Article

Laparoscopic excision of endometriosis: A randomized, placebo-controlled trial

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Abstract

To examine the effect on pain and quality of life for women with all stages of endometriosis undergoing laparoscopic surgery compared with placebo surgery. A randomized, blinded, crossover study. A tertiary referral unit in a district general hospital. Thirty-nine women with histologically proven endometriosis completed the 12-month study. Women were randomized to receive initially either a diagnostic procedure (the delayed surgical group) or full excisional surgery (the immediate surgery group). After 6 months, repeat laparoscopy was performed, with removal of any pathology present. The end points were changes from baseline values of visual analogue pain scores, validated quality-of-life instruments (EQ-5D and SF-12), and sexual activity questionnaire scores. Patients and assessors of outcomes were blinded to the treatment-group assignment. Significantly more of the 39 women operated on according to protocol reported symptomatic improvement after excisional surgery than after placebo: 16 of 20 (80%) vs. 6 of 19 (32%); chi(2)(1) = 9.3. Other aspects of quality of life were also significantly improved 6 months after excisional surgery but not after placebo. Progression of disease at second surgery was demonstrated for women having only an initial diagnostic procedure in 45% of cases, with disease remaining static in 33% and improving in 22% of cases. Nonresponsiveness to surgery was reported in 20% of cases. Laparoscopic excision of endometriosis is more effective than placebo at reducing pain and improving quality of life. Surgery is associated with a 30% placebo response rate that is not dependent on severity of disease. Approximately 20% of women do not report an improvement after surgery for endometriosis.

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... Pre-, peri-and postoperative co-interventions were reported in 45 (47%), 45 Trials offering the treatment intervention to patients allocated to placebo Forty-three (45%) trials [45][46][47][48][49]51,[54][55][56]58,59,61,62,64,66,[68][69][70][71][73][74][75]77,78,84,85,[88][89][90]95,97,99,107,109,111,112,114,119,121,122,124,125,132 reported that the treatment intervention was offered to patients in the placebo group. Seven trials 59,73,74,85,109,112,119 were formal crossover trials and one 112 had a four-group trial design that randomised the order of intervention delivery. ...
... Pre-, peri-and postoperative co-interventions were reported in 45 (47%), 45 Trials offering the treatment intervention to patients allocated to placebo Forty-three (45%) trials [45][46][47][48][49]51,[54][55][56]58,59,61,62,64,66,[68][69][70][71][73][74][75]77,78,84,85,[88][89][90]95,97,99,107,109,111,112,114,119,121,122,124,125,132 reported that the treatment intervention was offered to patients in the placebo group. Seven trials 59,73,74,85,109,112,119 were formal crossover trials and one 112 had a four-group trial design that randomised the order of intervention delivery. Rationales were given by 16 (37%) trials. ...
... The degree of operator skill was reported in 22 trials (23%), 13,47,50,51,55,59,69,70,74,78,79,83,85,91,94,99,100,105,110,121,123,128 independent data monitoring was reported in 28 trials (29%) 13,45,46,52,55,57,60,61,68,69,71,72,78,82,84,[97][98][99][100]103,104,106,113,114,121,125,128,136 and an unblinding protocol was provided in one study. 84 Ninety-six placebo-controlled surgical trials were identified. ...
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Background The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. Funding Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council–National Institute for Health Research Methodology Research programme.
... As discussed above, surgery offers people the opportunity to not only have their condition diagnosed but possibly treated. Abbott et al. (2004) performed a blinded study in which subjects were randomized to initially receive either a diagnostic or operative laparoscopy. Operative laparoscopy was demonstrated to be more effective at reducing pain and improving QoL as compared to diagnostic laparoscopy 135 . ...
... Abbott et al. (2004) performed a blinded study in which subjects were randomized to initially receive either a diagnostic or operative laparoscopy. Operative laparoscopy was demonstrated to be more effective at reducing pain and improving QoL as compared to diagnostic laparoscopy 135 . A prospective study of women who underwent an operative laparoscopy for endometriosis demonstrated that the reduced pain and improved QoL state persisted up to five years 136 . ...
... An observational study demonstrated that consistent peritonectomy in women with altered peritoneum followed by adjuvant hormonal therapy resulted in improved pregnancy outcomes and decreased disease recurrence 137 . There is, in addition, a wellknown placebo effect of laparoscopy in the management of endometriosis 135,138,139 . In Abbott et al.'s randomized trial, at 6 months, 30% of subjects within the placebo group reported symptomatic improvement. ...
Article
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Endometriosis is a chronic systemic disease that can cause pain, infertility, and reduced quality of life in those affected. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Diagnostic test accuracy research in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this state‐of‐the‐art review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical exam including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis, and histopathology. Our review suggests that although non‐invasive diagnostic methods such as clinical assessment, ultrasound and MRI do not yet formally qualify as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely appropriate for advanced states of endometriosis. We also demonstrate through our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold standard diagnostic method for endometriosis, but rather multiple accepted diagnostic methods depending on the circumstances. This article is protected by copyright. All rights reserved.
... Due to these symptoms, endometriosis may have a profound impact on quality of life and mental health of the patients affected. In 2004 Abbot et al. (19) demonstrated that surgical excision of endometriosis determines a symptomatic improvement signi cantly more than placebo. ...
... A transabdominal ultrasound scan of the kidneys was also routinely performed to rule out hydroureteronephrosis (an indirect marker for parametrial nodules). (19) Eventually, they underwent pelvic magnetic resonance with rectal injection of 10-50 ml of sterile gel to con rm dimension and depth of in ltration of the bowel lesions (if any) and to de ne the parametrial/ureteral involvement. ...
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Objective: Complete eradication of parametrial nodules of Deep Infiltrating Endometriosis (DIE) is associated with a high risk of iatrogenic nerves damage and pelvic organs dysfunction. The aim of this study is to evaluate via validated questionnaires the effect of laparoscopic excision of parametrial DIE on quality of life as first outcome and on pain symptoms and post- operative voiding function (bladder and rectal) as secondary outcome. Study design: All patients undergoing laparoscopic excision of posterior or lateral parametrial DIE by a single expert surgeon between January 2013 and March 2017 were included in the study. A nerve-sparing approach was adopted in all patients. Quality of life (QoL) and Functional outcomes were evaluated using validated questionnaires (EHP-30 for the health profile, NBD score for intestinal function, ICIQ-FLUTS for urinary function), administered preoperatively and after surgery. Pain scores were collected before and after surgery using Visual Analogue Scale (VAS). Results: During the study period a total of fifty-nine patients met the inclusion criteria. Fifty-one patients agreed to fill out questionnaires for post-operative outcomes. EHP-30 scores had a significant improvement in all the domains analyzed even in the relationship with children and fertility module despite to the small number of patients answering those questions. No differences were found in terms of urinary function between pre and post-operative questionnaires (ICIQ-FLUTS). Bowel function improved in patients’ subjective perception. The NBD score showed that intestinal dysfunction related only to constipation and was reported as very minor by 76.4% of patients, minor by 11.8%, moderate by 5.9% by and severe by 5.95% of patients. Pain symptoms (VAS score) decreased significantly after surgery with the exception of chronic pelvic pain. (p value < 0,05). Conclusions: Laparoscopic nerve-sparing radical excision of parametrial DIE is safe and effective when performed by an expert surgical equipe. This approach can favorably impact on patients QoL. Moreover, it has proved to result in pain score and voiding function improvements.
... 21 in a randomized control trial (rct) evaluating women with severe endometriosis, the authors noted a reduction of CPP in 80% of patients after surgical excision compared to 32% of controls, with a strong improvement in Qol. 20 The beneficial effect of conservative surgery on QoL was recently confirmed by Rindos et al. who observed a long-term improvement in all aspects of Qol and pain reduction for up to 6.8 years after laparoscopy. 22 Unfortunately, pain may return after surgery even in the absence of lesion recurrence. ...
... 19 surgical excision of endometriotic lesions may be effective on pain in about 80% of cases, at least for a while, thus supporting the theory that endometriosis is the cause of pain. 20 in women with minimal and moderate endometriosis, surgery resulted in a statistically significant reduction in overall pain at 6 and 12 months, 514 MiNerVa Obstetrics aNd GyNecOlOGy October 2021 ...
Article
Introduction: Endometriosis is a chronic inflammatory disease that affects approximately 10% of women of reproductive age. Its clinical manifestations are highly heterogeneous, but pelvic pain is the most frequent, causing functional disability. Cyclic or acyclic chronic pelvic pain (CPP), dysmenorrhea and dyspareunia are frequent symptoms which often compromise all aspects of the women's quality of life (QoL). The pathophysiology of endometriosis-related pain is extremely complex and not always clear. The aim of this systematic review was to focus on recent updates on the clinical presentation, the pathophysiology and the most important mechanisms involved in the pathogenesis of pelvic pain in endometriosis. Evidence acquisition: A literature search in the Cochrane library, PubMed, Scopus and web of Science databases has been performed, identifying articles from January 1995 to November 2020. Evidence synthesis: Several processes seem to be involved in the pathogenesis of pain, but many aspects are still unclear. Scientific evidence has shown that a correlation between pain severity and stage of endometriosis rarely occurs, whereas there is a significant correlation between pain and the presence of deep endometriosis. Onset and intensity of pain may be due to a complex process involving central sensitization and peripheral activation of nociceptive pathways as well as dysfunction of the immune system and of the hypothalamic-pituitary-adrenal (HPA) axis. Conclusions: A deeper understanding of these different pathogenetic mechanisms may improve future treatments in women with painful endometriosis.
... However, this is based on one small randomised trial of 24 participants that did not report blinding [15] and a larger RCT of 178 participants that lacked explanation of how ablation or excision were done or which method was used to treat ovarian endometriomas [16]. An RCT showed that laparoscopic excision of endometriosis lesions was more effective than placebo (80% vs 32%) in terms of reducing pain and improving quality of life [17]. However this study lacked power with only 19 women in the placebo arm vs 20 women in the treated arm. ...
... Likewise, in another study comparing de nitive surgery and uterine-sparing laparoscopic excision in the treatment of endometriosis, it was observed that there was an improvement in the quality of life in both groups postoperatively [22]. In a randomized controlled study, a decrease in pain scores and an increase in quality of life were observed during patients' 6-and 12-month follow-ups [23]. ...
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Purpose Endometriosis affects the quality of life, sleep, and sexual life of patients due to pain. This study compared the scores of endometriosis patients in these three areas before and after surgery. Methods Patients between the ages of 18–60 with a prediagnosis of endometriosis were enrolled. Postoperative histopathological diagnosis of endometriosis was confirmed in all patients. This study included 56 patients who completed pre- and postoperative (three months) evaluation of quality scale questionnaires: a visual analog scale for pelvic pain, the Pittsburgh Sleep Quality Index, Morningness-Eveningness Questionnaire, Endometriosis Health Profile-30 Questionnaire, and Female Sexual Function Index were administered prior to and three months after each patient’s surgery. Results Among the 56 female patients included in this study, statistically significant improvement statistically significant improvement was observed in pain scores, quality of life, sexual function, and sleep of all patients regardless of endometriosis stage. Conclusion Endometriosis is a disease that progresses, with increasing pain scores; it has negative effects on the quality of life, sexual function, and sleep of patients. Surgical or medical treatment can be performed considering the complaints and fertility status of the patients.
... How difficult it is to diagnose endometriosis based only on a medical interview is emphasized by the fact that the diagnosis is made after many years, even though the first symptoms appear in adolescence or early youth. According to literature data, there is a long delay in diagnosis from the onset of symptoms [6,[26][27][28]. Currently, the time from the onset of the first symptoms to making the diagnosis is from about 5 years in Ireland and Belgium to about 10 years in Germany, Austria, and the USA [29][30][31]. ...
Article
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Background: Chronic pelvic pain affects approximately 15% of reproductive age women. It is mainly caused by adhesions (20-40%). Despite CPP being the main symptom of endometriosis, the disease is confirmed by laparoscopy only in 12-18% of cases. The aim of this study was to evaluate the results of laparoscopy in women with CCP and to assess the sensitivity and specificity of elements of an interview and clinical examination. Materials and methods: The study included 148 women with CPP. Each patient underwent laparoscopy. In laparoscopy, the presence of endometriosis and/or peritoneal adhesions was confirmed. Then, the sensitivity and specificity and the positive and negative predictive value of endometriosis symptoms or abnormalities in the gynecological examination were statistically calculated. Results: After previous surgery, adhesions were found in almost half (47%) of patients. In patients without a history of surgery, adhesions were diagnosed in 6.34% of patients. Endometriosis without coexisting adhesions was more often diagnosed in women without previous surgery (34.9%), compared to 10.58% in the group with a history of surgery (p < 0.05). Conclusions: Intraperitoneal adhesions are most common in women after pelvic surgery and with chronic ailments. The best results for sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of endometriosis are found in women with irregular menstruations during which the pain increases. Laparoscopy still remains the primary diagnostic and therapeutic method for these women.
... 9 However, there is also a notable, though variable, placebo effect associated with endometriosis surgery. 10,11 It has been noted that surgery offers very high placebo effects across different disciplines, which may be secondary to the intensiveness, perceived innovation, pre-existing beliefs of curative effect, and further strengthened by a surgeon's counselling regarding expectations. Misal et al . ...
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At first glance, endometriosis appears to be a relatively simple disease, characterised by endometrial-like glands and stroma where they are not supposed to be. In practice, however, endometriosis is far from a simple disease. Non-specific symptoms often accompany the classical clinical phenotype of dysmenorrhea, dyspareunia, and dyschezia, leading to confusion in symptom aetiology and treatment pathways. Medical treatment of endometriosis has changed little in the past decades and relies on ovulation suppression. Performing surgery to treat all visible disease and restore normal anatomy remains a cornerstone of managing endometriosis, though many jurisdictions reserve this for those who fail medical management. We are often guilty of blindly following this algorithmic approach despite its ineffectiveness for some patients. Until we have more effective, tolerable, and endometriosis-specific therapies available, we should aim to optimise our current therapeutic options. This optimisation may be possible through a deeper understanding and appropriate utilisation of the often overlooked placebo and nocebo effects. Before discussing these effects, we must be abundantly clear that in no way are we suggesting that patients fabricate reports of treatment ineffectiveness or the experience of side effects. Not only is that not our intent, but it is simply not true. The patients’ experience with a therapy (both medical and surgical), whether effective or ineffective, are indeed authentic . With this in mind, our aim with this commentary is to bring awareness to placebo and nocebo effects in the treatment of endometriosis, recognise how our words and actions can affect treatment outcomes, and suggest how to further our understanding of these phenomena in our field.
... Consideration of patients' feelings about their symptoms and the impact of various diseases or symptoms on their quality of life has developed substantially in recent years with the increasing use of patient-reported outcomes (PROs), assessed by questionnaires or other tools [4]. PROs for assessing symptoms and quality of life are frequently used with patients with endometriosis to assess the potential benefits of treatment [3,[5][6][7]. The literature includes various scales for pain assessment in endometriosis, most often visual analogue scales. ...
Article
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Objectives: To study the measurement properties, the responsiveness and the minimal clinically important difference of the ENDOPAIN-4D: a new questionnaire for assessing pain in endometriosis. Methods: A prospective, observational, multicentre study was conducted including all women ≥18 years consulting for symptomatic proven endometriosis between 1 January 2017 and 30 June 2018 and volunteering to participate. Each patient had to answer a new self-administered patient-reported outcome (PRO) questionnaires (the ENDOPAIN-4D) at inclusion (T0) and 12 months after medical or surgical treatment (T1). Criteria defined by COSMIN were used to validate the questionnaire's measurement properties. The minimal clinically important difference was estimated by the anchor-based method. Results: The study included 199 women. The ENDOPAIN-4D score had a four dimensional structure with good internal consistency (measured by Cronbach α): (I) pain-related disability (α = 0.79), (II) painful bowel symptoms (α = 0.80), (III) dyspareunia (α = 0.83), and (IV) painful urinary tract symptoms (α = 0.77). They produced four subscores that can be summed to obtain a single score (α = 0.61). The ENDOPAIN-4D total score ranged from 0 to 94.00 (mean ± SD: 46.7 ± 22). The total score was significantly correlated with the PROs used in endometriosis. Sensitivity to change was good with large effect sizes (ES) (mean of the differences: 36.3 p = 1.8 10-7, ES 0.76). The minimal clinically important difference of the global score was determined to be 10.9. Conclusions: The ENDOPAIN-4D questionnaire is easy to use, valid, and effective in assessing patient reported pain symptoms in women treated for endometriosis. This new instrument can be used as the primary outcome for future clinical trials and as a tool for routine patient follow-up.
... In a randomized, placebo-controlled trial by Abbott et al. comparing immediate excision with delayed surgery on 39 women, of whom about 50% had rAFS stage I and II, surgery was associated with a 30% placebo response rate, not dependent on the severity of the disease. Approximately 20% of women did not report an improvement after surgery for endometriosis [34]. In another classical study by Sutton et al. on the same question (but on women with mostly stage I disease receiving laparoscopic ablation) the nonresponse rate was 38% [35]. ...
Article
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Purpose To analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility. Methods Using our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in minimal invasive surgery, and included a suspended hormonal pretreatment for 2 months. Postoperative outcomes including complications, fertility and recurrence rates were analysed. Results Laparoscopic peritonectomy was performed on 94 women. Follow-up data were available in 87% of these cases. At the time of surgery, almost all patients tested showed signs of stage I or II endometriosis (44.7 and 48.9%, respectively). More than three-quarters of the women reported pain relief, inter alia, due to the post-surgical hormonal therapy. About one-third of the patients wanted to have children after the procedure. 62% of them became pregnant and the majority did so without the need for assisted reproductive therapy. In seven women a re-operation was performed. Conclusion According to our data, a consistent excision of altered peritoneum followed by adjuvant hormonal therapy and multimodal concepts results in better outcomes for the patient, particularly in regards to pregnancy and recurrence rates.
... Some individuals with severe pain have minimal disease (26), and some individuals with severe disease have no pain (27). Laparoscopic surgical removal of endometriotic lesions reduces pain in some, but not all, individuals (28,29). Current guidelines recommend access to a multidisciplinary pain management service as needed (30)(31)(32). ...
Article
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Endometriosis-associated pain and the mechanisms responsible for its initiation and persistence are complex and difficult to treat. Endometriosis-associated pain is experienced as dysmenorrhea, cyclical pain related to organ function including dysuria, dyschezia and dyspareunia, and persistent pelvic pain. Pain symptomatology correlates poorly with the extent of macroscopic disease. In addition to the local effects of disease, endometriosis-associated pain develops as a product of peripheral sensitization, central sensitization and cross sensitization. Endometriosis-associated pain is further contributed to by comorbid pain conditions, such as bladder pain syndrome, irritable bowel syndrome, abdomino-pelvic myalgia and vulvodynia. This article will review endometriosis-associated pain, its mechanisms, and its comorbid pain syndromes with a view to aiding the clinician in navigating the literature and terminology of pain and pain syndromes. Limitations of our current understanding of endometriosis-associated pain will be acknowledged. Where possible, commonalities in pain mechanisms between endometriosis-associated pain and comorbid pain syndromes will be highlighted.
... 37 The prognosis for women who undergo laparoscopic excision of endometriosis post-operatively is quite good according to many studies, with reports of significant decrease in symptoms in as many as 80% of the participants. [38][39] However, in cases where little or no change in pain following excision surgery is reported, it is often suggested that the persistence of symptoms is because of the presence of deep endometriosis lesions that were not successfully excised. The possibility of PFM overactivity or spasm as a potential cause of persistent pain is not always taken into consideration, despite the known fact that many women with endometriosis have PFD. ...
Article
Background: Pelvic pain and abnormal pelvic floor muscle (PFM) tension frequently are present in individuals with endometriosis and often persist even after surgical excision of the endometriosis lesions. Physical therapists are educated in improving muscle tone and function for individuals who have sustained injury, have had surgery, or have required rehabilitation for various pelvic health conditions. More scientific evidence is needed to support the benefits of physical therapy (PT) interventions for individuals with a history of endometriosis. Case Description: The 50-year old female patient presented in this case report underwent laparoscopic excision of endometriosis, yet she continued to experience discomfort in her left lower abdomen and vaginal area after surgery. Within a four month period, the patient participated in ten sessions of pelvic physical therapy that included manual therapy, instruction in relaxation techniques, and a home program. Outcomes: At the time of her discharge from physical therapy, the patient reported a reduction in symptoms on the Pelvic Floor Impact Questionnaire - Short Form 7 (PFIQ-7) and was able to resume activities that she had not previously tolerated because of abdominal and pelvic pain. Discussion: Identifying effective interventions for patients that have received surgical management is important. Pelvic physical therapy may help individuals avoid surgery and eliminate or reduce the use of medications. Because of the positive outcomes of this case report, it is recommended that when endometriosis is suspected or diagnosed, a pelvic physical therapy evaluation should be considered. Further research is needed to assess physical therapy as part of the standard of care for women with suspected or diagnosed endometriosis.
... These include drugs that suppress ovarian function (which can have adverse effects [5]) or surgery for the lesions (usually laparoscopically). Surgical removal is often considered the best option for symptomatic endometriosis [6], but it does not reduce pain in 20%-28% of patients who undergo surgery [7,8]. ...
Article
Background Endometriosis is a chronic inflammatory condition affecting 6%-10% of women of reproductive age and is defined by the presence of endometrial-like tissue outside the uterus (lesions), commonly affecting the pelvis and ovaries. It is associated with debilitating pelvic pain, infertility, and fatigue and often has devastating effects on the quality of life (QoL). Although it is as common as back pain, it is poorly understood, and treatment and diagnosis are often delayed, leading to unnecessary suffering. Endometriosis has no cure. Surgery is one of several management options. Quantifying the probability of successful surgery is important for guiding clinical decisions and treatment strategies. Factors predicting success through pain reduction after endometriosis surgery have not yet been adequately identified. Objective This study aims to determine which women with confirmed endometriosis benefit from surgical improvement in pain and QoL and whether these women could be identified from clinical symptoms measured before laparoscopy. Methods First, we will carry out a systematic search and review and, if appropriate, meta-analysis of observational cohort and case-control studies reporting one or more risk factors for endometriosis and postsurgical treatment success. We will search PubMed, Embase, and Cochrane databases from inception without language restrictions and supplement the reference lists by manual searches. Second, we will develop separate clinical prediction models for women with confirmed and suspected diagnoses of endometriosis. A total of three suitable databases have been identified for development and external validation (the MEDAL [ISRCTN13028601] and LUNA [ISRCTN41196151] studies, and the BSGE database), and access has been guaranteed. The models will be developed using a linear regression approach that links candidate factors to outcomes. Third, we will hold 2 stakeholder co-design workshops involving eight clinicians and eight women with endometriosis separately and then bring all 16 participants together. Participants will discuss the implementation, delivery, usefulness, and sustainability of the prediction models. Clinicians will also focus on the ease of use and access to clinical prediction tools. Results This project was funded in March 2018 and approved by the Institutional Research Ethics Board in December 2019. At the time of writing, this study was in the data analysis phase, and the results are expected to be available in April 2021. Conclusions This study is the first to aim to predict who will benefit most from laparoscopic surgery through the reduction of pain or increased QoL. The models will provide clinicians with robustly developed and externally validated support tools, improving decision making in the diagnosis and treatment of women. International Registered Report Identifier (IRRID) DERR1-10.2196/20986
... Hysterectomy was frequently recommended although pain reoccurrence associated with advanced stage endometriosis following hysterectomy has rates as high as 62%. 51 Similarly, approximately 20% of people with endometriosis report no change or worsening of their symptoms following laparoscopy, 52,53 and over 60% of patients have repeat laparoscopy. 5 54 and are frequently associated with adverse effects. ...
Article
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Background Females with persistent pelvic pain (PPP) report great variability in treatments they are recommended despite the availability of clinical practice guidelines (CPGs) that aim to standardise care. A clear consensus for the best practice care for PPP is required. Objective Identify and summarise treatment recommendations across CPGs for the management of PPP, and appraise their quality. Search strategy MEDLINE, CENTRAL, EMBASE, EmCare, SCOPUS, the Cochrane Database of Systematic Reviews, Web of Science Core Collection, and relevant guideline databases were searched from their inception to June 2021. Selection criteria Included CPGs were those for the management of urogynaecological conditions in adult females published in English, of any publication date, and endorsed by a professional organisation or society. Data collection and Analysis We screened 1,379 records and included 20 CPGs. CPG quality was assessed using The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Descriptive synthesis compiled treatment recommendations across CPGs. Main Results CPGs for seven conditions provided 281 individual recommendations. On quality appraisal, guidelines on average scored ‘excellent’ for the domains ‘scope and purpose’ (80.6%, SD=13.3) and ‘clarity and presentation’ (74.4%, SD=12.0); for other domains, average scores were satisfactory or poor. Four guidelines (Endometriosis, NICE, RANZCOG, ESHRE; PCOS, Teede et al. 2018) were deemed recommended for use. Recommendations were most frequent for pharmaceutical and surgical interventions. Recommendations were variable for psychological, physiotherapy, and other conservative interventions. Conclusions The quality of CPGs for PPP is generally poor. Several CPGs endorse the consideration of biopsychosocial elements of PPP. Yet most recommend pharmaceutical, surgical, and other biomedical interventions.
... Likewise, in another study comparing definitive surgery and uterinesparing laparoscopic excision in the treatment of endometriosis, it was observed that there was an improvement in the quality of life in both groups postoperatively [22]. In a randomized controlled study, a decrease in pain scores and an increase in quality of life were observed during patients' 6-and 12-month follow-ups [23]. ...
Article
Full-text available
Purpose Endometriosis affects the quality of life, sleep, and sexual life of patients due to pain. This study compared the scores of endometriosis patients in these three areas before and after surgery. Methods Patients between the ages of 18 and 60 with a prediagnosis of endometriosis were enrolled. Postoperative histopathological diagnosis of endometriosis was confirmed in all patients. This study included 56 patients who completed pre- and postoperative (three months) evaluation of quality scale questionnaires: a visual analog scale for pelvic pain, the Pittsburgh Sleep Quality Index, Morningness–Eveningness Questionnaire, Endometriosis Health Profile-30 Questionnaire, and Female Sexual Function Index were administered prior to and 3 months after each patient’s surgery. Results Among the 56 female patients included in this study, statistically significant improvement was observed in pain scores, quality of life, sexual function, and sleep of all patients regardless of endometriosis stage. Conclusion Endometriosis is a disease that progresses, with increasing pain scores; it has negative effects on the quality of life, sexual function, and sleep of patients. Surgical or medical treatment can be performed considering the complaints and fertility status of the patients.
... 99,100 The outcomes of surgical therapies are not better as 20% of women show no improvement and the recurrence rates range from 30% to 50%. 101,102 Thus, there is a need for exploring future treatment modalities that reduce pain and infertility with fewer side effects. Finally, addressing mental health problems associated with endometriosis like depression and grieving and evaluating cognitive-behavioral therapies and coping strategies may also be a crucial part of the multidisciplinary approach in future endometriosis research. ...
Article
Endometriosis is a relatively common condition in which endometrial tissue is established in locations outside the uterus where, like the eutopic endometrium, it responds to hormonal stimuli and develops internal bleeding, inflammation, and fibrosis. These changes are associated with chronic and often debilitating cyclic pain and infertility. The pathogenesis of endometriosis is multifactorial, and several theories have been proposed to explain it. These include retrograde menstruation, celomic metaplasia, embryologic rests, and lymphovascular spread. Hormones, immunologic status, and genetic factors may also play a role. In most patients, the disease involves pelvic organs, but rarely it may also extend to a large variety of distant locations in the body. Patients with ovarian endometriosis are at higher risk for developing ovarian carcinomas including endometrioid and clear cell carcinomas. Some of these carcinomas may arise in a background of structural and/or nuclear atypia within the endometriotic foci. There is no known cure for endometriosis and treatment mostly consists of managing chronic pain or infertility.
... In addition, the response to NSAIDs is often ineffective [5]. In the case of surgery, it does not reduce pain in 20-28%, [23,24], failing in 50% of patients before 1 year [18] and requiring another surgery within 2 to 5 years in 25.5% and 40-50% of the cases, respectively [10]. There are also rare events such as progesterone resistance, relief of pain symptoms after GnRHa therapy in patients who did not previously respond to progesterone treatment [22,25], or pain recurrences after surgery in the absence of new lesions [26]. ...
Article
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Background: Although several treatments are currently available for chronic pelvic pain, 30-60% of patients do not respond to them. Therefore, these therapeutic options require a better understanding of the mechanisms underlying endometriosis-induced pain. This study focuses on pain management after failure of conventional therapy. Methods: We reviewed clinical data from 46 patients with endometriosis and chronic pelvic pain unresponsive to conventional therapies at Puerta de Hierro University Hospital Madrid, Spain from 2018 to 2021. Demographic data, clinical and exploratory findings, treatment received, and outcomes were collected. Results: Median age was 41.5 years, and median pain intensity was VAS: 7.8/10. Nociceptive pain and neuropathic pain were identified in 98% and 70% of patients, respectively. The most common symptom was abdominal pain (78.2%) followed by pain with sexual intercourse (65.2%), rectal pain (52.1%), and urologic pain (36.9%). A total of 43% of patients responded to treatment with neuromodulators. Combined therapies for myofascial pain syndrome, as well as treatment of visceral pain with inferior or superior hypogastric plexus blocks, proved to be very beneficial. S3 pulsed radiofrequency (PRF) plus inferior hypogastric plexus block or botulinum toxin enabled us to prolong response time by more than 3.5 months. Conclusion: Treatment of the unresponsive patient should be interdisciplinary. Depending on the history and exploratory findings, therapy should preferably be combined with neuromodulators, myofascial pain therapies, and S3 PRF plus inferior hypogastric plexus blockade.
... Interventions for endometriosis-associated symptoms result in suboptimal patient outcomes. Laparoscopic removal of endometriosis is the preferred treatment method, but is often associated with unchanged or worsening pain, and high rates of repeat surgery [12,13]. Pharmaceutical interventions are common, including hormonal therapies and analgesics, but limited efficacy and bothersome side effects often lead to serial medication trials [14] and polydrug use [15]. ...
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Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies – of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.
... In addition, endometriosis pain is probably not only caused by the local immune response since it is well known that not in all cases, the removal of lesions improves pain relief (20-28% of patients do not have pain relief after surgery) 37,38 . ...
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Endometriosis is a chronic gynecological disorder involved in the pathogenesis of chronic pelvic pain, based on a probable up regulation of the inflammatory system. The objective of the study is to investigate the peritoneal and serum levels of ENA-78 with the severity of endometriosis symptoms (dysmenorrhea, chronic pelvic pain and dyspareunia) using the visual analogue scale (VAS). This is a prospective case–control study that included 53 symptomatic women with evidence of endometriosis and 53 age-matched controls who underwent elective laparoscopic surgery for benign diseases. The concentration of ENA-78 was assessed in blood and peritoneal fluid samples in the follicular phase. In peritoneal fluid and plasma, the concentration of ENA-78 was significantly higher in cases than in controls (p < 0.001). A significant correlation was observed between peritoneal fluid ENA-78 levels and the severity of dysmenorrhea (Spearman Rho = 0.237; p = 0.014), and chronic pelvic pain (Spearman Rho = 0.220; p = 0.022) in endometriosis patients. Plasma levels ENA-78 showed a significant correlation with the severity (VAS score) of chronic pelvic pain (Spearman Rho = 0.270, p = 0.005 for cases), though a weak correlation was evident between plasma levels of ENA-78 and severity of dysmenorrhea (Spearman Rho = 0.083, p = 0.399 for cases). In conclusion, chronic pelvic pain in endometriosis is caused by changes of local and systemic activated chemokine patterns. These modifications involve the relationship between pro-inflammatory, angiogenic and angiostatic chemokines that modulate the severity of endometriosis associated symptoms.
Chapter
Robotic platform, despite its limitations, has made surgeries to be performed more easily in a minimally invasive way. This platform is a reliable and durable way to be precise in dissection and reconstruction, enabling surgeons to bridge the gap between laparotomy and laparoscopy. Endometriosis is an enigmatic disease that exists in many forms, like peritoneal endometriosis, ovarian endometriosis, and extragenital endometriosis. The main goal of surgical treatment is restoration of anatomy and removal of all endometriotic implants, with the hope of alleviating pain and improving fertility.
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Endometriosis is a painful inflammatory disorder affecting ~10% of women of reproductive age. Although chronic pelvic pain (CPP) remains the main symptom of endometriosis patients, adequate treatments for CPP are lacking. Animal models that recapitulate the features and symptoms experienced by women with endometriosis are essential for investigating the etiology of endometriosis, as well as developing new treatments. In this study, we used an autologous mouse model of endometriosis to examine a combination of disease features and symptoms including: a 10 week time course of endometriotic lesion development; the chronic inflammatory environment and development of neuroangiogenesis within lesions; sensory hypersensitivity and altered pain responses to vaginal, colon, bladder, and skin stimulation in conscious animals; and spontaneous animal behavior. We found significant increases in lesion size from week 6 posttransplant. Lesions displayed endometrial glands, stroma, and underwent neuroangiogenesis. Additionally, peritoneal fluid of mice with endometriosis contained known inflammatory mediators and angiogenic factors. Compared to Sham, mice with endometriosis displayed: enhanced sensitivity to pain evoked by (i) vaginal and (ii) colorectal distension, (iii) altered bladder function and increased sensitivity to cutaneous (iv) thermal and (v) mechanical stimuli. The development of endometriosis had no effect on spontaneous behavior. This study describes a comprehensive characterization of a mouse model of endometriosis, recapitulating the clinical features and symptoms experienced by women with endometriosis. Moreover, it delivers the groundwork to investigate the etiology of endometriosis and provides a platform for the development of therapeutical interventions to manage endometriosis‐associated CPP.
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Background: Up to 28% of endometriosis patients do not get pain relief from therapeutic laparoscopy but this subgroup is not defined. Objectives: To identify any prognostic patient-specific factors (such as but not limited to patients’ type or location of endometriosis, sociodemographics and lifestyle) associated with a clinically meaningful reduction in post-surgical pain response to operative laparoscopic surgery for endometriosis. Search strategy: PubMed, Cochrane and Embase databases were searched from inception to 19th May 2020 without language restrictions. Backward and forward citation tracking was used. Selection criteria, data collection and analysis: Cohort studies reporting prognostic factors, along with scores for domains of pain associated with endometriosis before and after surgery, were included. Studies that compared surgeries, or laboratory tests, or outcomes without stratification were excluded. Results were synthesised but variation in study designs and inconsistency of outcome reporting precluded us from doing a meta-analysis. Main results: Five studies were included. Quality assessment using the Newcastle Ottawa Scale graded three studies as high, one as moderate and one as having a low risk of bias. Four of five included studies separately reported that a relationship exists between more severe endometriosis and stronger pain relief from laparoscopic surgery Conclusion: Currently there are few studies of appropriate quality to answer the research question. We recommend future studies report core outcome sets to enable meta-analysis. Funding: NIHR PB-PG-0317-20018 Prospero: CRD42018108604 Keywords: endometriosis, laparoscopy, systematic review, surgery
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Background: Persistent pelvic pain affects between 10-20% of women with a significant impact on their physical and mental health, sexual relationships, families and society. Estimates of the cost to women and the community is over $9 billion/annum. Although endometriosis is considered a leading cause of pelvic pain, no symptoms reliably allow the identification of those with and without endometriosis. Furthermore, the significance of mild endometriosis is now debated. The optimal clinical approach for pelvic pain and endometriosis remains unclear, with increasing evidence of other contributing factors such as central sensitisation. Studies to date have significant limitations due to their sample size, relatively short follow-up, and inclusion of only women with laparoscopically identified endometriosis. Aims: To undertake a real-world study of women referred with pain to gynaecology outpatients of a women's hospital and explore factors influencing three-year outcomes. Materials and methods: Five hundred women will be randomised to one of two gynaecology units. The units will provide routine clinical care but their approaches to management of women with pelvic pain and endometriosis differ: one with skilled endoscopic gynaecologists has greater emphasis on surgery, the other, gynaecologists have more medical expertise in managing pain and menstrual problems. Participants will complete six-monthly questionnaires regarding pain and quality of life for three years. This information will not be available to clinicians. Their medical care will be followed from their medical records. The cost of outpatient care and admissions will be calculated. Data will be analysed using STATA software with appropriate post hoc tests. Australian and New Zealand Clinical Trials Registry (ANZCTR:ACTRN12616000150448).
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Aim: To describe the characteristics, management and outcomes of a cohort of young people with dysmenorrhea presenting to a tertiary adolescent gynecology service, managed primarily with medical interventions. Methods: A retrospective cohort study was conducted at the Royal Children's Hospital in Melbourne, Australia. Data were collected from medical records of patients presenting with dysmenorrhea and/or pelvic pain. Results: Of 154 patients, mean age of presentation was 15.7 years (SD = 2.2) and mean duration of pain was 14.9 months (SD = 10.8). Regular cycles were reported by 64.5%, and heavy menstrual bleeding (HMB) in 67.8%. Patients self-reporting HMB reported less pain on the day prior to menses than those not reporting HMB (P < 0.005). At follow-up, therapeutic interventions included nonsteroidal anti-inflammatory drugs, tranexamic acid and cyclic or continuous combined oral contraceptive pills. Laparoscopies were undertaken in 12 (8.1%) patients, with normal findings in 8 (66.7%). Secondary dysmenorrhea was identified in 10 patients: of these, endometriosis was identified in one patient and unilateral obstructive Müllerian anomalies in six. Overall, 92.2% of patients had improvement in symptoms after treatment. Conclusion: Laparoscopy and endometriosis rates in patients presenting to a tertiary center were lower than previously reported, with most patients achieving symptom improvement without laparoscopy.
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Background and objective: Endometriosis, affecting approximately 176 million adults and adolescents worldwide, is a debilitating condition in which uterine tissue grows outside the uterus. The condition costs the US economy approximately $78 billion annually in pain-related disability. By understanding the neural underpinnings of endometriosis-associated pain (EAP) and risk factors for chronification, translational research methods could lessen diagnostic delays and maximize successful pain remediation. This can be accomplished by the novel use of a known method, offset analgesia (OA), to better elucidate the neural mechanisms that may contribute to and maintain EAP. This commentary will provide justification and rationale for the use of OA in the study of EAP. Conclusion: Utilizing an OA paradigm in patients with endometriosis, especially adolescents, may (1) provide insight into neural mechanisms contributing to pain maintenance, which could capture those at-risk for the transition to chronic pelvic pain, (2) provide a metric for the development of future centrally mediated treatment options for this population, and (3) elucidate the brain changes that result in resistance to treatment and pain chronification.
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Objective: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual aspects of trials identified through systematic review methods. Summary background: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. Methods: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted 'projected' design aspects from protocols and 'actual' design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ('completed') and were concluded in a timely fashion. Pairs of authors assessed risk of bias. Results: Of 24 trials with data available to analyse; three were completed and concluded within target timeframe; ten were completed and concluded outside the target timeline; four were completed without clear target timeframes; two were incomplete and concluded within the target framework; five were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. Conclusions: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. Review registration: PROSPERO (CRD42019133296).
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Objective The aim of this systematic review and meta-analysis is to perform an updated analysis of the literature in regard to the surgical management of minimal to mild endometriosis. This study evaluates reproductive aged women with superficial endometriosis to determine if surgical excision compared to ablation results in improved pain scores post-operatively. Data Sources The following databases were searched from inception to May 2020 for relevant studies: Cochrane CENTRAL, Pubmed (MEDLINE), Ovid (MEDLINE), Scopus, and Web of Science. Methods of Study Selection From our literature search, a total of 2,633 articles were identified and screened. Ultimately, four randomized controlled trials were selected and included in our systematic review. The combined total number of subjects was 346 from these four studies, with sample sizes ranging from 24 to 170 participants. Data from three of the included studies were able to be compared and analyzed for a meta-analysis. The primary outcome was reduction in the visual analog scale (VAS) score for endometriosis-associated pain (dysmenorrhea, dyschezia, and dyspareunia), with follow up time ranging from 6 to 60 months post-operatively. Tabulation Data was extracted from each study included mean reduction in VAS score from baseline. A random effects model was used due to significant heterogeneity across studies. Statistical analyses were performed using Review Manager 5.3 software (Cochran Collaboration, Oxford, UK). Integration and Results Meta-analyses showed no significant differences between excision and ablation groups in mean reduction in VAS scores from baseline to 12 months postoperative for dysmenorrhea (mean difference [MD] =-0.03; 95% confidence interval [CI] -1.27 to 1.22, p=0.97), dyschezia (MD=0.46, 95% CI -1.09 to 2.02, p=0.56), and dyspareunia (MD=0.10, 95% CI -2.36 to 2.56, p=0.94). In addition, there were no significant differences between excision and ablation groups in mean VAS scores at 12 month follow-up and beyond for dysmenorrhea (MD=-0.11, 95% CI -2.14 to 1.93, p=0.92), dyschezia (MD=0.01, 95% CI -0.70 to 0.72, p=0.99), and dyspareunia (MD=0.34, 95% CI -1.61 to 2.30, p=0.73). Conclusion Based on the data from our systematic review and pooled meta-analysis, no significant difference between laparoscopic excision and ablation was noted in regard to improving pain from minimal to mild endometriosis. However, in order to make definitive conclusions on this topic, larger randomized controlled trials are needed with longer follow up.
Chapter
Colorectal endometriosis represents the most severe form of endometriosis and affects up to 12% of women and is defined by the infiltration of the muscular layer of the bowel. Little is known about its pathophysiology, especially in infertility and its management is still in debate. The latest ESHRE recommendations emphasize on the benefits of surgery of deep infiltrating endometriosis (DIE) on the quality of life but do not recommend surgery for improving fertility outcomes. New data have been published in the literature and demonstrated that complete removal of DIE lesions in patients with negative factors (failed IVF/ICSI cycles, low AMH levels, and adenomyosis) is associated with a high rate of spontaneous and assisted pregnancies in patients less than 35 years. The pregnancy rates are the highest in the first year after surgery. In cases of chronic pelvic pain, many studies have found that complete removal of lesions is associated with pain reduction (especially dysmenorrhea) and higher quality of life. In conclusion, infertile and pelvic pain patients could benefit from surgery if performed by skilled surgeons.
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The pathophysiology of endometriosis-associated pain involves inflammatory and hormonal alterations and changes in brain signaling pathways. Although medical treatment can provide temporary relief, most patients can achieve long-term sustained pain relief when it is combined with surgical intervention. Owing to its complexity, there is an ongoing debate about how to optimally manage endometriosis-associated pain. We believe optimal management for this condition requires (1) possible egg preservation in affected young patients with and without endometriomas, (2) preoperative medical suppression to inhibit ovulation and to avoid removal of functional cysts that might look like endometriomas, and (3) postoperative hormonal suppression to decrease recurrence, but this treatment should be modified according to disease severity, symptoms, and fertility goals.
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Diagnostic laparoscopy has traditionally been described as the gold standard for diagnosing endometriosis. However, advances in imaging and an increasingly risk-averse population has led many to question if diagnostic laparoscopy is now antiquated. In this paper, we will examine the risks and benefits of performing a diagnostic laparoscopy. We will argue that diagnostic laparoscopy is safe and both positive and negative laparoscopy are vitally important to the individual. Imaging and other non-surgical workup also has a vital role, but should complement rather than replace diagnostic laparoscopy. The available evidence supports this assertion. Diagnostic laparoscopy will not be antiquated any time in the near future.
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Endometriosis can take one of three forms depending on its clinical presentation and management: endometriotic ovarian cyst (ovarian endometrioma), superficial or peritoneal endometriosis and deep infiltrating endometriosis (DIE).1Among them, DIE is considered the most aggressive, and the patient is often affected by more than one type together. The therapeutic methodology should not be influenced by a combination of different types of endometriotic lesion. According to the clinical context and the patient's needs, the treatment of this pathology can be medical or surgical. Although medical therapy could improve endometriosis-associated symptoms, it never offers a definite treatment for symptomatic patients, who often require surgical treatment. The rationale behind endometriosis surgical treatment is to achieve the complete removal of all lesions through a one-step surgical procedure; to obtain promising long-term results for pelvic pain, recurrence rate, and fertility; and to protect the functionality of the involved organs. Achieving these results depends on the total removal of the pathology from the pelvis, in an attempt to preserve, as much as possible, the healthy tissues surrounding the site of the disease. The choice of a surgical approach rather than medical therapy is subject to the patient's expectations, such as pregnancy desire, the effectiveness of treatment compared to possible complications, the type of pain and its intensity, and the location and severity of the disease. In this context, surgical management using a multidisciplinary endometriosis team is an important factor for achieving good outcomes.
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Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, setting, and participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main outcomes and measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.
Chapter
While endometriosis has been historically considered a disease affecting reproductive aged women, the disease can frequently occur in adolescents as well. Adolescents with endometriosis may be asymptomatic or have debilitating and distressing symptoms, interfering with school and social activities. Many adult women experience their endometriosis symptoms starting in adolescence, but most young women do not receive timely treatment. Thus, clinicians should be aware of how endometriosis may present in adolescents in order to proceed with prompt evaluation and treatment. Early prevention in adolescence may help mitigate the long-term sequelae of endometriosis including chronic pelvic pain and infertility.
Article
Objective To identify metabolites in presurgical blood associated with risk of persistent postsurgical pelvic pain 1 year after endometriosis surgery in adolescent and young adult patients. Design Prospective observational study within the Women’s Health Study: From Adolescence to Adulthood, a US-based longitudinal cohort of adolescents and women enrolled from 2012–2018. Setting Two tertiary care hospitals. Patient(s) Laparoscopically confirmed endometriosis patients (n = 180) with blood collected before their endometriosis surgery. Of these, 77 patients additionally provided blood samples 5 weeks to 6 months after their surgery. We measured plasma metabolites using liquid chromatography tandem mass spectrometry, and a total of 390 known metabolites were included in our analysis. Intervention(s) None. Main Outcome Measure(s) Persistent postsurgical pelvic pain, defined as severe, life-impacting pelvic pain 1 year after endometriosis surgery. Result(s) Most patients (>95%) were at stage I/II of the revised American Society for Reproductive Medicine classification. Their average age at diagnosis was 18.7 years, with 36% reporting persistent postsurgical pelvic pain. Of the 21 metabolites in presurgical blood that were associated with risk of persistent postsurgical pelvic pain, 19 metabolites, which were mainly lipid metabolites, were associated with increased risk. Only 2 metabolites—pregnenolone sulfate (odds ratio = 0.64, 95% confidence interval = 0.44–0.92) and fucose (odds ratio = 0.69, 95% confidence interval = 0.47–0.97)—were associated with decreased risk. Metabolite set enrichment analysis revealed that higher levels of lysophosphatidylethanolamines (false discovery rate = 0.01) and lysophosphatidylcholines (false discovery rate = 0.01) in presurgical blood were associated with increased risk of persistent postsurgical pelvic pain. Conclusion(s) Our results suggest that dysregulation of multiple groups of lipid metabolites may play a role in the persistence of pelvic pain postsurgery among young endometriosis patients.
Article
Background Chronic pelvic pain (CPP) is a common gynaecological condition accounting for 20% of all gynaecological referrals. There are wide ranges of causes with overlapping symptomatology, therefore the management of the condition is a formidable challenge for clinicians. The aetiology of CPP is heterogeneous and in many cases, no clear diagnosis can be reached. It is in this scenario that the label of chronic pelvic pain syndrome (CPPS) can be applied. We defined women with CPPS as having a minimum duration of pain of at least 6 months, including with a diagnosis of pelvic congestion syndrome, but excluding pain caused by a condition such as endometriosis. Many surgical interventions have been tried in isolation or in conjunction with non-surgical interventions in the management with variable results. Surgical interventions are invasive and carry operative risks. Surgical interventions must be evaluated for their e?ectiveness prior to their prevalent use in the management of women with CPPS. Objectives To review the e?ectiveness and safety of surgical interventions in the management of women with CPPS. Search methods We searched the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO, on 23 April 2021 for any randomised controlled trials (RCT) for surgical interventions in women with CPPS. We also searched the citation lists of relevant publications, two trial registries, relevant journals, abstracts, conference proceedings and several key grey literature sources. Selection criteria RCTs with women who had CPPS. The review authors were prepared to consider studies of any surgical intervention used for the management of CPPS. Outcome measures were pain rating scales, adverse events, psychological outcomes, quality of life (QoL) measures and requirement for analgesia. Data collection and analysis Two review authors independently evaluated studies for inclusion and extracted data using the forms designed according to Cochrane guidelines. For each included trial, we collected information regarding the method of randomisation, allocation concealment, blinding, data reporting and analyses. We reported pooled results as mean di?erence (MDs) or odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. If similar outcomes were reported on di?erent scales, we calculated the standardised mean di?erence (SMD). We applied GRADE criteria to judge the overall certainty of the evidence. Main results Four studies met our inclusion criteria involving 216 women with CPP and no identifiable cause. Adhesiolysis compared to no surgery or diagnostic laparoscopy We are uncertain of the e?ect of adhesiolysis on pelvic pain scores postoperatively at three months (MD −7.3, 95% CI −29.9 to 15.3; 1 study, 43 participants; low-certainty evidence), six months (MD −14.3, 95% CI −35.9 to 7.3; 1 study, 43 participants; low-certainty evidence) and 12 months postsurgery (MD 0.00, 95% CI −4.60; 1 study, 43 participants; very low-certainty evidence). Adhesiolysis may improve both the emotional wellbeing (MD 24.90, 95% CI 7.92 to 41.88; 1 study, 43 participants; low-certainty evidence) and social support (MD 23.90, 95% CI −1.77 to 49.57; 1 study, 43 participants; low-certainty evidence) components of the Endometriosis Health Profile-30, and both the emotional component (MD 32.30, 95% CI 13.16 to 51.44; 1 study, 43 participants; low-certainty evidence) and the physical component of the 12-item Short Form (MD 22.90, 95% CI 10.97 to 34.83; 1 study, 43 participants; low-certainty evidence) when compared to diagnostic laparoscopy. We are uncertain of the safety of adhesiolysis compared to comparator groups due to low-certainty evidence and lack of structured adverse event reporting. No studies reported on psychological outcomes or requirements for analgesia. Laparoscopic uterosacral ligament ablation or resection compared to diagnostic laparoscopy/other treatment We are uncertain of the e?ect of laparoscopic uterosacral ligament/nerve ablation (LUNA) or resection compared to other treatments postoperatively at three months (OR 1.26, 95% CI 0.40 to 3.93; 1 study, 51 participants; low-certainty evidence) and six months (MD −2.10, 95% CI −4.38 to 0.18; 1 study, 74 participants; very low-certainty evidence). At 12 months post-surgery, we are uncertain of the e?ect of LUNA on the rate of successful treatment compared to diagnostic laparoscopy. One study of 56 participants found no di?erence in the e?ect of LUNA on non-cyclical pain (P = 0.854) or dyspareunia (P = 0.41); however, there was a di?erence favouring LUNA on dysmenorrhea (P = 0.045) and dyschezia (P = 0.05). We are also uncertain of the e?ect of LUNA compared to vaginal uterosacral ligament resection on pelvic pain at 12 months (MD 2.00, 95% CI 0.47 to 3.53; 1 study, 74 participants; very low-certainty evidence). We are uncertain of the safety of LUNA or resection compared to comparator groups due to the lack of structured adverse event reporting. Women undergoing LUNA may require more analgesia postoperatively than those undergoing other treatments (P < 0.001; 1 study, 74 participants). No studies reported psychological outcomes or QoL. Authors' conclusions We are uncertain about the benefit of adhesiolysis or LUNA in management of pain in women with CPPS based on the current literature. There may be a QoL benefit to adhesiolysis in improving both emotional wellbeing and social support, as measured by the validated QoL tools. It was not possible to synthesis evidence on adverse events as these were only reported narratively in some studies, in which none were observed. With the inadequate objective assessment of adverse events, especially long-term adverse events, associated with adhesiolysis or LUNA for CPPS, there is currently little to support these interventions for CPPS.
Article
Endometriosis is a chronic disorder characterized by the presence of endometrial glands and stroma outside the uterine cavity. It affects 8%-10% of women in their reproductive years, and represents a major clinical problem with deleterious social, sexual and reproductive consequences. Current treatment options include pain relief, hormonal intervention and surgical removal. However, these treatments are deemed unsatisfactory owing to varying success, significant side effects and high recurrence rates. Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly anti-angiogenic, anti-proliferation, anti-metastasis, and apoptosis induction. In recent years, preclinical studies have proposed the use of green tea to inhibit the growth of endometriosis. Herein, the aim of this review is to summarize the potential therapeutic effects of green tea on molecular and cellular mechanism through inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis in endometriosis.
Article
This study was designed to determine the rates of reoperation following laparoscopic management of endometriosis, with additional aims to examine long-term fertility and quality of life outcomes. This is a retrospective study and a prospective questionnaire of subjects who underwent laparoscopic surgery for pelvic pain and/or endometriosis from 2010 to 2015. The rate of reoperation was 8.60%. Following surgery, 83.3% of previously infertile subjects with endometriosis attempted to conceive with an 80.0% success rate. Subjects had significant improvement in each quality of life measurement and most sexual function indices analysed. • Impact Statement • What is already known on this subject? Endometriosis is estimated to affect around 35–50% of women experiencing chronic pelvic pain and/or infertility. Surgical management of endometriosis is recommended for patients who desire fertility, are afflicted by a more severe form of endometriosis, or have had persistent or recurrent pain in spite of medical management. • What the results of this study add? The overall rate of reoperation for subjects was low at 8.6%. The majority of infertile patients were able to conceive following surgery. • What the implications are of these findings for clinical practice and/or further research? Laparoscopic management of endometriosis is an effective management tool with low rates of reoperation and high efficacy in treating infertility caused by endometriosis.
Article
Resume Objectif : Déterminer l’intérêt ou non de la réalisation de certains gestes prophylactiques en association à une procédure chirurgicale gynécologique. Conception : Un comité de consensus de 19 experts a été constitué. Une politique de déclaration et de suivi des liens d’intérêts a été appliquée et respectée durant tout le processus de réalisation du référentiel. De même, celui-ci n’a bénéficié d’aucun financement provenant d’une entreprise commercialisant un produit de santé (médicament ou dispositif médical). Le comité de consensus devait respecter et suivre la méthode GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la qualité des données factuelles sur lesquelles étaient fondées les recommandations. Les inconvénients potentiels de faire des recommandations fortes en présence de données factuelles de mauvaise qualité ou insuffisantes ont été soulignés. Peu de recommandations ont été non graduées. Méthodes : Le comité a étudié 22 questions concernant 7 thématiques. Les gestes associés à une procédure chirurgicale gynécologique étudiés étaient les suivants : 1) Salpingectomie, 2) Réalisation d’une fimbriectomie, 3) Annexectomie, 4) Destruction d’endométriose superficielle, 5) Adhésiolyse, 6) Destruction endométriale, 7) Ablation du col utérin. Résultats : Le travail de synthèse des experts et l’application de la méthode GRADE ont abouti à 34 recommandations. Parmi les recommandations formalisées, six ont un niveau de preuve élevé (GRADE 1+/-) et 28 un niveau de preuve faible (GRADE 2+/-). Pour deux questions, la méthode GRADE ne pouvait pas s’appliquer en raison d’une absence de littérature médicale, ne permettant pas d’aboutir à une recommandation. Conclusion : Un accord important existait parmi les experts sur des recommandations fortes dans le but de d’améliorer les pratiques pour la réalisation ou non de certains gestes prophylactiques en association à une chirurgie gynécologique.
Article
Objective To identify self-care interventions used by women living in the United States to manage endometriosis-related pain, describe frequency of use, and determine perceived effectiveness. Design Mixed-methods design with an online survey. Setting A survey link was posted on endometriosis support group Facebook pages. Participants The online survey was completed by 98 women living in the United States who were members of Facebook support groups. Measurements Quantitative measures included demographic and health-related characteristics; self-care intervention frequency of use and perceived effectiveness; knowledge, confidence, and support managing endometriosis symptoms; pain intensity; and quality of life (QOL) operationalized with the Endometriosis Health Profile–30. Descriptive statistics and correlation coefficients were used to analyze data. Qualitative perspectives were captured through open-ended questions and analyzed for themes. Results Women used an average of 5.8 self-care interventions more than once per week. Heat, rest, over-the-counter pain medications, and diet changes were perceived as most effective, with >75% reporting at least slight improvement. Frequent use of multiple strategies was significantly correlated with worse scores for pain-related QOL (p < .01), all other QOL dimensions (p < .01), and less confidence in one’s ability to control symptoms (p < .05). Endometriosis pain management perspectives showed three themes: Daily Struggle With Mental and Physical Health, Lack of Knowledge and Understanding From Health Care Providers, and Lack of Understanding From Everybody Else. Conclusion These results strengthen evidence for the effectiveness of heat, rest, and dietary changes for endometriosis-related pain and underscore an individual’s desire for support and understanding from health care professionals, family, and friends. Nurses can provide evidence-based self-care intervention teaching to help mitigate endometriosis-related pain, prevent adverse effects, and assist individuals in discovering what works for them. It is imperative that nurses deliver and advocate for well-informed, empathetic, and supportive care from all health care professionals.
Article
Objective To provide guidelines from the French College of Obstetricians and Gynecologists (CNGOF), based on the best currently available evidence, for the prophylactic procedures associated with gynecological surgery for benign disease such as superficial endometriosis lesions and adhesions. Methods The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade that reflects the quality of evidence (QE) (clinical practice guidelines). Results Endometriosis and pelvic pain Superficial endometriosis can be entirely asymptomatic. Surgical treatment of asymptomatic superficial peritoneal endometriosis is not recommended in women of childbearing age for the prevention of pelvic pain, especially in case of proximity to noble organs (e.g., the ureters, rectum and sigmoid, and ovaries in nulligravida) as there is no evidence that the disease will progress to become symptomatic (low level of evidence). In case of accidental discovery of superficial endometriosis in women of childbearing age with pelvic pain, it is recommended that that the lesions are excised, if surgically accessible. Removal of superficial endometriosis lesions in patients with painful symptoms improves quality of life and pain (low level of evidence). Endometriosis and infertility It appears that women with isolated superficial endometriosis diagnosed by laparoscopy with histological confirmation have a significantly higher incidence of primary infertility than patients without endometriosis. However, there is no data regarding the impact of treatment of these lesions on the fertility in these women or on the natural course of their disease (low level of evidence). It is recommended that excision is performed rather than monopolar coagulation of superficial endometriosis lesions in infertile women, as this results in a higher spontaneous pregnancy rate (low level of evidence). Adhesions and pelvic pain There is limited data in the literature regarding the benefit of performing systematic adhesiolysis during laparoscopy to prevent pelvic pain when incidental pelvic adhesions are discovered. For patients with pelvic pain, it is probably better not to perform adhesiolysis to prevent pelvic pain, although this can be decided on a case-by-case basis depending on the extent of the adhesions, the topography, and the type of surgery considered (low level of evidence). For asymptomatic patients, it is recommended not to perform adhesiolysis to prevent pelvic pain due to the lack of clear efficacy both short- or long-term and due to the increased risk of surgical injuries (low level of evidence). Adhesions and infertility There is limited data in the literature regarding the potential benefit of performing systematic adhesiolysis when there is an incidental discovery of pelvic adhesions during laparoscopy to prevent infertility. For infertile women, in the event of fortuitous discovery of adhesions at laparoscopy, it is probably better not to perform complex adhesiolysis. Only adhesiolysis of tubo-ovarian adhesions that are minimal or slight in terms of their extension and/or their nature may be useful to improve the chances of spontaneous pregnancy. However, it remains to be decided on a case-by-case basis depending on other potential causes of infertility (low level of evidence). For women without known infertility issues, it is probably better not to perform systematic adhesiolysis in order to improve their pregnancy chances, considering the balance between the unknown benefit and the risks of complications inherent to surgery (low level of evidence). Conclusion Further investigations are needed in order to increase the quality of management regarding associated interventions such as the treatment of superficial endometriosis or adhesions performed during a gynecologic surgical procedure and, thereby, bolster these recommendations.
Article
Background: Endometriosis is a chronic and incurable gynecological disease that mainly affects women of reproductive age worldwide. It imposes clinical and economic burdens on patients, families, and society. A better understanding of the determinants of preferences towards early diagnosis of endometriosis may help develop programs and interventions to reduce the risk of more severe illness. We quantified patient preferences for early endometriosis diagnosis and explored whether preferences vary on the patient characteristics and pre-established social determinants of health. Methods: A discrete choice experiment (DCE) was designed to elicit women's preferences and willingness to pay for early diagnosis of endometriosis. Women ages 18 and older were eligible to participate in the study. The attributes (and levels) considered to describe hypothetical scenarios included diagnosis (immediate/postponed), the chance of advanced endometriosis and more severe illness (low/ high), time away from living, and professional activities (8 days, 15 days, 22 days and 30 days), and possible out-of pocket costs ($0, $15, $60 and $210). The effects of participants' characteristics and social determinants of health on the preference for early diagnosis were modeled using a Tobit model. Results: A total of 66 women with (2) or at-risk (64) of endometriosis completed the experiment. The respondents' age and insurance statuses significantly influenced their preference or choice for early diagnosis. On average, respondents were willing to give up $61.55 out-of-pocket cost to have a low risk of advanced endometriosis and more severe disease. The Tobit model indicates only age and insurance variables significantly affected early diagnosis preference. The results suggest that older ages and not having insurance increase the likelihood of respondents choosing early diagnosis than the younger age group and having insurance. Conclusions: This study indicates the importance of considering the patient characteristics and social determinants of health when designing and implementing health programs and interventions for endometriosis.
Article
Assuming we know the perfect management for endometriosis or pelvic pain is folly, but we should be celebrating our successes, not abandoning everything that we currently know.
Article
Deep endometriosis (DE) is classically defined as disease that infiltrates structures by more than 5 mm, such as bowel, ureters, bladder and vagina. The two major symptoms related to DE are pain and infertility. A lot of debate goes on upon the best treatment choice for DE. Treatments include medical therapy with oral progestins or combined contraceptives, and surgery for resection of DE nodules. In this review we focus on the best option treatment for the symptomatic patients with DE not seeking conception. We performed a narrative review of literature searching for the latest evidence on efficacy and outcomes of medical and surgical treatment of DE patients. Results showed that 2/3 of patients with DE will be satisfied with hormonal treatment, and surgery will be effective in improving QoL in most patients with DE. Most studies published regarding surgical outcomes involve bowel endometriosis, and their complication rates should not be extrapolated to all DE. DE that does not infiltrate pelvic viscera accounts for most cases of DE. Together with DE affecting the urinary tract, a much lower rate of severe complications is reported when compared to bowel endometriosis. This distinction should influence decision making. Medical treatment should be first option for non-complicated DE patients not seeking conception. Surgery should be indicated for those who do not tolerate nor improve with medical treatment, as well as those cases complicated by visceral impairment.
Article
Abstract Objective: To gain insight into patients’ understanding of endometriosis, utilised sources of information on endometriosis and perceptions of available treatment options. Design: Observational cross-sectional study. Setting: Data were collected from an outpatient specialist endometriosis clinic within a tertiary hospital. Participants: New patients referred with symptoms suggestive of endometriosis. Methods: A paper based questionnaire was completed by new patients on their first presentation to the clinic. Main outcome measures: Patient understanding of symptoms and causes of endometriosis, types and expectations of treatment, and sources of information utilised by patients in researching endometriosis. Results: Approximately half of all included patients were unsure of the aetiology of endometriosis. Patients who relied on information from specialist gynaecologists were more optimistic about the outcome of surgical treatment, while those who relied on general practitioners were more optimistic about the outcome of medical treatment, when compared to those who sought information from online sources. Conclusions: Endometriosis is a chronic and debilitating condition, yet there is limited data available regarding both the sources of information that patients’ access, and their perceptions of the disease. Given the high proportion of patients in our study who lacked knowledge of endometriosis, and the negative correlation between the use of social media for information and perception of treatment, there is a clear need for improved access to evidence-based resources for patient education.
Article
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Regression methods were used to select and score 12 items from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to reproduce the Physical Component Summary and Mental Component Summary scales in the general US population (n=2,333). The resulting 12-item short-form (SF-12) achieved multiple R squares of 0.911 and 0.918 in predictions of the SF-36 Physical Component Summary and SF-36 Mental Component Summary scores, respectively. Scoring algorithms from the general population used to score 12-item versions of the two components (Physical Components Summary and Mental Component Summary) achieved R squares of 0.905 with the SF-36 Physical Component Summary and 0.938 with SF-36 Mental Component Summary when cross-validated in the Medical Outcomes Study. Test-retest (2-week)correlations of 0.89 and 0.76 were observed for the 12-item Physical Component Summary and the 12-item Mental Component Summary, respectively, in the general US population (n=232). Twenty cross-sectional and longitudinal tests of empirical validity previously published for the 36-item short-form scales and summary measures were replicated for the 12-item Physical Component Summary and the 12-item Mental Component Summary, including comparisons between patient groups known to differ or to change in terms of the presence and seriousness of physical and mental conditions, acute symptoms, age and aging, self-reported 1-year changes in health, and recovery for depression. In 14 validity tests involving physical criteria, relative validity estimates for the 12-item Physical Component Summary ranged from 0.43 to 0.93 (median=0.67) in comparison with the best 36-item short-form scale. Relative validity estimates for the 12-item Mental Component Summary in 6 tests involving mental criteria ranged from 0.60 to 107 (median=0.97) in relation to the best 36-item short-form scale. Average scores for the 2 summary measures, and those for most scales in the 8-scale profile based on the 12-item short-form, closely mirrored those for the 36-item short-form, although standard errors were nearly always larger for the 12-item short-form.
Article
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Surgical procedures are frequently introduced into general practice on the basis of uncontrolled studies that are less rigorous than those required for the approval of medical interventions.1 The standard for the evaluation of surgical therapy is lower because of the complexity of designing and conducting scientifically valid and ethically acceptable clinical trials of surgical procedures.2 As a result, many surgical trials fail to control for investigator bias or placebo effects.3,4 The list of inadequately studied invasive or surgical procedures that became part of standard medical practice only to be abandoned after closer scrutiny includes bloodletting, routine tonsillectomy, routine circumcision, . . .
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Background Placebo treatments have been reported to help patients with many diseases, but the quality of the evidence supporting this finding has not been rigorously evaluated. Methods We conducted a systematic review of clinical trials in which patients were randomly assigned to either placebo or no treatment. A placebo could be pharmacologic (e.g., a tablet), physical (e.g., a manipulation), or psychological (e.g., a conversation). Results We identified 130 trials that met our inclusion criteria. After the exclusion of 16 trials without relevant data on outcomes, there were 32 with binary outcomes (involving 3795 patients, with a median of 51 patients per trial) and 82 with continuous outcomes (involving 4730 patients, with a median of 27 patients per trial). As compared with no treatment, placebo had no significant effect on binary outcomes, regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect, but the effect decreased with increasing sample size, indicating a possible bias related to the effects of small trials. The pooled standardized mean difference was significant for the trials with subjective outcomes but not for those with objective outcomes. In 27 trials involving the treatment of pain, placebo had a beneficial effect, as indicated by a reduction in the intensity of pain of 6.5 mm on a 100-mm visual-analogue scale. Conclusions We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.
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Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee. A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial. At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference. In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.
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This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.
Article
Objective: To assess the effect of endometriosis and radical laparoscopic excision on the quality of life of women with this condition. Design: A prospective study. Setting: The Northern Endometriosis Centre at South Cleveland Hospital, Middlesbrough and St. James's University Hospital, Leeds. Population: Fifty-seven consecutive patients undergoing laparoscopic excision of invasive endometriosis. Methods: Questionnaires, both pre-operatively and four-month post-operatively, for a number of different symptoms associated with endometriosis were completed by patients. Details of fertility, previous treatments and quality of life as measured by SF12 and EuroQOL (EQ-5D) and sexual activity questionnaire, as well as linear pain scores for several symptoms, were recorded. Details of intra-operative findings was also collected. Main outcome measures: Effect of laparoscopic excision on pain scores and quality of life, operative findings, type of surgery, length of surgery and incidence of intra- and post-operative complications. Results: Patients with endometriosis were severely ill with significant pain and impairment of quality of life and sexual activity. Four months after radical laparoscopic excision for deep endometriosis there was significant improvement in all the parameters measured including their quality of life based on EuroQOL evaluation: EQ-5D (0 x 595:0 x 729, P = 0 x 002) and EQ thermometer (68 x 9:77 x 7, P = 0 x 008); SF12 physical score (44 x 8:51 x 9, P = 0 x 015); sexual activity (habit P = 0 x 002, pleasure P = 0 x 002 and discomfort P < or = 0 x 001). Only the mental health score of SF12 failed to show any statistical improvement (47 x 1:48 x 4, P = 0 x 84). Symptomatically, there was a significant reduction in dysmenorrhoea (median 8 x 0:4 x 0, P < or = 0 x 001), pelvic pain (median 7 x 0:2 x 0, P < or = 0 x 001), dyspareunia (median 6 x 0:0 x 0, P < 0 x 001) and rectal pain scores (median 4 x 0:0 x 0, P < 0 x 001). Complications were noted, but were deemed to be acceptable for the extent of the surgery. Conclusions: This is an early analysis of the first 57 cases studied, but structured evaluation suggests that meaningful improvements in clinical symptoms and quality of life can be obtained with this approach with acceptable levels of operative morbidity. Further follow up of this series is required, but early evidence would suggest that the technique should be further evaluated as part of a randomised trial.
Article
The placebo effect will have a growing importance in the field of nuclear medicine as the potentials for palliative therapy with internal sources are realized. It is important for nuclear medicine physicians and their colleagues to be familiar with the role of placebo responses in clinical trials, especially when such trials involve the subjective assessment of pain. A summary of the literature on the placebo effect in pain studies is presented in which traditional values for placebo responses are contrasted with more current thinking in the field. The few published double-blind studies of pain relief after treatment with radiotherapeutic agents are summarized specifically with respect to their cited placebo response.
Article
A criteria-based quality assurance process for hysterectomy was instituted at a large teaching hospital. After this process was initiated, the overall frequency of hysterectomy decreased by 24%, p less than 0.001. Significant reductions were seen in hysterectomy rates for the following indications: chronic pelvic pain (77%, p less than 0.0001), recurrent uterine bleeding (46%, p less than 0.001), preinvasive disease of the uterus (55%, p less than 0.005), and severe infection (70%, p less than 0.025). Adenomyosis was the single indication for which an increase in hysterectomy rate was observed. This increase, however, was completely reversed during the last 2 years of the study. This quality assurance process also resulted in a significant increase in the histologic verification rate (i.e., 82% vs 93%, p less than 0.001). These observations suggest that using such a criteria-based process can reduce the number of hysterectomies performed and improve the accuracy of the preoperative diagnosis.
Article
The impact of endometriosis on the general population has been well documented, and the prevalence rate is quoted as 10%. The records of 6,456 women in the United States Army were reviewed with respect to age, race and active duty status. The active duty records were further evaluated for total sick days from endometriosis-related problems. This evaluation revealed a mean sick time of 15 days per admission per active-duty patient regardless of age or race. The estimate of lost duty time was 21,746 days, considering all active-duty patients in the study (five years of records). The prevalence of endometriosis in the female U.S. Army population was 6.2%. Diagnosis and treatment of endometriosis should be aggressively pursued whenever the disease is suspected.
Article
Few previous studies have examined the relationship between the preoperative and pathologic diagnoses for hysterectomy. To determine the percentage of preoperative diagnoses that were confirmed by pathologic examination, we analyzed data from the Collaborative Review of Sterilization, a multicenter study of hysterectomies and tubal sterilizations in women aged 15 to 44 years. Data were collected from patient interviews and chart reviews. Of the 1851 women included in this study, 1283 (69%) had abdominal hysterectomies and 568 (31%) had vaginal hysterectomies. Overall, 52% of the hysterectomies were performed for a preoperative diagnosis that could potentially be confirmed by pathologic examination. Pathologic examination actually confirmed the preoperative diagnosis of endometrial hyperplasia in 95% of the cases, cervical intraepithelial neoplasia in 89%, leiomyomas in 84%, pelvic inflammatory disease in 75%, adenomyosis in 48%, and endometriosis in 47%. Among all of the potentially confirmable diagnoses, 80% were confirmed. The remaining 48% of the women who had hysterectomies had preoperative diagnoses that were not amenable to confirmation by pathology. Most of these were for one of three diagnoses: menstrual bleeding disorders, pelvic pain, or pelvic relaxation. In 47% of these cases, pathologic examination showed leiomyoma or adenomyosis; no abnormalities were found in 38% of these cases.
Article
To assess the efficacy of laser laparoscopic surgery in the treatment of pain associated with minimal, mild, and moderate endometriosis. A prospective, randomized, double-blind, and controlled clinical study. Royal Surrey County Hospital, Guildford, United Kingdom, a referral center for the laser laparoscopic treatment of endometriosis. Sixty-three patients with pain (dysmenorrhoea, pelvic pain, or dyspareunia) and minimal to moderate endometriosis. The patients were randomized at the time of laparoscopy to laser ablation of endometriotic deposits and laparoscopic uterine nerve ablation or expectant management. Pain symptoms were recorded subjectively and by visual analogue scale. The women were unaware of the treatment allocated as was the nurse who assessed them at 3 and 6 months after surgery. Improvement or resolution of pain symptoms assessed subjectively and by visual analogue score. Laser laparoscopy results in statistically significant pain relief compared with expectant management at 6 months after surgery. Sixty-two and a half percent of the lasered patients reported improvement or resolution of symptoms compared with 22.6% in the expectant group. Results were poorest for minimal disease and, if patients with mild and moderate disease only are included, 73.7% of patients achieved pain relief. There were no operative or laser complications. Laser laparoscopy is a safe, simple, and effective treatment in alleviating pain symptoms in women with stages I, II, and III endometriosis.
Article
Deep endometriosis has been defined as endometriosis infiltrating deeper than 5 mm under the peritoneum. A model for the development and propagation of endometriosis is presented. Subtle and non-pigmented lesions are suggested to occur intermittently in all women. Infiltration occurs generally to a few millimeters of depth only, and these lesions become typical, burnt out lesions. In some 20% of women, severe endometriosis develops either as deeply infiltrating disease or as cystic ovarian disease. Arguments are given to consider deep endometriosis and cystic ovarian endometriosis as two specific entities of endometriotic disease. A possible causal relationship with dioxin pollution is discussed. Diagnosis of deep endometriosis is made by clinical examination and palpation during surgery. Clinical examination during menstruation and CA-125 concentrations in plasma are useful to help in the diagnosis of smaller deep lesions. Surgical excision can be carried out by laparoscopy, laparotomy or vaginally using sharp dissection, electrosurgery or with the use of a CO2 laser. Excision is the treatment of choice because of a high pregnancy rate, a complete cure of pain in most women, and a low recurrence rate. Medical treatment is probably less effective to treat infertility, but highly effective in relieving pelvic pain. Medical therapy, by luteinizing hormone-releasing hormone agonists, danazol, or gestrinone, also seems useful as a pretreatment for surgery. The choice of treatment will therefore depend on the local expertise with minimal invasive surgery, certainly if a first excision has been incomplete and pain symptoms recur.
Article
Sexual activity is an important dimension of quality of life. Therefore it is important to assess the impact that any treatment may have on sexual functioning so that patients can be warned of possible side effects and interventions offered to help ameliorate these. The Sexual Activity Questionnaire (SAQ) was developed to investigate the impact of long-term tamoxifen on the sexual functioning of women at high risk of developing breast cancer. It was also tested on a sample of women with no such risk. The majority of variance in sexual functioning can be explained by three factors: pleasure from sexual intercourse, discomfort during sexual intercourse and habit. We found that the frequency of sexual activity decreased steadily with age. Furthermore, pleasure dropped and discomfort increased in women aged over 55. We report psychometric data showing that the SAQ is a valid, reliable and acceptable measure for describing the sexual functioning of women in terms of activity, pleasure and discomfort. It is quick and easy to administer and has good face validity discriminating between the sexual functioning of pre- and post-menopausal women.
Article
Physicians have long recognized that therapeutic effects of pharmacologically inactive agents can be a complicating factor in medical research. Not only pills but also other features of the physician-patient encounter may recruit the healing response. Deliberate use of the placebo response may improve both patient satisfaction and treatment efficacy.
Article
The EuroQol Group first met in 1987 to test the feasibility of jointly developing a standardised non-disease-specific instrument for describing and valuing health-related quality of life. From the outset the Group has been multi-country, multi-centre, and multi-disciplinary. The EuroQol instrument is intended to complement other forms of quality of life measures, and it has been purposefully developed to generate a cardinal index of health, thus giving it considerable potential for use in economic evaluation. Considerable effort has been invested by the Group in the development and valuation aspects of health status measurement. Earlier work was reported upon in 1990; this paper is a second 'corporate' effort detailing subsequent developments. The concepts underlying the EuroQol framework are explored with particular reference to the generic nature of the instrument. The valuation task is reviewed and some evidence on the methodological requirements for measurement is presented. A number of special issues of considerable interest and concern to the Group are discussed: the modelling of data, the duration of health states and the problems surrounding the state 'dead'. An outline of some of the applications of the EuroQol instrument is presented and a brief commentary on the Group's ongoing programme of work concludes the paper.
Article
Placebos have been traditionally regarded as deceptive therapies and have not been understood in the broader context of social symbols and of interpersonal factors that surround the healing process itself. Although the power of inert substances to heal is well recognized, the placebo effect also influences the outcome of conventional therapies. The role of the placebo in modern medicine is poorly defined because of a lack of a common understanding of what the placebo effect is and because of the negative connotions associated with its use. The response rate to placebo varies by illness. The natural course of disease and patient or physician bias can be misinterpreted as a placebo response. In research, the placebo effect is therapeutic noise to be removed by placebo-controlled trials. Few studies are designed to measure the placebo response rate directly. Placebos are a reminder of how little is known about mind-body interaction. The placebo effect may be one of the most versatile and underused therapeutic tools at the disposal of physicians.
Article
Additional complexity has been added to the healthcare decision-making process by the socioeconomic constraints of the industry and a population that is increasingly educated about healthcare. As a result, decisions balanced on the basis of outcomes and economic realities are needed. This modeling of surgical versus medical treatment costs for chronic pelvic pain and endometriosis factors in the large number of women with chronic pelvic pain, direct and indirect costs of the condition, and clinical benefits, projected costs, and savings of the therapies. This process of calculation becomes an aid for decision making in the current healthcare system.
Article
To examine the impact of treating endometriosis with nafarelin or leuprolide acetate depot on patient quality of life (QOL) and subjective clinical measures. A randomized, multicenter study was conducted on 192 women with endometriosis. Patients received nafarelin or leuprolide for six months and were followed for up to six months after treatment. QOL was defined by seven items, including symptom severity, daily activities, pain medication use and need for bed rest. No significant differences were found at baseline between treatments for patients with mild, moderate or no endometriosis symptoms. Those with severe symptoms of endometriosis at baseline and taking nafarelin had a significantly greater improvement in QOL at the last posttreatment visit than those receiving leuprolide (P < .01). Nafarelin was associated with significantly fewer days with moderate or severe hot flashes than leuprolide during treatment (P < .05) and with significantly fewer moderate or severe hypoestrogenic symptoms overall at three months of treatment (P < .05). Additionally, poorer QOL was significantly associated with hypoestrogenic and endometriosis symptoms. Treatment of endometriosis with nafarelin was associated with fewer days of moderate or severe hot flashes as compared to leuprolide and with greater improvement in QOL after treatment in patients with severe symptoms at baseline.
Article
The purpose of this study was a quantification of changes in endometriosis-associated pain and quality of life during the stimulatory phase of gonadotropin-releasing hormone agonist therapy. One hundred twenty women with significant endometriosis-associated pain participated in a 1-month double-blind, randomized, placebo-controlled trial. Pain was measured at baseline and at 2 and 4 weeks with visual analog scales and the Endometriosis Symptom Severity score. Quality of life was measured with the SF-36 instrument. Group means and SEMs were calculated. Paired t tests were used after determination of data normality. Compared with placebo-treated control subjects women treated with gonadotropin-releasing hormone agonist had a statistically (P <. 0001) and clinically significant temporary increase in pain and a concomitant decrease in quality of life. The stimulatory phase of gonadotropin-releasing hormone agonist therapy is associated with an increase in endometriosis-associated pain and a decrease in quality of life.
Article
The placebo response is commonly invoked as a factor in the therapeutic relationship between the family physician and the patient, but important recent literature can be difficult for family physicians to access. Coordinated interdisciplinary research into the placebo response as it occurs in primary care settings is lacking. Although there is controversy about the nature and scope of the placebo response, important suggestions are emerging about its psychological mechanisms (expectancy and conditioning) and the biochemical pathways that act as psychosomatic linkages (endorphins, catecholamines and cortisol, psychoneuroimmumunology). The available research justifies interventions by family physicians that maximize the placebo response in everyday patient encounters. These include the sustained partnership approach, working with patients on the narratives they construct to explain illness, listening to patients, providing them with satisfactory explanations, expressing care and concern, and enhancing their sense of control. Notable opportunities exist for family medicine investigators to expand the understanding of this phenomenon.
Article
To assess whether hormonal treatment of endometriosis improves quality of life for women with endometriosis. In a prospective, randomized, double-blind, double-dummy study on 48 women with verified endometriosis, the pain pattern and quality of life were registered before, during and after treatment with nafarelin or medroxyprogesterone acetate. The distribution of the studied parameters were tested by means of a Skewness test. ANOVA analysis was used for normally distributed variables and Friedman's analysis and Mann-Whitney U-test for non normally distributed variables. There was a difference between the 30 women who participated all through the study and the 18 who dropped out. It was noticeable that anxiety-depression and sleep disturbances were significantly more common among the drop outs. There was a significant reduction in symptom score during the study, without any significant difference between the treatment groups. The sleep disturbances and anxiety-depression score improved significantly from before treatment to the end of the follow-up, but the anxiety-depression score increased during the nafarelin treatment period. There was a statistically significant improvement of paid working life in the nafarelin treated group. All the other psycho-social parameters as well as emotional balance improved during the study period without difference between groups. When hormonal treatment is planned it is very important to take into consideration previous psychosocial experiences of the patient. Factors of importance for quality of life such as sleep disturbances and anxiety-depression improved significantly after treatment with nafarelin or medroxyprogesterone acetate.
Article
To evaluate symptom relief following a laparoscopic technique designed for treatment of complete obliteration of the cul-de-sac associated with endometriosis, with fertility preserved. Preoperative and postoperative questionnaire study of a cohort of patients with complete obliteration of the cul-de-sac undergoing a standardized laparoscopic surgical treatment. American tertiary referral center for the surgical treatment of endometriosis. Eighty-four consecutive patients undergoing laparoscopic treatment of endometriosis with complete cul-de-sac obliteration with 67 replying to a postoperative questionnaire. Laparoscopic excision of all endometriosis including treatment of complete obliteration of the cul-de-sac by en bloc resection and bowel resection as needed. Symptom relief as measured on a 5-point ranked ordinal scale administered before and after surgery, as well as perioperative complications, postoperative fertility, and prognostic value of preoperative findings on pelvic examination. Symptom reduction was obtained for all symptoms related to cul-de-sac disease, particularly for patients with severe or debilitating symptoms preoperatively. There was no significant complication, and the postoperative fertility rate was 43%. Seventy-three percent of patients with obliteration of the cul-de-sac had histologically proved rectal endometriosis. Nodularity and tenderness on examination were predictive of symptom improvement. Aggressive laparoscopic excision of endometriosis carried out in a specialist center offers good symptom relief, especially for those with severe or debilitating symptoms. To ensure complete removal of all disease, intestinal surgery is required in most patients with complete obliteration of the cul-de-sac.
Article
To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. The review aims to compare the effectiveness of any laparoscopic procedure versus any other treatment modality, including expectant management. The search strategy of the Menstrual Disorders and Subfertility Review Group was used to identify all publications that described or might have described randomised trials of laparoscopic surgery in the treatment of symptomatic endometriosis. For a full description of the Review Group strategy see the Review Group details. Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis, with other treatment modalities or placebo. One study had data appropriate for inclusion within the review. This study compared laparoscopic laser surgery with diagnostic laparoscopy. Pain relief was the primary outcome measure. The data was extracted independently by two reviewers. In comparison to expectant treatment there is a significant degree of pain relief at six months after surgery with laser laparoscopic surgery for minimal, mild and moderate endometriosis. Odds Ratio (OR) 4.97, 95% Confidence Interval (CI) 1.85,13.39 The combined surgical approach of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation is likely to be a beneficial treatment for pelvic pain associated with minimal, mild and moderate endometriosis. As only one trial is included in the analysis, this conclusion should be interpreted with caution.
Article
This article has no abstract; the first 100 words appear below. CONSIDERABLE relief of symptoms has been reported for patients with angina pectoris subjected to bilateral ligation of the internal mammary arteries.¹²³⁴ The physiologic basis for the relief of angina afforded by this rather simple operation is not clear. Allegedly, increased coronary flow is facilitated through collateral channels proximal to the site of ligation; these potential channels apparently do exist, as demonstrated by the injection studies of Battezzati et al.¹ and Kitchell, Glover and Kyle.² However, definitely increased coronary flow after bilateral internal-mammary-artery ligation has not been shown. Furthermore, this procedure does not afford protection to dogs after ligation of the . . . *From the departments of Medicine and Surgery, University of Washington School of Medicine. Supported in part by a grant-in-aid (H908C6) from the National Heart Institute, National Institutes of Health, United States Public Health Service. **One patient in the ligated group inadvertently was not exercised before surgery. Source Information SEATTLE, WASHINGTON †Instructor in medicine, University of Washington School of Medicine. ‡Instructor in surgery, University of Washington School of Medicine; associate chief of surgery, Veterans Administration Hospital. §Instructor in surgery, University of Washington School of Medicine. ¶Professor of surgery, University of Washington School of Medicine. ∥Associate professor of medicine, University of Washington School of Medicine.
Surgical management of deeply infiltrating endometriosis Endometriosis— current understanding and management
  • P Koninckx
  • Martin
Koninckx P, Martin D. Surgical management of deeply infiltrating endometriosis. In: Shaw R, ed. Endometriosis— current understanding and management. Oxford: Blackwell Scientific, 1995:264 – 81.
Excision of endometriosis for pain: RCT
  • Abbott
884 Abbott et al. Excision of endometriosis for pain: RCT Vol. 82, No. 4, October 2004