and 84.6 and 98.2%, respectively, for differentiating cystic teratoma from other ovarian masses, calculated for each visualized cyst (n = 123). Conclusion Transvaginal ultrasonography has a better predictive ability for differentiating cystic teratoma from other ovarian masses (kappa value 0.84) than in screening for cystic teratomas (kappa value 0.69).

Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women.

The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women.

Transvaginal ultrasonography combined with CA-125 plasma levels in the diagnosis of endometrioma

OBJECTIVE To assess the role of transvaginal ultrasonography combined with CA-125 plasma levels in the diagnosis of endometrioma. DESIGN Prospective study with pathological confirmation of the diagnosis. SETTING Department of Obstetrics and Gynecology of the University of Cagliari, Italy. PATIENTS One hundred one consecutive premenopausal nonpregnant women submitted to laparoscopy or laparotomy, from November 1993 to October 1994, because of the presence of an adnexal mass. INTERVENTIONS Within 2 days before surgery all patients underwent transvaginal ultrasonography and evaluation of CA-125 plasma levels. The ultrasonographic impression and the CA-125 value were then compared with the histopathological diagnosis. MAIN OUTCOME MEASURE The overall agreement between the test result and the actual outcome was calculated using the kappa index for the transvaginal ultrasonography used alone and for the combination of transvaginal ultrasonography and CA-125 values, for each chosen cutoff and range. RESULTS Transvaginal ultrasonography has a strong agreement between test and surgery (kappa value 0.76) whereas the combined use of the two methods is associated with a lower kappa index, ranging from 0.40 to 0.69. CONCLUSION Transvaginal ultrasonography used alone has a better predictive capacity in differentiating endometrioma from other adnexal masses than combined methods.

Spontaneous reversibility of bone loss induced by gonadotropin-releasing hormone analog treatment *

OBJECTIVE To verify if a 6-month period of hypoestrogenism due to chronic treatment with GnRH analogue (GnRH-a) causes irreversible bone loss in young women. DESIGN Controlled clinical study in volunteer women. SETTING Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. PATIENTS Twenty-eight women (mean age +/- SE 81.1 +/- 0.99 years) with endometriosis diagnosed by laparoscopy and 25 healthy, normally cycling women of the same age (28.3 +/- 1.14 years). INTERVENTIONS In women with endometriosis, six SC implants of the GnRH-a compound, 3.6 mg goserelin acetate depot, were administered every 28 days starting within 15 days of laparoscopy. Compounds interfering with bone metabolism or hormonal formulations were not taken by control women during the entire period of the study. MAIN OUTCOME MEASURE Evaluation of lumbar bone mineral density at the start of the study and 6, 12, and 30 months later. RESULTS At the onset of the study, lumbar bone mineral density did not differ in women with endometriosis and control women. Lumbar bone mineral density values significantly decreased after 6 months of GnRH-a treatment. This reduction was still evident 6 months after GnRH-a interruption. However, 24 months after treatment withdrawal, bone mineral density reduction disappeared and bone mineral density values were completely superimposable (+/- O.4 percent) to those observed before treatment. In contrast, control women lumbar bone mineral density values did not change during the entire period of observation. CONCLUSIONS These data suggest that GnRH-a treatment for 6 months is not associated with long-term effects on lumbar bone density.