How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

High-Content Screening Pipeline for Natural Products Targeting Oncogenic Signaling in Melanoma.

The incidence of melanoma, the most fatal dermatological cancer, has dramatically increased over the last few decades. Modern targeted therapy with kinase inhibitors induces potent clinical responses, but drug resistance quickly develops. Combination therapy improves treatment outcomes. Therefore, novel inhibitors targeting aberrant proliferative signaling in melanoma via the MAPK/ERK and PI3K/AKT pathways are urgently needed. Biosensors were combined that report on ERK/AKT activity with image-based high-content screening and HPLC-based activity profiling. An in-house library of 2576 plant extracts was screened on two melanoma cell lines with different oncogenic mutations leading to pathological ERK/AKT activity. Out of 140 plant extract hits, 44 were selected for HPLC activity profiling. Active thymol derivatives and piperamides from Arnica montana and Piper nigrum were identified that inhibited pathological ERK and/or AKT activity. The pipeline used enabled an efficient identification of natural products targeting oncogenic signaling in melanoma.

Non-Coding RNAs as Prognostic Markers for Endometrial Cancer.

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification.

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair.

New adverse obstetrics outcomes associated with endometriosis: a retrospective cohort study.

PURPOSE: The main aim of this study was to evaluate the incidence of endometriosis and intrahepatic cholestasis (ICP) and induction of labor in pregnant women with endometriosis compared with women without endometriosis. The secondary aim was to confirm increased incidence of already known endometriosis-related pregnancy complications in these patients. METHODS: This is a retrospective cohort study performed at a tertiary hospital between January 2009 and December 2014 to compare obstetrics outcome between women with endometriosis and women without endometriosis. Pregnant patients with endometriosis were included in the study group. Patients were divided in the following subgroups: patients with deep infiltrating endometriosis (DIE subgroup) and patients without deep infiltrating endometriosis (non-DIE subgroup); patients with singleton pregnancy and spontaneous conception (subgroup A) and patients with multiple pregnancy and/or patients who underwent assisted reproductive technology (subgroup B). To form a control group, for each patient with endometriosis, two patients without endometriosis were selected as the control group by means of matched sample. RESULTS: The study population included 262 pregnant women with endometriosis and 524 controls. Patients of the study population had significantly increased risks of placenta praevia (p < 0.05), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01). DIE patients had a significantly higher percentage only of preterm birth (p < 0.01), while in non-DIE group all complications had a higher incidence except for placenta praevia, which did not differ with control. Subgroup A had a statistically higher incidence of placenta praevia (p < 0.01), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01) compared to its control subgroup. There was no difference in distribution of pregnancy complications between subgroup B and control subgroup. CONCLUSIONS: Our results showed for the first time that women with endometriosis are at higher risk of developing ICP and experiencing an induced labor. Further studies are warranted to clarify whether the history of endometriosis might be taken into account in the antenatal care of these patients.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

How to Manage Bowel Endometriosis: The ETIC Approach.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 35-year-old patient desiring pregnancy with a history of previous surgery for endometrioma and bowel obstruction symptoms. Many questions that this paradigmatic patient may pose to the clinician are addressed, and various clinical scenarios are discussed. A decision algorithm derived from this discussion is proposed as well.

Pelvic Sentinel Lymph Node Biopsy for Endometrial Cancer with Multi-Modal Infrared Signal Technology: A Video Article.

This video article summarizes a case study involving the use of pelvic sentinel lymph node (SLN) biopsy for endometrial cancer (EC) staging and treatment utilizing a multi-modal infrared signal technology. This innovative approach combines cervical injection of fluorescent dye indocyanine green (ICG) and near-infrared imaging to enhance SLN detection rates in early-stage EC patients. The study showcases the successful application of advanced technology in improving surgical staging procedures and reducing postoperative morbidity for patients. Multi-modal infrared signal technology consists of different modes of fluorescence imaging used to identify lymph nodes based on near-infrared signals. Each mode serves a specific purpose: overlay image combines white light and near-infrared signals in green, monochromatic visualization shows near-infrared signal in greyscale, and intensity map combines signals in a color scale to differentiate signal intensity. Yellow denotes strong near-infrared signals while blue represents weaker signals. By utilizing a multi-modal approach, surgeons can accurately identify and remove SLN, thus avoiding unnecessary removal of secondary or tertiary echelons.

Tubal Cancer Clinical Management: Two Exceptional Scenarios and a Review of the Literature.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with practical expertise in the oncological field. This article also includes two special clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements in tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity and to which many of the concepts extracted from the literature can apply.

Pre-cervical ripening and hygroscopic cervical dilators in pre-labor induction.

INTRODUCTION: Induction of labor (IOL) is becoming a universal topic in Obstetrics, when the risk of continuing a pregnancy outweighs the benefits. Preinduction is a more recent tool to prepare the cervix when the BISHOP-score is low. About one-third of IOL cases require cervical ripening, which is the physical softening, thinning, and dilation of the cervix in preparation for labor and birth. We report a single center experience regarding the use of hygroscopic dilators in the pre-labor phase to obtain cervical ripening before labor induction. MATERIALS & METHODS: We conducted a retrospective observational study comparing patient records from the Gynecology and Obstetrics Unit in "Santo Stefano" Hospital in Prato, Tuscany. The inclusion criteria for participants were women who had undergone pre-labor induction because of a BISHOP-score < 3. The gestational age of all the pregnant women was at term (> 37 weeks). RESULTS: From January 2022 to April 2022, a total of 581 women delivered at term of gestational age at the Gynecology and Obstetrics Unit in "Santo Stefano" Hospital. Cervical ripening was necessary for 82 women with a Bishop score < 3 and hygroscopic cervical dilators were used in 35/82 (42.7%) patients. All patients showed a change in Bishop-score upon removal of the dilators. All 35 patients (100%) reported an increase in terms of consistency and dilation of the cervix but not in terms of length. None of the patients reported discomfort during the 24 h that they kept the hygroscopic dilators in place. No patients reported uterine tachysystole on cardiotocographic tracing, vaginal bleeding, rupture of membranes or cervical tears. CONCLUSIONS: Our results are in line with those in the literature, demonstrating the validity of hygroscopic dilators in cervical maturation of pregnancies at term and their efficacy was again highlighted in terms of both maternal and fetal safety and patient satisfaction.

Case report: vertical transmission of Plesiomonas shigelloides. Is it time to strengthen information on safety concerns for raw seafood dietary exposure in pregnancy?

The consumption of raw seafood, generally considered to be a healthy food, has greatly increased worldwide. Pathogens of fish can cause foodborne illnesses in humans, especially following the consumption of raw seafood from contaminated water.Foodborne illness in pregnant women is seldom the cause of neonatal infection, but, as in the reported cases, it has been associated with a high degree of morbidity and mortality.We present the case of a newborn with septicemia and meningitis caused by Plesiomonas shigelloides acquired via the transplacental route. There was a maternal history of ingestion of raw seafood 1 week prior to delivery. A few similar cases are described in the existing literature, which reports 7 neonatal deaths.Therefore, the primary objective of this paper is to highlight the fact that the popularity of raw seafood such as sushi, sashimi, and oysters, requires an improvement in dietary advice regarding unsafe choices in pregnancy in order to avoid preventable foodborne diseases, sometimes fatal for the newborn.

The role of progesterone in maternal and fetal medicine.

Progesterone is an essential hormone in the process of reproduction. It has been extensively studied in the treatment of different gynecological pathologies, as a contraceptive and in assisted reproductive technologies. However, the use of progesterone in the pathophysiology of pregnancy remains controversial. Progesterone, and its synthetic form 17 α-hydroxyprogesterone caproate (17 OHP-C), offer an effective intervention when the continuation of pregnancy is at risk from immunological factors, luteinic and neuroendocrine deficiencies, and myometrial hypercontractility. Progesterone has been successfully used as prophylaxis in the prevention of spontaneous miscarriage, with treatment beginning from the first trimester of pregnancy. There is substantial evidence, too, to indicate that women with idiopathic recurrent miscarriage may benefit from the immunomodulatory properties of progesterone in early pregnancy. The use of progesterone and 17 OHP-C has been extensively studied in the prevention of preterm birth in a variety of settings. Transvaginal ultrasound measurement of cervical length in singleton pregnancies between 19 and 24 weeks' gestation has been deemed the best way to identify women (approximately 2% of the pregnant population) who would benefit from prophylactic progesterone treatment for the prevention of spontaneous preterm birth. This paper reviews the evidence for the safety and efficacy of the use of progesterone in each of these indications.

Contrast Agents during Pregnancy: Pros and Cons When Really Needed.

Many clinical conditions require radiological diagnostic exams based on the emission of different kinds of energy and the use of contrast agents, such as computerized tomography (CT), positron emission tomography (PET), magnetic resonance (MR), ultrasound (US), and X-ray imaging. Pregnant patients who should be submitted for diagnostic examinations with contrast agents represent a group of patients with whom it is necessary to consider both maternal and fetal effects. Radiological examinations use different types of contrast media, the most used and studied are represented by iodinate contrast agents, gadolinium, fluorodeoxyglucose, gastrographin, bariumsulfate, and nanobubbles used in contrast-enhanced ultrasound (CEUS). The present paper reports the available data about each contrast agent and its effect related to the mother and fetus. This review aims to clarify the clinical practices to follow in cases where a radiodiagnostic examination with a contrast medium is indicated to be performed on a pregnant patient.

Techniques of laparoscopic myomectomy.

Myomectomy is one of the commonest gynaecological operations. Laparoscopic myomectomy has emerged over the last two decades as a possible alternative to the traditional laparotomy. Most studies have revealed that the laparoscopic procedure is at least as safe as the open procedure as to the rate of complications and may retain relevant advantages in terms of shorter admission and recovery times. Currently laparoscopic myomectomy is still a challenging operation that requires a well-trained surgical team, adequate instrumentation and accurate patient selection; the increasing slant of gynaecologists towards laparoscopic techniques, along with the advances in surgical instrumentation and suturing materials, will hopefully contribute to keep laparoscopic myomectomy no longer confined to tertiary care centres.

Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer.

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse.

Recurrent Bilateral Salpingitis in a Sexually Inactive Adolescent: Don't Forget about the Appendix.

BACKGROUND: Salpingitis is an acute inflammation of the fallopian tubes and is extremely uncommon in patients who are sexually inactive or premenarchal. CASE: We describe a 15-year-old sexually inactive patient with recurrent bilateral salpingitis. After the second episode, she underwent an exploratory laparoscopy and was diagnosed with chronic appendicitis. SUMMARY AND CONCLUSION: Appendicular involvement should be kept in mind in recurrent salpingitis episodes, especially if previous imaging studies do not show signs of appendicitis. Imaging studies should be repeated in experienced centers in case of recurrent episodes. Laparoscopy is the gold standard for the diagnosis of salpingitis and can confirm appendicular or other abdominal involvement. Early diagnosis can help to prevent recurrent episodes of salpingitis and thus reduce the risk of sequelae.

Use of a No. 11 blade scalpel and reusable blunt trocar to establish pneumoperitoneum: description of a safe and inexpensive technique.

First access is crucial in laparoscopic surgery because of its potentially life-threatening complications. A number of procedures using a variety of instruments have been previously described; however, the safest approach remains uncertain. Herein, we describe a simple and inexpensive method for direct trocar insertion using reusable instruments that was developed over 10 years in a series of 4721 consecutive gynecologic laparoscopic procedures. Observed data revealed that the technique is feasible, rapidly performed, and safe, with a likely cost savings, using a small set of reusable instruments. This procedure should be compared with other access methods in randomized studies to confirm the observed advantages.

Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.

Myostatin is a growth factor member of the transforming growth factor ß superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-ß type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.