A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding (p < .005), easy bruising (p = .028), fissures (p = .008), petechiae/splinter hemorrhages (p < .001), and bleeding/blistering or open sores (p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum (p = .013) and the perianal region (p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population (p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population (p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism as a Risk Factor for Endometriosis: A Retrospective Case-Control Study.

This study was conducted to evaluate the role of methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism as a risk factor for endometriosis. A retrospective case-control study was conducted from January 2020 to December 2022 on all patients attending the gynecological outpatient clinic of our institution who had performed an MTHFR polymorphisms test. Patients with endometriosis were considered cases, while those without endometriosis were considered controls. The presence of an MTHFR C677T homozygous polymorphism was defined as exposure. Risk factors for endometriosis were considered confounders in a binomial logistic regression, with endometriosis diagnosis as the dependent variable. Among the 409 included patients, 106 (25.9%) cases and 303 (74.1%) controls were identified. A higher rate of MTHFR C677T homozygous polymorphism was found in patients with endometriosis (24.5% vs. 15.8%, p = 0.0453), with an adOR of 1.889 (95% CI 1.076-3.318, p = 0.0269) at the binomial logistic regression. A history of no previous pregnancy was associated with an endometriosis diagnosis (adOR 2.191, 95% CI 1.295-3.708, p = 0.0035). An MTHFR C677T homozygous polymorphism could be considered a risk factor for endometriosis. Epigenetic modifications may be the most important mechanism explaining the observed association through the processes of altered DNA methylation and reduced activity of antioxidant systems.

Inter-rater agreement of CDC criteria and ASEPSIS score in assessing surgical site infections after cesarean section: a prospective observational study.

Objective: To assess and compare the inter-rater agreement of the CDC criteria and the ASEPSIS score in identifying surgical site infections after cesarean section. Methods: Prospective observational study including 110 patients subjected to a cesarean section at our institution. Surgical wounds were managed according to standard care and were photographed on the third, seventh, and thirtieth postoperative day or during any evaluation in case of complications. Three expert surgeons reviewed the prospectively gathered data and photographs and classified each wound using CDC criteria and the ASEPSIS score. The inter-rater agreements of CDC criteria and ASEPSIS score were determined with Krippendorff's Alpha with linear weights and compared with a confidence interval approach. Results: The weighted α coefficient for CDC criteria was 0.587 (95%CI, 0.411-0.763, p < 0.001, "moderate" agreement according to Altman's interpretation of weighted agreement coefficient), while the weighted α coefficient for the ASEPSIS score was 0.856 (95%CI, 0.733-0.980, p < 0.001, "very good" agreement). Conclusion: ASEPSIS score presents a "very good" inter-rater agreement for surgical site infections identification after cesarean, resulting in a more objective method than CDC criteria ("moderate" inter-rater agreement). ASEPSIS score could represent an objective tool for managing and monitoring surgical site infections after cesarean section, also by photographic evaluation.

Primary intestinal-type adenocarcinoma of the vulva. A case report and review of the literature.

Background: Primary non-squamous cell carcinomas of the vulva are rare entities including various tumor types. Among these, primary vulvar intestinal-type adenocarcinoma (vPITA) is extremely rare. Until 2021, less than twenty-five cases have been reported in the literature. Case presentation: We report a case of vPITA in a 63 years old woman with a histopathological diagnosis of signet-ring cell intestinal type adenocarcinoma at vulvar biopsy. Accurate clinical and pathological work-up excluded secondary metastatic localization, and vPITA was diagnosed. The patient was treated with radical vulvectomy and bilateral inguinofemoral dissection. Adjuvant chemo-radiotherapy was performed because of a positive lymph node. At 20 months follow-up the patient was alive and free of disease. Conclusion:  The prognosis of this very rare disease is unclear and optimal treatment is not well established. About 40% of clinical early-stage diseases reported in literature had positive inguinal nodes, more than in vulvar squamous cell carcinomas. A proper histopathologic and clinical diagnosis is mandatory to exclude secondary disease and to recommend an adequate treatment.

Extramammary Paget's Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications.

Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are represented by squamous lesions. Cervical adenocarcinoma causes about a quarter of cervical cancers. In contrast to squamous lesions, cervical glandular disease is HPV-negative in about 15-20% of cases. HPV-negative cervical adenocarcinomas typically present in advanced stages at clinical evaluation, resulting in a poorer prognosis. The overall and disease-free survival of glandular lesions is lower than that of squamous lesions. Treatment options require definitive treatments, as fertility-sparing is not recommended. Moreover, the impact of HPV vaccination and primary HPV screening is likely to affect these lesions less; hence, the interest in this challenging topic for clinical practice. An updated review focusing on clinical and molecular characterization, prognostic factors, and therapeutic options may be helpful for properly managing such cervical lesions.

Effect of the mode of delivery on the risk of endometriosis recurrence: a retrospective cohort study.

OBJECTIVE: To evaluate the risk of endometriosis recurrence according to the mode of delivery (cesarean section vs. vaginal birth) in patients who had become pregnant with a live birth after surgery for endometriosis. DESIGN: A retrospective cohort study. A Cox proportional-hazards regression was performed to evaluate the risk factors for endometriosis recurrence at 36 months of follow-up after the last pregnancy. SETTING: Academic hospital. PATIENT(S): Patients who have had ≥1 pregnancy with a live birth following conservative surgery for ovarian endometriosis performed from January 2009 to December 2016 at our institution. INTERVENTION(S): Patients who underwent ≥1 cesarean section after surgery for endometriosis. MAIN OUTCOME MEASURES: The recurrence rate of endometriosis after live-birth pregnancies obtained after the first surgery for endometriosis. RESULTS: Patients with a history of ≥1 cesarean section after surgery for endometriosis have a higher risk of endometriosis recurrence than the patients who have had a vaginal birth, with an adjusted hazard ratio of 2.25 (95% confidence interval, 1.27-3.96). CONCLUSION: A cesarean section after surgery for endometriosis is associated with a twofold high risk of endometriosis recurrence with respect to vaginal birth. A different follow-up approach may be needed in those patients, and avoiding inappropriate indications for cesarean sections in pregnant patients with a history of surgery for endometriosis is necessary.

Histopathological findings in hysterectomy for cervical stenosis in postmenopausal women: A retrospective case series.

OBJECTIVE: To analyze the histopathological findings in postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis, evaluating the incidental findings of preinvasive or invasive uterine and cervical disease. METHODS: Retrospective case series of postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis at Gynecological Oncology Unit of Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico Aviano-National Cancer Institute from January 2014 to January 2021. RESULTS: During the study period, 36 women underwent hysterectomy for postsurgical cervical stenosis at our institution. Cervical stenosis occurred 10.2 ± 5.6 years from the onset of menopause. In particular, 26 (72.2%) patients underwent a single loop electrosurgical excision procedure or carbon dioxide (CO2)-laser conization before the onset of stenosis. The remaining 10 (27.8%) women had multiple surgical excision before the onset of stenosis. At the final histopathological analysis, 17 (47.2%) patients had a preinvasive or invasive gynecological disease. In particular, 9 cases of cervical disease (including 1 case of endocervical squamous cell carcinoma pT1a) and 6 cases of endometrial hyperplasia emerged. Also, 2 cases of tubo-ovarian diseases were found. CONCLUSIONS: Postsurgical cervical stenosis is a challenging clinical condition, especially in women treated for cervical intraepithelial neoplasia or microinvasive cervical cancer. As shown, cervical stenosis can prevent an adequate gynecological follow-up and a prompt diagnosis of malignancies. Therefore, postmenopausal women with cervical stenosis should be carefully counseled, and hysterectomy could be a reasonable option, especially in those cases in which a conservative approach is not feasible, failed, or is not accepted by the patient.

Hysterectomy for cervical intraepithelial neoplasia: A retrospective observational multi-institutional study.

OBJECTIVE: To analyze the clinical management, the outcomes, and the trend in hysterectomy rates (HR) in patients who underwent this procedure for cervical intraepithelial neoplasia (CIN). METHODS: Multicentric retrospective observational study conducted on 242 patients who underwent hysterectomy for CIN between 2010 and 2020 in nine Italian institutions. Hysterectomy for invasive or micro-invasive neoplasia, sub-total hysterectomy, or trachelectomy were excluded. RESULTS: A significant increase in the trend of HR for CIN was recorded (P = 0.002, r = 0.81; C.I. 95%: 0.415-0.949); HR increased from 0.46% in the year 2010 to 3.32% in 2020. The mortality rate was 0.4%, and 5% had operative complications. On definitive histopathology examination, a CIN of any grade was recorded in 71.5% of cases, and an occult invasive cancer in 1.24%. No pathology or CIN1 was found in 26.8% of cases, suggesting over treatment. During follow-up, a vaginal lesion was recorded in 5% of cases. CONCLUSION: A significant increase in the number of hysterectomies performed for CIN in the last 10 years was recorded. Hysterectomy for CIN can lead to complications, risk of the onset of vaginal lesions, and risk of overtreatment, and remains, in the first instance, an unacceptable treatment, to be proposed only after adequate counseling.

Malignant Transformation of Postmenopausal Endometriosis: A Systematic Review of the Literature.

Objective: This study aimed to systematically review the existing literature on malignant transformation of postmenopausal endometriosis to provide information about patient characteristics, hormonal replacement therapy (HRT) use, and outcomes over a period of 52 years (1969-2021). Methods: According to PRISMA guidelines, we searched for (endometriosis OR endometriotic) AND (cancer OR malignancy OR malignant transformation) AND (menopause OR menopausal OR postmenopause OR postmenopausal) in Pubmed (all fields) (accessed on 12 February 2021) and Scopus (Title/Abstract/Keywords) (accessed on 12 February 2021) databases. The only filter used was the English language. Relevant articles were obtained in full-text format and screened for additional references. Eligibility/inclusion criteria: studies including full case description of malignant transformation of endometriosis-related lesions in postmenopause. Results: 75 studies, including 90 cases, were retrieved. The mean age was 55.8 ± 8.5 years. Overall, about 65% of women had a positive personal history of endometriosis/adenomyosis, and 64% of women underwent previous hysterectomy ± bilateral salpingo-oophorectomy. Forty-nine of 74 women used HRT (66.2%). Among the women who used HRT, estrogen-only treatment was taken by approximately 75%. Duration of HRT was longer than five years in 63.3% of cases. About 70% of subjects had histology of endometrioid adenocarcinoma or clear cell carcinoma. Follow-up outcome, available for 61 women, showed a survival rate of 78.7%, recurrence of 9.8%, death of 11.5%. The duration of follow-up had a median of 12 months (interquartile range, 6.75-25 months). Interestingly, over the years of case publication there was a significant inverse correlation with previous history of endometriosis (r = -0.28, p = 0.007), HRT use (r = -0.31, p = 0.006), and previous definitive surgery (r = -0.42, p < 0.001). Conclusions: In the malignant transformation of postmenopausal endometriosis, there are some recurrent clinical conditions: previous endometriosis, major definitive surgery before menopause, and estrogen-only HRT for a relatively long time. However, these clinical conditions have shown a drastic decrease over time. This could likely be the consequence of different attitudes and management of gynecologists linked to up-to-date scientific evidence about the use of major surgery in gynecological pathologies. Malignant transformation of postmenopausal endometriosis is a clinical challenge to be explored further.