Nicolò Clemente

Number and size of uterine fibroids and obstetric outcomes

Abstract Objective: Estimating the impact of sonographically identified multiple or large (≥5 cm in diameter) fibroids on obstetric outcomes. Methods: Retrospective cohort study of 219 women with uterine fibroids (identified on a routine second-trimester ultrasound survey over a 3-year period, 2010–2012) and their age-matched controls. Inclusion criteria were singleton pregnancy, delivery at >24 weeks of gestation and no pathological conditions (chronic hypertension, gestational diabetes or pre-existing diabetes mellitus, uterine anomalies or fetal malformations). Results: Compared to women with no fibroids, women with multiple fibroids (n = 34) had a significantly higher rate of preterm birth (29.4% versus 5%, p < 0.001), cesarean section (73.5% versus 37%, p < 0.001) and breech presentation (11.8% versus 2.7%, p = 0.04). Women with large fibroids (n = 48) had a higher rate of preterm birth (16.7% versus 5%, p = 0.01) and pPROM (10.4% versus 0.5%, p < 0.001). By multivariate analysis, only multiple fibroids and previous preterm birth showed an independent significant association with preterm birth (OR = 7.37, 95% CI 2.50–21.68 and OR = 13.01, 95% CI 3.56–47.52, respectively). Conclusions: Women with uterine fibroids are at an increased risk of obstetric complications. In particular, multiple rather than large fibroids are associated with a significantly increased risk of preterm birth and cesarean delivery while large fibroids are associated with a higher risk of pPROM. No correlation with IUGR, placenta previa or placental abruption was found.

Loop electrosurgical excision procedure and risk of miscarriage

OBJECTIVE To evaluate the risk of miscarriage in the subsequent pregnancy after a loop electrosurgical excision procedure (LEEP), also considering time elapsed from LEEP to pregnancy. DESIGN Multicenter, retrospective cohort study. SETTING Tertiary care university hospitals. PATIENT(S) Women who had undergone LEEP from January 2000 to December 2011. Women with histologic assessment of low-grade cervical dysplasia, not requiring subsequent surgical treatment, constituted the control group. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The first pregnancy after the procedure was evaluated, and only women with singleton spontaneous pregnancies were considered. Women with time intervals of <12 months and women with intervals of ≥12 months or more from LEEP to pregnancy were then compared, to identify adjusted odds ratios for miscarriage. RESULT(S) In women previously treated with LEEP, a total of 116 cases of miscarriage (18.1%) was reported. The mean time interval from LEEP to pregnancy for women with miscarriage compared with women without miscarriage was significantly shorter (25.1 ± 11.7 months vs. 30.1 ± 13.3 months). A higher rate of miscarriage in women with a LEEP-to-pregnancy interval of <12 months compared with controls emerged (28.2% vs. 13.4%; adjusted odds ratio 2.60, 95% confidence interval 1.57-4.3). No significant difference in the rate of miscarriage in women with a LEEP-to-pregnancy interval of ≥12 months compared with controls emerged. CONCLUSION(S) Women with a time interval from LEEP to pregnancy of <12 months are at increased risk for miscarriage.

Length but not transverse diameter of the excision specimen for high-grade cervical intraepithelial neoplasia (CIN 2-3) is a predictor of pregnancy outcome.

The objective of this study was to analyze the impact of cone characteristics (depth, transverse diameter, and volume) on subsequent pregnancies after the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN 2–3). Pregnancy outcomes (preterm birth, gestational age at birth, mode of delivery, and birth weight) of 501 women with singleton gestations and no previous preterm birth or history of late miscarriage, who had previously undergone a single LEEP for CIN 2–3, were retrospectively analyzed with respect to length, transverse diameter, and volume of the excision specimen. The overall incidence of preterm birth was 2.4%. The rate of preterm birth in women with length greater than 20 mm or volume greater than 2.5 cm3 was significantly higher than that in women with length between 15 and 19 mm (15.6 vs. 3.9%, P=0.02) or women with volume between 2.0 and 2.4 cm3 (5.8 vs. 1.6%, P=0.04). A linear inverse correlation (r=−0.3, P<0.001) between gestational age at birth and length, but not volume (r=0.0, P=0.9) or transverse diameter (r=0.2, P<0.0001), emerged. The mode of delivery was not affected by cone characteristics. Length, but not transverse diameter and volume, of the excised specimen seems to be related to a lower gestational age at birth. When excisions are performed under strict colposcopic guidance, with a correct modulation of cone length, the risk for preterm birth and cesarean delivery in subsequent pregnancies is not increased.

Ovarian endometriosis and vitamin D serum levels

Abstract Aim: The aim of this study was to assess the vitamin D serum level in women with ovarian endometriosis; specifically, a possible correlation between the dimensions of ovarian endometriomas and vitamin D serum levels was evaluated. Materials and methods: This was an observational study of childbearing-age women diagnosed with singleton ovarian endometrioma from January 2015 to December 2015. Women diagnosed with multiple ovarian endometriomas or extraovarian endometriosis were excluded. Results: Forty-nine women constituted the initial study cohort. In these women, the mean (±SD) 25-OH-D3 serum level was 22.0 (±8.9) ng/ml, and 42 of them (85.7%) were diagnosed with hypovitaminosis D. In the “hypovitaminosis D women”, the mean (± SD) diameter of ovarian endometriomas was 40.2 ± 22.6 mm, while in the “normal vitamin D serum level women” it was 26.7 ± 12.1 mm (p = 0.1). However, a significant linear correlation between 25-OH-D3 serum level and the diameter of ovarian endometriomas was found (r = −0.3, p = 0.03). Conclusion: We found a relatively high rate of women with ovarian endometriosis and hypovitaminosis D. Interestingly, a significant linear correlation between 25-OH-D3 serum levels and the diameter of ovarian endometrioma emerged.

Primary Non-Hodgkin's Lymphoma of the Vulva: A Case Report and Literature Review.

AbstractThe aim of this study was to add a new case of primary non-Hodgkins malignant lymphoma of the vulva to the literature and to review the current literature.We searched the PubMed/MEDLINE databases for previous case reports using the key words “non-Hodgkins malignant lymphoma of the vulva,” “vulvar lymphoma,” and “primary vulvar non-Hodgkins lymphoma.” We found 29 cases of primary vulvar non-Hodgkins malignant lymphoma of the vulva reported until 2015. Among them, only 8 cases of diffuse large B-cell lymphoma (DLBCL), classified according to the most recent 2008 WHO classification, were reported.Moreover, only few studies reported the therapeutic management and clinical follow-up of patients affected by this condition.Due to its uncommon presentation, the primary non-Hodgkins malignant lymphoma of the vulva can be undiagnosed; thus gynecologists, oncologists, and pathologists should be aware of this condition, as a correct diagnosis is essential for an appropriate therapeutic management.

Enterouterine Fistula as Initial Presentation of Advanced Endometrial Cancer: Description of a Rare Case and Review of the Literature

Endometrial cancer is the most common gynecological malignancy, and it usually presents with abnormal uterine bleeding as initial symptom. Cases of advanced endometrial cancer with uncommon symptoms at presentation are reported in the literature but, to our knowledge, no case an of enterouterine fistula as the initial presentation of the disease has been previously described. We report the case of a 54-year-old woman, with a 2-month history of permanent vaginal discharge of partly non-digested stool masses due to an enterouterine fistula that was the initial presentation of an advanced endometrial cancer. Interestingly, in this case, not all the preoperative exams (CT, colonoscopy and hysteroscopy) identified the fistulous openings, and the enterouterine fistula was confirmed only at the time of surgery.

Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

Abstract The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2–VaIN 3) and the cytological abnormalities on the referral pap smear. All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed. A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001). The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory.

Laparoscopic Treatment of Sclerosing Stromal Tumor of the Ovary in a Woman With Gorlin-Goltz Syndrome: A Case Report and Review of the Literature.

Gorlin-Goltz syndrome is a rare hereditary multisystemic disease. Multiple basal cell carcinomas, odontogenic keratocysts, and skeletal abnormalities are the main clinical manifestations of the syndrome, but several organs can be involved. Moreover, this condition is associated with the development of various benign and malignant tumors, even in the genital tract. This report describes a rare association between Gorlin-Goltz syndrome and the sclerosing stromal tumor of the ovary. Because the ultrasound and magnetic resonance imaging patterns of this tumor can be similar to those of a malignant neoplasm, prompt surgical intervention and histological confirmation of diagnosis is mandatory; however, this is a benign lesion and thus can be approached with a laparoscopic fertility-sparing surgery. Gynecologists should be aware of this possible association to provide appropriate counseling for these women, and to take a fertility-sparing laparoscopic approach whenever possible.

Hypovitaminosis D and "small burden" uterine fibroids: Opportunity for a vitamin D supplementation.

AbstractThe aim of this study was to evaluate the effect of vitamin D supplementation in women with hypovitaminosis D and “small burden” uterine fibroids.This study focused on 208 women diagnosed with uterine fibroids and concomitant hypovitaminosis D, from January to December 2014. One hundred eight women of the initial study population were diagnosed with “small burden” uterine fibroids. Among them, those who underwent a proper vitamin D supplementation constituted the “study group” (n = 53), while women who spontaneously refused the therapy or did not perform it properly, constituted the “control group” (n = 55). The characteristics of uterine fibroids, the fibroid-related symptoms, and the vitamin D serum levels were evaluated 12 months after the initial diagnosis.In women with uterine fibroids, a negative correlation emerged between the baseline 25-hydroxy-cholecalciferol (25-OH-D3) concentration and both the volume of the largest fibroid (r = −0.18, P = 0.01) and the total volume of fibroids (r = −0.19, P = 0.01). No correlation was found between the baseline 25-OH-D3 levels and the number of fibroids per patient (r = −0.10, P = 0.16). In women of the “study group,” a significant increase in the 25-OH-D3 serum level was observed after 12 months of supplementation, and a lower rate of surgical or medical treatment due to the “progression to extensive disease” was reported (13.2% vs 30.9%, P = 0.05).Supplementation therapy with 25-OH-D3 restores normal vitamin D serum levels in women with “small burden” fibroids. In these women, vitamin D supplementation seems to reduce the progression to an extensive disease, and thus the need of conventional surgical or medical therapy.

Extramammary Paget disease of the vulva: immunohistochemical analysis of neoangiogenesis and epithelial-mesenchymal transition markers expression

BackgroundExtra-mammary Paget’s disease of the vulva (EMPDV) is an infrequent chronic disease that often recurs. The aim of the study was to assess the presence of neoangiogenesis and the expression of epithelial-mesenchymal transition (EMT) markers in EMPDV, and their potential correlation with stromal invasion.MethodsAll the women consecutively treated for EMPDV at our Institute, between January 2011 and December 2014, were studied for neoangiogenesis, analysed by microvessel density (MVD) using antibodies against CD31 and CD34. Immunohistochemical expression of E- / N-cadherin, β-catenin and SLUG was also evaluated. In each slide, three fields with the highest number of capillaries and small venules were identified at low power. In these three fields, the highest vessel density (HVD) and the average vessel density (AVD) at 200× and 400× magnification were counted. Immunohistochemical reactions for non-vascular markers were semiquantitatively scored by two pathologists, using a three-tier scale.ResultsSeventeen cases of EMPDV (including 10 cases of invasive disease) were included. The AVD at 200× and 400× and the HVD at 400× magnification were significantly associated with invasive EMPDV (p = 0.02, 0.03, 0.03 respectively). No significant correlation between MVD, EMT-markers expression and risk of recurrence was detected.ConclusionThese results indicate that MVD, as a measure of neoangiogenesis, may be associated with histological progression of EMPDV. EMT could also be linked to an invasive potential of EMPDV but larger series are required to confirm this hypothesis.