Publications by authors named "Fulvio Zullo"

320 Publications

Use of Youtube as source of information for medical conditions.

Eur J Obstet Gynecol Reprod Biol 2022 May 5. Epub 2022 May 5.

Department of Obstetrics and Gynecology, University Magna Grecia di Catanzaro, Catanzaro, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ejogrb.2022.04.024DOI Listing
May 2022

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Vaccines (Basel) 2022 Apr 9;10(4). Epub 2022 Apr 9.

Department of Woman's and Child's Health, Obstetrics and Gynecological Unit, San Camillo-Forlanini Hospital, 00152 Rome, Italy.

Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.
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http://dx.doi.org/10.3390/vaccines10040579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029732PMC
April 2022

Diagnostic and prognostic value of Bcl-2 in uterine leiomyosarcoma.

Arch Gynecol Obstet 2022 Mar 28. Epub 2022 Mar 28.

Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy.

Background: Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS.

Objective: To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis.

Methods: Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value < 0.05 was considered significant.

Results: Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses.

Conclusion: Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies.
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http://dx.doi.org/10.1007/s00404-022-06531-2DOI Listing
March 2022

Clinicopathological Features Associated with Microsatellite Instability/Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Quantitative Systematic Review.

Pathobiology 2022 Mar 1:1-7. Epub 2022 Mar 1.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.

Introduction: Recent studies suggested that microsatellite instability/mismatch repair deficiency (MSI/MMR-d) might define a clinicopathologically distinct subset of uterine carcinosarcomas (UCSs).

Objective: The aim of this study was to compare clinicopathological features between MSI/MMR-d and microsatellite-stable/mismatch repair-proficient (MSS/MMR-p) UCSs.

Methods: A quantitative systematic review was performed by searching electronic databases from January 2000 to January 2021. All studies assessing MSI/MMR status in UCS were included. Odds ratio (OR) with a significant two-tailed p value <0.05 was used to assess the association of MSI/MMR-d with clinicopathological features.

Results: Eleven studies with 783 patients were included. MSI/MMR-d was directly associated with endometrioid (pure: p < 0.001; pure + mixed: p < 0.001), undifferentiated/dedifferentiated (p < 0.001), and clear cell carcinoma component (p = 0.046), and inversely associated with age >60 (p = 0.034), serous carcinoma component (pure: p < 0.001; pure + mixed: p < 0.001), heterologous sarcoma component (p = 0.027), TP53-mutation/p53-abnormal expression (p < 0.001), and recurrence (p < 0.001). MSI/MMR-d showed no significant association with advanced FIGO stage (OR = 1.259; p = 0.517), low-grade carcinoma component (pure: p = 0.596; pure + mixed: p = 0.307), mixed carcinoma component (p = 1), and proportion of patients "dead of disease" (p = 0.352), "alive with disease" (p = 1) or with "no evidence of disease" (p = 0.458).

Conclusion: MSI/MMR-d UCSs show younger age, more common endometrioid, undifferentiated or clear cell carcinoma component, and less common serous carcinoma component, heterologous sarcoma component, and TP53 mutation than MSS/MMR-p UCSs. Given the discrepancy between recurrence rate and oncologic outcomes at the last follow-up, further studies are necessary to define whether MSI/MMR-d UCSs have better prognosis.
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http://dx.doi.org/10.1159/000521876DOI Listing
March 2022

Successful Vaginal Delivery after Induction of Labour in a Patient Treated for Non-Hodgkin's Lymphoma of the Cervix: A Case Report and Literature Review.

Case Rep Obstet Gynecol 2022 10;2022:3541046. Epub 2022 Feb 10.

Unit of Obstetrics and Gynaecology, "Magna Graecia" University, Catanzaro, Italy.

Objective: Primary non-Hodgkin's lymphomas of the cervix are rare; they represent about 1% of all cases. There are no available guidelines regarding the safest mode of delivery after treatment and resolution of a cervical lymphoma. . We report the first case of a successful vaginal delivery after induction of labour in a woman recovered from a primary large B-cell lymphoma of the cervix and a literature review.

Conclusion: In carefully selected patients with fully treated non-Hodgkin's lymphoma of the cervix with no residual disease, induction of labour via prostaglandins pessary may be a safe option if indicated.
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http://dx.doi.org/10.1155/2022/3541046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853783PMC
February 2022

Monofilament vs multifilament suture for uterine closure at the time of cesarean delivery: a randomized clinical trial.

Am J Obstet Gynecol MFM 2022 May 4;4(3):100592. Epub 2022 Feb 4.

Department of Public Health, School of Medicine, University of Naples Federico II, Naples, Italy (Drs Angelis and Di Spiezio Sardo).

Background: Different factors may influence the closure of the uterine wall, including suture material. Suture materials may indeed influence tissue healing and therefore the development of scar defects.

Objective: To test whether uterine closure using synthetic absorbable monofilament sutures at the time of cesarean delivery would reduce the rate of cesarean scar defects compared with uterine closure using synthetic absorbable multifilament sutures.

Study Design: Parallel-group, nonblinded, randomized clinical trial of women with singleton pregnancies undergoing cesarean delivery at term in a single center in Italy. The inclusion criteria were singleton pregnancy, first or second cesarean delivery, scheduled and emergent or urgent cesarean deliveries, and gestational age between 37 0/7 and 42 0/7 weeks. Eligible participants were randomly allocated in a 1:1 ratio to either the monofilament group (polyglytone 6211 [Caprosyn]; Covidien, Dublin, Ireland) or the multifilament suture group (coated polyglactin 910 suture with Triclosan [Vicryl Plus]; Ethicon, Inc, Raritan, NJ). The primary outcome was the incidence of cesarean scar defect at ultrasound at the 6-month follow-up visit. The secondary outcomes were residual myometrial thickness and symptoms.

Results: Overall, 300 women were included in the trial. Of the randomized women, 151 were randomized to the monofilament group and 149 to the multifilament group. However, 27 women were lost to follow-up: 15 in the monofilament group and 12 in the multifilament group. Of note, 6 months after delivery, the incidence rates of cesarean scar defect were 18.4% (25 of 136 patients) in the monofilament group and 23.4% (32 of 137 patients) in the multifilament group (relative risk, 0.79; 95% confidence interval, 0.41-1.25; P=.31). The mean residual myometrial thicknesses were 7.6 mm in the monofilament group and 7.2 mm in the multifilament group (mean difference, +0.40 mm; 95% confidence interval, -0.23 to 1.03). There was no between-group substantial difference found in the incidence of symptoms, including pelvic pain, painful periods, and dyspareunia.

Conclusion: In singleton pregnancies undergoing primary or second cesarean delivery, the use of synthetic absorbable monofilament sutures at the time of uterine wall closure was not associated with a reduction in the rate of cesarean scar defect 6 months after delivery compared with the use of synthetic absorbable multifilament sutures.
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http://dx.doi.org/10.1016/j.ajogmf.2022.100592DOI Listing
May 2022

Lymphovascular space invasion in endometrial carcinoma: A prognostic factor independent from molecular signature.

Gynecol Oncol 2022 04 23;165(1):192-197. Epub 2022 Jan 23.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.

Background: The 2020 ESGO/ESTRO/ESP guidelines stratify the prognosis of endometrial carcinoma (EC) patients combining The Cancer Genome ATLAS (TCGA) molecular signature and pathological factors, including lymphovascular space invasion (LVSI). However, little is known about the prognostic independence of LVSI from molecular signature.

Aim: To assess whether the prognostic value of LVSI is independent from the TCGA signature.

Material And Methods: A systematic review and meta-analysis was performed by searching 5 electronic databases from their inception to March 2021. All peer-reviewed studies reporting assessing LVSI as a prognostic factor independent from the TCGA groups in EC were included. Multivariate HRs with 95% confidence interval (CI) were pooled separately for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). The absence of LVSI was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study.

Results: Six studies with 3331 patients were included in the systematic review and three studies with 2276 patients in the meta-analysis. LVSI showed a pooled multivariate HR of 1.818 (CI 95%, 1.378-2.399) for OS, 1.849 (CI 95%, 1.194-2.863) for DSS, 1.377 (CI 95%, 1.008-1.880) for DFS excluding one study, 1.651 (CI 95%, 1.044-2.611) for DFS additionally considering locoregional recurrence from one study, and 1.684 (CI 95%, 1.05-2.701) for DFS additionally considering distant recurrence from the same study.

Conclusion: LVSI has a prognostic value independent of TCGA signature, as well as age and adjuvant treatment, increasing the risk of death of any cause, death due to EC and recurrent or progressive disease by 1.5-2 times.
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http://dx.doi.org/10.1016/j.ygyno.2022.01.013DOI Listing
April 2022

Histological Prognostic Factors of Endometrial Cancer in Patients with Adenomyosis: A Systematic Review and Meta-Analysis.

Pathobiology 2022 Jan 20:1-8. Epub 2022 Jan 20.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, Italy.

Background: A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological prognostic factors. However, pooled risk of EC unfavorable histological prognostic factors in patients with adenomyosis has never been calculated.

Objectives: We aimed to assess the risk of EC unfavorable histological prognostic factors in patients with adenomyosis.

Methods: All studies with data about histological prognostic factors of EC in patients with and without adenomyosis were included. Relative risk for each unfavorable histological prognostic factor of EC, such as nonendometrioid histotype, FIGO grade 3, FIGO stage II-IV, lymphovascular space invasion (LVSI), and deep myometrial invasion, was calculated in patients with adenomyosis compared to patients without adenomyosis.

Results: Seven studies with 4,439 patients were included in the quantitative analysis. EC patients with adenomyosis showed a pooled RR of 0.77 (p = 0.05) for nonendometrioid histotype, 0.55 (p < 0.00001) for FIGO grade 3, 0.60 (p = 0.005) for FIGO stage II-IV, 0.75 (p = 0.004) for LVSI, and 0.65 (p = 0.001) for deep myometrial invasion.

Conclusion: EC patients with adenomyosis have a significantly decreased risk for unfavorable histological prognostic factors of EC compared to EC patients without adenomyosis. Such findings might explain the supposed better EC prognosis in patients with adenomyosis.
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http://dx.doi.org/10.1159/000521105DOI Listing
January 2022

Maternal and perinatal complications according to maternal age: A systematic review and meta-analysis.

Int J Gynaecol Obstet 2022 Jan 19. Epub 2022 Jan 19.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.

Objective: To evaluate the risk levels for maternal and perinatal complications at > 40, > 45 and > 50 years old compared with younger controls.

Methods: Electronic databases were searched from their inception until March 2021. We included studies reporting pregnancy outcome in pregnant women aged 40, 45, and 50 years or older compared with controls at the time of delivery. Case reports and case series were excluded. The primary outcome was the incidence of stillbirth. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Heterogeneity was measured using I (Higgins I ). Subgroup analyses in women older than 45 years and in those older than 50 years were performed.

Results: Twenty-seven studies, including 31 090 631 women, were included in the meta-analysis. The overall quality of the included studies was moderate to high. Most of the included studies were retrospective cohort studies (21/27), four were population-based studies, and two were cross-sectional studies. Women aged ≥40 years had significantly higher risk of stillbirth (RR 2.16, 95% CI 1.86-2.51), perinatal mortality, intrauterine growth restriction, neonatal death, admission to neonatal intensive care unit, pre-eclampsia, preterm delivery, cesarean delivery, and maternal mortality compared with women younger than 40 years old (RR 3.18, 95% CI 1.68-5.98). The increased risks for maternal mortality were 42.76 and 11.60 for women older than 50 years and for those older than 45 years, respectively, whereas those for stillbirth were 3.72 and 2.32. The risk of stillbirth and cesarean delivery was significantly higher in women >45 years compared with those aged 40-45 years, and in those aged >50 years compared with those aged 45-50 years. The risk of maternal mortality was significantly higher in women aged >50 years compared with those aged 40-45 (RR 60.40, 95% CI 13.28-274.74).

Conclusion: The risk of stillbirth, cesarean delivery, and maternal mortality increases with advancing maternal age. The risk ratios for maternal mortality were 3.18, 11.60, and 42.76 in women older than 40, older than 45, and older than 50 years, respectively. These data should be used when women with advanced maternal age are counseled regarding their risk in pregnancy.

Systematic Review Registration: The review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration No.: CRD42020208788).
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http://dx.doi.org/10.1002/ijgo.14100DOI Listing
January 2022

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis.

Arch Gynecol Obstet 2022 Jan 16. Epub 2022 Jan 16.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081, Baronissi, Italy.

Background: In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP).

Objective: To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis.

Methods: Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I-II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05.

Results: Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026).

Conclusion: CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.
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http://dx.doi.org/10.1007/s00404-021-06385-0DOI Listing
January 2022

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic.

J Gynecol Oncol 2022 01 12;33(1):e10. Epub 2021 Nov 12.

Clinica Ostetrica e Ginecologica - Dipartimento Scienze Mediche - Università di Ferrara, Ferarra, Italy.

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients.

Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak.

Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001).

Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.
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http://dx.doi.org/10.3802/jgo.2022.33.e10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728669PMC
January 2022

Dusp6 immunohistochemistry is associated with the response of atypical endometrial hyperplasia and early endometrial cancer to conservative treatment.

Int J Gynaecol Obstet 2021 Nov 27. Epub 2021 Nov 27.

Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.

Objective: Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. However, its predictive accuracy has never been calculated. We aimed to define it in conservatively treated AEH and EEC.

Methods: All patients <45 years with AEH or EEC and conservatively treated with hysteroscopic resection + LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve.

Results: Thirty-six women were included. Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR = 16 (P = 0.0074); predictive accuracy analysis showed sensitivity = 80%, specificity = 90%, PPV = 57.1%, NPV = 96.4%, AUC = 0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR = 0.4; P = 0.53).

Conclusion: Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy.
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http://dx.doi.org/10.1002/ijgo.14050DOI Listing
November 2021

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: A systematic review and meta-analysis of survival.

Int J Gynaecol Obstet 2021 Nov 19. Epub 2021 Nov 19.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, Italy.

Background: It is unclear whether uterine carcinosarcoma (UCS) is more aggressive than endometrial serous carcinoma (SC) and clear cell carcinoma (CCC).

Objectives: To compare the prognosis of UCS to that of endometrial SC and CCC, through a systematic review and meta-analysis.

Methods: Four electronic databases were searched from January 2000 to October 2020. All studies assessing hazard ratio (HR) for death in UCS vs SC and/or CCC. HRs for death with 95% confidence interval were extracted and pooled by using a random-effect model. A significant P-value <0.05 was adopted.

Results: Six studies with 11 029 patients (4995 with UCS, 4634 with SC, 1346 with CCC and 54 with either SC or CCC) were included. UCS showed a significantly worse prognosis than SC/CCC both overall (HR = 1.51; P = 0.008) and at early stage (HR = 1.58; P < 0.001). Similar results were found for UCS vs SC (HR = 1.53; P < 0.001) and UCS vs CCC (HR = 1.60; P < 0.001).

Conclusions: Compared to SC and CCC, UCS has a significantly worse prognosis, with a 1.5-1.6-fold increased risk of death. This might justify a more aggressive treatment for UCS compared to SC and CCC. Further studies are necessary to define the prognostic impact of different molecular subgroups.
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http://dx.doi.org/10.1002/ijgo.14033DOI Listing
November 2021

An integrated approach based on advanced CTG parameters and Doppler measurements for late growth restriction management.

BMC Pregnancy Childbirth 2021 Nov 16;21(1):775. Epub 2021 Nov 16.

Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano, Milan, Italy.

Background: The clinical diagnosis of late Fetal Growth Restriction (FGR) involves the integration of Doppler ultrasound data and Fetal Heart Rate (FHR) monitoring through computer assisted computerized cardiotocography (cCTG). The aim of the study was to evaluate the diagnostic power of combined Doppler and cCTG parameters by contrasting late FGR -and healthy controls.

Methods: The study was conducted from January 2018 to May 2020. Only pregnant women who had the last Doppler measurement obtained within 1 week before delivery and cCTG performed within 24 h before delivery were included in the study. Two hundred forty-nine pregnant women fulfilling the inclusion criteria were enrolled in the study; 95 were confirmed as late FGR and 154 were included in the control group.

Results: Among the extracted cCTG parameters, Delta Index, Short Term Variability (STV), Long Term Variability (LTV), Acceleration and Deceleration Phase Rectified Slope (APRS, DPRS) values were lower in the late FGR participants compared to the control group. In the FGR cohort, Delta, STV, APRS, and DPRS were found different when stratifying by MCA_PI (MCA_PI <5th centile or > 5th centile). STV and DPRS were the only parameters to be found different when stratifying by (UA_PI >95th centile or UA_PI <95th centile). Additionally, we measured the predictive power of cCTG parameters toward the identification of associated Doppler measures using figures of merit extracted from ROC curves. The AUC of ROC curves were accurate for STV (0,70), Delta (0,68), APRS (0,65) and DPRS (0,71) when UA_PI values were > 95th centile while, the accuracy attributable to the prediction of MCA_PI was 0.76, 0.77, 0.73, and 0.76 for STV, Delta, APRS, and DPRS, respectively. An association of UA_PI>95th centile and MCA_PI<5th centile with higher risk for NICU admission, was observed, while CPR < 5th centile resulted not associated with any perinatal outcome. Values of STV, Delta, APRS, DPRS were significantly lower for FGR neonates admitted to NICU, compared with the uncomplicated FGR cohort.

Conclusions: The results of this study show the contribution of advanced cCTG parameters and fetal Doppler to the identification of late FGR and the association of those parameters with the risk for NICU admission.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s12884-021-04235-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594236PMC
November 2021

Role of prenatal magnetic resonance imaging in fetuses with isolated severe ventriculomegaly at neurosonography: A multicenter study.

Eur J Obstet Gynecol Reprod Biol 2021 Dec 23;267:105-110. Epub 2021 Oct 23.

Department of Medicine and Surgery, Unit of Surgical Sciences, Obstetrics and Gynecology, University of Parma, Italy.

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography.

Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (
Results: 187 fetuses with a prenatal diagnosis of isolated severe ventriculomegaly on neurosonography were included in the analysis. Additional structural anomalies were detected exclusively at prenatal MRI in 18.1% of cases. When considering the type of anomaly, malformations of cortical development were detected on MRI in 32.4% cases, while midline or acquired (hypoxemic/hemorrhagic) lesions were detected in 26.5% and 14.7% of cases, respectively. There was no difference in the rate of additional anomalies when stratifying the analysis according to either gestational age at MRI or laterality of the lesion. At multivariate logistic regression analysis, the presence of additional anomalies only found at MRI was significantly higher in bilateral compared versus unilateral ventriculomegaly (OR: 4.37, 95% CI 1.21-15.76; p = 0.04), while neither maternal body mass index, age, severity of ventricular dilatation, interval between ultrasound and MRI, nor gestational age at MRI were associated with the likelihood of detecting associated anomalies at MRI.

Conclusion: The rate of associated anomalies detected exclusively at prenatal MRI in fetuses with isolated severe ventriculomegaly is lower than previously reported, but higher compared to isolated mild and moderate ventriculomegaly. Fetal MRI should be considered as a part of the prenatal assessment of fetuses presenting with isolated severe ventriculomegaly at neurosonography.
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http://dx.doi.org/10.1016/j.ejogrb.2021.10.014DOI Listing
December 2021

Risk of Recurrence in Uterine Leiomyoma with Bizarre Nuclei: a Systematic Review and Meta-Analysis.

Geburtshilfe Frauenheilkd 2021 Nov 4;81(11):1217-1223. Epub 2021 Nov 4.

Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola Hospital, University of Bologna, Bologna, Italy.

Leiomyoma with bizarre nuclei (LBN) is a variant of uterine leiomyoma, which has replaced the previous category of "atypical leiomyoma" and must be distinguished from smooth muscle tumors of uncertain malignant potential (STUMP). However, previously published series of "atypical leiomyoma" might have included both LBN and STUMP, due to the lack of strict diagnostic criteria. Based on such hypothesis, we aimed to define the risk of recurrence in LBN. A systematic review and meta-analysis was performed by searching 4 electronic databases for all studies assessing the outcome of patients with "atypical leiomyoma" or LBN. The pooled absolute risk of recurrence was calculated. The included studies were subdivided into two subgroups based on the criteria used: "LBN + STUMP" or "LBN-only". Twelve studies with 433 patients were included. The pooled risk of recurrence was 5.5% overall. The funnel plot showed two cluster of studies which superimposed to the two subgroups. In the LBN + STUMP cluster/subgroup, the pooled risk of recurrence was 7.7%. In the LBN-only cluster/subgroup, the pooled risk of recurrence was 1.9%. Statistical heterogeneity was null in all analyses. Our results show a risk of recurrence of 1.9% for LBN; higher recurrence rates in older studies are likely due to the inclusion of STUMPs.
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http://dx.doi.org/10.1055/a-1533-1651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568503PMC
November 2021

Ki67 as a prognostic marker in uterine leiomyosarcoma: A quantitative systematic review.

Eur J Obstet Gynecol Reprod Biol 2021 Nov 28;266:119-124. Epub 2021 Sep 28.

Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy.

Ki67 labeling index (LI) has been proposed as a prognostic factor in uterine leiomyosarcoma (uLMS), although the evidence in this field is still unclear. We aimed to assess the prognostic value of ki67 LI in uLMS. A systematic review was performed by searching electronic databases from their inception to August 2020 for all studies assessing the prognostic value of ki67 LI in uLMS. Ki67 LI was assessed to the nearest 10% to define the most prognostically accurate threshold. Cox regression survival analysis with calculation of hazard ratio (HR) of death was performed; a p-value < 0.05 was considered significant. Ten studies were included in the qualitative review, out of which 6 were suitable for quantitative review. The absolute risk of death was 0.29 for a ki67 LI < 10%, remained stable at 0.49 in the 10%-39% LI range and increased to 0.65 for a LI ≥ 40%. On univariate analysis, both 10% and 40% thresholds were significantly associated with the hazard of death, with HRs of 3.349 (p = 0.007) and 3.172 (p = 0.001), respectively. On multivariate analysis, only the 10% threshold was significantly associated with the hazard of death (HR = 2.712; p = 0.028). In conclusion, a Ki67 LI ≥ 10% is a significant prognostic factor in uLMS.
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http://dx.doi.org/10.1016/j.ejogrb.2021.09.026DOI Listing
November 2021

Invasive prenatal diagnosis during COVID-19 pandemic.

Arch Gynecol Obstet 2022 03 7;305(3):797-801. Epub 2021 Oct 7.

Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, Federico II University of Naples, Via Sergio Pansini no. 5, 80131, Naples, Italy.

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http://dx.doi.org/10.1007/s00404-021-06276-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495187PMC
March 2022

DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas.

J Vasc Res 2022 14;59(1):61-68. Epub 2021 Sep 14.

Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli,", Naples, Italy.

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value <0.05). The Mann-Whitney U test was used for comparison between the 2 groups. For the first time, our study revealed that in fetal aortas obtained from hypercholesterolemic mothers, the SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5'UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.
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http://dx.doi.org/10.1159/000518513DOI Listing
February 2022

Urinary Incontinence after Planned Cesarean Hysterectomy for Placenta Accreta.

Urol Int 2021 18;105(11-12):1099-1103. Epub 2021 Aug 18.

Department of Neuroscience, Reproductive Science and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.

Introduction: Data regarding the risk of incontinence after cesarean hysterectomy are lacking. We aimed to assess the risk of urinary incontinence in women who underwent planned cesarean hysterectomy for placenta accreta.

Methods: This was a retrospective study of women who underwent planned cesarean hysterectomy for placenta accreta. The primary outcome was the incidence of post-cesarean hysterectomy urinary incontinence, defined as involuntary loss of urine between 3 and 12 months after cesarean hysterectomy. Outcomes were compared in a cohort of women who underwent planned cesarean hysterectomy for placenta accreta with a control group of women who underwent scheduled cesarean section without hysterectomy.

Results: Forty-seven singleton gestations who underwent planned cesarean hysterectomy for placenta accrete were included in the study and were compared with 100 controls. Eight cases of bladder injuries were reported, 7 in the planned cesarean hysterectomy group and one in the planned cesarean delivery group. Overall, urinary incontinence was reported in 10 women of the planned cesarean hysterectomy group and in 8 women of the planned cesarean section group (21.3% vs. 8.0%; p = 0.03).

Conclusion: Planned cesarean hysterectomy for placenta accreta is a risk factor for urinary incontinence.
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http://dx.doi.org/10.1159/000518114DOI Listing
February 2022

p53, p16 and ki67 as immunohistochemical prognostic markers in uterine smooth muscle tumors of uncertain malignant potential (STUMP).

Pathol Res Pract 2021 Oct 25;226:153592. Epub 2021 Aug 25.

Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy; Ospedale Maggiore Policlinico Milano, Milan, Italy.

The risk stratification in gynecologic smooth muscle tumors of uncertain malignant potential (STUMP) is a crucial issue, but at present there are no validated prognostic markers. We aimed to assess p53, p16 and ki67 as immunohistochemical prognostic markers in STUMP through a systematic review and meta-analysis. Electronic databases were searched from their inception to July 2020. All studies assessing p53, p16 and/or ki67 immunohistochemistry in gynecologic STUMP series were included. Immunohistochemical patterns were categorized as "abnormal" vs "wild-type" for p53, "diffuse" vs "focal/negative" for p16, ≥ 10% vs 10% for ki67. The prognostic value for recurrence was assessed through Cox regression analysis; a p-value 0.05 was considered significant. Markers that resulted significant were assessed for prognostic accuracy with calculation of area under the curve (AUC) and post-test probability of recurrence. Seven studies with 171 patients were included. Significant association with disease-free survival was found for p53 (p 0.0001) and p16 (p 0.0001), but not for ki67 (p = 0.911). p53 showed sensitivity= 83%, specificity= 86%, AUC= 0.89, and post-test recurrence probabilities of 54% and 7% in the case of abnormal and wild-type expression, respectively. p16 showed sensitivity= 84%, specificity= 88%, AUC= 0.91 and post-test recurrence probabilities of 56% and 7% in the case of diffuse and focal/negative expression, respectively. In conclusion, p53 and p16 might be useful in the risk assessment of STUMP, despite not being suitable as stand-alone prognostic markers.
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http://dx.doi.org/10.1016/j.prp.2021.153592DOI Listing
October 2021

Placental dysfunction in uncomplicated and complicated intrauterine growth restriction by preeclampsia and neonatal outcome.

J Matern Fetal Neonatal Med 2021 Sep 1:1-7. Epub 2021 Sep 1.

Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.

Objectives: To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes. .

Study Design: A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. -test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A value < .05 was considered significant for all analyses.

Results: Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR,  = .008), Delta ( = .018), Short Term Variability (STV,  = .021), Long Term Variability (LTV,  = .028), Acceleration Phase Rectified Slope (APRS,  = .018) and Deceleration Phase Rectified Slope (DPRS,  = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR ( = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO; STV, LTI, Delta and ApEn with pO; HF with base excess; FHR and LF with lactates.

Conclusions: cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients' management.
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http://dx.doi.org/10.1080/14767058.2021.1965980DOI Listing
September 2021

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

Eur J Clin Microbiol Infect Dis 2022 Jan 30;41(1):45-51. Epub 2021 Aug 30.

Department of Neuroscience, Reproductive Sciences and Dentistry , University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.
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http://dx.doi.org/10.1007/s10096-021-04337-9DOI Listing
January 2022

Obstetric A&E unit admission and hospitalization for obstetrical management during COVID-19 pandemic in a third-level hospital of southern Italy.

Arch Gynecol Obstet 2022 04 29;305(4):859-867. Epub 2021 Aug 29.

Gynecology and Obstetrics Unit, Department of Neurosciences, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Via Sergio Pansini, 5, 80131, Naples, Italy.

Background: The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March-May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions.

Methods: Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March-May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI).

Results: Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of - 101.3 (95% CI - 103.5 to - 99.1; p < 0.0001). Mean ± SD of patients monthly hospitalized to our department was 194 ± 19.1 in the year 2020, 213.7 ± 4.7 in 2019, with a mean difference of - 19.7 (95% CI - 23.8 to - 15.6; p < 0.0001).

Conclusion: A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric-gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures.
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http://dx.doi.org/10.1007/s00404-021-06212-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403252PMC
April 2022

Third Trimester Myocardial Performance Index in Fetuses from Women with Hyperglycemia in Pregnancy: A Systematic Review and Meta-Analysis.

Ultraschall Med 2021 Aug 23. Epub 2021 Aug 23.

Obstetrics and High-Risk Pregnancy Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.

Introduction:  The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls.

Materials And Methods:  Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis.

Results:  14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p < 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p < 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96).

Conclusion:  Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.
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http://dx.doi.org/10.1055/a-1499-7265DOI Listing
August 2021

Prenatal diagnosis and postnatal management of congenital unilateral hydrocephalus for stenosis of the foramen of Monro.

Radiol Case Rep 2021 Sep 3;16(9):2530-2533. Epub 2021 Jul 3.

Department of Neurosurgery, Santobono-Pausilipon Children's Hospital, Naples, Italy.

Congenital hydrocephalus and ventriculomegaly can be diagnosed reliably with prenatal ultrasound and Magnetic Resonance Imaging (MRI). Unilateral hydrocephalus is uncommon, and the prognosis depends on etiology and postnatal management. Here, we present a case of a 32-years-old woman with prenatal diagnosis of unilateral hydrocephalus associated with stenosis of the foramen of Monro. Unilateral hydrocephalus is an uncommon feature that can be detected prenatally on ultrasound and MRI. In case of isolated stenosis of the foramen of Monro prognosis is good.
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http://dx.doi.org/10.1016/j.radcr.2021.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260955PMC
September 2021

Impact of adenomyosis on the prognosis of patients with endometrial cancer.

Int J Gynaecol Obstet 2022 May 18;157(2):265-270. Epub 2021 Jul 18.

Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC, IRCCS Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola Hospital, University of Bologna, Bologna, Italy.

Background: Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear.

Objective: To assess the prognostic value of coexistent adenomyosis in patients with EC.

Methods: A systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable.

Results: Three studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis.

Conclusion: In EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.
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http://dx.doi.org/10.1002/ijgo.13818DOI Listing
May 2022

CIN 2 in childbearing-age women: may colposcopy help in choosing the proper management?

Minerva Obstet Gynecol 2021 Jun 28. Epub 2021 Jun 28.

Gynecological Oncology Unit, Centro di Riferimento Oncologico - National Cancer Institute, IRCCS, Aviano, Pordenone, Italy -

Background: CIN2 is considered a biologically equivocal lesion falling between low and high grade cervical dysplasia, but it is often managed with cervical conization as a high-grade lesion. However, since cervical conization can lead to an increased risk of adverse obstetric events, it might be interesting to identify, by colposcopy, a subgroup of women with a low risk of "occult" CIN3 who could be managed with a "wait and see" approach.

Methods: All the women with CIN2 cervical biopsy from 1999 to 2019 were retrospectively identified. Their colposcopic patterns at the time of biopsy and the histopathological findings on the final cone specimen were compared.

Results: Among the 354 women with CIN2 biopsy included, the overall CIN3+ lesion rate on final cone specimen was 21.4%. The rate of CIN3 on final specimen was higher in women with G2 colposcopy compared to G1 (27,2% vs 15.9%, p= 0.01). Among women with G1 colposcopy, the rate of CIN3+ lesions was significantly higher in women with fine punctation (p=0.02) while no differences in women with thin acetowhite epithelium or fine mosaic emerged.

Conclusions: In women with CIN2 biopsy, when a G2 pattern or G1 with fine punctation on colposcopy is detected, there is an increased risk of CIN3+ on final histology, therefore an excisional treatment should be preferred. Otherwise, in women with CIN2 biopsy and other G1 patterns on colposcopy, a "wait and see" approach could be considered.
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http://dx.doi.org/10.23736/S2724-606X.21.04844-2DOI Listing
June 2021

Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials.

Reprod Biol Endocrinol 2021 Jun 21;19(1):91. Epub 2021 Jun 21.

University of Naples Federico II, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy.

Introduction: Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction.

Material And Methods: Using a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles. We calculated the pooled odds ratio (OR) for dichotomous data and the weight mean difference (WMD) for continuous data with an associated 95% confidence interval (CI). The meta-analyses were conducted using the random-effect model. P values < 0.05 were considered statistically significant. Subgroup analyses of all primary and secondary outcomes were performed only in women aged 35-40 years.

Results: Twelve studies were identified. In women aged between 35 and 40 years, r-hFSH/r-hLH co-treatment was associated with higher clinical pregnancy rates (OR 1.45, CI 95% 1.05-2.00, I = 0%, P = 0.03) and implantation rates (OR 1.49, CI 95% 1.10-2.01, I = 13%, P = 0.01) versus r-hFSH monotherapy. Fewer oocytes were retrieved in r-hFSH/r-hLH-treated patients than in r-hFSH-treated patients both in women aged ≥35 years (WMD -0.82 CI 95% -1.40 to - 0.24, I = 88%, P = 0.005) and in those aged between 35 and 40 years (WMD -1.03, CI - 1.89 to - 0.17, I = 0%, P = 0.02). The number of metaphase II oocytes, miscarriage rates and live birth rates did not differ between the two groups of women overall or in subgroup analysis.

Conclusion: Although more oocytes were retrieved in patients who underwent r-hFSH monotherapy, this meta-analysis suggests that r-hFSH/r-hLH co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology. However, more RCTs using narrower age ranges in advanced age women are warranted to corroborate these findings.
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http://dx.doi.org/10.1186/s12958-021-00759-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215738PMC
June 2021

Prognostic value of myometrial invasion and TCGA groups of endometrial carcinoma.

Gynecol Oncol 2021 08 1;162(2):401-406. Epub 2021 Jun 1.

Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC)., IRCCS Azienda Ospedaliero-Universitaria di Bologna. S. Orsola Hospital. University of Bologna, Via Massarenti 13, Bologna 40138, Italy.

Background: 2021 ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma (EC) encourage molecular classification and propose a new prognostic risk stratification based on both pathologic and molecular features. Although deep myometrial invasion (DMI) has been considered as a crucial risk factor in EC, it is unclear if its prognostic value is independent from The Cancer Genome ATLAS (TCGA) groups.

Aim: To assess if the prognostic value of DMI is independent from the TCGA groups in EC patients.

Materials And Methods: A systematic review and meta-analysis was performed by searching through 5 electronic databases, from their inception to March 2021, for all studies that allowed to assess DMI as a prognostic factor independent of the TCGA groups in EC patients. Pooled hazard ratio (HR) of DMI for overall survival (OS) and disease-free survival (DFS) was calculated at multivariable analyses including TCGA groups as a variable. Superficial myometrial invasion (<50% of myometrial thickness) was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study.

Results: Five studies with 2469 patients were included in the systematic review and 3 studies with 1549 patients in the meta-analysis. Pooled HR of DMI was 1.082 (CI 95% 0.85-1.377; p = 0.524) for OS, 1.709 (CI 95% 1.173-2.491; p = 0.005) for DFS, 1.585 (CI 95% 1.154-2.178; p = 0.004) for DFS additionally considering locoregional recurrence for one study, and 1.701 (CI 95% 1.235-2.344, p = 0.001) for DFS additionally considering distant recurrence for the same study.

Conclusions: DMI does not appear as an independent prognostic factor for OS in EC patients; instead, it seems to affect the risk of recurrence independently from the TCGA groups. Further studies are necessary to confirm these findings and to assess the prognostic impact of DMI separately in each TCGA group.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.029DOI Listing
August 2021
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