Publications by authors named "Mario Preti"

77 Publications

Low-Grade Uterine Endometrial Stromal Sarcoma: Prognostic Analysis of Clinico-Pathological Characteristics, Surgical Management, and Adjuvant Treatments. Experience From Two Referral Centers.

Front Oncol 2022 30;12:883344. Epub 2022 Jun 30.

Division of Gynecology and Obstetrics 1, "City of Health and Science University Hospital", University of Turin, Turin, Italy.

Objective: Low-grade uterine endometrial stromal sarcoma (LG-ESS) is a rare tumor characterized by an overall good survival but showing a indolent behavior and a variable risk of recurrence. There is no clear consensus on the optimal management of these tumors and no prognostic or predictive factors have been established. With this study, we evaluated the prognostic relevance of several clinical, surgical, and pathological features in patients affected by LG-ESS to identify risk factors associated with recurrence.

Methods: We retrospectively analyzed 52 LG-ESS cases, treated from January 1st, 1994, to May 31st, 2020, in two referral centers. The relationship between recurrence and clinicopathological characteristics as well as surgical treatment was investigated. Risk of recurrence and disease-free survival (DFS) were estimated by Cox regression and the Kaplan-Meier analysis, respectively.

Results: Of 52 patients with LG-ESS, 8 experienced recurrence (15%). The median follow-up was 100 months (SD ± 96, range: 15-336). By univariate analysis, fragmentation/morcellation, tumor size, FIGO stage, higher mitotic count, presence of necrosis, and lymphovascular space invasion (LSVI) resulted associated with a poorer outcome. Conversely, the surgical modality (laparotomic vs laparoscopic and hysterectomy with bilateral salpingo-oophorectomy vs local excision) and pelvic lymphadenectomy were not. Even the different modalities of adjuvant therapy (hormonal therapy, radiotherapy, and chemotherapy) showed no prognostic significance. Tumor fragmentation/morcellation and higher mitotic count resulted independent prognostic variables at multivariate analysis.

Conclusions: This data supports the avoidance of any type of morcellation if LG-ESS is suspected preoperatively. Higher mitotic count and, possibly, tumor size, advanced FIGO stage, necrosis, and LVSI could be exploited to tailor the adjuvant therapy, but these results need to be confirmed in larger prospective studies.
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http://dx.doi.org/10.3389/fonc.2022.883344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280128PMC
June 2022

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.

J Low Genit Tract Dis 2022 Jul 21;26(3):229-244. Epub 2022 Jun 21.

Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Abstract: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
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http://dx.doi.org/10.1097/LGT.0000000000000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232287PMC
July 2022

SIIV position paper: clinical approach to vulval diseases: need for quality standards.

Minerva Obstet Gynecol 2022 Jun 22. Epub 2022 Jun 22.

Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

This paper summarizes the position of the Italian Society of Vulvology (SIIV) on the clinical approach to vulval disease. A thorough history (general medical, gynaecological, and vulval history) is essential for a successful and fruitful vulvological examination. Characteristics of pruritus (itch) and pain, that are the two main vulval symptoms, should be collected and reported with precision, according to duration, temporal course, location, provocation, and intensity. Physical examination must consider both the general condition of the patient and the specific vulval region, that must be examined following a standardized methodology. The physical examination of the vulva is carried out with thenaked eye and adequate natural or halogen lighting. The subsequent use of instrumental magnification can be considered on particular parts of skin/mucosa, already highlighted with the first inspection. Also palpation is essential, allowing to appreciate physical features of vulval lesions: consistency, surface, soreness, adherence to underlying plans. Finally, the five step approach of the International Society for the Study of Vulvo-vaginal Disease (ISSVD) about Terminology and Classification of Vulvar Dermatological Disorders (2012) is summarized. A vulval biopsy may be useful in the following situations: when clinical diagnosis is uncertain, lesion not responding to treatment; histologic confirmation for a clinical diagnosis and exclusion or confirmation of a suspected neoplastic intraepithelial or invasive pathology.
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http://dx.doi.org/10.23736/S2724-606X.22.04944-2DOI Listing
June 2022

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.

Int J Gynecol Cancer 2022 Jun 21. Epub 2022 Jun 21.

Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
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http://dx.doi.org/10.1136/ijgc-2021-003262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279839PMC
June 2022

Vulvar Paget's disease: outcomes of 51 patients treated with imiquimod cream.

Maturitas 2022 Sep 27;163:23-27. Epub 2022 May 27.

Division of Gynecology and Obstetrics 1, Department of Surgical Sciences, "City of Health and Science University Hospital", University of Turin, 10126 Turin, Italy.

Background: Vulvar Paget's disease (VPD) is a rare neoplasm with high recurrence rates even after surgical treatment. Imiquimod topical cream is a promising therapy; however, experience with it is limited to small series or case reports. This study aims to analyze the effectiveness and safety of topical imiquimod in a large cohort of patients with VPD.

Methods: Fifty-five cases of histologically proven- VPD treated with topical imiquimod at the Gynecologic and Obstetric Division 1 U, S. Anna Hospital, University of Turin were retrospectively reviewed. We investigated the potential factors related to clinico-pathological response to imiquimod using univariate and multivariate logistic regression to estimate odds ratios (ORs).

Results: Four women discontinued the treatment due to side-effects. Of the remaining 51 (42 in situ tumors, and 9 micro-invasive tumors) who completed treatment, 22 (43%) achieved a complete clinico-pathological response. Among the women who had a complete response, there were no cases of recurrence (mean follow-up: 66 months). Symptomatic lesions (burning: OR 0.15, CI 0.03-0.67; itching: OR 0.07, CI 0.008-0.64), smaller tumors <60 mm (OR 0.15, CI 0.006-0.43), non-recurrent VPD (OR 0.19, CI 0.04-0.43) and treatment frequency of three application per week (OR 0.13, CI 0.04-0.50) were associated with a lower risk of persistence. Perianal involvement was associated with treatment failure (OR 7.79, CI 1.88-32.2). Multivariate analysis confirmed a predictive role for smaller tumors, non-recurrent VPD, and a treatment frequency of three applications per week.

Conclusion: Imiquimod can be safely used for the treatment of VPD, even for micro-invasive tumors. Furthermore, we report some potential predictors of treatment response.
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http://dx.doi.org/10.1016/j.maturitas.2022.05.010DOI Listing
September 2022

From Uterus to Brain: An Update on Epidemiology, Clinical Features, and Treatment of Brain Metastases From Gestational Trophoblastic Neoplasia.

Front Oncol 2022 13;12:859071. Epub 2022 Apr 13.

Division of Gynecology and Obstetrics 1, "City of Health and Science University Hospital", University of Turin, Turin, Italy.

In this review, we provide the state of the art about brain metastases (BMs) from gestational trophoblastic neoplasia (GTN), a rare condition. Data concerning the epidemiology, clinical presentation, innovations in therapeutic modalities, and outcomes of GTN BMs are comprehensively presented with particular attention to the role of radiotherapy, neurosurgery, and the most recent chemotherapy regimens. Good response rates have been achieved thanks to multi-agent chemotherapy, but brain involvement by GTNs entails significant risks for patients' health since sudden and extensive intracranial hemorrhages are possible. Moreover, despite the evolution of treatment protocols, a small proportion of these patients ultimately develops a resistant disease. To tackle this unmet clinical need, immunotherapy has been recently proposed. The role of this novel option for this subset of patients as well as the achieved results so far are also discussed.
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http://dx.doi.org/10.3389/fonc.2022.859071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045690PMC
April 2022

Vulvar Cancer: Facing a Rare Disease.

Cancers (Basel) 2022 Mar 20;14(6). Epub 2022 Mar 20.

Division of Gynecologic Oncology, Fondazione Policlinico Universitario A Gemelli IRCCS, 00168 Roma, Italy.

"We must never be afraid to go too far, for truth lies beyond [...].
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http://dx.doi.org/10.3390/cancers14061581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945918PMC
March 2022

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review.

J Low Genit Tract Dis 2022 Jul 11;26(3):250-257. Epub 2022 Mar 11.

Research Institute of the Azrieli Faculty of Medicine, Bar-Ilan University, Galilee Medical Center, Safed, Israel.

Objective: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP.

Materials And Methods: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database.

Results: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively.

Conclusions: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.
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http://dx.doi.org/10.1097/LGT.0000000000000673DOI Listing
July 2022

Perineural Invasion in Vulvar Squamous-Cell Carcinoma Is an Independent Risk Factor for Cancer-Specific Survival, but Not for Locoregional Recurrence: Results from a Single Tertiary Referral Center.

Cancers (Basel) 2021 Dec 28;14(1). Epub 2021 Dec 28.

Division of Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science University Hospital, University of Turin, 10126 Turin, Italy.

The aims of this study were to assess the prevalence of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) and its prognostic role in locoregional recurrence (LRR) and cancer-specific survival (CSS). We performed a retrospective analysis of 223 consecutive stage IB-IIIC surgically treated VSCCs at S. Anna Hospital, University of Turin, from 2000 to 2019. We identified 133/223 (59.6%) patients with PNI-positive VSCCs. PNI was associated with aggressive biological features (i.e., advanced FIGO stage, larger tumor diameter, greater depth of invasion, a higher number of metastatic lymph nodes, and lymphovascular invasion) and shorter 5-year CSS (78% vs. 90%, log-rank = 0.02) compared with PNI-negative VSCCs. Multivariate analysis showed that PNI (HR 2.99 CI 95% 1.17-7.63; = 0.02) and the presence of tumor cells on pathological surgical margins (HR 3.13 CI 95% 1.37-7.13; = 0.007) are independent prognostic factors for CSS. PNI does not appear to be related to LRR, but is an independent prognostic factor for worse survival outcomes. Future studies are necessary to explore the possible value of PNI in tailoring the choice of adjuvant treatment.
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http://dx.doi.org/10.3390/cancers14010124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750970PMC
December 2021

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review.

J Low Genit Tract Dis 2022 01;26(1):32-37

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Objectives: Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women.

Materials And Methods: A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC.

Results: The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method.

Conclusions: Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.
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http://dx.doi.org/10.1097/LGT.0000000000000631DOI Listing
January 2022

G-spot: Fact or Fiction?: A Systematic Review.

Sex Med 2021 Oct 9;9(5):100435. Epub 2021 Sep 9.

Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

Introduction: The G-spot, a putative erogenous area in the anterior vaginal wall, is a widely accepted concept in the mainstream media, but controversial in medical literature.

Aim: Review of the scientific data concerning the existence, location, and size of the G-spot.

Methods: Search on Pubmed, Pubmed Central, Cochrane, clinicaltrials.gov and Google Scholar from inception to November 2020 of studies on G-spot's existence, location and nature. Surveys, clinical, physiological, imaging, histological and anatomic studies were included.

Main Outcome Measure: Existence, location, and nature of the G-spot.

Results: In total, 31 eligible studies were identified: 6 surveys, 5 clinical, 1 neurophysiological, 9 imaging, 8 histological/anatomical, and 2 combined clinical and histological. Most women (62.9%) reported having a G-spot and it was identified in most clinical studies (55.4% of women); in 2 studies it was not identified in any women. Imaging studies had contradictory results in terms of its existence and nature. Some showed a descending of the anterior vaginal wall, that led to the concept of clitourethrovaginal complex. In anatomic studies, one author could systematically identify the G-spot, while another group did not find it. Studies on innervation of the vaginal walls did not systematically identify an area with richer innervation.

Conclusion: The different studies did systematically agree on the existence of the G-spot. Among the studies in which it was considered to exist, there was no agreement on its location, size, or nature. The existence of this structure remains unproved. Vieira-Baptista P, Lima-Silva J, Preti M, et al. G-spot: Fact or Fiction?: A Systematic Review. Sex Med 2021;9:100435.
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http://dx.doi.org/10.1016/j.esxm.2021.100435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498956PMC
October 2021

Superficially Invasive Vulvar Squamous Cell Carcinoma: A 37-Year-Long Experience of a Tertiary Referral Center.

Cancers (Basel) 2021 Jul 31;13(15). Epub 2021 Jul 31.

Division of Gynecology and Obstetrics 1, Department of Surgical Sciences, "City of Health and Science University Hospital", University of Turin, 10126 Turin, Italy.

Superficially, invasive vulvar squamous cell carcinoma (SISCCA) (FIGO stage IA) is a rare subset of vulvar cancer defined as a single lesion measuring ≤2 cm with a depth of invasion of ≤1.0 mm. This is a retrospective study performed on 48 patients with SISCCA, surgically treated between 1981 and 2018 at the S. Anna Hospital, University of Turin, to evaluate pathological characteristics and prognosis of these tumors. Ten patients (21%) recurred: seven (14%) as SISCCA and three (7%) as deeply invasive carcinoma. One case with perineural invasion and groin node metastasis at recurrence. No patient had groin lymph node metastases at initial diagnosis. Site of SISCCA, type of surgery, status of surgical margins, and histopathological features did not differ between recurrent and non-recurrent patients. We observed a non-significant trend towards an increase of recurrences in younger women (median age: 63 years vs. 70 years, = 0.09), while, surprisingly, smaller tumors (<12 mm) were significantly related to tumor relapse ( = 0.03). Overall, SISCCA has a good long-term prognosis, regardless of the pathological characteristics and the type of surgical treatment. We recommend close follow-up, especially for younger patients and for small tumors, due to the possibility of recurrence or re-occurrence even after years.
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http://dx.doi.org/10.3390/cancers13153859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345506PMC
July 2021

Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters.

PLoS One 2021 5;16(8):e0254875. Epub 2021 Aug 5.

Gynecology and Obstetrics 1, Sant Anna University Hospital, Department of Surgical Sciences, City of Health and Science, University of Turin, Turin, Italy.

Evidence for the real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on preterm birth is unclear, as available series report composite pregnancy outcomes and/or do not stratify patients according to disease severity. The purpose of the research was to determine the real impact of asymptomatic/mild SARS-CoV-2 infection on preterm birth not due to maternal respiratory failure. This case-control study involved women admitted to Sant Anna Hospital, Turin, for delivery between 20 September 2020 and 9 January 2021. The cumulative incidence of Coronavirus disease-19 was compared between preterm birth (case group, n = 102) and full-term delivery (control group, n = 127). Only women with spontaneous or medically-indicated preterm birth because of placental vascular malperfusion (pregnancy-related hypertension and its complications) were included. Current or past SARS-CoV-2 infection was determined by nasopharyngeal swab testing and detection of IgM/IgG antibodies in blood samples. A significant difference in the cumulative incidence of Coronavirus disease-19 between the case (21/102, 20.5%) and the control group (32/127, 25.1%) (P= 0.50) was not observed, although the case group was burdened by a higher prevalence of three known risk factors (body mass index > 24.9, asthma, chronic hypertension) for severe Coronavirus disease-19. Logistic regression analysis showed that asymptomatic/mild SARS-CoV-2 infection was not an independent predictor of spontaneous and medically-indicated preterm birth due to pregnancy-related hypertension and its complications (0.77; 95% confidence interval, 0.41-1.43). Pregnant patients without comorbidities need to be reassured that asymptomatic/mild SARS-CoV-2 infection does not increase the risk of preterm delivery. Preterm birth and severe Coronavirus disease-19 share common risk factors (i.e., body mass index > 24.9, asthma, chronic hypertension), which may explain the high rate of indicated preterm birth due to maternal conditions reported in the literature.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254875PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341509PMC
August 2021

Vulvar Paget's disease and stromal invasion: Clinico-pathological features and survival outcomes.

Surg Oncol 2021 Sep 16;38:101581. Epub 2021 Apr 16.

Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science, University of Torino, Torino, Italy.

Purpose: To evaluate clinico-pathological features, treatments and survival outcomes of vulvar Paget's disease (VPD).

Methods: We retrospectively reviewed VPD diagnosed between 1983 and 2018 at the Department of Surgical Sciences, Sant'Anna Hospital, Turin. Clinico-pathological characteristics and surgical treatment outcomes were investigated according to the depth of invasion.

Results: A total of 122 patients were identified. Eighty-seven patients were diagnosed with intraepithelial VPD, 22 with microinvasive (<=1 mm) VPD and 16 with invasive VPD. The median follow-up was 94.6 months (interquartile range 25th-75th, 26-120). Most of patients 95/122 (77%) were treated by surgery. Local recurrence was observed in 69/95 (73%) patients without significant difference between the 3 groups (p = 0.33), however, total vulvectomy showed better local control in microinvasive and invasive VPD than in intraepithelial tumors. At 120 months the cancer-specific survival was 100% for intraepithelial and microinvasive VPD versus 31% for invasive VPD (log-rank p = <0.0001) Age ≥65 years (OR: 4.17 CI 1.12-15.5, p = 0.03) and VPD's area ≥15 cm (OR: 5.83 CI 1.75-19.3, p = 0.004) were associated with risk of invasiveness.

Conclusion: Microinvasive VPD has an identical prognosis to intraepithelial VPD, suggesting the omission of lymphadenectomy or adjuvant treatments are safe in this subset of patients. We recommend caution to propose medical treatment in patients who are ≥65 years old and with wide tumor area, as they are at the greatest risk of invasiveness.
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http://dx.doi.org/10.1016/j.suronc.2021.101581DOI Listing
September 2021

Gut Microbiota and Gynecological Cancers: A Summary of Pathogenetic Mechanisms and Future Directions.

ACS Infect Dis 2021 05 13;7(5):987-1009. Epub 2021 Apr 13.

Obstetrics and Gynecology Unit 1, Sant' Anna Hospital, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy.

Over the past 20 years, important relationships between the microbiota and human health have emerged. A link between alterations of microbiota composition (dysbiosis) and cancer development has been recently demonstrated. In particular, the composition and the oncogenic role of intestinal bacterial flora has been extensively investigated in preclinical and clinical studies focusing on gastrointestinal tumors. Overall, the development of gastrointestinal tumors is favored by dysbiosis as it leads to depletion of antitumor substances (e.g., short-chain fatty acids) produced by healthy microbiota. Moreover, dysbiosis leads to alterations of the gut barrier, promotes a chronic inflammatory status through activation of toll-like receptors, and causes metabolic and hormonal dysregulations. However, the effects of these imbalances are not limited to the gastrointestinal tract and they can influence gynecological tumor carcinogenesis as well. The purpose of this Review is to provide a synthetic update about the mechanisms of interaction between gut microbiota and the female reproductive tract favoring the development of neoplasms. Furthermore, novel therapeutic approaches based on the modulation of microbiota and their role in gynecological oncology are discussed.
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http://dx.doi.org/10.1021/acsinfecdis.0c00839DOI Listing
May 2021

Four-decade trends in lymph node status of patients with vulvar squamous cell carcinoma in northern Italy.

Sci Rep 2021 03 11;11(1):5661. Epub 2021 Mar 11.

Department of Surgical Sciences, University of Torino, Torino, Italy.

The 4-decade (1980-2017) trends in lymph node status of patients with vulvar squamous cell carcinoma (VSCC) in a province of northern Italy were investigated. Information was collected on lymph node dissection, number of lymph nodes dissected, lymph node involvement, and number of positive lymph nodes from a series of 760 patients admitted to a tertiary referral centre for vulvar disease. The adjusted odds ratios (ORs) for lymph node involvement, for ≥ 2 positive nodes, and for a lymph node ratio ≥ 20% were estimated from multiple logistic regression models. The adjusted OR for lymph node dissection was greater in the 2000s and 2010s versus the 1980s. The adjusted OR for lymph node involvement was 1.36 (95% confidence interval (CI), 0.72-2.60) in the 1990s, 1.31 (95% CI, 0.72-2.38) in the 2000s and 1.32 (95% CI, 0.73-2.41) in the 2010s versus the 1980s. The adjusted OR for ≥ 2 positive nodes was 1.36 (95% CI, 0.68-2.72), 0.86 (95% CI, 0.44-1.65) and 0.67 (95% CI, 0.34-1.31), respectively. The adjusted OR for lymph node ratio ≥ 20% was 1.45 (95% CI, 0.62-3.43), 1.21 (95% CI, 0.54-2.72) and 0.81 (95% CI, 0.35-1.89), respectively. This stagnation indicates the need for a serious rethink of the local model for the care of VSCC.
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http://dx.doi.org/10.1038/s41598-021-85030-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952703PMC
March 2021

Longitudinal analysis of antibody response following SARS-CoV-2 infection in pregnancy: From the first trimester to delivery.

J Reprod Immunol 2021 04 2;144:103285. Epub 2021 Feb 2.

Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science, University of Turin, Turin, Italy.

We report herein the longest-lasting study of SARS-CoV-2 antibody profile in pregnancy, from first trimester-infection to delivery. Seventeen out of 164 pregnant women tested positive for COVID-19. Throughout pregnancy, the neutralizing antibody titer remained stable, whilst a significant decline in the non-neutralizing antibodies was observed after 16 weeks of gestation. All the newborns of women who developed IgG antibodies showed the presence of the same antibodies in arterial cord blood. Knowledge on the longevity and type of SARS-CoV-2 antibody response may help to guide vaccination strategies in pregnancy.
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http://dx.doi.org/10.1016/j.jri.2021.103285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973007PMC
April 2021

Anyplex II HPV test in detection and follow-up after surgical treatment of CIN2+ lesions.

J Med Virol 2021 11 15;93(11):6340-6346. Epub 2021 Feb 15.

Division of Laboratory Medicine, European Institute of Oncology IRCCS, Milan, Italy.

Human papillomavirus (HPV) tests differ for technology, targets, and information on the genotype and viral load. In this study, we evaluated the performance of the Seegene Anyplex II HPV HR (Anyplex) assay in the detection of cervical intraepithelial lesions (CIN) and as a test-of-cure in the follow-up after surgical treatment. One hundred and sixty-seven women referred to the European Institute of Oncology, Milan, for surgical treatment of CIN2+ were enrolled. A cervical sample was taken before treatment and at the first follow-up visit: on these samples, Qiagen Hybrid Capture 2 (HC2), Roche Linear Array HPV Test (Linear Array), cytology and histology were performed at baseline, HC2, and cytology at follow-up. Anyplex genotyping HPV test was performed on a post aliquot from liquid-based cytology specimens when available. The concordance between Anyplex and HC2 was 93.6% at baseline and 76.7% at follow-up (3-9 months after treatment), respectively. The concordance between Anyplex and Linear Array was evaluable only at baseline (92.9%). No recurrence occurred in women without the persistence of the same genotype at follow-up. Seven women relapsed: six had persistence of the same genotypes (five HPV16, one HPV33, and one HPV39), while one tested negative not only with Anyplex but also with HC2 for the persistence of low-risk genotype infection (HPV73 only detected by Linear Array). Anyplex test represents a valid option for HPV detection and genotyping in order to stratify women at risk of high-grade lesions at baseline and to monitor patients treated for CIN2+ lesions during follow-up.
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http://dx.doi.org/10.1002/jmv.26862DOI Listing
November 2021

Knowledge of Vulvar Anatomy and Self-examination in a Sample of Italian Women.

J Low Genit Tract Dis 2021 Apr;25(2):166-171

Department of Surgical Sciences University of Torino, Torino, Italy.

Objective: The aim of the study was to investigate the knowledge of vulvar anatomy and vulvar self-examination (VSE) in a sample of Italian women attending a gynecology clinic.

Methods: For this original research from May to July 2019, 512 women attending the Lower Genital Tract Clinic at the Department of Surgical Sciences of the University of Torino were invited to participate in a 29-question survey about vulvar anatomy, VSE, and sociodemographic details. Data were analyzed using descriptive statistics.

Results: Of 512 patients, 500 completed the questionnaire (98% response rate). The mean age of respondents was 41 years (range = 17-77 years). Education level was evenly distributed between elementary, high school, and university graduates. Only 15% of interviewed women were able correctly sketching vulvar anatomy. Seventy-six percent of the women had not heard about VSE, and 61% of the women approach their genitalia with feelings of shame and embarrassment. Only 23% of the women would seek medical advice after identification of possible abnormalities during VSE. A majority (69%) of the women would like to have more information about VSE and vulvar health through educational videos and social media.

Conclusions: Education about VSE may lead to earlier diagnosis of vulvar cancers and other pathologies. Further efforts are needed to disperse information about normal external female genital anatomy and VSE to achieve self-confidence among women.
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http://dx.doi.org/10.1097/LGT.0000000000000585DOI Listing
April 2021

Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review.

Int J Mol Sci 2020 Dec 27;22(1). Epub 2020 Dec 27.

Division of Gynecology and Obstetrics 1, Department of Surgical Sciences, "City of Health and Science University Hospital", University of Turin, 10126 Turin, Italy.

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.
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http://dx.doi.org/10.3390/ijms22010190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796178PMC
December 2020

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation.

J Low Genit Tract Dis 2021 Jan;25(1):57-70

University of Torino, Torino, Italy.

Objective: The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM).

Materials And Methods: The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership.

Results: Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN.

Conclusions: Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.
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http://dx.doi.org/10.1097/LGT.0000000000000572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748053PMC
January 2021

Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia.

BMC Cancer 2020 Oct 7;20(1):972. Epub 2020 Oct 7.

Department of Surgical Sciences University of Torino, Via Ventimiglia 3, 10126, Torino, Italy.

Background: The aim was to estimate the risk of subsequent extra-cervical Human Papillomavirus (HPV) related cancer in patients surgically treated for high grade cervical intraepithelial neoplasia (CIN 2-3). This is the first study in Italy investigating the occurrence of extra-cervical tumors in this cohort of patients.

Methods: 3184 patients surgically treated for CIN2-3 since 1992 at the Department of Surgical Sciences of University of Torino were considered. The risk of HPV-related cancer was calculated as Standardized Incidence Ratio (SIR), using as expected values tumour age specific incidence of resident population.

Results: 173 second primary cancer (SCPs) were identified. SIR to develop cancer after treatment for CIN2-3 was 2.2 (CI 95% 1.89-2.50). Among these occurrences, 10 are in HPV related sites: 1 anus (SIR = 1.8; 0.04-10.0), 3 vagina (SIR = 12.4; 2.56-36.3), 1 vulva (SIR = 1.7; 0.04-9.59), 5 oropharynx (SIR = 8.5; 2.76-19.8). Significant risk has been also recorded for pulmonary (SIR = 3.1; 0.70-5.27) and bladder (SIR = 4.05; 1.10-10.56), with smoking as possible cofactor. We also found increased risk for breast (SIR = 2.4; 2.07-2.84) and ovarian cancers (SIR = 2.1; 1.13-3.49), probably due to an higher adherence to spontaneous and programmed screening programs.

Conclusions: Our study supports the hypothesis of an increased risk of HPV-related tumours for CIN treated patients, mostly for CIN3. It is conceivable the need of early diagnosis for these cancers in this higher-risk populations.
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http://dx.doi.org/10.1186/s12885-020-07452-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542855PMC
October 2020

Management of Vulvar Cancer Precursors: A Survey of the International Society for the Study of Vulvovaginal Disease.

J Low Genit Tract Dis 2020 Oct;24(4):387-391

Department of Surgical Sciences, University of Torino, Torino, Italy.

Objective: The aim of the study was to determine how experts treat vulvar high-grade squamous intraepithelial neoplasia (VHSIL) and differentiated vulvar intraepithelial neoplasia (dVIN).

Method: A 26-question survey was designed through a literature review, reviewed by the Survey Committee of the International Society for the Study of Vulvovaginal Disease (ISSVD), and distributed to all ISSVD members via e-mail in January 2019.

Results: Overall, 90 of 441 physician members consented to participate and 78 of 90 were eligible to complete the survey. Most respondents were gynecologists (77%), followed by dermatologists (12%). Forty-five percent responded that their pathology was being reported using the 2015 ISSVD terminology of vulvar squamous intraepithelial lesions. The most common first-line treatments were as follows: unifocal VHSIL-excision (65%), multifocal VHSIL-imiquimod 5% (45%), VHSIL in a hair-bearing area-excision (69%), and clitoral disease-imiquimod 5% (47%). In the recurrent VHSIL, excision was favored (28%), followed by imiquimod 5% (26%) and laser (19%). Differentiated vulvar intraepithelial neoplasia was most often first treated with excision (82%), and more patients were referred to gynecologic oncology. Most patients were seen in follow-up at 3 months (range: 1 week-6 months). Sixty-seven respondents provided 26 different ways to follow treated patients, which were most commonly every 6 months for 2 years and then yearly (25%), followed by every 6 months indefinitely (18%).

Conclusions: Treatment of VHSIL and dVIN varies among vulvar experts with excision being the most common treatment, except in multifocal VHSIL where imiquimod is commonly used. There is wide variation in how patients are followed after treatment.
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http://dx.doi.org/10.1097/LGT.0000000000000559DOI Listing
October 2020

Clarification about vulvar cancer precursor lesions.

J Gynecol Obstet Hum Reprod 2021 03 17;50(3):101890. Epub 2020 Aug 17.

Obstetrics and Gynecology Department, Galilee Medical Center, Nahriya, Israel; Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel. Electronic address:

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http://dx.doi.org/10.1016/j.jogoh.2020.101890DOI Listing
March 2021

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis.

Cancers (Basel) 2020 Aug 4;12(8). Epub 2020 Aug 4.

Department of Surgical Sciences, University of Turin, 10126 Turin, Italy.

With this review, we provide the state of the art concerning brain metastases (BMs) from ovarian cancer (OC), a rare condition. Clinical, pathological, and molecular features, treatment options, and future perspectives are comprehensively discussed. Overall, a diagnosis of high-grade serous OC and an advanced disease stage are common features among patients who develop brain metastases. and gene mutations, as well as the expression of androgen receptors in the primary tumor, are emerging risk and prognostic factors which could allow one to identify categories of patients at greater risk of BMs, who could benefit from a tailored follow-up. Based on present data, a multidisciplinary approach combining surgery, radiotherapy, and chemotherapy seem to be the best approach for patients with good performance status, although the median overall survival (<1 year) remains largely disappointing. Hopefully, novel therapeutic avenues are being explored, like PARP inhibitors and immunotherapy, based on our improved knowledge regarding tumor biology, but further investigation is warranted.
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http://dx.doi.org/10.3390/cancers12082156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464214PMC
August 2020

The "scar" of a pandemic: Cumulative incidence of COVID-19 during the first trimester of pregnancy.

J Med Virol 2021 01 13;93(1):537-540. Epub 2020 Aug 13.

Gynecology and Obstetrics 1, Department of Surgical Sciences, School of Health and Science, University of Turin, Turin, Italy.

Congenitally- or perinatally-acquired viral infections can be harmful to the fetus but data are limited about prevalence and outcomes of coronavirus disease 2019 (COVID-19) disease during the first trimester of pregnancy. We report epidemiologic data from a study investigating a cohort of women who became pregnant just before or during the COVID-19 pandemic. We recruited 138 consecutive pregnant women attending for first trimester screening (11-13 weeks of gestation) at Sant'Anna Hospital, Turin, Piedmont, Italy, during the plateau and the falling phase of the COVID-19 epidemic curve. Patients were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M/immunoglobulin G antibody levels and SARS-CoV-2 detection in sera and nasopharyngeal swab samples. COVID-19 cumulative incidence during the first trimester was of 10.1% with high prevalence of asymptomatic patients (42.8%). Similar to the course of the disease in non pregnant adults, 80% to 90% of infections were not severe.The prevalence of reported symptoms was four-fold higher in SARS-CoV-2 positive patients (57%) than in those negative (13%) (P < .001), suggesting that direct self-testing should open doors to confirmatory testing for COVID-19. Our findings support the need for COVID-19 screening in early pregnancy in epidemic areas to plan materno-fetal health surveillance programs.
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http://dx.doi.org/10.1002/jmv.26267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361535PMC
January 2021

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

Gynecol Oncol 2020 06 7;157(3):656-663. Epub 2020 Apr 7.

Catania, Messina, and Enna Cancer Registry, Catania, Italy.

Objective: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.

Method: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models.

Results: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945.

Conclusions: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.
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http://dx.doi.org/10.1016/j.ygyno.2020.03.013DOI Listing
June 2020

Role of human papillomavirus infection in the etiology of vulvar cancer in Italian women.

Infect Agent Cancer 2020 1;15:20. Epub 2020 Apr 1.

2International Agency for Research on Cancer, Lyon, France.

Background: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract. We aimed to determine the mucosal high-risk human papillomavirus (HPV)-attributable fraction of VSCCs from Italian women using multiple markers of viral infections.

Methods: VSCCs and 8 metastatic lymph node samples from 107 Italian women were analyzed by a highly type-specific multiplex genotyping assay for the presence of DNA from 119 different HPVs. Tissues were further analyzed for HPV RNA and for upregulation of the cellular protein p16.

Results: The rate of mucosal HPV-related tumors defined by viral DNA and RNA positivity was low (7.8%). HPV16 was the most prevalent, followed by 53, 56, and 58. Only five (4.9%) p16-positive tumors were also positive for both viral DNA and RNA. One (14.3%) metastatic lymph node sample was positive for all three markers. DNA of cutaneous HPVs was detected in only two VSCCs, i.e. genus beta types 5 and 110.

Conclusion: A small proportion of Italian VSCCs is putatively HPV-related, i.e. positive for both viral DNA and RNA of the same type, thus reinforcing the importance of HPV vaccination. Moreover, this study suggests that a direct role of HPV from genus beta and gamma in vulvar carcinogenesis is unlikely.
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http://dx.doi.org/10.1186/s13027-020-00286-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110671PMC
April 2020

International Society for the Study of Vulvovaginal Disease 2019 Presidential Address.

Authors:
Mario Preti

J Low Genit Tract Dis 2020 07;24(3):334-335

Department of Surgical Sciences University of Torino, Torino, Italy.

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http://dx.doi.org/10.1097/LGT.0000000000000533DOI Listing
July 2020
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