Giuseppe Pelusi

Accuracy of three-dimensional ultrasound in diagnosis and classification of congenital uterine anomalies

OBJECTIVEnTo assess the accuracy of three-dimensional (3D) ultrasound in the diagnosis of congenital uterine anomalies.nnnDESIGNnProspective study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nNulliparae with three or more consecutive miscarriages.nnnINTERVENTION(S)nAll women underwent 3D transvaginal ultrasound study of the uterine cavity.nnnMAIN OUTCOME MEASURE(S)nWomen with negative ultrasound findings subsequently underwent office hysteroscopy, whereas a combined laparoscopic-hysteroscopic assessment was performed in cases of suspected Müllerian anomaly.nnnRESULT(S)nA specific Müllerian malformation was sonographically diagnosed in 54 women of the 284 included in the study group. All negative ultrasound findings were confirmed at office hysteroscopy. Among the women with abnormal ultrasound findings, the presence of a Müllerian anomaly was endoscopically confirmed in all. Concordance between ultrasound and endoscopy around the type of anomaly was verified in 52 cases, including all those with septate uterus and two out of three with bicornuate uterus.nnnCONCLUSION(S)nVolume transvaginal ultrasound appears to be extremely accurate for the diagnosis and classification of congenital uterine anomalies and may conveniently become the only mandatory step in the assessment of the uterine cavity in patients with a history of recurrent miscarriage.

Diagnostic accuracy of 18F-FDG PET/CT in characterizing ovarian lesions and staging ovarian cancer: correlation with transvaginal ultrasonography, computed tomography, and histology.

AimsTo (a) assess the accuracy of 18F-FDG PET/CT in distinguishing malignant from benign pelvic lesions, compared to transvaginal ultrasonography (TVUS) and (b) to establish the role of whole-body 18F-FDG PET/CT, compared to contrast enhanced computed tomography (CT), in staging patients with ovarian cancer. PatientsFifty consecutive patients with a pelvic lesion, already scheduled for surgery on the basis of physical examination, TVUS, and serum Ca125 levels, were enrolled in the study. Patients age ranged between 23 and 89 years (mean 64). All patients underwent TVUS including a colour Doppler study followed by a thorax and abdominal CT scan, and whole-body 18F-FDG PET/CT within 2 weeks prior to surgery. Histological findings obtained at surgery were taken as the ‘gold standard’ to compare 18F-FDG PET/CT and TVUS, and 18F-FDG PET/CT vs. CT. When tissue analysis showed ovarian cancer, the accuracy of 18F-FDG PET/CT and CT were compared for the purpose of obtaining a precise staging. ResultsAt surgery, the ovarian lesions were malignant in 32/50 patients (64%) and benign in the remaining 18/50 patients (36%). The sensitivity, specificity, NPV, PPV and accuracy of 18F-FDG PET/CT were 87%, 100%, 81%, 100% and 92%, respectively, compared with 90%, 61%, 78%, 80% and 80%, respectively, for TVUS. In staging ovarian cancer, 18F-FDG PET/CT results were concordant with final pathological staging in 22/32 (69%) patients while CT results were concordant in 17/32 (53%) patients. CT incorrectly down-staged four out of six stage IV patients by missing distant metastasis in the liver, pleura, mediastinum, and in left supraclavicular lymph nodes, which were correctly detected by 18F-FDG PET/CT. ConclusionPET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients.

Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer

OBJECTIVESnThe aims of our study were to evaluate the possibility of identifying the sentinel lymph node (SLN) in patients with endometrial cancer (EC) and to directly compare two injection techniques, cervical and hysteroscopic injection.nnnMETHODSnFifty-four patients with endometrial carcinoma, clinical stages I and II, were submitted to complete surgical staging through laparoscopy, as recommended by FIGO in 1988. For the mapping procedure the patients were divided into two groups of injection: the cervical injection group and hysteroscopic injection group. Technetium (Tc) 99m radiocolloid was used as tracer.nnnRESULTSnIntraoperative detection rate of SLN was 70% in cervical group and 65% in the hysteroscopic group (p=n.s.). In the cervical group, all patients had SLN in the pelvis only and the mean SLN removed was 18 (range 2-26). In the hysteroscopic group, all patients had SNLs in the pelvis and two patients had SLN both in the pelvis and above the bifurcation of the aorta. Mean pelvic SLN removed was 20 (range 8-42).nnnCONCLUSIONSnOur data shows that it is possible to identify the SLN in tumours of the endometrium. Both cervical and hysteroscopic techniques are feasible but the hysteroscopic procedure might represent the only method able to highlight the complete lymphatic drainage of the uterus as suggested by the presence of paraaortic positive SLN only in this group.

Effect of Long‐Term Testosterone Administration on the Endometrium of Female‐to‐Male (FtM) Transsexuals

INTRODUCTIONnLong term safety of testosterone (T) administration in women is still unknown. In particular few and discordant data exists on the effects of T on the endometrium.nnnAIMnThe aim of this study was to investigate the effects of long-term T treatment on endometrium histology and proliferation in female to male transsexual subjects (FtM). We compared these endometria with those of young women in the proliferative phase (PM) of the cycle and with those of post menopausal women (M).nnnMETHODnEndometrial samples from 27 FtM treated with T (intramuscular injection of 100 mg Testoviron Depot /10 days for at least one year), 30 M undergoing vaginal hysterectomy, and 13 PM undergoing hysteroscopy for infertility problems were collected. Endometrial proliferation was evaluated on the basis of histopathology and expression of the proliferation marker Ki-67. Both M and PM women had not received any hormonal treatment for at least one year.nnnMAIN OUTCOME MEASUREnCirculating total testosterone (TT), estradiol (E), progesterone (P), insulin and glucose levels were measured in FtM and PM subjects.nnnRESULTSnFtM had received T for 33.6 +/- 21.3 months (mean +/- SD). In FtM subjects, histological analysis found inactive endometrium similar to the atrophic menopausal endometrium. The expression of Ki-67 in the glands, stroma and glands and stroma together was significantly (p < 0.0005) lower in FtM than in PM women and was similar in the FtM and M groups. Small polyps were detected in 5 of the 27 FtM subjects.nnnCONCLUSIONSnIn conclusion our data suggest that exogenous T administration does not stimulate endometrial proliferation in FtM transsexuals and indeed may have atrophic effects.

Prevalence of sexual dysfunction among postmenopausal women with and without metabolic syndrome.

INTRODUCTIONnThe metabolic syndrome (MetS) is a multifactorial disease characterized by the co-occurrence of impaired glucose tolerance/diabetes, central obesity, high levels of triglycerides, low levels of high-density lipoprotein, and hypertension. Its prevalence is higher in menopausal women. We, and others, have recently shown that female sexual dysfunction (FSD) affects menopausal women. Whether the presence of MetS may be linked to a higher risk of FSD in menopausal women is unknown.nnnAIMSnnnnTHE AIMS OF OUR STUDY WEREn(i) to evaluate the prevalence of FSD in women with MetS (based on National Cholesterol Education program-Adult Treatment Panel III 2009 criteria) in comparison with healthy controls and (ii) to evaluate the influence of singular components of MetS on female sexual function.nnnMETHODSnThe Female Sexual Function Index (FSFI) questionnaire, the Female Sexual Distress Scale (FSDS), and The Middlesex Hospital Questionnaire were administered to 103 postmenopausal women with MetS and 105 healthy postmenopausal controls (HC). Female sexuality was defined as dysfunctional when FSFI score was <23 and FSDS was >15.nnnMAIN OUTCOME MEASURESnFSFI and FSDS were completed by women with and without MetS.nnnRESULTSnThe prevalence of women with sexual dysfunction was higher in MetS women than HC (39/103 [37.9%] vs. 20/105 [19%], P = 0.003). The prevalence of both pathological scores in every FSFI domain and FSDS score was higher in MetS women than HC. The logistic regression, considering age and the length of relationship as a common starting point, shows that higher levels of triglycerides are linked to a higher risk of presenting FSD (odds ratio = 2.007 95% confidence interval [1.033-3.901]) in the whole population.nnnCONCLUSIONSnOur preliminary results suggest that prevalence of FSD is higher in women with MetS in comparison with healthy controls. Higher levels of triglycerides are linked to a higher risk of presenting FSD.

Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells

Human natural killer (NK) cells constitutively express the β‐ and γ‐chains of the interleukin 2 (IL‐2)/IL‐15 receptor, and both IL‐2 and IL‐15 are able to activate NK cell proliferation and cytotoxicity. When IL‐2‐primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the β2‐integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL‐2‐primed NK cells; (ii) endothelial‐ and K562 cell‐induced apoptosis is significantly lower in IL‐15 than in IL‐2‐stimulated NK cells; (iii) a critical role in the apoptosis of IL‐2‐primed NK cells is played by the α‐chain of the IL‐2 receptor. Our data show for the first time that IL‐2‐activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL‐15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL‐15 produced early in the immune response, when T cells are not yet activated, generates lymphokine‐activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL‐2 that overcomes the effect of IL‐15 on NK cells, paving the way for their death by apoptosis.

Effects of Testosterone Undecanoate Administered Alone or in Combination with Letrozole or Dutasteride in Female to Male Transsexuals

INTRODUCTIONnTestosterone undecanoate (TU) has potential as androgen therapy for ovariectomized female to male (FtM) transsexual subjects; however, the long-term physiologic effects of TU treatment, the significance of testosterone (T), and the T metabolites dihydrotestosterone (DHT) and estradiol (E) on specific outcome parameters are currently unknown.nnnAIMnThe aim of this study was to investigate the long-term treatment of TU with regard to bone metabolism, body composition, and lipid profile in FtM subjects, and to evaluate the relationship between observed effects and circulating levels of T, E, and DHT.nnnMAIN OUTCOME MEASURESnCirculating follicle-stimulating hormone, luteinizing hormone, T, E, DHT, and lipid concentrations were measured, as well as bone metabolism, body composition, and insulin resistance.nnnMETHODSnThis was a 1-year, randomized treatment, open-label, uncontrolled safety study. Fifteen ovariectomized FtM subjects from an outpatient clinic were divided into three groups to receive TU 1,000 mg alone or in combination with oral administration of letrozole (L) 2.5 mg/die or dutasteride (D) 0.5 mg/die for a period of 54 weeks.nnnRESULTSnTU alone and TU + D treatments were successful in terms of hormone adjustment, did not result in any adverse effects, and were well-tolerated. Bone mineral density decreased by an average of 0.9 g/cm(2) in the TU + L group, and the addition of D resulted in a failure to gain lean mass.nnnCONCLUSIONSnThis study confirmed that TU is a successful and safe treatment for FtM subjects. These data indicate that E has an important role in bone metabolism and that DHT may play a role in muscle metabolism.

The Impairment of Sexual Function Is Less Distressing for Menopausal than for Premenopausal Women

INTRODUCTIONnMenopause requires psychological and physical adjustments because of the occurring significant hormonal changes. Sexuality is one of the aspects that undergoes the most profound modifications. Preliminary data suggest that sometimes women do not regard sexual changes as problematic and often readjust their life and relationship according to their new physical status.nnnAIMnThe aim of our study was to evaluate sexual function and the way women feel by comparing healthy postmenopausal and premenopausal women.nnnMETHODSnOne hundred menopausal (M) and 100 premenopausal (pM) healthy women were asked to complete anonymous questionnaires to assess sexual function and stress related to sexual activity.nnnMAIN OUTCOME MEASURESnFemale Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS) were completed by M and pM women. Results. Medium FSFI score was 20.5 +/- 9.6 and 26.4 +/- 7.7 (P < 0.0005) and medium FSDS score was 12.1 +/- 11.7 (95% CI 9.7-14.4) and 11.3 +/- 10.2 (P = 0.917) for M and pM women, respectively. Twenty-five of the 69 M women and 20 of the 31 pM women with a pathological score in the FSFI questionnaire scored higher than 15 in the FSDS (P < 0.0005). The overall prevalence of sexual dysfunction was 20% and 25% (P = 0.5) in the M and pM women.nnnCONCLUSIONSnOur data confirm that menopause is associated with changes in sexual function that may be compatible with sexual dysfunction. However, personal distress caused by these changes in sexual life appears to be lower among menopausal women (36.2%) as compared with premenopausal women (64.5%). These data suggest that medical treatment for sexual health in menopause must be highly personalized and carefully prescribed.

Outcome of conservatively treated microinvasive squamous cell carcinoma of the uterine cervix during a 10-year follow-up.

Objective: To assess the rate, the cumulative proportion, and the predictors of cervical intraepithelial neoplasia grades 2-3 (CIN 2-3) and invasive disease during the follow-up of patients conservatively treated for microinvasive (stage Ia1-2) squamous cell carcinoma (MIC) of the uterine cervix. Methods: Two hundred thirty women (median age, 37 years; range, 20-69 years) conservatively treated for MIC were followed up for 10 years and analyzed for cumulative proportion of CIN 2-3/invasive disease. The multivariate survival analysis was used to assess the clinicopathological features predicting the development of CIN 2-3/SCC. Results: Of the 230 patients primarily treated by cone, 76 (33%) underwent hysterectomy as the immediate retreatment, and 13 had a residual disease. The remaining 154 women were subjected to posttreatment follow-up. The depth of stromal invasion was strongly associated with the prevalence of positive lymph nodes and lymphovascular space invasion (LVSI). The detection rate of CIN 2-3/SCC was stable at the first 2 visits (6.5% and 6.9%) and dropped thereafter. The cumulative proportion of patients whose conditions were diagnosed as CIN 2-3/carcinoma was 0.07, 0.09, 0.15, and 0.19 at 6, 12, 36, and 120 months, respectively. In multivariate survival analysis, involvement of 4 quadrants (odds ratio [OR], 5.8), LVSI (OR, 4.5), and cone margin involvement (OR, 5.6) were significant independent predictors of CIN 2-3/SCC after treatment. The upper age tertile (42-69 years) was an independent protective factor (OR, 0.3; 95% confidence interval, 0.1-0.9). Conclusions: A close, long-term surveillance should be scheduled for the MIC patients conservatively treated. Cone margin involvement, LVSI, and the number of quadrants involved on colposcopy are independent risk factors for disease persistence and/or progression to SCC.

Sclerosing stromal tumor of the ovary - A hormonal, histochemical and ultrastructural study

Three new cases of sclerosing stromal tumor of the ovary have been studied by hormonal, immunohistochemical and electron microscopic analysis. The results confirm that this tumor may have hormonal activity. Ultrastructural study shows findings different from those previously reported. The authors propose an origin from the ovarian stroma with luteinization of stromal tumor cells.