Patient experiences of being advised by a healthcare professional to get pregnant to manage or treat endometriosis: a cross-sectional study.

BACKGROUND: There is a lack of evidence that pregnancy reduces endometriotic lesions or symptoms, however studies indicate that people with endometriosis are commonly advised to get pregnant to manage or treat endometriosis. This study sought to examine the impact of this advice on patients with endometriosis when the advice was provided by healthcare professionals. METHODS: The Endometriosis Patient Experience Survey was a self-reported, community-based, cross-sectional online survey of people who had been medically diagnosed with endometriosis. Descriptive statistics were used to analyse the quantitative survey data and thematic analysis was undertaken for the qualitative survey data. RESULTS: 1892 participants had received the advice to get pregnant or have a baby to manage or treat their endometriosis, with 89.4% of participants receiving this advice from healthcare professionals. In exploring the qualitative data, seven themes were contextualised relating to the impact of this advice in terms of health literacy, accepting the advice, rejecting the advice, major life decisions, healthcare interactions, mental health and relationships. CONCLUSIONS: This study demonstrates profound and often negative patient impacts of the advice from healthcare professionals to get pregnant to manage or treat endometriosis. Impacts ranged from planning for pregnancy, hastening the making of major life decisions, eroding trust with healthcare professionals, worsening mental health and straining relationships. Providing evidence-based information on the treatment and management of endometriosis is essential. Pregnancy or having a baby should not be suggested as a treatment for endometriosis and the provision of this advice by healthcare professionals can have negative impacts on those who receive it.

Altered immune environment in peritoneal endometriotic lesions: relationship to lesion appearance.

OBJECTIVE: To study the localization of and quantify different immune cell populations in red, black, and white peritoneal endometriotic lesions and compare immune cell densities between lesions and the surrounding tissue. DESIGN: Cross-sectional study. SETTING: Teaching hospital, university research laboratory. PATIENT(S): Participants undergoing laparoscopic excision of endometriosis were recruited from gynecological operating theaters at Royal Prince Alfred Hospital, Sydney (n = 28). INTERVENTION(S): Immunohistochemical staining for and quantification of dendritic cells (mature and immature), T cells (effector, cytotoxic, and regulatory), B cells, and macrophages in endometriotic peritoneal lesions and the surrounding tissue. MAIN OUTCOME MEASURE(S): Immune cell densities and aggregates were quantified. RESULT(S): Red and black lesions are significantly more likely to be surrounded by immune cell aggregates than white lesions (P=.036). In the tissue surrounding the peritoneal endometriotic lesions, there was a consistent pattern of greater and more variable density of immune cell populations for red lesions than black or white lesions and a range of significant positive correlations between densities of different immune populations (all P≤.004; not observed within the lesion stroma). CONCLUSION(S): There is a greater presence of immune cells in the tissue surrounding earlier/red and black lesions than older scarred white lesions, particularly in the form of immune cell aggregates, indicating an immunologic response in close proximity to the adjacent lesion. The relationship between densities of immune populations in the tissue surrounding the lesions suggests complementary recruitment and local interactions between cells. Categorizing immune cell populations in proximity to peritoneal endometriotic lesions may improve the understanding of lesion persistence and transition to older white appearances. Early (red) peritoneal endometriotic lesions are surrounded by a greater density of immune cells, including immune aggregates, than later (black or white) lesions. These immune cells may support lesion persistence.

Top 10 research priorities for people living with pulmonary fibrosis, their caregivers, healthcare professionals and researchers.

INTRODUCTION: People with pulmonary fibrosis (PF) experience a high symptom burden, reduced quality of life and a shortened lifespan. Treatment options are limited and little is known about what patients, caregivers and healthcare professionals (HCPs)/researchers consider as the most important research priorities. This study aimed to identify the top 10 research priorities for PF across all stakeholders. METHODS: Participants included people with PF, caregivers and HCPs/researchers involved with PF. The research priority setting exercise involved three stages: (1) identifying priorities using an open-ended questionnaire and thematic analysis, (2) development of specific research questions at a face-to-face workshop, and (3) online ranking of research questions to identify the top 10 research priorities using nominal group ranking method. RESULTS: 196 participants completed stage 1 generating 560 questions and 14 research themes were identified. Stage 2 involved 32 participants and generated 53 indicative questions from which 39 were used for the final ranking. Stage 3 was completed by 270 participants. The top ranked priorities focussed on medications to reverse scarring in the lungs (ranked 1st), improving lung function (ranked 2nd, 6th and 8th), interventions aimed at alleviating symptoms (ranked 5th and 7th), prevention of PF (ranked 3rd and 4th) and the best exercise programme for PF (ranked 10th). There was good consensus among patients/carers and HCPs/researchers on the top 10 priorities, however, causes of acute exacerbations and early diagnosis for improving survival, was ranked higher by HCPs/researchers. CONCLUSION: Interventions for preserving lung health and alleviation of symptom burden were top research priorities for PF stakeholders.

The supportive care needs of people living with pulmonary fibrosis and their caregivers: a systematic review.

BACKGROUND: People with pulmonary fibrosis often experience a protracted time to diagnosis, high symptom burden and limited disease information. This review aimed to identify the supportive care needs reported by people with pulmonary fibrosis and their caregivers. METHODS: A systematic review was conducted according to PRISMA guidelines. Studies that investigated the supportive care needs of people with pulmonary fibrosis or their caregivers were included. Supportive care needs were extracted and mapped to eight pre-specified domains using a framework synthesis method. RESULTS: A total of 35 studies were included. The most frequently reported needs were in the domain of information/education, including information on supplemental oxygen, disease progression and prognosis, pharmacological treatments and end-of-life planning. Psychosocial/emotional needs were also frequently reported, including management of anxiety, anger, sadness and fear. An additional domain of "access to care" was identified that had not been specified a priori; this included access to peer support, psychological support, specialist centres and support for families of people with pulmonary fibrosis. CONCLUSION: People with pulmonary fibrosis report many unmet needs for supportive care, particularly related to insufficient information and lack of psychosocial support. These data can inform the development of comprehensive care models for people with pulmonary fibrosis and their loved ones.

Peer Connect Service for people with pulmonary fibrosis in Australia: Participants' experiences and process evaluation.

BACKGROUND AND OBJECTIVE: People living with pulmonary fibrosis (PF) report unmet needs for information and support. Lung Foundation Australia (LFA) have developed the Peer Connect Service to facilitate telephone support for people with PF across Australia. This project documented the experiences of participants and the resources required to support the service. METHODS: Consenting participants took part in semi-structured interviews by telephone. Primary peers (peers who agreed to initiate contact) and secondary peers (eligible patients who sought a peer match) were interviewed. Thematic analysis was undertaken by two independent researchers. Data were collected on the number of matches and contacts required to establish each match. RESULTS: Interviews were conducted with 32 participants (16 primary peers, 15 secondary peers and 1 who was both), aged from 53 to 89 years with 56% being male. Major themes included the value of shared experiences, providing mutual support and the importance of shared personal characteristics (e.g. gender and hobbies) in allowing information and emotional support needs to be met. Participants saw face-to-face contact with peers as highly desirable whilst acknowledging the practical difficulties. Primary peers were cognizant that their role was not to provide medical advice but to listen and share experiences. In the 12-month period, 60 peer matches were made, each match requiring a minimum of seven staff contacts. CONCLUSION: The Peer Connect Service provides a unique opportunity for people with PF to share experiences and offer mutual support. This telephone matching model may be useful in providing peer support for individuals with rare diseases who are geographically dispersed.

The Lymphatic System in Endometriosis: a Pilot Study of Endometrial-Like Cells and Immune Cell Populations in Lymph Nodes Associated with Deep Infiltrating Bowel Lesions.

In endometriosis, the lymphatic and immune systems are implicated in disease establishment and progression. The objective of this pilot study was to examine endometrial-like, and for the first time, immune cell populations in lymph nodes associated with deep infiltrating endometriosis (DIE) bowel lesions. Premenopausal women undergoing excision of endometriosis and/or hysterectomy were included. DIE bowel lesion-associated (n = 10) and other pelvic (n = 15) lymph nodes were studied. Samples were immunohistochemically stained for endometrial-like cells (CD10), T cells (CD3, CD4, CD8, and FoxP3), dendritic cells (DC; DC-Lamp and DC-Sign), B cells (CD20, CD79 and plasma), macrophages (CD68), and natural killer cells (NK; CD57). Cell abundance (percentage positive area) and antigen expression (optical density; OD) were quantified. Endometrial-like cells and each immune cell population were present in all studied nodes. The DIE bowel lesion-associated nodes showed features of immune activation, with T cell proliferation (CD3+ area p = 0.007, CD4+ area p = 0.015 compared with other pelvic nodes); and a mixture of helper and regulatory T cells, B cells, DCs, macrophages, and plasma cells present in the paracortex. In DIE bowel lesion-associated compared with other pelvic nodes, CD10+ endometrial-like cells were reduced (percentage positive area p < 0.001, OD p = 0.004). This study provides new insight into lymphatic and immune system involvement in advanced endometriosis. In particular, we have shown evidence of immune activation in DIE lesion-associated nodes. This was despite lower endometrial-like cell numbers compared with other pelvic nodes. The observations contribute to a developing understanding of the local immune response to advanced disease.

Expression of vascular endothelial growth factor A isoforms is dysregulated in women with endometriosis.

Angiogenesis is a critical step in the development of ectopic lesions during endometriosis. Although total vascular endothelial growth factor (VEGF) A is elevated in the peritoneal fluid of women with endometriosis, there are contradictory reports on how levels of total endometrial VEGFA are altered in this disease. Furthermore, limited research is available on different VEGFA isoforms in women with endometriosis. Thus, the aim of the present study was to analyse levels of various VEGFA isoforms in women with and without endometriosis at different stages of the menstrual cycle. Quantitative polymerase chain reaction analysis showed that total VEGFA was highest during menstruation in endometriosis compared with controls (P=0.0373). VEGF121 and VEGF189 were similarly highest during menstruation in endometriosis compared with controls (P=0.0165 and 0.0154 respectively). The present study is also the first to identify the natural expression of VEGF111 in human tissue, which is also highest during menstruation in endometriosis (P=0.0464). This discovery of the natural production of VEGF111 in human endometrium, as well as the upregulation of VEGFA isoforms during menstruation in endometriosis, may shed further light on the development and progression of the disease, and improve our understanding of the regulation of endometrial angiogenesis.

The role of the lymphatic system in endometriosis: a comprehensive review of the literature.

Endometriosis is a benign gynecological disorder characterized by the presence of tissue resembling the endometrium in locations outside the uterus. The pathogenesis of endometriosis is still unknown; however, it is believed that the lymphatic system plays major roles in the development and progression of the disease. The lymphatic dissemination theory has been proposed to explain the presence of endometrial and/or endometriotic tissue in lymphatic vessels, lymph nodes, and rare sites, as well as high reoccurrence rates following treatment. Despite the importance of the lymphatic system in many aspects of endometriosis, there has been no previous thorough scientific update on its role in the disease. A review of scientific literature on the lymphatic system, lymphangiogenesis, and immunological changes associated with endometriosis was conducted. Lymphangiogenic potential is disturbed and lymphatic vessel density increased in the eutopic endometrium of women with endometriosis, likely promoting the entry of endometrial tissues into the lymphatic circulation. Endometriotic lesions and endometrial-like cells are present in uterine-draining nodes and various other pelvic lymph nodes. Immune responses are impaired in uterine-draining nodes, likely favoring the survival of endometrial cells and lesion establishment. In addition, lymphangiogenesis in endometriotic lesions may contribute to lesion growth and persistence, and promote the spread of endometrial cells to draining lymph nodes. The evidence reviewed in this paper supports the theory of lymphatic dissemination of endometriosis and highlights the roles of the lymphatic system in the pathogenesis and persistence of endometriosis. Understanding these roles is crucial for establishment of novel therapeutic approaches.

Peripheral and endometrial dendritic cell populations during the normal cycle and in the presence of endometriosis.

BACKGROUND: Dysfunctional immune response may be implicated in endometriosis pathogenesis, and dendritic cells (DC) may play greater roles in this response than previously recognized. This study set out to evaluate peripheral blood and endometrial DC population changes in the presence and absence of endometriosis pathology. METHODS: Endometrial (n = 83) and peripheral blood samples (n = 30) were subjected to immunohistochemical techniques and flow cytometry, respectively, to assess DC populations in women with and without endometriosis. Three circulating DC subsets (MDC1, MDC2 and PDC, expressing CD1c, CD303 and CD141), and late-stage mature endometrial DCs (using DC-LAMP antibody) were investigated. RESULTS: A highly significant reduction in CD1c intensity on MDC1 populations in peripheral blood was observed between normal cycle proliferative and menstrual phases (p = 0.025), but not in women with endometriosis, in whom CD1c intensity was markedly increased at the time of menstruation (p = 0.05). A significant reduction in peripheral blood MDC2 (p = 0.016) and apparent reduction in endometrial DC-LAMP+ DC (trend, p = 0.062) were observed in women with endometriosis compared with controls, consistent with our preliminary DC data. CONCLUSIONS: Cyclical variation in endometrial and circulating DC populations appears to be crucial during normal menstrual cycles and in the establishment of pregnancy. In endometriosis, circulating and endometrial DC populations are significantly dysregulated at a number of levels, and are likely to contribute to inefficient immunological targeting of endometrial fragments shed at menstruation, facilitating their survival and establishment of endometriosis.

Cellular immune environment in endometrial polyps.

STUDY OBJECTIVE: To investigate the immune environment of endometrial polyps (EPs). DESIGN: Prospective case-control study. SETTING: Teaching hospital and university research laboratory. PATIENT(S): Reproductive-age women undergoing hysteroscopy dilation and curettage for benign indications. Samples were collected from women with (n = 23) and without (n = 40) EPs. INTERVENTION(S): Endometrial samples were immunohistochemically stained with antibodies against mast cells (MCs) and regulatory T cells (Tregs). MAIN OUTCOME MEASURE(S): Tryptase+, chymase+, and c-Kit+ MCs and Foxp3+ Tregs were quantified in EPs and polyp-adjacent, polyp-distant, and control endometrium. RESULT(S): Densities of all MC types were highly significantly increased in EPs compared with adjacent, distant, and control endometrium. Chymase+ and c-Kit+ MCs were increased in density in adjacent compared with control endometrium. c-Kit+ MCs were also increased in distant compared with control endometrium. Foxp3+ Treg density was increased in EPs compared with distant and control endometrium and decreased in distant compared with control endometrium. CONCLUSION(S): This study provides novel insights into localized disturbances in the cellular immune environment within EPs consistent with EPs being inflammatory lesions associated with MC overactivity. Tregs are likely to be recruited to EPs in an attempt to suppress the inflammatory process due to the greatly increased presence of MCs. These immunologic disturbances are likely to be involved in the causation of abnormal bleeding and infertility in premenopausal women with EPs, and their role in the pathophysiology requires further research.

Angiogenesis, lymphangiogenesis and neurogenesis in endometriosis.

Endometriosis is a common, benign gynecological disease affecting 10 - 15% of reproductively aged women. It is characterized by the presence of endometrial-like tissue at sites outside the uterus. The most widely accepted theory of endometriosis pathogenesis proposes that shed menstrual endometrium can reach the peritoneum, implant and grow as endometriotic lesions. Angiogenesis, lymphangiogenesis and neurogenesis are implicated in successful ectopic establishment and the generation of endometriosis-associated symptoms. This review considers these processes as they occur in the eutopic endometrium and ectopic endometriotic lesions of women with endometriosis. Their regulation is inter-connected and complex. Dysregulation in endometriosis occurs on a background of accumulating evidence that endometriosis is an endometrial disease with underlying genetic influences and cross talk with endometriotic lesions. Understanding the roles of angiogenesis, lymphangiogenesis and neurogenesis in endometriosis pathophysiology is essential for the development of novel therapeutic approaches.

A novel pilot study of endometrial stromal cells and immune cell populations in sentinel uterine-draining lymph nodes during the menstrual cycle and in endometriosis.

Recent studies suggest that changes in certain uterine immune cell populations in endometrium of women with endometriosis are likely to precede changes at ectopic sites. This preliminary study is a first look into the function of uterine-draining lymph nodes (LNs) during the menstrual cycle and in the presence of endometriosis. Paraffin-embedded obturator LNs were obtained from women with (n = 7, mean age 44.3) and without (n = 9, mean age 38.4) endometriosis, who had undergone hysterectomy for cervical or ovarian cancer and in whom LN involvement was not detected. Immunohistochemical staining for endometrial stromal cells and a range of immune cell populations was performed. The CD10+ endometrial stromal cells were detected in uterine-draining LNs throughout the menstrual cycle with numbers peaking during menstruation. The inflammatory process of menstruation was also associated with increased numbers of CD3+, CD4+, Foxp3+, DC-Sign+, CD68+, CD20+, CD79+, and plasma cells. In endometriosis, CD10+ endometrial stromal cells were further increased in numbers, but CD3+, CD4+, DC-Lamp+, FoxP3+, and plasma cells were reduced. This study indicates that efficient immunological responses may be required to contain shed endometrial fragments within the draining uterine LNs thus preventing their further dissemination with establishment of ectopic lesions at distant sites.

The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition.

BACKGROUND: Endometriosis is an inflammatory condition, associated with highly dysregulated immune response at both uterine and peritoneal levels. Surprisingly, Foxp3+ regulatory T-cells, which control and suppress a range of immune responses, have not previously been investigated in endometriosis. METHODS AND RESULTS: Immunohistochemical analysis of Foxp3+ cells in 127 eutopic endometrial samples and 59 ectopic peritoneal lesions revealed that these immune cell populations are highly disturbed in women suffering from endometriosis. We showed that Foxp3+ cells remained highly up-regulated during the secretory phase of the menstrual cycle, while at this time their expression is significantly down-regulated in women without endometriosis (P < 0.001). Foxp3+ cells were detected in the stroma of 18 of the 59 peritoneal endometriotic lesions, but not in the surrounding or control peritoneal tissue. CONCLUSIONS: We propose that in eutopic endometrium in women with endometriosis Foxp3+ cells decrease the ability of newly recruited immune cell populations to effectively recognize and target endometrial antigens shed during menstruation, allowing their survival and ability to implant in ectopic sites. At these ectopic sites, variable expression of Foxp3+ cells within some peritoneal endometriotic lesions is likely to be linked to the characteristics and stage of individual lesion development and be playing key roles in pathogenesis and progression of this unique condition.