A Psychological Point of View on Endometriosis and Quality of Life: A Narrative Review.

Endometriosis is a chronic gynecological disorder with a multifactorial etiology that has not yet been fully elucidated. What is known, however, are the pathological tissue dynamics that lead to the complex symptoms that women suffer from. The known symptoms are mainly fertility problems and pain. Both dimensions have an impact that varies from case to case, but that is certainly decisive concerning a woman's health, specifically by affecting the overall quality of life (QoL). In this publication, we will deal with the descriptive aspects of endometriosis's pathology and then present a review of the aspects impacting QoL and their psycho-social consequences. Finally, the experience of pain in the context of the mind-brain-body relationship will be discussed, describing the complexity of this dimension and emphasizing the importance of a multi-professional approach that considers the relevance of the contribution that a psychotherapy intervention based on up-to-date neurobiological models can make for women with endometriosis. A review of the literature and current knowledge on the neural and psychological aspects of pain lead to the conclusion that it is of the utmost importance to provide informed psychological support, alongside medical treatments and sexual counseling, to patients with endometriosis.

Subserosal pregnancy: Systematic review with proposal of new diagnostic criteria and ectopic pregnancy classification.

Ectopic pregnancy (EP) is a pregnancy where the growing blastocyst implants outside the endometrial cavity. EP account approximately for 0.5-1% of all pregnancies, and extrauterine implant is the leading cause of woman mortality in the first trimester of gestation. Non-tubal pregnancies (NTP) account for less than 5% of all EP. NTP are accompanied by a 7-8 times higher risk of maternal mortality when compared to tubal pregnancies, and their treatment might sometimes be very challenging. Subserosal pregnancy (SP) has been defined as rare variant of intramural pregnancy, where a portion of the gestational sac was surrounded only by the serosa of the uterus. Whereas the treatment of the ectopic pregnancies is crucial for patients' lives and for adequate fertility sparing and considering the need for surgical treatment in many cases, an early diagnosis is important; thus we believe it g might be useful to define some criteria to guide subserosal pregnancy identification, and to distinguish it from other types of non-tubal ectopic pregnancy. A systematic review on Pubmed, Scopus, Web of Science and Google Scholar was performed. Case reports, randomized controlled trials, prospective controlled studies, prospective cohort studies, retrospective studies, and case series were considered eligible. In all databases mentioned were considered manuscripts published from 1990 up to March 2023. Only four articles were eligible for inclusion in this review. All patients underwent to surgical management in laparoscopy. The main risk factors for this type of ectopic pregnancy were previous uterine surgery with opening of the endometrial cavity and assisted reproductive techniques procedures. Considering our results, we propose new classification and diagnostic criteria for subserosal pregnancy, to distinguish it from other types of non-tubal ectopic pregnancies with the aim to preserve fertility following the most correct management.

In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells.

BACKGROUND: The identification of novel therapeutic strategies for ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with the cysteine-dependent deubiquitinating enzyme (DUB) UCHL5, thus affecting the ubiquitin-proteasome-dependent degradation of proteins. METHODS: 2c phenotypic/molecular effects were studied in two OC 2D/3D culture models and in a mouse xenograft model. Furthermore, we propose an in silico model of 2c interaction with DUB-UCHL5. Finally, we have tested the effect of 2c conjugated to several linkers to generate 2c/derivatives usable for improved drug delivery. RESULTS: 2c effectively impairs the OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs proteasome activity and triggers apoptosis, most likely by interacting with DUB-UCHL5. We also propose a mechanism for the interaction with DUB-UCHL5 via an in silico evaluation of the enzyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcription factor E2F1. Eventually, 2c activity is often retained after the conjugation with linkers. CONCLUSION: Our data strongly support the potential therapeutic value of 2c/derivatives in OC.

The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer.

Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions-data-dependent acquisition (DDA) and data-independent acquisition (DIA)-on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM.

Genital Dysbiosis and Different Systemic Immune Responses Based on the Trimester of Pregnancy in SARS-CoV-2 Infection.

Respiratory infections are common in pregnancy with conflicting evidence supporting their association with neonatal congenital anomalies, especially during the first trimester. We profiled cytokine and chemokine systemic responses in 242 pregnant women and their newborns after SARS-CoV-2 infection, acquired in different trimesters. Also, we tested transplacental IgG passage and maternal vaginal-rectal microbiomes. IgG transplacental passage was evident, especially with infection acquired in the first trimester. G-CSF concentration-involved in immune cell recruitment-decreased in infected women compared to uninfected ones: a beneficial event for the reduction of inflammation but detrimental to ability to fight infections at birth. The later the infection was acquired, the higher the systemic concentration of IL-8, IP-10, and MCP-1, associated with COVID-19 disease severity. All infected women showed dysbiosis of vaginal and rectal microbiomes, compared to uninfected ones. Two newborns tested positive for SARS-CoV-2 within the first 48 h of life. Notably, their mothers had acute infection at delivery. Although respiratory infections in pregnancy are reported to affect babies' health, with SARS-CoV-2 acquired early during gestation this risk seems low because of the maternal immune response. The observed vaginal and rectal dysbiosis could be relevant for neonatal microbiome establishment, although in our series immediate neonatal outcomes were reassuring.

Flagellar beating forces of human spermatozoa with different motility behaviors.

BACKGROUND: One of the causes of male infertility is associated with altered spermatozoa motility. These sperm features are frequently analyzed by image-based approaches, which, despite allowing the acquisition of crucial parameters to assess sperm motility, they are unable to provide details regarding the flagellar beating forces, which have been neglected until now. RESULTS: In this work we exploit Fluidic Force Microscopy to investigate and quantify the forces associated with the flagellar beating frequencies of human spermatozoa. The analysis is performed on two groups divided according to the progressive motility of semen samples, as identified by standard clinical protocols. In the first group, 100% of the spermatozoa swim linearly (100% progressive motility), while, in the other, spermatozoa show both linear and circular motility (identified as 80 - 20% progressive motility). Significant differences in flagellar beating forces between spermatozoa from semen sample with different progressive motility are observed. Particularly, linear motile spermatozoa exhibit forces higher than those with a circular movement. CONCLUSIONS: This research can increase our understanding of sperm motility and the role of mechanics in fertilization, which could help us unveil some of the causes of idiopathic male infertility.

Protective role of complement factor H against the development of preeclampsia.

Pregnancy is an immunologically regulated, complex process. A tightly controlled complement system plays a crucial role in the successful establishment of pregnancy and parturition. Complement inhibitors at the feto-maternal interface are likely to prevent inappropriate complement activation to protect the fetus. In the present study, we aimed to understand the role of Factor H (FH), a negative regulator of complement activation, in normal pregnancy and in a model of pathological pregnancy, i.e. preeclampsia (PE). The distribution and expression of FH was investigated in placental tissues, various placental cells, and in the sera of healthy (CTRL) or PE pregnant women via immunohistochemistry, RT-qPCR, ELISA, and Western blot. Our results showed a differential expression of FH among the placental cell types, decidual stromal cells (DSCs), decidual endothelial cells (DECs), and extravillous trophoblasts (EVTs). Interestingly, FH was found to be considerably less expressed in the placental tissues of PE patients compared to normal placental tissue both at mRNA and protein levels. Similar results were obtained by measuring circulating FH levels in the sera of third trimester CTRL and PE mothers. Syncytiotrophoblast microvesicles, isolated from the placental tissues of PE and CTRL women, downregulated FH expression by DECs. The present study appears to suggest that FH is ubiquitously present in the normal placenta and plays a homeostatic role during pregnancy.

Pelvic floor function after third and fourth degree perineal lacerations: a case-control study on quality of life.

BACKGROUND: The primary aim of this study was to compare the quality of life between women with obstetric anal sphincter injury (OASI) and women with intact perineum or minor vaginal tears following their first vaginal birth through a validated urogynaecological questionnaire. As a secondary aim, we wanted to identify the specific symptoms for pelvic floor dysfunction after a vaginal birth. METHODS: One hundred thirty-three cases (III- and IV-degree vaginal tears) and 133 controls (intact perineum or I- and II-degree vaginal tear) were asked to fill the PFDI-20 condition-specific and quality of life survey at three and 12 months after vaginal delivery. The survey evaluates pelvic floor dysfunction symptoms through three subsections: the Pelvic Organ Prolapse Distress Inventory (POPDI), the Colorectal-Anal Distress Inventory (CRADI), and Urinary Distress Inventory, (UDI). The scoring system ranges from 0 (no distress) to 100 (maximum distress) for each subsection, subsequently summed up to obtain the summary score (0 to 300). The patients recruited were asked to complete the survey at 3- and 12-months follow-up visit. Accordingly, data collection started. Categorical variables were subjected to Chi-square test or Fisher's Exact test. Quantitative variables were compared through Student's t-test or Mann-Whitney test. RESULTS: All surveys have shown statistically significant differences when comparing the cases to the control group. Consequently, PFDI-20 has shown a strong correlation between III- and IV-grade lacerations and pelvic floor dysfunction persistence at 12 months after delivery. Intestinal symptoms were the most reported disturbances among women with previous OASI. CONCLUSIONS: Major vaginal tears have demonstrated to have a strong impact on women's quality of life up to a follow-up of 12 months. The use of PFDI-20 questionnaire is a useful and valid tool in the diagnosis and follow-up of genital prolapse, fecal and urinary incontinence in primiparous women with a history of OASI. Thus, its application in clinical practice can help offering the most adequate rehabilitative treatment.

Use of Indocyanine Green to Evaluate Ovarian Perfusion After Laparoscopic Detorsion. A Step-By-Step Demonstration Video.

OBJECTIVE: Demonstrate the usefulness of using indocyanine green after laparoscopic ovarian detorsion to save the ovary. DESIGN: A step-by-step video demonstration of a surgical technique. SETTING: Ovarian torsion is one of the most common gynecological emergencies, mainly affecting patients younger than 20 years of age [1], and causes 2% to 7% of acute abdomens [2]. It is not advisable to routinely perform ovariectomy even with a necrotic ovary appearance [1]. Furthermore only in a small percentage of cases (16%) necrosis has been confirmed histologically [2]. Some studies have demonstrated that using indocyanine green to evaluate ovarian perfusion is inexpensive, low risk, and easily reproducible [3-5]. INTERVENTIONS: A 17-year-old patient was referred to our hospital for acute abdominal pain. Ultrasound revealed ovarian torsion; therefore, the patient underwent surgical treatment. During laparoscopy, the presence of a right ovarian torsion was confirmed. A lesion compatible with a hemorrhagic corpus luteum of 6 cm was present on the ovary affected. Before ovarian detorsion, indocyanine green was administered intravenously at a 0.5 mg/kg dose. The first aspect noted was the total lack of ovarian vascularization; then ovarian detorsion was performed. At this point, using technology of Rubina (KARL STORZ SE & Co. KG, Tuttlingen, Germany), it was possible to highlight the progressive ovarian revascularization. Ovarian reperfusion occurred starting from the ovarian hilum and ending at the periphery. We proceeded with enucleation of the hemorrhagic corpus luteum by stripping technique, with subsequent ovarian reconstruction with continuous 2-0 monofilament suture. Finally, we fixed the ovary to the stump of the right round ligament. The final view highlights good ovarian vascularization. No complications occurred; the patient was discharged on the first postoperative day. A 6-month follow-up ultrasound confirmed the recovery of the vascularization of ovary. CONCLUSION: Using indocyanine green represents a valid option to evaluate ovarian perfusion after detorsion. It could help the surgeon decide to save the ovary and thus allow fertility-sparing surgery in more cases.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.

BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

The Use of Methotrexate and Mifepristone for Treatment of Interstitial Pregnancies: An Overview of Effectiveness and Complications.

Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a maternal mortality rate of 2-2.5%. Implantation happens in the proximal portion of the fallopian tube as it passes through the myometrium. The resolution of interstitial pregnancy after medical treatment should be assessed by a decline in serum ß-hCG, which occurs in about 85-90% of cases. Nonetheless, its effectiveness and consequences have been presented through case reports and case series. However, few cases of interstitial pregnancies treated totally medically with the use of methotrexate and mifepristone have been presented in the literature. Complications of this medical treatments have also never been reviewed before. In the present manuscript, we present a case of interstitial pregnancy treated with methotrexate and mifepristone. The patient after treatment developed a uterine arteriovenous malformation, treated with uterine artery embolization. Furthermore, we performed a systematic review of the literature using Scopus, PubMed and Google Scholar. A total of 186 papers were found, and 7 papers which included 10 cases were assessed for eligibility. The systemic medical treatment with the use of methotrexate and mifepristone was effective in 7 of the 10 cases. Two cases of hemoperitoneum following combined methotrexate and mifepristone treatment were reported. The applicability of this medical conservative treatment should be tailored to the patient, taking into account their obstetric history, gestational age at diagnosis and desire for future pregnancies. Complete resolution after this treatment was achieved in most of the cases reported without major complications. The appearance of uterine arteriovenous malformation can be managed conservatively, and we propose uterine artery embolization as an effective treatment of this rare complication.

A Multi-Omics Approach Revealed Common Dysregulated Pathways in Type One and Type Two Endometrial Cancers.

Endometrial cancer (EC) is the most frequent gynecologic cancer in postmenopausal women. Pathogenetic mechanisms that are related to the onset and progression of the disease are largely still unknown. A multi-omics strategy can help identify altered pathways that could be targeted for improving therapeutical approaches. In this study we used a multi-omics approach on four EC cell lines for the identification of common dysregulated pathways in type 1 and 2 ECs. We analyzed proteomics and metabolomics of AN3CA, HEC1A, KLE and ISHIKAWA cell lines by mass spectrometry. The bioinformatic analysis identified 22 common pathways that are in common with both types of EC. In addition, we identified five proteins and 13 metabolites common to both types of EC. Western blotting analysis on 10 patients with type 1 and type 2 EC and 10 endometria samples confirmed the altered abundance of NPEPPS. Our multi-omics analysis identified dysregulated proteins and metabolites involved in EC tumor growth. Further studies are needed to understand the role of these molecules in EC. Our data can shed light on common pathways to better understand the mechanisms involved in the development and growth of EC, especially for the development of new therapies.

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.

Introduction: Immune-checkpoint inhibitors (ICIs) have emerged as a core pillar of cancer therapy as single agents or in combination regimens both in adults and children. Unfortunately, ICIs provide a long-lasting therapeutic effect in only one third of the patients. Thus, the search for predictive biomarkers of responsiveness to ICIs remains an urgent clinical need. The efficacy of ICIs treatments is strongly affected not only by the specific characteristics of cancer cells and the levels of immune checkpoint ligands, but also by other components of the tumor microenvironment, among which the extracellular matrix (ECM) is emerging as key player. With the aim to comprehensively describe the relation between ECM and ICIs' efficacy in cancer patients, the present review systematically evaluated the current literature regarding ECM remodeling in association with immunotherapeutic approaches. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022351180). PubMed, Web of Science, and Scopus databases were comprehensively searched from inception to January 2023. Titles, abstracts and full text screening was performed to exclude non eligible articles. The risk of bias was assessed using the QUADAS-2 tool. Results: After employing relevant MeSH and key terms, we identified a total of 5070 studies. Among them, 2540 duplicates, 1521 reviews or commentaries were found and excluded. Following title and abstract screening, the full text was analyzed, and 47 studies meeting the eligibility criteria were retained. The studies included in this systematic review comprehensively recapitulate the latest observations associating changes of the ECM composition following remodeling with the traits of the tumor immune cell infiltration. The present study provides for the first time a broad view of the tight association between ECM molecules and ICIs efficacy in different tumor types, highlighting the importance of ECM-derived proteolytic products as promising liquid biopsy-based biomarkers to predict the efficacy of ICIs. Conclusion: ECM remodeling has an important impact on the immune traits of different tumor types. Increasing evidence pinpoint at ECM-derived molecules as putative biomarkers to identify the patients that would most likely benefit from ICIs treatments. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351180, identifier CRD42022351180.

Morphological and lipid metabolism alterations in macrophages exposed to model environmental nanoplastics traced by high-resolution synchrotron techniques.

The release of nanoplastics (NPs) in the environment is a significant health concern for long-term exposed humans. Although their usage has certainly revolutionized several application fields, at nanometer size, NPs can easily interact at the cellular level, resulting in potential harmful effects. Micro/Nanoplastics (M/NPs) have a demonstrated impact on mammalian endocrine components, such as the thyroid, adrenal gland, testes, and ovaries, while more investigations on prenatal and postnatal exposure are urgently required. The number of literature studies on the NPs' presence in biological samples is increasing. However, only a few offer a close study on the model environmental NP-immune system interaction exploited by advanced microscopy techniques. The present study highlights substantial morphological and lipid metabolism alterations in human M1 macrophages exposed to labeled polypropylene and polyvinyl chloride nanoparticles (PP and PVC NPs) (20 µg/ml). The results are interpreted by advanced microscopy techniques combined with standard laboratory tests and fluorescence microscopy. We report the accurate detection of polymeric nanoparticles doped with cadmium selenide quantum dots (CdSe-QDs NPs) by following the Se (L line) X-ray fluorescence emission peak at higher sub-cellular resolution, compared to the supportive light fluorescence microscopy. In addition, scanning transmission X-ray microscopy (STXM) imaging successfully revealed morphological changes in NP-exposed macrophages, providing input for Fourier transform infrared (FTIR) spectroscopy analyses, which underlined the chemical modifications in macromolecular components, specifically in lipid response. The present evidence was confirmed by quantifying the lipid droplet (LD) contents in PP and PVC NPs-exposed macrophages (0-100 µg/ml) by Oil Red O staining. Hence, even at experimental NPs' concentrations and incubation time, they do not significantly affect cell viability; they cause an evident lipid metabolism impairment, a hallmark of phagocytosis and oxidative stress.

Puzzling Out the Genetic Architecture of Endometriosis: Whole-Exome Sequencing and Novel Candidate Gene Identification in a Deeply Clinically Characterised Cohort.

Endometriosis (EM) is a common multifactorial gynaecological disorder. Although Genome-Wide Association Studies have largely been employed, the current knowledge of the genetic mechanisms underlying EM is far from complete, and other approaches are needed. To this purpose, whole-exome sequencing (WES) was performed on a deeply characterised cohort of 80 EM patients aimed at the identification of rare and damaging variants within 46 EM-associated genes and novel candidates. WES analysis detected 63 rare, predicted, and damaging heterozygous variants within 24 genes in 63% of the EM patients. In particular, (1) a total of 43% of patients carried variants within 13 recurrent genes (FCRL3, LAMA5, SYNE1, SYNE2, GREB1, MAP3K4, C3, MMP3, MMP9, TYK2, VEGFA, VEZT, RHOJ); (2) a total of 8.8% carried private variants within eight genes (KAZN, IL18, WT1, CYP19A1, IL1A, IL2RB, LILRB2, ZNF366); (3) a total of 24% carried variants within three novel candidates (ABCA13, NEB, CSMD1). Finally, to deepen the polygenic architecture of EM, a comprehensive evaluation of the analysed genes was performed, revealing a higher burden (p < 0.05) of genes harbouring rare and damaging variants in the EM patients than in the controls. These results highlight new insights into EM genetics, allowing for the definition of novel genotype-phenotype correlations, thereby contributing, in a long-term perspective, to the development of personalised care for EM patients.

Phospho-DIGE Identified Phosphoproteins Involved in Pathways Related to Tumour Growth in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic malignancy of the endometrium. This study focuses on EC and normal endometrium phosphoproteome to identify differentially phosphorylated proteins involved in tumorigenic signalling pathways which induce cancer growth. We obtained tissue samples from 8 types I EC at tumour stage 1 and 8 normal endometria. We analyzed the phosphoproteome by two-dimensional differential gel electrophoresis (2D-DIGE), combined with immobilized metal affinity chromatography (IMAC) and mass spectrometry for protein and phosphopeptide identification. Quantities of 34 phosphoproteins enriched by the IMAC approach were significantly different in the EC compared to the endometrium. Validation using Western blotting analysis on 13 patients with type I EC at tumour stage 1 and 13 endometria samples confirmed the altered abundance of HBB, CKB, LDHB, and HSPB1. Three EC samples were used for in-depth identification of phosphoproteins by LC-MS/MS analysis. Bioinformatic analysis revealed several tumorigenic signalling pathways. Our study highlights the involvement of the phosphoproteome in EC tumour growth. Further studies are needed to understand the role of phosphorylation in EC. Our data shed light on mechanisms that still need to be ascertained but could open the path to a new class of drugs that could hinder EC growth.

Management of Primary Uterine Cervix B-Cell Lymphoma Stage IE and Fertility Sparing Outcome: A Systematic Review of the Literature.

The female genital tract can be involved as a secondary manifestation of disseminated lymphomas or leukaemia but can rarely be the primary site of so-called extranodal lymphomas. Primary lymphomas of the female genital tract can affect the uterine corpus, uterine cervix, vulva, vagina, or adnexa. Only about 0.008% of all cervical tumours are primary malignant lymphomas. The most common clinical presentation of primary cervical lymphomas is a history of prolonged minor abnormal uterine bleeding, while unstoppable bleeding at presentation is rarely reported in the literature. "B" symptoms related to nodal lymphomas are usually absent. Since vaginal bleeding is a nonspecific symptom, the first diagnostic hypothesis is usually of one of the more common female genital conditions such as cervical or endometrial carcinoma or sarcoma, fibroids, adenomyosis, or endometriosis. Cervical cytology is usually negative. Preoperative diagnosis requires deep cervical biopsy. No guidelines regarding optimal treatment exists; radiotherapy, chemotherapy, and surgery are used in different combinations. Conservative treatment with the combination of surgery and chemotherapy or surgery and radiotherapy has been reported in a few cases with apparent success. With this review, we aim to understand what the best therapeutic approaches for this rare pathology in young and elderly women are. Moreover, we find favorable pregnancy outcome in patients treated with a fertility sparing approach.

The clinical impact of the first-trimester nuchal translucency between the 95th-99th percentiles.

OBJECTIVES: To evaluate the clinical significance of nuchal translucency (NT) between the 95th-99th percentile in terms of typical and atypical chromosomal abnormalities (ACAs), associated fetal congenital defects and postnatal outcome. METHODS: A retrospective cohort study of fetuses with NT between the 95th-99th percentile. Data regarding the rate of associated fetal defects, genetic abnormalities and postnatal outcome were collected. RESULTS: A total of 306 cases of fetuses with an NT between the 95th-99th percentiles were included. The overall rate of genetic abnormalities was 12.1% (37/306). Chromosomal abnormalities were found in 10.1% (31/306) of cases and 2% were ACA (6/306). Within this group, two were pathogenic Copy Number Variants (CNVs) and four were single gene disorders. The overall rate of fetal congenital defects was 13.7% (42/306). All ACAs were found in fetuses with congenital defects. Postnatally, a new diagnosis of a single gene disorder was made in 0.85% of cases (2/236). CONCLUSIONS: The presence of an NT between the 95th-99th percentiles carries a 10-fold increased risk of fetal defects, representing an indication for referral for a detailed fetal anatomy evaluation. The risk of ACA is mainly related to the presence of fetal defects, irrespective of the combined test risk.

Image-guided cancer surgery: a narrative review on imaging modalities and emerging nanotechnology strategies.

Surgical resection is the cornerstone of solid tumour treatment. Current techniques for evaluating margin statuses, such as frozen section, imprint cytology, and intraoperative ultrasound, are helpful. However, an intraoperative assessment of tumour margins that is accurate and safe is clinically necessary. Positive surgical margins (PSM) have a well-documented negative effect on treatment outcomes and survival. As a result, surgical tumour imaging methods are now a practical method for reducing PSM rates and improving the efficiency of debulking surgery. Because of their unique characteristics, nanoparticles can function as contrast agents in image-guided surgery. While most image-guided surgical applications utilizing nanotechnology are now in the preclinical stage, some are beginning to reach the clinical phase. Here, we list the various imaging techniques used in image-guided surgery, such as optical imaging, ultrasound, computed tomography, magnetic resonance imaging, nuclear medicine imaging, and the most current developments in the potential of nanotechnology to detect surgical malignancies. In the coming years, we will see the evolution of nanoparticles tailored to specific tumour types and the introduction of surgical equipment to improve resection accuracy. Although the promise of nanotechnology for producing exogenous molecular contrast agents has been clearly demonstrated, much work remains to be done to put it into practice.