Protocol for the Endometriosis Research Queensland Study (ERQS): an integrated cohort study approach to improve diagnosis and stratify treatment.

INTRODUCTION: Endometriosis is a common gynaecological disease associated with pelvic pain and subfertility. There are no non-invasive diagnostic tests, medical management requires suppression of oestrogens and surgical removal is associated with risk. Endometriosis is a complex genetic disease with variants in at least 27 genetic regions associated with susceptibility. Previous research has implicated a variety of biological mechanisms in multiple cell types. Endometrial and endometriotic epithelial cells acquire somatic mutations at frequency higher than expected in normal tissue. Stromal cells have altered adhesive capacity and immune cells show altered cytotoxicity. Understanding the functional consequences of these genetic variants on each cell type requires the collection of patient symptoms, clinical and genetic data and disease-relevant tissue in an integrated program. METHODS AND ANALYSIS: The aims of this study are to collect tissue associated with endometriosis, chart the genetic architecture related to endometriosis in this tissue, isolate and propagate patient-specific cellular models, understand the functional consequence of these genetic variants and how they interact with environmental factors in pathogenesis and treatment response.We will collect patient information from online questionnaires prior to surgery and at 6 and 12 months postsurgery. Treating physicians will document detailed surgical data. During surgery, we will collect blood, peritoneal fluid, endometrium and endometriotic tissue. Tissue will be used to isolate and propagate in vitro models of individual cells. Genome wide genotyping and gene expression data will be generated. Somatic mutations will be identified via whole genome sequencing. ETHICS AND DISSEMINATION: The study has been approved and will be monitored by the Metro North Human Research Ethics committee (HREC) and research activities at the University of Queensland (UQ) will be overseen by the UQ HREC with annual reports submitted. Research results will be published in peer-reviewed journals and presented at conferences were appropriate. This study involves human participants and was approved by RBWH Human Research Ethics Committee; HREC/2019/QRBW/56763.The University of Queensland; 2017002744. Participants gave informed consent to participate in the study before taking part.

The relationship between visual impairments and activity of the neck/shoulder muscles among surgeons during simulated surgical tasks.

BACKGROUND: Minimally Invasive Surgery (MIS) has an impact on surgeons' musculoskeletal and visual systems. However, the relationship between visual symptoms and musculoskeletal problems is not well understood. AIM OF THE STUDY: This study used surface electromyography (sEMG) to examine changes in fatigue of the neck/shoulder muscles among surgeons with visual impairments when performing simulated surgical tasks in 2D and 3D viewing modes. DESIGN: Cross-sectional laboratory study. METHODS: Changes in median frequency (MDF, an indicator of muscle fatigue) were examined in 17 experienced gynaecologists. Four simulated surgical laparoscopy tasks were performed in 2D and 3D viewing modes. The MDF of three neck/shoulder muscles (cervical erector spinae, [CES], upper trapezii [UT], and anterior deltoids [AD]) were examined bilaterally. Visual parameters (accommodation, convergence, and stereoacuity) were measured prior to commencement. RESULTS: There was a downward shift of MDF from simple to more complex tasks for the right and left CES and AD muscles but not the UT, which was consistent for surgeons with mild accommodation/convergence impairment and/or good stereoacuity. There were significant differences in the level of muscle fatigue of the neck/shoulder muscles according to the severity of visual impairment, muscle side, task and surgical performance level. CONCLUSIONS: The results show a relationship between the degree of visual impairments and muscle fatigue of the neck/shoulder muscles among MIS surgeons. These findings have important implications in understanding the concurrence of musculoskeletal problems and visual symptoms.

When is it too late? Ovarian preservation and duration of symptoms in ovarian torsion.

This 10-year retrospective study between 2008 and 2018, aims to investigate the duration of symptoms of ovarian torsion and the subsequent rate of ovarian preservation. Eighty-six women with surgically confirmed ovarian torsion were included. The median duration from the onset of pain symptoms to presentation (26.0 vs 6.0 h, p < .001) and from presentation to surgery (11.0 vs 5.5 h, p = .010) were significantly longer in women who required an oophorectomy compared to women who had conservative surgery. There was no significant difference in symptoms, signs or investigations except ultrasound finding of an enlarged ovary (94.9% vs 76.9%, p = .026). Awareness of the condition among the community and healthcare is crucial and routine investigations should not delay management as positive Doppler flow on ultrasound does not exclude an ovarian torsion.Impact StatementWhat is already known on this subject? Ovarian torsion is a gynaecological emergency and may lead to ovarian necrosis, infection and peritonitis. Early recognition is essential in preserving the ovary, particularly in patients with future fertility aspirations. Currently there is no consensus regarding the time period of ovarian viability after the onset of symptoms.What do the results of this study add? We have demonstrated a significant difference in the duration from the onset of symptoms to surgery. Furthermore, the duration from the onset of symptoms to presentation (26.0 vs 6.0 h, p<.001) and from presentation to surgery (11.0 vs 5.5 h, p=.010) were significantly longer in women who required an oophorectomy compared to women who had conservative surgery. There was no significant difference in symptoms, signs or investigations except ultrasound finding of an enlarged ovary.What are the implications of these findings for clinical practice and/or further research? Women with known ovarian cysts in particular should be educated of the risk of ovarian torsion. Routine investigations should not delay management as it does not exclude an ovarian torsion. Although our study suggests that early presentation and management would reduce the risk of oophorectomy, prospective studies are required to confirm the findings.

Visual symptoms, Neck/shoulder problems and associated factors among surgeons performing Minimally Invasive Surgeries (MIS): A comprehensive survey.

PURPOSE: Minimally Invasive Surgery (MIS) is demanding on the musculoskeletal and visual systems. Prevalence, severity and association of neck/shoulder problems and visual symptoms were examined among MIS surgeons. The associations of workplace and individual factors with these symptoms independently and combined were also examined. METHODS: MIS surgeons completed a comprehensive online survey inclusive of 52 questions about individual and workplace physical factors, neck/shoulder problems and visual symptoms. Binary logistic regression models were conducted to determine the associations of the neck/shoulder problems, visual symptoms and combined symptoms with workplace and individual factors. RESULTS: 290 surgeons completed the survey. Neck/shoulder problems and visual symptoms were reported by 31.0% and 29.0%, respectively, 15.5% reported both problems. The prevalence and severity of neck/shoulder problems and visual symptoms were significantly associated (p < 0.001). Several workplace and individual factors were associated with these symptoms (p ≤ 0.05). CONCLUSIONS: Several factors in the workplace environment (temperature, asymmetrical weight bearing and forward head movement) and individual (being female and wearing vision correction glasses) were significantly associated with neck/shoulder problems and visual symptoms. Evaluation of different strategies to minimise the strain on the neck/shoulder region and the visual system is required.

Characteristics of headaches among surgeons and associated factors: A cross-sectional study.

BACKGROUND: Surgeons performing Minimally Invasive Surgery (MIS) report significant neck/shoulder problems and visual symptoms. Headache is another commonly reported symptom but publications about the characteristics and associated risk factors are limited. PURPOSE OF THE STUDY: To determine the characteristics of headache among MIS surgeons and the associations of headache with neck/shoulder problems, visual symptoms and other associated factors. DESIGN: A cross-sectional study. METHODS: A comprehensive online survey was sent to MIS surgeons inclusive of 63 questions about individual and workplace physical factors, characteristics of headache, neck/shoulder problems and visual symptoms. Binary logistic regression models were conducted to determine the associations of the prevalence and severity of headache with risk factors. THE MAIN FINDINGS: Headaches in the last 7 days were reported by 36% of surgeons, with 37% of these of moderate to severe intensity. Frequent intense headaches were often preceded by neck pain. Surgeons with headache were eight times more likely to also experience visual symptoms and four times more likely to experience neck/shoulder problems. Several factors (frequently adopting forward head movement, surgical specialty, sex and age) were significantly associated with headaches (p ≤ 0.05). CONCLUSIONS: This study revealed headaches were present in one-third of MIS surgeons. During surgery, surgeons report adopting non-neutral neck/shoulder/head positions, which may explain headaches, neck/shoulder problems and visual symptoms. Evidence based strategies to assist surgeons better manage these symptoms are warranted.

Impact of early surgical management on tubo-ovarian abscesses.

This 5-year retrospective study aimed to investigate whether early surgical management improves outcomes in patients presenting with a tubo-ovarian abscess (TOA). Patient characteristics, investigation results and treatment outcomes were compared. 50 women were diagnosed with a TOA during the study period. Nineteen (38.0%) were treated with antibiotics (medical group) and thirty one (62.0%) were treated surgically on admission (early surgical group). The early surgical group was associated with a high success rate of 96.8% and the lowest risk of readmission within 12 months (16.1%). There was no significant difference in the length of stay between the early surgical and the successful medical group.Impact StatementWhat is already known on this subject? Tubo-ovarian abscess (TOA) is an inflammatory mass that forms most commonly as a complication of untreated pelvic inflammatory disease (PID). Traditionally, TOAs are treated first with broad-spectrum intra-venous antibiotics, with surgical intervention considered after 72 h. It is not known whether early surgical intervention would be beneficial to patient outcomes compared to traditional management.What do the results of this study add? In this study, we have demonstrated a high success rate with early surgical management. Readmission rate was lowest in the early surgical group compared to the medical and late surgical group. This suggests that early surgical intervention may be beneficial, compared to the standard management of trialling antibiotics and then proceeding to surgery 72 h later.What are the implications of these findings for clinical practice and/or further research? Our study suggests that early surgery may be beneficial in the management of TOAs. Although we were unable to demonstrate statistical significance, our data suggest that it would be worthwhile to investigate white blood cell (WBC) and C-reactive protein (CRP) further as a potential predictor for failure of medical management. In the future, more studies comparing early surgical management with medical and late surgical management could inform clinicians of the best mode of treatment for these patients.

Impact of accommodation, convergence and stereoacuity on perceived symptoms and surgical performance among surgeons.

BACKGROUND: Minimally invasive surgery (MIS) is not without impact on surgeons' neck/shoulder/head and eyes. However, the mechanisms for concurrent symptoms are not clear. This study aims to examine the effect of visual impairments on physical symptoms and surgical performance among surgeons performing simulated surgical tasks using two-dimensional (2D) and three-dimensional (3D) viewing modes. METHODS: Gynaecologists with experience in laparoscopy performed four simulated surgical tasks in the 2D and 3D viewing modes. Visual parameters (accommodation, convergence and stereoacuity) were measured prior to commencement. Objective performance measures were derived from the laparoscopic tasks, and surgeons also self-reported their mental and physical workload using the NASA-TLX. In addition, perceived symptoms were measured using Visual Analogue Scales, the Simulator Sickness Questionnaire and the Computer Vision Syndrome Questionnaire. RESULTS: Seventeen healthy gynaecologists participated in this study. There were significant relationships between visual impairments and both the perceived symptoms and surgical performance scores of MIS surgeons. Surgeons with a higher number of accommodation/convergence dysfunctions and/or poorer stereoacuity tended to have poorer objective performance scores on simulated surgical tasks in both viewing modes. NASA-TLX scores indicated that surgeons with poorer stereoacuity also perceived themselves to have been less successful at accomplishing tasks. However, these surgeons also reported less intense physical symptoms and simulator sickness. CONCLUSIONS: Surgeons' performance for the simulated surgical tasks correlated with visual functions, and it also impacted on the symptoms experienced. Regular screening of surgeons' vision and vision therapy may be required to decrease physical symptoms and improve surgical performance.

The role of the endocannabinoid system in aetiopathogenesis of endometriosis: A potential therapeutic target.

Endometriosis affects a large proportion of women during their reproductive years and is associated with pain and infertility, also affecting psychological wellbeing and quality of life. The pathogenesis of the disease remains unclear, although it is believed to be multifactorial. The endocannabinoid system (ECS) consists of a number of ligands, receptors and enzymes, and has gained interests in endometriosis research. This review aims to summarise all available evidence reporting the roles of the ECS in endometriosis. A literature search of the PubMed, EMBASE, and Web of Science electronic medical databases was performed. Original and review articles published in peer-reviewed journals were included. No publication date or publication status restrictions were imposed. Significant differences in the concentrations and expressions of the components of the ECS were reported in the eutopic and ectopic endometrium, and the systemic circulation of women with endometriosis compared to controls. Endometriosis appears to be associated with downregulation of CB1 receptors and upregulation of TRPV1 receptors. The role of CB1 and progesterone in anti-inflammatory action and the role of TRPV1 in inflammation and pain are of particular interests. Furthermore, the ECS has been reported to be involved in processes relevant to endometriosis, including cell migration, cell proliferation, apoptosis, inflammation, and interacts with sex steroid hormones. The ECS may play a role in disease establishment, progression, and pain in endometriosis. However, reports are based on studies of limited size and there are inconsistencies among the definition of their control groups. There are also conflicting reports regarding precise involvement of the ECS in endometriosis. Future research with larger numbers, strict inclusion and exclusion criteria and detailed clinical information is imperative.

Neck/Shoulder Problems and Visual Disturbances Among Surgeons: A Scoping Review.

BACKGROUND: Minimally invasive surgeries are the surgical techniques that lower the size of incisions needed but may increase the physical problems such as neck/shoulder problems and visual disturbances among surgeons. This study aims to determine the prevalence, severity, proposed risk factors, and evidence for a relationship for neck/shoulder problems and visual disturbances (separately and concurrently) among surgeons. MATERIALS AND METHODS: A scoping review using the five-stage framework proposed by Arksey and O'Malley was conducted. This included identification of a research question and relevant studies, study selection, charting of data and collating, summarizing, and reporting of the results. Databases searched were PubMed, Embase, CINAHL, Cochrane Library and Web of Science, and Scopus, alongside a hand-search. An Appraisal tool for Cross-Sectional Studies was used to determine methodological quality of studies. RESULTS: Ten articles met the inclusion criteria from 744 identified. Prevalence were reported by all the studies and ranged from 6% to 74% (neck); 7%-35% (right shoulder); 8%-39% (left shoulder); 9%-80% (both shoulders), and 0.4%-63% (visual disturbances). Severity of these concerns was assessed in four studies and was variable. The risk factors for neck/shoulder problems and visual disturbances included workplace physical ergonomic factors, surgery factors, and surgeon-related factors. None of the included studies proposed a relationship between neck/shoulder problems and visual disturbances. CONCLUSIONS: There was great variability in the reported prevalence of neck/shoulder problems and visual disturbances among surgeons. Neck/shoulder problems and visual disturbances shared several risk factors, but the link between the two issues has not been fully investigated.

Management of caesarean scar pregnancy with high dose intravenous methotrexate infusion therapy: 10-year experience at a single tertiary centre.

OBJECTIVE: Incidence of caesarean scar pregnancy (CSP) is increasing due to rising caesarean section rate and advanced imaging modalities. At present, there is no consensus to recommend any specific intervention. In our centre, we have adopted the high dose intravenous methotrexate therapy followed by folinic acid for the management of CSP. In this retrospective study, we report the success rate and safety of this regimen. STUDY DESIGN: This was a 10-year retrospective study of women with CSP who received high dose methotrexate therapy with folinic acid at a tertiary centre from 1 st January 2008 to 31 st December 2017. Treatment regimen consisted of a bolus dose of intravenous methotrexate followed by methotrexate infusion over 12 h. Oral folinic acid rescues were given post treatment. Successful treatment was confirmed with either resolution of serum beta-human chorionic gonadotropin or subsequent intrauterine pregnancy. RESULTS: Of 28 women with CSP who were treated with the regimen, 24 women (85.7%) were treated successfully with methotrexate alone. 3 women (10.7%) required suction evacuation following initial treatment with methotrexate and folinic acid. There was no serious side effect from methotrexate. Advanced gestational age, higher serum ß-hCG, larger gestational sac diameter and crown-rump length, and the presence of embryonic cardiac activity were associated with methotrexate failure or need for additional therapy. CONCLUSIONS: Our high dose intravenous methotrexate infusion therapy with folinic acid is effective and well tolerated. Caution is needed with factors associated with failure. Ensuring follow up ultrasound for live CSP and follow up ß-hCG for all women with CSP is essential.

Idiopathic ovarian vein thrombosis: a rare cause of pelvic pain - case report and review of literature.

Ovarian vein thrombosis is a condition most commonly identified in the puerperium and in association with malignancy, pelvic infections, surgery and thrombophilia. We report a case of idiopathic ovarian vein thrombosis and therefore highlight the importance of considering the diagnosis in women presenting with lower abdominal pain, in whom more common diagnoses cannot be identified.

Reactionary hemorrhage in gynecological surgery.

BACKGROUND: Bleeding is a major complication in contemporary gynecological surgery. We discusses this rare, albeit potentially serious, unexpected complication. The authors mean by "reactionary," hemorrhage that occurs within the first 24 hours after surgery. More or less, all gynecological surgeons have had to deal with this situation at some stage of their career. The seriousness of this complication stems from the fact that often the surgeon is not in the immediate vicinity to promptly step in and treat the patient. Nevertheless, the key to successful management is prompt diagnosis, immediate resuscitation, and operative intervention. METHODS: By using the collective hospital database, we reviewed 719 patient records. The authors operated on these patients between November 1990 and March 2007 (inclusive) in one hospital, Royal Brisbane and Women's Hospital, the main teaching hospital in Brisbane, Queensland, Australia. The procedures performed in the 719 patients comprised 476 vaginal hysterectomies and 243 laparoscopic hysterectomies. Both public and private patients were included. The objective of the review was to establish the incidence of postoperative reactionary hemorrhage following the initial operation, as defined by the number of patients returning to the operating theatre (OT) because of postoperative hemorrhage within 24 hours of the initial hysterectomy. RESULTS: Of the 719 patients, 6 experienced reactionary postoperative hemorrhage, 3 each in the vaginal hysterectomy and laparoscopic hysterectomy groups. That would make the incidence of postoperative reactionary hemorrhage 0.6% in the vaginal hysterectomy and 1.2% in the laparoscopic hysterectomy group. None of these 6 patients had any preoperative hemorrhagica diatheses. There was neither ureteric, bladder, intestinal, nor any other injuries in the whole series. No long-term complications or mortalities occurred. CONCLUSION: Reactionary postoperative hemorrhage is a rare, albeit serious, complication of contemporary gynecological surgery; this complication may occur despite meticulous surgical technique. The key to successful management is prompt diagnosis, urgent resuscitation, and return to the OT to arrest the bleeding.