Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

Vaginal dilator use to promote sexual wellbeing after radiotherapy in gynecological cancer survivors

AbstractThis study investigated the efficacy of a vaginal dilator (VD) for the treatment of radiation-induced vaginal stenosis (VS) and the effect of a VD on sexual quality of life.Fifty three patients with endometrial or cervical cancers participated in this prospective observational study. All participants were treated with radical or adjuvant external beam radiotherapy and/or brachytherapy. They were routinely examined 4 times after radiotherapy (RT) and were also asked to complete a validated sexual function-vaginal changes questionnaire. SPSS version 20 and Minitab version 16 were used for the statistical analysis. The statistical significance was set at P < .05.The VS grading score decreased and the comfortably insertable VD size gradually increased throughout a year of VD use; all patients with initial grade 3 showed a VS of grade 2 after 12 months of VD use and 65.8% of the patients with initial grade 2 demonstrated a final VS of grade 1, while 77.8% of the participants who started with the first size of VD reached the third size after 12 months. Starting VD therapy ≤3 months after the end of RT was associated with a significant decrease in VS. A total of 60.9% of participants reported that they did not feel their vaginas were too small during intercourse after 12 months of dilation, whereas only 11.5% gave the same answer before starting dilation. Furthermore, 47.17% rated their satisfaction with their sexual life 5 out of 7 and only 3.77% gave a score of 3 after 12 months of dilation.Endometrial and cervical cancer survivors are encouraged to use VD to treat VS and for sexual rehabilitation after RT. This study recommends starting vaginal dilation no more than 3 months after treatment at least 2 to 3 times a week for 10 to 15 minutes over 12 months. However, larger, well-designed randomized clinical trials should be conducted to develop specific guidelines for VD use and efficacy in VS and sexual sexual quality of life after RT. © 2022 Lippincott Williams and Wilkins. All rights reserved

Vaginal stenosis after radiation therapy for pelvic cancer: Prevention and treatment options - A review of the current literature

Purpose: Pelvic radiotherapy holds a vital role in the management of gynaecological and pelvic gastrointestinal cancers. However, radiotherapy can result in shortening and narrowing of the vagina which is known as vaginal stenosis. The objective of this paper is to review the prevention and treatment options of radiation-induced vaginal stenosis and discuss their benefits and side-effects as well. Materials and Methods: A literature search was performed (1972-2017) on PubMed, Cochrane Database of Controlled Trials, and SCOPUS with no language restrictions. Cross references from the included studies were hand-searched. The criteria for the included studies were any and every measure for preventing radiation-induced vaginal stenosis. Results: The use of vaginal dilators, sexual intercourse, and topical therapies are the current options for the management of vaginal stenosis after pelvic radiotherapy. Conclusion: Vaginal dilation should be encouraged in cancer survivors after pelvic radiotherapy, with counseling by expertized medical and paramedical personnel. Limited evidence exists in favor of the use of vaginal lubricating creams for radiation-related vaginal irritation. © 2019 S.O.G. CANADA Inc. All rights reserved

ERS statement on tracheomalacia and bronchomalacia in children

Tracheomalacia and tracheobronchomalacia may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stridor or fixed wheeze, recurrent infections, brassy cough and even near-death attacks, depending on the site and severity of the lesion. Diagnosis is usually made by flexible bronchoscopy in a free-breathing child but may also be shown by other dynamic imaging techniques such as low-contrast volume bronchography, computed tomography or magnetic resonance imaging. Lung function testing can provide supportive evidence but is not diagnostic. Management may be medical or surgical, depending on the nature and severity of the lesions, but the evidence base for any therapy is limited. While medical options that include bronchodilators, anti-muscarinic agents, mucolytics and antibiotics (as well as treatment of comorbidities and associated conditions) are used, there is currently little evidence for benefit. Chest physiotherapy is commonly prescribed, but the evidence base is poor. When symptoms are severe, surgical options include aortopexy or posterior tracheopexy, tracheal resection of short affected segments, internal stents and external airway splinting. If respiratory support is needed, continuous positive airway pressure is the most commonly used modality either via a face mask or tracheostomy. Parents of children with tracheobronchomalacia report diagnostic delays and anxieties about how to manage their child&apos;s condition, and want more information. There is a need for more research to establish an evidence base for malacia. This European Respiratory Society statement provides a review of the current literature to inform future study. Copyright © ERS 201

ERS Statement on Tracheomalacia and Bronchomalacia in Children.

Tracheomalacia (TM) and tracheobronchomalacia (TBM) may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stridor or fixed wheeze, recurrent infections, brassy cough and even near-death attacks, depending on the site and severity of the lesion. Diagnosis is usually made by flexible bronchoscopy in a free-breathing child but may also be shown by other dynamic imaging techniques such as low contrast volume bronchography, computed tomography or magnetic resonance imaging. Lung function testing can provide supportive evidence but is not diagnostic. Management may be medical or surgical, depending on the nature and severity of the lesions but the evidence base for any therapy is limited. While medical options that include bronchodilators, anti-muscarinic agents, mucolytics and antibiotics, (as well as treatment of co-morbidities and associated conditions) are used, there is currently little evidence for benefit. Chest physiotherapy is commonly prescribed, but the evidence base is poor. When symptoms are severe, surgical options include aortopexy or posterior tracheopexy, tracheal resection of short affected segments, internal stents and external airway splinting. If respiratory support is needed, CPAP is the most commonly used modality either via a facial mask or tracheostomy. Parents of children with TBM report diagnostic delays and anxieties about how to manage their child's condition, and want more information. There is a need for more research to establish an evidence base for malacia. This statement provides a review of the current literature to inform future study