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.

Raf kinase inhibitor protein expression in smooth muscle tumours of the uterus: a diagnostic marker for leiomyosarcoma?

RESEARCH QUESTION: What is the expression pattern of Raf kinase inhibitory protein (RKIP) in different subtypes of leiomyoma (usual type, cellular, apoplectic or haemorrhagic leiomyoma, leiomyoma with bizarre nuclei and lipoleiomyoma) and leiomyosarcoma specimens, and what is its biological role in leiomyosarcoma cells? DESIGN: Leiomyoma and leiomyosarcoma specimens underwent immunohistochemistry staining. Leiomyosarcoma SK-LMS-1 cell line was RKIP knocked down and RKIP overexpressed, and cell viability, wound healing migration and clonogenicity assays were carried out. RESULTS: A higher immunohistochemical expression of RKIP was observed in bizarre leiomyomas, than in usual-type leiomyomas. Decreased expression was also found in cellular leiomyoma, with generally absent staining in leiomyosarcomas. Upon RKIP expression manipulation in SK-LMS-1 cell line, no major differences were observed in cell viability and migration capacity over time. RKIP knockout, however, resulted in a significant increase in the cell's ability to form colonies (P = 0.011). CONCLUSION: RKIP distinct expression pattern among leiomyoma histotype and leiomyosarcoma, and its effect on leiomyosarcoma cells on colony formation, encourages further studies of RKIP in uterine smooth muscle disorders.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment-Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology.

OBJECTIVE: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. METHODS: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed. RESULTS: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). CONCLUSION: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.

Atypical Endometrial Hyperplasia and Concurrent Cancer: A Comprehensive Overview on a Challenging Clinical Condition.

The present review regarding atypical endometrial hyperplasia (AEH) focused on the main debated factors regarding this challenging clinical condition: (i) predictive variables of occult endometrial cancer (EC); (ii) the rate of EC underestimation according to different endometrial sampling methods; and (iii) the appropriateness of lymph node status assessment. When cancer is detected, approximately 90% of cases include low-risk EC, although intermediate/high-risk cases have been found in 10-13% of women with cancer. Older age, diabetes, high BMI, and increased endometrial thickness are the most recurrent factors in women with EC. However, the predictive power of these independent variables measured on internal validation sets showed disappointing results. Relative to endometrial sampling methods, hysteroscopic endometrial resection (Hys-res) provided the lowest EC underestimation, ranging between 6 and 11%. Further studies, including larger sample sizes of women undergoing Hys-res, are needed to confirm these findings. These data are urgently needed, especially for female candidates for conservative treatment. Finally, the evaluation of lymph node status measured on 660 of over 20,000 women showed a lymph node positivity of 2.3%. Although there has been an increase in the use of this procedure in AEH in recent years, the present data cannot recommend this option in AEH based on a cost/risk/benefit ratio.

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.

The In Vitro Effects of Romina Strawberry Extract on 3D Uterine Leiomyosarcoma Cells.

Leiomyosarcoma is an aggressive soft tissue sarcoma derived from the smooth muscle cells of the uterus. We tested the effect of Romina strawberry extract treatment on three-dimensional cultured uterine leiomyosarcoma cells. We established 3D cultures in agarose gel, where the cells seeded were able to form spheroids. We performed the observation and counting of the spheroids with a phase-contrast optical microscope, finding a decrease in the number of spheroids formed in the plates after 24 and 48 h treatment with 250 µg/mL of cultivar Romina strawberry extract. We also characterized the spheroids morphology by DNA binding fluorescent-stain observation, hematoxylin and eosin stain, and Masson's trichrome stain. Finally, the real-time PCR showed a reduced expression of extracellular matrix genes after strawberry treatment. Overall, our data suggest that the fruit extract of this strawberry cultivar may be a useful therapeutic adjuvant for the management of uterine leiomyosarcoma.

In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix and HPV-Type Impact: Pathologic Features, Treatment Options, and Follow-Up Outcomes-Cervical Adenocarcinoma Study Group (CAS-Group).

It is unknown whether human papillomavirus (HPV) status impacts the prognosis of early stage cervical glandular lesions. This study assessed the recurrence and survival rates of in situ/microinvasive adenocarcinomas (AC) according to HPV status during a 5-year follow-up. The data were retrospectively analyzed in women with available HPV testing before treatment. One hundred and forty-eight consecutive women were analyzed. The number of HPV-negative cases was 24 (16.2%). The survival rate was 100% in all participants. The recurrence rate was 7.4% (11 cases, including four invasive lesions (2.7%)). Cox proportional hazards regression showed no difference in recurrence rate between HPV-positive and HPV-negative cases (p = 0.148). HPV genotyping, available for 76 women and including 9/11 recurrences, showed a higher relapse rate for HPV-18 than HPV-45 and HPV-16 (28.5%, 16.6%, and 9.52%, p = 0.046). In addition, 60% and 75% of in situ and invasive recurrences, respectively, were HPV-18 related. The present study showed that most ACs were positive for high-risk HPV, and the recurrence rate was unaffected by HPV status. More extensive studies could help evaluate whether HPV genotyping may be considered for recurrence risk stratification in HPV-positive cases.

High levels of hypusinated eIF5A in leiomyoma and leiomyosarcoma pathologies: a possible novel therapeutic target.

RESEARCH QUESTION: Is the hypusinated form of the eukaryotic translation initiation factor 5A (EIF5A) present in human myometrium, leiomyoma and leiomyosarcoma, and does it regulate cell proliferation and fibrosis? DESIGN: The hypusination status of eIF5A in myometrial and leiomyoma patient-matched tissues was evaluated by immunohistochemistry and Western blotting as well as in leiomyosarcoma tissues by immunohistochemistry. Myometrial, leiomyoma and leiomyosarcoma cell lines were treated with N1-guanyl-1,7-diaminoheptane (GC-7), responsible for the inhibition of the first step of eIF5A hypunization, and the proliferation rate was determined by MTT assay; fibronectin expression was analysed by Western blotting. Finally, expression of fibronectin in leiomyosarcoma tissues was detected by immunohistochemistry. RESULTS: The hypusinated form of eIF5A was present in all tissues examined, with an increasing trend of hypusinated eIF5A levels from normal myometrium to neoplastic benign leiomyoma up to neoplastic malignant leiomyosarcoma. The higher levels in leiomyoma compared with myometrium were confirmed by Western blotting (P = 0.0046). The inhibition of eIF5A hypusination, with GC-7 treatment at 100 nM, reduced the cell proliferation in myometrium (P = 0.0429), leiomyoma (P = 0.0030) and leiomyosarcoma (P = 0.0044) cell lines and reduced the expression of fibronectin in leiomyoma (P = 0.0077) and leiomyosarcoma (P = 0.0280) cells. The immunohistochemical staining of leiomyosarcoma tissue revealed that fibronectin was highly expressed in the malignant aggressive (central) part of the leiomyosarcoma lesion, where hypusinated eIF5A was also highly represented. CONCLUSIONS: These data support the hypothesis that eIF5A may be involved in the pathogenesis of myometrial benign and malignant pathologies.

A survey on the current practice of indicating an elective cesarean after a previous myomectomy.

OBJECTIVE: The objective of this study was to evaluate the attitude of obstetricians/gynecologists toward indicating an elective cesarean delivery in pregnant patients with a previous myomectomy. MATERIALS AND METHODS: Web-based multiple-choice questions survey evaluating the attitude to indicate a cesarean with a composite summated score (range 56-280) from a 56-item Likert scale: score 56-112: weak attitude, 113-168: moderate, 169-224: strong, and 225-280: very strong. The reliability of the score (internal consistency) was evaluated with Cronbach's alpha coefficient. The association between the score and participants' characteristics was determined with a bivariate analysis followed by linear regression analysis. The "global importance" of each risk factor was defined as the prevalence of the answers: "moderately important", "very important", and "extremely important" on the Likert scale. Factors with a "global importance" >75% were considered "crucial" in influencing the choice to indicate a cesarean. RESULTS: One-hundred-twenty obstetricians/gynecologists responded (response rate 70.6%). The mean ± SD composite summated score was 137 ± 31; 30 (25.0%) participants presented a "weak attitude to cesarean", 68 (56.7%) a "moderate attitude", 22 (18.3%) a "strong attitude", and none a "very strong attitude". The Cronbach's alpha was 0.934 (high internal consistency). A self-reported number of myomectomies performed per year >50 was associated with a lower score (-25 points, 95% CI -50 to -1, p = 0.04). Eight criteria resulted "crucial" in indicating a cesarean: opening of the endometrial cavity, monopolar electrosurgery, time surgery-pregnancy <6 months, 2+ previous myomectomies, hematoma formation in the surgical wound, 3+ removed fibroids, and a FIGO4 or FIGO3 removed fibroid. CONCLUSIONS: Obstetricians/gynecologists are cautious to indicate a cesarean in pregnant patients with a previous myomectomy, except for cases at hypothetic high-risk for uterine rupture, mainly supported by weak evidence. Information to patients and among clinicians is crucial to avoid inappropriate cesarean indications.KEY MESSAGESObstetricians/gynecologists are cautious to indicate a cesarean in pregnant patients with a previous myomectomy.Information to patients and among clinicians is crucial to avoid inappropriate cesarean indications in pregnant patients with a previous myomectomy.

Gestational Diabetes Mellitus and Small-for-Gestational-Age: An Insight into the Placental Molecular Biomarkers.

Gestational diabetes mellitus (GDM) and small-for-gestational-age (SGA) are two metabolic-related diseases that could affect women during pregnancy. Considering that the chorionic villi (CVs) are crucial structures for the feto-maternal exchange, the alterations in their conformation have been linked to an imbalanced metabolic environment of placenta. In this study, a multidisciplinary approach has been carried out to describe the changes occurring in the placental CVs of GDM and SGA patients. The results revealed higher levels of superoxide dismutase 1 (SOD-1) and catalase (CAT), especially in the GDM placentae, which could be correlated with the hyperglycemic environment characteristic of this pathology. Furthermore, spectroscopy and histologic analyses revealed that both pathologies modify the placental lipid composition altering its structure. However, SGA induces lipid peroxidation and reduces collagen deposition within the CVs. Since the endocannabinoid system (ECS) is involved in placentation and different metabolic activities, the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV-1) were analyzed. No changes have been observed either at general or specific levels in the CVs comparing control and pathological samples, suggesting the non-involvement of the cannabinoid system in these two pathologies.

Microbiome Changes in Pregnancy Disorders.

The human microbiota comprises all microorganisms, such as bacteria, fungi, and viruses, found within a specific environment that live on our bodies and inside us. The last few years have witnessed an explosion of information related to the role of microbiota changes in health and disease. Even though the gut microbiota is considered the most important in maintaining our health, other regions of the human body, such as the oral cavity, lungs, vagina, and skin, possess their own microbiota. Recent work suggests a correlation between the microbiota present during pregnancy and pregnancy complications. The aim of our literature review was to provide a broad overview of this growing and important topic. We focused on the most significant changes in the microbiota in the four more common obstetric diseases affecting women's health. Thus, our attention will be focused on hypertensive disorders, gestational diabetes mellitus, preterm birth, and recurrent miscarriage. Pregnancy is a unique period in a woman's life since the body undergoes different adaptations to provide an optimal environment for fetal growth. Such changes also involve all the microorganisms, which vary in composition and quantity during the three trimesters of gestation. In addition, special attention will be devoted to the potential and fundamental advances in developing clinical applications to prevent and treat those disorders by modulating the microbiota to develop personalized therapies for disease prevention and tailored treatments.

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.

Monitoring the activities of Italian colposcopy clinics before and during the COVID-19 pandemic.

OBJECTIVE: To evaluate the impact of healthcare reorganization during the severe acute respiratory syndrome coronavirus 2 pandemic on Italian colposcopy clinic activities, focusing on cervical excision procedures, follow-ups for conservative management of low-grade lesions, and follow-ups post cervical excision. METHODS: Retrospective study conducted in 14 Italian colposcopy clinics. The number and clinical characteristics of cervical excisions, follow-ups for conservative management of low-grade lesions, and follow-ups after cervical excision were compared between the period March 1, 2019 to February 29, 2020 (pre-pandemic) and March 1, 2020 to February 28, 2021 (pandemic) with a Poisson regression analysis. RESULTS: In the pandemic period, the number of cervical excisions was reduced by 8.8% (95% confidence interval [CI]=-15.6% to -2%; p=0.011). Excisions were less frequently performed in the operating room (-35.1%; 95% CI=-47.6% to -22.6%; p<0.001), the number of patients from spontaneous screening was reduced by -14.0% (95% CI=-23.4% to -4.6%; p=0.003), and the CO2-laser technique was used less frequently (-30%; 95% CI=-45.1% to -15.0%; p<0.001). As compared to the pre-pandemic period, the number of follow-ups for conservative management of low-grade lesions was reduced by -26.7% (95% CI=-39.0% to -14.4%; p<0.001), and the follow-up appointments after cervical excision were reduced by -51.0% (95% CI=-58.1% to -43.9%; p<0.001). CONCLUSION: The most significant impact of the healthcare reorganization during the coronavirus disease 2019 pandemic was on follow-ups after cervical excision. The resumption of disrupted activities should follow a risk-based prioritization, starting from women in follow-up after cervical excision. It is advisable that the trend of performing cervical excision as an outpatient procedure is maintained in the post-pandemic period.

Should attention be paid to the cone depth in the fully visible transformation zone? Retrospective analysis of 517 patients with cervical intraepithelial neoplasia grade 3.

OBJECTIVE: The predictors of positive endocervical margin (EM) and a cone-depth cutoff value are not established in the fully visible transformation zone (TZ). The present study aimed to assess the independent variables associated with positive EM in women with high-grade cervical intraepithelial neoplasia (CIN) and fully visible TZ. METHODS: The current investigation was a retrospective study including women with fully visible TZ and CIN 3 cone histology between 2014 and 2019. The sample was divided into women with positive versus those with negative EM. Univariate and multivariate analyses were performed. Finally, receiver operating characteristic curve analysis was also used. RESULTS: A total of 123 of 517 women (23.8%) showed positive EM at conization. Multivariate analysis found a positive association with type 2 TZ (odds ratio [OR], 2.17 [95% confidence interval (CI), 1.19-3.94]) and lesion extension ≥2 cervical quadrants (OR, 35.57 [95% CI, 17.96-70.45]). Cone depth was inversely related to positive EM (OR, 0.71 [95% CI, 0.63-0.80]). In women with type 2 TZ and lesion extension ≥2 cervical quadrants, the cutoff value was achieved at 8-mm cone depth (area under the curve, 0.79 [95% CI, 0.67-0.90]). CONCLUSION: In women with high-grade CIN and fully visible TZ undergoing conization, the lesion extension and the TZ subtype (1 or 2) should be considered. A no less than 9-mm cone depth provided a fair predictive value in achieving free EM.

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

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.

Preeclampsia Correlates with an Increase in Cannabinoid Receptor 1 Levels Leading to Macromolecular Alterations in Chorionic Villi of Term Placenta.

Preeclampsia is a human pregnancy-specific disease characterized by abnormal placentation that usually presents with maternal hypertension and proteinuria. The main hallmark of preeclampsia, impaired trophoblast migration, and the subsequent disruption of uterine arteries remodeling lead to several molecular alterations in the placental compartments with those occurring in the chorionic villi being of the utmost importance. Given the essential role of the endocannabinoid system during preimplantation and trophoblast migration, we have combined the histological and hyperspectral imaging analyses to shed light on the involvement of two cannabinoid receptors in the macromolecular alterations related to preeclampsia. The results obtained by immunohistochemistry showed a significant increase in the protein levels of cannabinoid receptor 1 (CB1) in the preeclamptic chorionic villi. However, no changes were reported regarding transient receptor potential vanilloid 1 (TRPV-1) levels either in the bulk placental samples or chorionic villi when comparing control and preeclamptic patients. Histological analysis and Fourier-transform infrared spectroscopy (FTIRI) showed an increase in collagen deposition together with higher levels of lipid peroxidation and phosphorylated compounds in the pathological villi. Since CB1 enhancement has been described as promoting fibrosis and oxidative stress in several tissues, we proposed that the higher receptor abundance in preeclampsia could be triggering similar molecular effects in preeclamptic term placentas.

Pathogenic Role of the Sphingosine 1-Phosphate (S1P) Pathway in Common Gynecologic Disorders (GDs): A Possible Novel Therapeutic Target.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid, noteworthy for its involvement both in the modulation of various biological processes and in the development of many diseases. S1P signaling can be either pro or anti-inflammatory, and the sphingosine kinase (SphK)-S1P-S1P receptor (S1PR) axis is a factor in accelerating the growth of several cells, including endometriotic cells and fibrosis. Gynecologic disorders, including endometriosis, adenomyosis, and uterine fibroids are characterized by inflammation and fibrosis. S1P signaling and metabolism have been shown to be dysregulated in those disorders and they are likely implicated in their pathogenesis and pathophysiology. Enzymes responsible for inactivating S1P are the most affected by the dysregulation of S1P balanced levels, thus causing accumulation of sphingolipids within these cells and tissues. The present review highlights the past and latest evidence on the role played by the S1P pathways in common gynecologic disorders (GDs). Furthermore, it discusses potential future approaches in the regulation of this signaling pathway that could represent an innovative and promising therapeutical target, also for ovarian cancer treatment.

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.