Publications by authors named "Antonio Mollo"

107 Publications

Accuracy of cytological examination of Tao brush endometrial sampling in diagnosing endometrial premalignancy and malignancy.

Int J Gynaecol Obstet 2022 Apr 1. Epub 2022 Apr 1.

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

Although Tao brush has become one of the most studied and used endometrial cytological samplers, concerns remain about the adequacy of the cytological sample compared with definitive histology. We aimed to assess accuracy of cytological examination from Tao brush sampling in diagnosing endometrial premalignancy and malignancy through a systematic review and meta-analysis. Seven electronic databases were searched from January 2000 to July 2021 for all studies which allowed assessment of accuracy of Tao brush in diagnosing endometrial premalignancy and malignancy. We calculated sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on summary receiver operating characteristic (SROC) curve. Five studies with 774 patients were included. In diagnosing endometrial premalignancy and malignancy, cytological examination from Tao brush endometrial sampling showed pooled sensitivity of 0.95 (95% CI, 0.90-0.98), specificity of 0.92 (95% CI, 0.90-0.94), LR+ of 12.73 (95% CI, 3.94-41.18), LR- of 0.09 (95% CI, 0.05-0.18), DOR of 184.84 (95% CI, 24.37-1401.79), AUC of 0.9757 (standard error: 0.013). In conclusion, cytological examination from Tao brush seems to have a high diagnostic accuracy and might be proposed as both screening and diagnostic tool. However, further studies are necessary to confirm these findings.
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http://dx.doi.org/10.1002/ijgo.14204DOI Listing
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

Sentinel Lymph Node Biopsy in Surgical Staging for High-Risk Groups of Endometrial Carcinoma Patients.

Int J Environ Res Public Health 2022 03 21;19(6). Epub 2022 Mar 21.

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

Background: In endometrial carcinoma (EC) patients, sentinel lymph node (SLN) biopsy has shown the potential to reduce post-operative morbidity and long-term complications, and to improve the detection of low-volume metastasis through ultrastaging. However, while it has shown high sensitivity and feasibility in low-risk EC patient groups, its role in high-risk groups is still unclear.

Aim: To assess the role of SLN biopsy through the cervical injection of indocyanine green (ICG) in high-risk groups of early-stage EC patients.

Materials And Methods: Seven electronic databases were searched from their inception to February 2021 for studies that allowed data extraction about detection rate and accuracy of SLN biopsy through the cervical injection of ICG in high-risk groups of early-stage EC patients. We calculated pooled sensitivity, false negative (FN) rate, detection rate of SLN per hemipelvis (DRh), detection rate of SLN per patients (DRp), and bilateral detection rate of SLN (DRb), with 95% confidence interval (CI).

Results: Five observational cohort studies (three prospective and two retrospective) assessing 578 high risk EC patients were included. SLN biopsy sensitivity in detecting EC metastasis was 0.90 (95% CI: 0.03-0.95). FN rate was 2.8% (95% CI: 0.6-11.6%). DRh was 88.4% (95% CI: 86-90.5%), DRp was 96.6% (95% CI: 94.7-97.8%), and DRb was 80% (95% CI: 75.4-83.9).

Conclusion: SLN biopsy through ICG cervical injection may be routinely adopted instead of systematic pelvic and para-aortic lymphadenectomy in surgical staging for high-risk groups of early-stage EC patients, as well as in low-risk groups.
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http://dx.doi.org/10.3390/ijerph19063716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949341PMC
March 2022

Endometrial giant cell carcinoma: new insights from a morphological, immunohistochemical, and molecular analysis of three cases.

Virchows Arch 2022 Mar 19. Epub 2022 Mar 19.

Gynecopathology and Breast Pathology Unit, Department of Woman and Child's Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Herein, we present a morphological, immunohistochemical, and molecular analysis of three cases of endometrial giant cell carcinoma (EGCC) with a literature review. Patient age was 55 to 76 years. The tumors were limited to the uterus and showed dyshesive, bizarre giant cells with numerous atypical mitoses. Minor components were low-grade endometrioid, spindled/myxoid (case nos. 1 and 2), serous (case no. 3), and undifferentiated (all cases). The giant cells were e-cadherin-, cytokeratins/EMA + (focal/multifocal), hormone receptors + (focal/multifocal), vimentin + , p16 + (diffuse), CD68-, α-FP-, β-HCG-, muscle markers-, CD10-, and ERG-. Case no. 3 was p53-abnormal. All cases were mismatch repair-proficient and microsatellite-stable. No POLE mutations were detected. Based on our and previous reports, EGCC is often accompanied by a conventional carcinomatous component (mostly endometrioid) and shows partial loss epithelial markers and negativity for specific differentiation markers. EGCC shows evident similarities to both undifferentiated/dedifferentiated carcinoma and carcinosarcoma and should be managed similarly. Unlike the latter two, EGCC might preferentially derive from "no-specific-molecular-profile" carcinomas.
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http://dx.doi.org/10.1007/s00428-022-03310-xDOI 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

The impact of hysterectomy on oncological outcomes in patients with borderline ovarian tumors: A systematic review and meta-analysis.

Gynecol Oncol 2022 04 26;165(1):184-191. Epub 2022 Jan 26.

Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy.

Background: Surgical management of Borderline ovarian tumors (BOT) can range from unilateral cystectomy to a more extensive surgical staging. However, the role of hysterectomy within the surgical staging is still debated.

Aim: To assess the impact of hysterectomy on survival outcomes in BOT patients.

Materials And Methods: 5 electronic databases were searched from their inception to April 2021 for all peer-reviewed, retrospective or prospective studies, which compared treatment including hysterectomy versus treatment not including hysterectomy for BOT, in terms of recurrence and/or death. Pooled odds ratios (OR) with 95% confidence interval for recurrence, death due to BOT and death of any cause were calculated comparing hysterectomy group versus no hysterectomy group. Subgroup analyses for recurrence were based on BOT histotype (mucinous and serous) and FIGO stage (I and II-III).

Results: Twelve studies assessing 2223 patients were included. Compared to no hysterectomy group, hysterectomy group showed an OR of 0.23 (p = 0.00001) for recurrence, 1.26 (p = 0.77) for death due to BOT and 4.23 (p = 0.11) for death of any cause. At subgroup analyses, compared to no hysterectomy group, hysterectomy group showed an OR for recurrence of 0.21 (p = 0.003) in serous subgroup, of 0.46 (p = 0.18) in mucinous subgroup, of 0.23 (p = 0.0006) in FIGO stage I subgroup, and of 0.29 (p = 0.04) in FIGO stage II-III subgroup.

Conclusions: Uterine-sparing surgery might be recommended in all BOT patients since it seems to increase the risk of recurrence, but not those of death due to disease or death of any cause.
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http://dx.doi.org/10.1016/j.ygyno.2022.01.019DOI Listing
April 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

3D Patient-Specific Virtual Models for Presurgical Planning in Patients with Recto-Sigmoid Endometriosis Nodules: A Pilot Study.

Medicina (Kaunas) 2022 Jan 6;58(1). Epub 2022 Jan 6.

Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola Hospital, University of Bologna, 40138 Bologna, Italy.

In recent years, 3D printing has been used to support surgical planning or to guide intraoperative procedures in various surgical specialties. An improvement in surgical planning for recto-sigmoid endometriosis (RSE) excision might reduce the high complication rate related to this challenging surgery. The aim of this study was to build novel presurgical 3D models of RSE nodules from magnetic resonance imaging (MRI) and compare them with intraoperative findings. A single-center, observational, prospective, cohort, pilot study was performed by enrolling consecutive symptomatic women scheduled for minimally invasive surgery for RSE between November 2019 and June 2020 at our institution. Preoperative MRI were used for building 3D models of RSE nodules and surrounding pelvic organs. 3D models were examined during multi-disciplinary preoperative planning, focusing especially on three domains: degree of bowel stenosis, nodule's circumferential extension, and bowel angulation induced by the RSE nodule. After surgery, the surgeon was asked to subjectively evaluate the correlation of the 3D model with the intra-operative findings and to express his evaluation as "no correlation", "low correlation", or "high correlation" referring to the three described domains. seven women were enrolled and 3D anatomical virtual models of RSE nodules and surrounding pelvic organs were generated. In all cases, surgeons reported a subjective "high correlation" with the surgical findings. Presurgical 3D models could be a feasible and useful tool to support surgical planning in women with recto-sigmoidal endometriotic involvement, appearing closely related to intraoperative findings.
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http://dx.doi.org/10.3390/medicina58010086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777715PMC
January 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

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

Impact of nerve-sparing posterolateral parametrial excision for deep infiltrating endometriosis on postoperative bowel, urinary, and sexual function.

Int J Gynaecol Obstet 2022 Jan 7. Epub 2022 Jan 7.

Division of Gynecological Oncology, Department for the Protection of Women's and Children's Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Objective: To evaluate the functional outcomes of nerve-sparing surgery for deep infiltrating endometriosis (DIE) with or without posterolateral parametrectomy.

Methods: A multicenter, observational, retrospective, cohort study was performed including all symptomatic women who underwent nerve-sparing laparoscopic excision of DIE and preoperative and postoperative assessment of functional outcomes through validated questionnaires between April 2019 and March 2020. Women with posterolateral parametrial DIE (P-group) and women with no parametrial involvement (NP-group) were compared in terms of preoperative and postoperative functional outcomes related to pelvic organs assessed through validated questionnaires (KESS and GIQLI for bowel function, BFLUTS for urinary function, and FSFI for sexual function); pain symptoms at 3-month follow up assessed through an 11-point visual analogue scale (VAS) for dyschezia, dysmenorrhea, dyspareunia and chronic pelvic pain; surgical outcomes; and rate of urinary voiding dysfunction at 3-month follow up.

Results: One-hundred patients were included: 69 in the P-group and 31 in the NP-group. Preoperative and postoperative values of questionnaires, pain symptoms, and postoperative complication rates were comparable between the two groups, except for postoperative dyspareunia and sexual dysfunction, which were statistically higher in the P-group. Only patients in the P-group experienced urinary voiding dysfunction, but no statistical significance was reached (P = 0.173).

Conclusion: Posterolateral parametrectomy for DIE appears to be associated with a higher risk of postoperative dyspareunia and sexual dysfunction.
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http://dx.doi.org/10.1002/ijgo.14089DOI Listing
January 2022

Pelvic floor dysfunction at transperineal ultrasound and chronic constipation in women with endometriosis.

Int J Gynaecol Obstet 2022 Jan 7. Epub 2022 Jan 7.

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

Objective: To assess the association between sonographic findings at transperineal ultrasound (TPU) and chronic constipation (CC) in women with endometriosis.

Methods: An observational prospective cohort study was performed by enrolling all women with endometriosis scheduled for surgery between September 2019 and October 2020. Women underwent TPU at rest and during Valsalva maneuver evaluating levator-hiatal-area (LHA), antero-posterior diameter (APD), and levator ani muscle (LAM) coactivation. Ultrasound findings were compared between women with and without CC in the whole study population, and subsequently in two subgroups (only ovarian endometriosis and deep infiltrating endometriosis [DIE]).

Results: In all, 87 women were enrolled: 29 (33%) with CC and 58 (67%) without CC. Women with endometriosis and CC showed a smaller LHA during Valsalva, less LHA and APD enlargement from rest to maximum Valsalva, and a higher prevalence of LAM coactivation compared with women without CC. In the ovarian subgroup, women with CC had smaller LHA at Valsalva, less enlargement of LHA and APD from rest to maximum Valsalva, and higher prevalence of LAM coactivation compared with non-CC patients. In the DIE subgroup, TPU did not significantly differ between CC and non-CC patients.

Conclusion: TPU signs of pelvic floor muscle hypertonia are more frequent in endometriosis patients with CC compared with those without constipation, particularly in women affected by isolated ovarian endometriosis.
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http://dx.doi.org/10.1002/ijgo.14088DOI Listing
January 2022

Oncologic outcomes of conservative treatment of atypical polypoid adenomyoma of the uterus: A two-center experience.

Int J Gynaecol Obstet 2021 Dec 18. Epub 2021 Dec 18.

Department of Public Health, School of Medicine, University of Naples Federico II, Naples, Italy.

Objective: Atypical polypoid adenomyoma (APA) is a rare uterine premalignant lesion mainly occurring in premenopausal and nulliparous women. Although hysteroscopic resection (HR) has showed promising results, the conservative management of APA in young women is not standardized, and few data are available in the literature. We aimed to assess oncologic outcomes of the conservative treatment of APA.

Methods: A multicenter observational retrospective cohort study was performed including all patients with APA who underwent conservative treatment from January 2006 to June 2020. Rates of each oncologic outcome (i.e. initial complete response, persistence, progression to cancer, recurrence, long-term treatment success, and treatment failure) were calculated for all conservative treatment together and separately.

Results: Twenty-five patients were included. Conservative treatments consisted of HR alone (n = 14) and HR + progestin (n = 11). Overall, 24 (96%) patients showed initial complete response, of which 21 (84%) showed long-term treatment success; four (16%) patients had progression to cancer, of which two (8%) first recurred as APA. Long-term treatment success was achieved in 13 of 14 (92.9%) patients with HR alone and 8 of 11 (72.3%) with HR + progestin.

Conclusion: Conservative treatment appears to be a safe option in women with APA. The four-steps HR might be considered as the first-line conservative approach, while the addition of progestin does not seem to improve oncologic outcomes. However, the risk of progression to cancer highlights the need for a close and long-term follow up with ultrasonography and hysteroscopic biopsies, and for hysterectomy in patients not desiring pregnancy.
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http://dx.doi.org/10.1002/ijgo.14077DOI Listing
December 2021

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

Cancer Stem Cell Assay for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer.

HSOA J Stem Cells Res Dev Ther 2021 9;7(3). Epub 2021 Sep 9.

Department of BioMolecular Sciences, National Center for Natural Products Research, University of Mississippi, University, MS, USA.

Background: Disease recurrence and progression of ovarian cancer is a common event, which is accompanied by the development of platinum-resistant or refractory disease. The presence of chemo-resistant Cancer Stem Cells (CSCs) contribute to tumor propagation, maintenance, and treatment resistance of this difficult to treat disease. We have developed ChemoID, a cytotoxic synergy assay against CSCs that identifies the most effective chemotherapy treatment from a panel of FDA-approved chemotherapies using fresh cancer biopsies.

Patients And Methods: Ascites or interventional radiology biopsies were collected under physician order from 78 consecutive patients affected by 3 relapsed ovarian cancer. Test results from the assay were used when possible to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, if needed. A chart analysis and review of CT and PET scans were performed to determine patients' outcomes for tumor response, Progression-Free Survival (PFS), and Overall Survival (OS).

Results: We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs drug response assay had an improvement in their median PFS and OS when compared to historical median PFS and OS and/or when compared to patients who could not receive high cell kill chemotherapies (PFS low cell kill 3.5 months vs. high cell kill 12.0 months; OS low cell kill 6.0 months vs. high cell kill 15.0 months).

Conclusion: This data indicates that the drug cytotoxicity assay aimed at targeting CSCs may be a useful tool for optimizing treatment selection when first-line therapy fails, and when there are multiple clinically-acceptable and -equivalent treatments available.
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http://dx.doi.org/10.24966/srdt-2060/100076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597976PMC
September 2021

Metabolic and production parameters of dairy cows with different dry period lengths and parities.

Acta Vet Hung 2021 Nov 15. Epub 2021 Nov 15.

4 Department of Veterinary Medicine, Università degli Studi di Milano, via dell'Università 6, 26900 Lodi, Italy.

To assess the effects of dry period (DP) length on metabolic, reproductive, and productive parameters, second- (SP) and third- (TP) parity cows were assigned to a traditional (9 weeks, T) or short (5 weeks, S) DP, obtaining four subgroups: second-parity cows with traditional (SPT = 8) and short (SPS = 8) DP, third-parity cows with traditional (TPT = 8) and short (TPS = 10) DP. Plasma insulin-like growth factor-I (IGF-I) and non-esterified fatty acid (NEFA) levels were assessed from 5 weeks before to 14 weeks after parturition. IGF-I concentrations were affected by parity (P < 0.05) and by the interaction of time and DP length (P < 0.01). NEFA levels were affected only by time (P < 0.01). S DP cows showed a shorter interval between calving and ovarian cyclicity resumption (P < 0.01) and a higher milk yield (P < 0.01) and fat and protein corrected milk (P < 0.01) compared with T DP cows. Decreased milk protein content was found in the SPS group compared to the SPT (P < 0.05) and the TPS (P < 0.05) group. In conclusion, a short DP length does not affect reproductive performances, except for hastening the resumption of ovarian cyclicity. A short DP appears to increase milk production and is associated with higher IGF-I levels both in the prepartum and the postpartum period.
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http://dx.doi.org/10.1556/004.2021.00049DOI Listing
November 2021

Clinical Characteristics of Patients with Endometrial Cancer and Adenomyosis.

Cancers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

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, Via Massarenti 13, 40138 Bologna, Italy.

A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been reported. Unfortunately, it is still unclear if this better prognosis is related to a more favorable clinical profile of adenomyosis patients. We aimed to evaluate differences in the clinical profiles of EC patients with and without adenomyosis. A systematic review and meta-analysis was performed by searching seven electronics databases for all studies that allowed extraction of data about clinical characteristics in EC patients with and without adenomyosis. Clinical characteristics assessed were: age, Body Mass Index (BMI), premenopausal status, and nulliparity. Mean difference in mean ± standard deviation (SD) or odds ratio (OR) for clinical characteristics between EC patients with and without adenomyosis were calculated for each included study and as a pooled estimate, and graphically reported on forest plots with a 95% confidence interval (CI). The Z test was used for assessing the overall effect by considering a value < 0.05 as significant. Overall, eight studies with 5681 patients were included in the qualitative analysis, and seven studies with 4366 patients in the quantitative analysis. Pooled mean difference in mean ± SD between EC women with and without adenomyosis was -1.19 (95% CI: -3.18 to 0.80; = 0.24) for age, and 0.23 (95% CI: -0.62 to 1.07; = 0.60) for BMI. When compared to EC women without adenomyosis, EC women with adenomyosis showed a pooled OR of 1.53 (95% CI: 0.92 to 2.54; = 0.10) for premenopausal status, and of 0.60 (95% CI: 0.41 to 0.87; = 0.007) for nulliparity. In conclusion, there are not significant differences in clinical characteristics between EC patients with and without adenomyosis, with the exception for nulliparity. Clinical features seem to not underlie the better EC prognosis of patients with adenomyosis compared to patients without adenomyosis.
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http://dx.doi.org/10.3390/cancers13194918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508080PMC
September 2021

Prognostic value of the TCGA molecular classification in uterine carcinosarcoma.

Int J Gynaecol Obstet 2021 Sep 18. Epub 2021 Sep 18.

Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy.

Background: The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd), "TP53-mutated/p53-abnormal" (TP53mut/p53abn), and "no specific molecular profile" (NSMP).

Objective: Prognostic assessment of the TCGA groups in uterine carcinosarcoma (UCS).

Search Strategy: Systematic review from January 2000 to January 2021.

Selection Criteria: Studies assessing the TCGA groups in UCS.

Data Collection And Analysis: Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox analyses (reference: TP53mut/p53abn group) and compared with endometrioid and serous carcinomas (original TCGA cohort), with a significant P < 0.050.

Main Results: Five studies with 263 UCS were included. Compared with TP53mut/p53abn UCS, MSI/MMRd UCS showed significantly better PFS (P < 0.001) but similar OS (P = 0.788), whereas NSMP UCS showed similar PFS (P = 0.936) and OS (P = 0.240). Compared with their endometrioid/serous counterparts, NSMP and TP53mut/p53abn UCS showed significantly worse PFS (P < 0.001 and P = 0.004) and OS (P < 0.001 and P < 0.001), while MSI/MMRd UCS showed similar PFS (P = 0.595) but significantly worse OS (P < 0.001). The POLEmut group showed neither recurrences nor deaths in both the UCS and the endometrioid/serous carcinoma cohorts.

Conclusion: POLEmut UCS show excellent prognosis, whereas TP53mut/p53abn and NSMP UCS show a prognosis even worse than that of TP53mut/p53abn endometrioid/serous carcinomas. The prognosis of MSI/MMRd UCS remains to be defined.
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http://dx.doi.org/10.1002/ijgo.13937DOI Listing
September 2021

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

Cimicifuga racemosa isopropanolic extract for menopausal symptoms: an observational prospective case-control study.

Gynecol Endocrinol 2021 Dec 3;37(12):1132-1137. Epub 2021 Sep 3.

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

Objective: We aimed to investigate the effectiveness of isopropanolic extract of Cimicifuga Racemosa (iCR) on reducing menopausal symptoms.

Materials And Methods: A single-center observational prospective case-control study was performed to assess the improvement of menopausal symptoms in menopausal women undergone iCR administration (cases) or no treatment (controls). Menopausal symptoms were assessed through a modified version of the Menopause Rating Scale questionnaire (mMRS) at T (baseline), T (1-month follow-up), and T (3 months follow-up). Univariate comparisons between cases and controls were performed by using the unpaired T test for two-tailed P value with α = 0.05 significance level.

Results: A total of 163 women (83 cases and 80 controls) were enrolled in the study. The difference in menopausal symptoms between cases and controls from T to T, and from T to T, was found significant for all analyses. In particular, the difference in all menopausal symptoms was 20.56 ± 0.90 points (95%CI: 18.77-22.33,  < .001) from T to T, and 10.69 ± 0.6 (95%CI: 9.49-11.88,  < .001) from T to T.

Conclusion: iCR may be effective in reducing menopausal symptoms, both after 1 month and after 3 months of treatment. The improvement was higher in vasomotor symptoms, sleep problems, and irritability.
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http://dx.doi.org/10.1080/09513590.2021.1974381DOI Listing
December 2021

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

Clear cell endometrial carcinomas with mismatch repair deficiency have a favorable prognosis: A systematic review and meta-analysis.

Gynecol Oncol 2021 09 12;162(3):804-808. Epub 2021 Jul 12.

Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy; Catholic University of Sacred Heart, Rome, Italy.

Introduction: In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear.

Objective: To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis.

Methods: Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value<0.05 was adopted.

Results: Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups.

Conclusion: MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.007DOI Listing
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

An emerging role for BAG3 in gynaecological malignancies.

Br J Cancer 2021 09 7;125(6):789-797. Epub 2021 Jun 7.

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

BAG3, a member of the BAG family of co-chaperones, is a multidomain protein with a role in several cellular processes, including the control of apoptosis, autophagy and cytoskeletal dynamics. The expression of bag3 is negligible in most cells but can be induced by stress stimuli or malignant transformation. In some tumours, BAG3 has been reported to promote cell survival and resistance to therapy. The expression of BAG3 has been documented in ovarian, endometrial and cervical cancers, and studies have revealed biochemical and functional connections of BAG3 with proteins involved in the survival, invasion and resistance to therapy of these malignancies. BAG3 expression has also been shown to correlate with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix. Some aspects of BAG3 activity, such as its biochemical and functional interaction with the human papillomavirus proteins, could help in our understanding of the mechanisms of oncogenesis induced by the virus. This review aims to highlight the potential value of BAG3 studies in the field of gynaecological tumours.
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http://dx.doi.org/10.1038/s41416-021-01446-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437940PMC
September 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

Laparotomic versus robotic surgery in elderly patients with endometrial cancer: A systematic review and meta-analysis.

Int J Gynaecol Obstet 2022 Apr 19;157(1):1-10. Epub 2021 Jun 19.

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

Background: Although robotics has been shown to improve outcomes in some high-difficulty surgical category patients, it is unclear if such an approach may improve outcomes in elderly patients with endometrial carcinoma (EC).

Objective: To compare robotic and laparotomic surgery in the treatment and staging of elderly EC patients.

Materials And Methods: A systematic review and meta-analysis was performed assessing the risk of overall, intra-operative, and peri-operative complications associated with the surgical approach (laparotomic vs robotic) for elderly patients with EC by relative risk (RR). Pooled means ± standard deviation of length of stay were compared with the unpaired t test. Subgroup analyses for overall complications were performed based on different age cut-offs (>70, >65, and >75 years) and severity of complications (minor and major). A value of P less than 0.05 was considered significant.

Results: Five studies with 7629 EC patients were included. Pooled RR for robotic compared with laparotomic surgery was 0.40 (P < 0.001) for overall, 0.46 (P = 0.18) for intra-operative, and 0.43 (P < 0.001) for peri-operative complications. Pooled difference between means ± standard deviation of length of stay for robotic versus laparotomic surgery was -3.34 (P < 0.001). At subgroup analyses, pooled RR of overall complications for robotic surgery versus laparotomic surgery was 0.34 (P < 0.001) in the >70 years, 0.51 (P < 0.01) in the >65 years, 0.20 (P = 0.12) in the >75 years groups. Pooled RR was 0.50 (P = 0.1) in the minor complications subgroup, and 0.42 (P = 0.002) in the major complications subgroup.

Conclusion: Robotics might be a viable alternative to the laparotomic approach for EC in elderly patients because it significantly decreases the risk of overall and peri-operative complications (mainly major complications), and the length of stay when compared with laparotomy. The decrease in risk of overall complications is greater with increasing patient age.
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http://dx.doi.org/10.1002/ijgo.13766DOI Listing
April 2022

Stanford parameters stratify the risk of recurrence in gynecologic smooth muscle tumors of uncertain malignant potential.

APMIS 2021 Jun 13;129(6):283-290. Epub 2021 Apr 13.

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

Smooth muscle tumor of uncertain malignant potential (STUMP) is an ill-defined category of neoplasms, which represent a diagnostic challenge. We aimed to assess whether the Stanford parameters, that is, high mitotic index (≥10/10HPF), significant atypia (moderate-to-severe), and coagulative tumor cell necrosis (CTCN), even when focal or ambiguous, may be used to stratify the risk of recurrence in gynecological smooth muscle tumor of uncertain malignant potential (STUMP). Electronic databases were searched from their inception to October 2019. All studies assessing the Stanford parameters in gynecological STUMP series were included. STUMPs were subdivided according to the presence of the three Stanford parameters: high mitotic index, significant atypia, and CTCN. A Kaplan-Meier survival analysis was performed for recurrence-free survival; hazard ratio (HR) was calculated in each category. Fourteen studies with 219 STUMPs were included. In 15.5% of cases, none of the three Stanford parameters were present, with a recurrence risk of 5.9%; 2.7% of cases showed high mitotic index alone, with a recurrence risk of 0% (HR = not calculable); 43.8% of cases showed significant atypia alone, with a recurrence risk of 18.7% (HR = 3.3; p = 0.012); 26.5% of cases showed CTCN alone, with a recurrence risk of 17.2% (HR = 3.1; p = 0.029); and 11.4% of cases showed at least two Stanford parameters, with a recurrence risk of 32% (HR = 7.5; p = 0.003). Stanford parameters may stratify the risk of recurrence of STUMP. Significant atypia and CTCN, but not high mitotic index, may be stand-alone risk factors for recurrence in STUMP. The presence of at least two Stanford parameters, even if equivocal (e.g., uncertain or focal CTCN, focal significant atypia, mitotic index around 10/10HPF), might still be enough to support a diagnosis of leiomyosarcoma. Further studies are necessary in this field.
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http://dx.doi.org/10.1111/apm.13135DOI Listing
June 2021
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