Conservative approach to rectosigmoid endometriosis: a cohort study

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1 AOGS ORIGINAL RESEARCH ARTICLE Conservative approach to rectosigmoid endometriosis: a cohort study ANNE G. EGEKVIST 1,2, EDVARD MARINOVSKIJ 3, AXEL FORMAN 1,2, ULRIK S. KESMODEL 4,5, MADS RIISKJÆR 1,2 & MIKKEL SEYER-HANSEN 1,2 1 Department of Clinical Medicine, Aarhus University, Aarhus, 2 Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, 3 The MR Center, Aarhus University Hospital, Aarhus, 4 Department of Obstetrics and Gynecology, Herlev and Gentofte University Hospital, Herlev, and 5 Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Key words Endometriosis, deeply infiltrating endometriosis, rectosigmoid endometriosis, medical,, laparoscopy Correspondence Anne Gisselmann Egekvist, Department of Clinical Medicine/Department of Obstetrics and Gynecology, Aarhus University, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. ageg@clin.au.dk Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Please cite this article as: Egekvist AG, Marinovskij E, Forman A, Kesmodel US, Riiskjær M, Seyer-Hansen M. Conservative approach to rectosigmoid endometriosis: a cohort study. Acta Obstet Gynecol Scand 2017; 96: Abstract Introduction. The aim of the study was to assess the risk of after initial of rectosigmoid endometriosis in relation to demographic data. Material and methods. The study was conducted on the tertiary endometriosis referral unit, Aarhus University Hospital. Medical records, from patients seen from January 2009 onwards with a diagnosis of rectosigmoid endometriosis and more than 6 months follow up were audited. Demographic data, results of magnetic resonance imaging and time to secondary for rectosigmoid endometriosis were registered. Results. Data on 238 patients diagnosed with rectosigmoid endometriosis were included. In all, 78 (32.8%) patients had primary, 27 (11.3%) had secondary and 133 (55.9%) continued throughout the observation period. Patients who underwent primary or secondary were younger than patients continuing. Conclusions. In a tertiary referral center where about half of patients with rectosigmoid endometriosis were scheduled for, more than 80% of these avoided. Abbreviations: DIE, deeply infiltrating endometriosis; MRI, magnetic resonance imaging; SD, standard deviation. Received: 19 October 2016 Accepted: 22 December 2016 DOI: /aogs Introduction Endometriosis is defined by ectopic presence of endometrium-like tissue (1). The prevalence may be up to 10% among fertile women and the disease is a major cause of pelvic pain and reduced quality of life (2,3). Deeply infiltrating endometriosis (DIE) is a severe form of the disease. This phenotype is defined by lesions invading more than 5 mm below the peritoneal surface (4). DIE can invade the rectosigmoid wall (rectosigmoid Key Message A cohort of 238 patients with rectosigmoid endometriosis was followed. About half of the patients could be treated ly and more than 80% of these avoided later. Median follow up was 22 months. ª 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 96 (2017)

2 Treatment of rectosigmoid endometriosis A.G. Egekvist et al. endometriosis), causing symptoms such as dyspareunia and dyschezia, in addition to chronic pelvic pain (5). Rectosigmoid endometriosis may cause obstruction, and DIE with ureter stenosis is also seen. Such cases represent absolute indications for, whereas pain represents a more relative indication where can be surgical or medical. Surgery for rectosigmoid endometriosis is complex, with a high risk of short-term complications (anastomotic leakage, ureteral injury). However, a recent study from our group showed a favorable long-term outcome (6). Medical with potential for long-term use should be the primary approach, provided that sufficient pain relief is achieved without unacceptable adverse effects. Such may involve continuous oral contraceptives, the levonorgestrel-intrauterine device or oral gestagens. Recent papers have provided detailed data on the longterm consequences of for rectosigmoid endometriosis (6 8). Less information is available on medical (9,10), and data on the need for bowel at a later stage seem to be missing. The aim of the present study was therefore to assess the risk of after initial of rectosigmoid endometriosis in relation to demographic data. Material and methods This cohort study was conducted at the Department of Obstetrics and Gynecology, Aarhus University Hospital, which is one of two tertiary referral centers for endometriosis in Denmark. According to rules by the Danish Health Authority, of advanced endometriosis is not allowed outside these two centers. Our team consisted of four doctors subspecialized in endometriosis. Surgery for rectosigmoid endometriosis was restricted to cases with aggravating pain despite acceptable medical, which included continuous oral contraceptives, the levonorgestrel-intrauterine device or oral gestagens. Conservatively treated patients with rectosigmoid endometriosis were monitored with at least one annual clinical outpatient visit. Women without a wish to conceive were advised to continue medical until menopause. In April 2013 a list of patients with a diagnosis of endometriosis affecting the rectosigmoid, vagina or the rectovaginal septum was drawn from the electronic patient record system according to ICD10 codes for DIE (DN-804, -804A, -804B, -804C, -805, -805A, -805B, -805C). Records from patients diagnosed with rectosigmoid endometriosis from 1 January 2009 onwards with a minimum of 6 months follow up (>182 days) were audited by the first author. Inclusion criteria were rectosigmoid endometriosis verified by transvaginal ultrasonography and/or magnetic resonance imaging (MRI). All MRI investigations were analyzed by the same subspecialized radiologist. Primary was defined as referral for laparoscopic rectosigmoid resection within 6 months (182 days) of the first outpatient visit, irrespective of any previous. Continued was defined as a minimum of 6 months of medical therapy. If patients, initially scheduled for continued, later underwent (secondary ), time to secondary was calculated as the timespan from the date of the first visit in the department to the date of the operation. During continued patients had regular follow up with the possibility to contact to the center. Data collected included demographic information, date of birth, weight and height, previous operations for endometriosis (number), oophorectomy status, current medical (at the time of audit), and results of MRI findings with respect to location(s) of endometriosis. Statistical analysis Data were entered directly into Microsoft â EXCEL (Microsoft Corp, Redmond, WA, USA) and transferred to STATA â IC/13.1 (StataCorp., College Station, TX, USA) for statistical analysis. Weight and height was imputed when missing (weight n = 68, height n = 70) by assigning an average weight in four age-categories and height in four weight-categories. No attempt was made to impute missing information about hormonal (n = 31). Differences in continuous variables were analyzed using Student s t-test for normally distributed data. Differences between categorical variables were analyzed using the chi-square test or Fisher s exact test where appropriate. Missing values were excluded from analysis. Time-to-event analysis (Kaplan Meier) was used to analyze and visualize time to secondary. Median with interquartile range (25/75 percentiles) was used to describe statistics for the time-to-event analysis. Differences were considered of statistical significance if p < The study was approved by the Danish Data Protection Agency (reference number: , 12 June 2013) and The Danish Health Authority (reference number: /1/, 13 April 2016). According to Danish legislation, approval from the ethics committee was not necessary because of the study design. Results Records from 238 patients diagnosed with rectosigmoid endometriosis in our department from 2009 to 2013 were 746 ª 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 96 (2017)

3 A.G. Egekvist et al. Treatment of rectosigmoid endometriosis identified. In all, 78 (32.8%) patients had primary, and 27 (11.3%) had secondary. Thus, 133 (55.9%) patients had continued throughout the observation period (Figure 1). Demographic data are presented in Table 1. Patients receiving primary and secondary were younger than patients receiving continued. No differences were found regarding body mass index, medical at the time of follow up, oophorectomy status or previous for endometriosis. Table 2 shows the distribution of endometriosis according to MRI. An MRI examination was available for analysis for 75 of the 78 patients referred for primary, 111 of the 133 patients who continued, and 26 of the 27 patients undergoing secondary. Patients undergoing primary more often had an MRI examination for analysis compared with patients on continued. There were no differences between patients who had and those who did not have MRI as regards the parameters in Table 1. No differences were observed between the groups in number of rectosigmoid nodules, distance from the anal verge or the occurrence of endometriomas and adenomyosis. Eleven (8.3%) of the patients receiving continued had infiltration in the rectosigmoid wall diagnosed by transvaginal ultrasonography only. Time to secondary was evaluated by Kaplan Meier analysis (Figure 2). In all, 160 patients were followed for a total of months. With a median follow up of 22.0 months ( ), 27 (16.9%) patients needed secondary. Median time to secondary was 17.6 months ( ). The longest follow up was 53.9 months. All patients undergoing secondary presented with pain. Three of these patients also had obstruction. One of these patients had total bowel obstruction and underwent acute at a gastrointestinal unit. Another had partial bowel obstruction and was scheduled for subacute in our department. Ureter stenosis with hydronephrosis was seen in one patient. These three cases developed during in vitro fertilization. Discussion In this study we describe a cohort of women with rectosigmoid endometriosis. In our setting, 67% of 238 patients with rectosigmoid endometriosis verified by imaging were scheduled for primary. Of these 160 patients treated ly, 27 (17%) were eventually referred for secondary within a median follow up of 22 months. Median time to secondary was 18 months. More than 80% of patients scheduled for avoided operation during the follow-up period. Patients in need of primary or secondary were younger than patients receiving continued. This was a study where patient data arose from an audit of records from a large cohort of patients with rectosigmoid endometriosis. Retrospective designs are prone to bias and results should be interpreted with caution. Information regarding medical can be difficult to identify, as reflected by the number of missing values in the dataset. The study design also impaired collection of pain response to medical, and analysis of type and severity of symptoms. However, all patients treated ly were seen at least once a year and examined with transvaginal ultrasonography and their clinical status was evaluated. Although we did not monitor these patients with VAS-score or regular questionnaires, these visits enabled us to monitor the clinical status of the patients. Longer follow up of this group would have given better information on the number of patients remaining stable without the need for. Strengths of the study included the size of the cohort and that patients received in one center only. Figure 1. Flowchart for surgical and medical for deeply infiltrating endometriosis with rectosigmoid affection. ª 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 96 (2017)

4 Treatment of rectosigmoid endometriosis A.G. Egekvist et al. Table 1. Demographic data in 238 patients with rectosigmoid endometriosis. Primary (n = 78) Continued (n =133) Primary vs. continued Secondary (n = 27) Mean SD Mean SD p-value Mean SD p-value Mean age at referral (7.4) Mean age at rectosigmoid Mean body mass index (4.5) b b n % n % n % Medical None Hormonal Missing a Oophorectomy None/unilateral Bilateral Previous for endometriosis a Missing values excluded from analysis. b Student s t-test was made on the log-transformed values of body mass index. Secondary vs. continued Not operated for bowel endometriosis Months since the patients first visit Figure 2. Time to secondary : Kaplan Meier survival estimate. [Color figure can be viewed at wileyonlinelibrary.com] We found a significant difference in age between surgically and ly treated patients. Previous studies have indicated that younger patients with DIE have a higher risk of recurrence of pain after than older patients (11,12). Cheong et al. (2008) found a higher risk of repeat if the woman was less than 30 years of age (13). Thus, young patients presenting with symptomatic rectosigmoid endometriosis may have more aggressive disease than patients diagnosed at a later age. In our series, 33% of patients with rectosigmoid endometriosis were referred for primary. Only 17% of women receiving primary needed referral to secondary within the follow-up period. More than half (56%) of our patients with rectosigmoid endometriosis could thus be treated ly for a prolonged period. This supports a approach to patients with DIE (14 16) rather than routine radical excision in cases without ureter or bowel obstruction. Patients with rectosigmoid endometriosis should be thoroughly informed regarding the potential risks and benefits of surgical or medical. Long-term medical is typically offered to patients without a current wish to conceive, whereas the situation is more complex when pregnancy is the first priority in younger patients. Many of these patients will be directly referred for in vitro fertilization, but may be an alternative, especially when pain is unacceptable to the patient. Some authors suggest that for rectosigmoid endometriosis might improve the outcome of in vitro fertilization (17,18), which could call for advising patients desiring to become pregnant to have such performed. However, available evidence is still limited on this issue. In our series, increasing pain was the main reason for secondary, but three patients also had de novo obstruction of bowel or ureter, without such pathology at the initial MRI. These complications developed during in vitro fertilization. More data are needed on the incidence of these problems during continued 748 ª 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 96 (2017)

5 A.G. Egekvist et al. Treatment of rectosigmoid endometriosis Table 2. Distribution of endometriosis found at MRI. Primary (n = 78) Continued (n =133) Primary vs. continued Secondary (n = 27) n % n % p-value n % p-value Patients having an MRI Retrocervical endometriosis Number of rectosigmoid nodules Unilateral endometriomas Bilateral endometriomas Adenomyosis Mean SD Mean SD Mean SD Continued vs. secondary Distance to rectosigmoid nodule closest to the anal verge (cm) Standard deviation (SD)., but in vitro fertilization seems to represent a risk factor (19,20). Overall, patients with DIE should be followed due to the risk of progression and the complexity of the disease. The need for thorough investigation and counseling suggests that these patients are followed in a tertiary referral center (21). No differences emerged in MRI findings between surgically and ly treated patients. Thus, the occurrence of adenomyosis, multiple nodules, retrocervical location and distance to the anal verge were similar. Neither did we find any difference in the distribution of endometriomas, which was seen in 48% of our patients with rectosigmoid endometriosis, in agreement with Roman et al. (22). In contrast, Chapron et al. found endometriomas in 23% in patient with DIE, but their study included patients without rectosigmoid disease (23,24). Taken together, we found no evidence in the present study that the phenotype of DIE found at MRI can predict future response to medical or the need for. Other aspects may be important, such as the individual predisposition to local growth of sensory autonomous nerves induced by the endometriotic tissue (25). Thus, patients with pain might represent an as yet undefined genetic subtype of endometriosis. Prospective studies incorporating systematic monitoring of pain symptoms and quality of life during for rectosigmoid endometriosis are needed. Conclusions More than 80% of patients, referred to a tertiary referral center with rectosigmoid endometriosis and initially scheduled for, seemed to respond favorably to this, thus avoiding major and associated complications. Young age at referral was a predictor of the need for surgical. Funding We would like to thank The Danish Endometriosis Society, which gave a grant for the project. The study is funded by The Graduate School of Health, Aarhus University. References 1. Fassbender A, Burney RO, O DF, D Hooghe T, Giudice L. Update on biomarkers for the detection of endometriosis. Biomed Res Int. 2015;2015: Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24: Bianconi L, Hummelshoj L, Coccia ME, Vigano P, Vittori G, Veit J, et al. Recognizing endometriosis as a social disease: the European Union-encouraged Italian Senate approach. Fertil Steril. 2007;88: Cornillie FJ, Oosterlynck D, Lauweryns JM, Koninckx PR. Deeply infiltrating pelvic endometriosis: histology and clinical significance. Fertil Steril. 1990;53: Darai E, Dubernard G, Coutant C, Frey C, Rouzier R, Ballester M. Randomized trial of laparoscopically assisted versus open colorectal resection for endometriosis: morbidity, symptoms, quality of life, and fertility. Ann Surg. 2010;251: Riiskjaer M, Greisen S, Glavind-Kristensen M, Kesmodel US, Forman A, Seyer-Hansen M. Pelvic organ function ª 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 96 (2017)

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