Impact of Endometriomas and Deep Infiltrating Endometriosis on Pregnancy Outcomes and on First and Second Trimester Markers of Impaired Placentation.

Background and objective: Previous studies did not draw a definitive conclusion about the influence of the role of deep endometriosis (DE) and ovarian endometrioma (OE) as risk factor for developing adverse perinatal outcomes in patients affected by endometriosis. This study aimed to investigate if adverse fetal and maternal outcomes, and in particular the incidence of small for gestational age (SGA) infants, are different in pregnant women with OE versus pregnant women with DE without OE. Material and methods: This study was based on a retrospective analysis of a database collected prospectively. The population included in the study was divided into three groups: patients with OE, patients with DE without concomitant OE, and patients without endometriosis (controls). The controls were matched on the basis of age and parity. Demographic data at baseline and pregnancy outcomes were recorded. Results: There was no statistically significant difference in first trimester levels of PAPP-A, first and mid-pregnancy trimester mean Uterine Artery Doppler pulsatile index, estimated fetal weight centile, and SGA fetuses' prevalence for patients with OE, and those with DE without OE in comparison to health women; moreover, there was no statistically significant difference with regard to SGA birth prevalence, prevalence of preeclampsia, and five-minute Apgar score between these three groups. Conclusions: The specific presence of OE or DE in pregnant women does not seem to be associated with an increased risk of delivering an SGA infant. These data seem to suggest that patients with endometriosis should be treated in pregnancy as the general population, thus not needing a closer monitoring.

Predictors of Non-Sentinel Lymph Node Metastasis in Patients with Positive Sentinel Lymph Node in Early-Stage Cervical Cancer: A SENTICOL GROUP Study.

BACKGROUND: The goal of this study was to identify the risk factors for metastasis in the remaining non-sentinel lymph nodes (SLN) in the case of positive SLN in early-stage cervical cancer. METHODS: An ancillary analysis of two prospective multicentric databases on SLN biopsy for cervical cancer (SENTICOL I and II) was performed. Patients with early-stage cervical cancer (FIGO 2018 IA to IIA1), with bilateral SLN detection and at least one positive SLN after ultrastaging, were included. RESULTS: 405 patients were included in SENTICOL I and Il. Fifty-two patients had bilateral SLN detection and were found to have SLN metastasis. After pelvic lymphadenectomy, metastatic involvement of non-SLN was diagnosed in 7 patients (13.5%). Patients with metastatic non-SLN were older (51.9 vs. 40.8 years, p = 0.01), had more often lympho-vascular space invasion (LVSI) (85.7% vs. 35.6%, p = 0.03), and had more often parametrial involvement (42.9% vs. 6.7%, p = 0.003). Multivariate analysis retained age (OR = 1.16, 95% IC = [1.01-1.32], p = 0.03) and LVSI (OR = 25.97, 95% IC = [1.16-582.1], p = 0.04) as independently associated with non-SLN involvement. CONCLUSIONS: Age and LVSI seemed to be predictive of non-SLN metastasis in patients with SLN metastasis in early-stage cervical cancer. Larger cohorts are needed to confirm the results and clinical usefulness of such findings.

Influence of maternal oral microbiome on newborn oral microbiome in healthy pregnancies.

BACKGROUND: Periodontal disease and its bacteria can be responsible for pregnancy complications and transmission of periodontal bacteria from mother to newborn. METHODS: A salivary swab to 60 healthy, full-term newborns and their mothers was taken immediately after birth. The test was performed with Real Time PCR method to evaluate the expression of the gene through DNA amplification. The species considered were: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum ssp. RESULTS: The newborn oral microbiome was composed primarily by saprophytes (98.38 + 4.88%), just like the mothers (98.8 + 3.69%). There was a statistically significant difference of the total microbiological density in newborns and mothers (p = 0.0001). Maternal and neonatal oral microbiome had a correlated total microbiological density only in 33.3% (N = 20/60) of cases. The analysis of the oral microbiome showed a pathological composition only in 12/60 babies (20%). The most frequent detected specie in newborns was Fusobacterium nucleatum (9/12 babies, 75%), as well as for the mothers (53.3%). However, the pathogen was present both in baby and his mother only in 3 dyads. Porphyromonas gingivalis showed the highest association mother-baby (4/12 dyads, 33%). Porphyromonas gingivalis was the pathogen with the highest bacterial load in the 12 mothers. We found a statistically significant difference in the total load of Porphyromonas gingivalis in mothers and babies (p = 0.02). CONCLUSIONS: There was a statistically significant difference in the richness of the microbiome from newborns and mothers. Even comparing the microbiological density in the oral cavity of the individual mother-child pairs, we did not find a significant concordance. These results seem to suggest a low influence of maternal oral microbiome on the richness of the oral neonatal one. We didn't find mother-child concordance (p = 0.0001) in the presence of pathogenic periodontal micro-organisms. Fusobacterium nucleatum was the most frequent specie detected. Porphyromonas gingivalis instead was the bacteria with the higher possibility of transmission. In conclusion in our study maternal oral health doesn't affect healthy, full-term newborns' oral microbiome. Further studies are needed to understand the maternal influence on newborn's oral microbiome and its effects on babies long-term health.

Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study.

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

A comprehensive review of hormonal and biological therapies for endometriosis: latest developments.

INTRODUCTION: Endometriosis is a chronic benign estrogen-dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal contraceptives and progestins, currently available first-line treatments for endometriosis, are efficacious and well tolerated for treating disease-related pain, some women experience partial or no improvement of pain or its recurrence is frequent after discontinuation of the therapies. For these reasons, new drugs are under investigation for the treatment of endometriosis. AREAS COVERED: This review aims to give to the reader a complete and updated overview of hormonal and biological therapies for the treatment of endometriosis, underlining the latest developments in this field of research. EXPERT OPINION: Among the new drugs investigated, late clinical trials on gonadotropin-releasing hormone (GnRH) antagonists and aromatase inhibitors (AIs) have demonstrated the most promising results. For this reason, elagolix, a new GnRH-antagonist, recently received the approval by the Food and Drug Administration (FDA) for treating pain associated to endometriosis. Other drugs with innovative targets have been identified, but the majority of these compounds have only been evaluated in pre-clinical studies or early clinical trials. Thus, a further extensive clinical research is necessary to better elucidate their pharmacologic characteristics, their efficacy, and safety for the treatment of this benign chronic disease.

Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas.

INTRODUCTION: Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 30% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are often vague and nonspecific. Moreover, as ULMS have an aggressive biologic behavior, affected women frequently have very poor prognosis. AREAS COVERED: The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials. EXPERT OPINION: Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted.