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An Atlas of ENDOMETRIOSIS An Atlas of ENDOMETRIOSIS Third Edition Edited by Caroline Overton MBBS MD MRCOG Consultant Gynaecologist, St Michael’s Hospital and University of Bristol, UK Colin Davis MD MRCOG Consultant Obstetrician and Gynaecologist, Specialist, St Bartholomew’s Hospital London, UK Lindsay McMillan FRCOG Consultant Gynaecologist, Portland Hospital London, UK Robert W Shaw CBE MD FRCOG Immediate Past President of the World Endometriosis Society; Head of Obstetrics and Gynaecology, University of Nottingham Derby City General Hospital, and Head of School of Human Development, University of Nottingham, UK Foreword by Charles Koh MD FACOG FRCOG Reproductive Specialty Center, Milwaukee, WI, USA CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2007 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20130426 International Standard Book Number-13: 978-1-4398-0476-6 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not necessarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medi- cal science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the drug companies’ printed instructions, and their websites, before administering any of the drugs recommended in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Contents Foreword vii Preface ix Acknowledgements xi 1 Aetiology 1 2 Basic science of endometriosis 5 3 Clinical features of endometriosis 9 4 Clinical findings 25 5 Classification and histological diagnosis 35 6 Ovarian endometriosis 45 7 Principles of treatment 51 8 Medical treatment of endometriosis 57 9 Surgical treatment of endometriosis 63 10 Ultrasound assessment of endometriosis 85 Bill Smith 11 Nutrition and endometriosis 105 Marilyn Glenville Appendix 111 Index 113 Foreword Endometriosis remains an enigma despite the many years Fortunately, an increasingly sophisticated understanding elapsing since its description by Samson. It continues to defy of deep endometriosis is now present in centers that treat research aimed at uncovering its etiology and the corre- rectovaginal endometriosis with complete excision of disease sponding rational management that would result. Equally to clear margins. In addition to providing longer term relief, perplexing is the fact that afflicted women do not suffer the such dissection also teaches the extent of such disease. In same symptoms and in fact some are completely asympto- 2005–2006 alone there were nine papers on laparoscopic matic. Research into the genomic characterisation of bowel resection for deep rectovaginal endometriosis, almost endometriosis may hold the greatest promise yet, and per- as much as in the previous 10 years. A very welcome trend haps variable expression may explain the variable affects of in such specialized centers is the emphasis on adequate the disease. But even this approach will see many false leads removal of disease, rather than resorting to hysterectomy before the etiology is finally elucidated. and castration, the latter in my opinion being an overzealous In the meantime however, the great number of women surgical extrapolation of Samson’s theory. This approach is suffering from endometriosis need effective treatment now, a tragedy for younger women. and it is important for the gynecologist to be up to date in Hence to clinically understand endometriosis one must their understanding of treatment algorithms so that maxi- astutely sift through literature and disqualify papers that mumbenefit can accrue to patients, and just as importantly, though well designed, were conducted at a time when little that harm is not done from ignorance or employment of was known of subtle and deep endometriosis. Only thus can outmoded treatment. cumulative knowledge be garnered, leading ultimately to The discerning student of endometriosis must fully precise clinical understanding of the disease and its treat- understand the temporal evolution of knowledge when ment. How does one begin on this path? Exactly by reading reviewing the literature and realize that much of the older this wonderfully crafted text – the Atlas of Endometriosis. data may not be extrapolated. In this third edition the authors have significantly updated For example, the recognition of the various morphological the content to reflect current understanding, management appearances of endometriosis other than the classical ‘powder and controversies resident in the treatment of endometrio- burn’, in particular the almost microscopic clear papule sis. The chapters are clearly written and will provide a basis visible only by laparoscopic magnification, postdated earlier for the understanding of current practice in endometriosis studies by laparotomy and unmagnified laparoscopy that treatment for the student, trainee and practitioner. For the reported the histological presence of endometriosis in ‘normal’ basic science researcher, this atlas gives a much needed sum- peritoneum. mary of clinical information that aids their understanding ‘Deep’ endometriosis was first defined in the early of the clinical disease, thus providing substantive underpin- nineties, prior to which it was considered only ‘scar’ tissue ning to their research at increasingly molecular levels. and therefore not necessary to treat. Hence studies on This is a very comprehensive and balanced publication surgical treatment efficacy and recurrence before this with up to date coverage of the theoretical, basic science, period should not, for example, be used in contemporary clinical, diagnostic and imaging, medical, surgical, and meta-analyses. nutritional aspects related to endometriosis. It is more vii FOREWORD substantive than being just an ‘atlas’, but certainly demon- The historical reflex of hysterectomy and oophorectomy as strates the strengths of an excellent atlas by including a surrogate treatment of deep endometriosis is correctly very comprehensive array of photographic examples of questioned in the light of excisional data, and offers women surgical findings, imaging, histopathology and assisted hopeof symptom relief without sacrificing fertility. reproductive technology. The authors are to be congratulated for producing this Fertility treatment is brought up to date with contem- excellent atlas which is definitely recommended reading for porary evidence based considerations of surgery versus the intended audience. assisted reproduction in the context of success rates related I can think of no better volume for the gynecologist, to disease severity. general surgeon, urologist, internist, family doctor to Pain amelioration strategies similarly give weight to obtain a ‘fast forward’ to currency of their knowledge of contemporary evidence of efficacy of excisional surgery by endometriosis from the last time they learnt it as medical laparoscopy, adjunctive measures like presacral neurectomy students. This allows them to more productively share in and the clear abandonment of procedures like LUNA. A the care of the patient as an effective ‘team’. This volume is clear enunciation of medical treatment in augmenting the also recommended for the resident, medical student and results of surgery is well discussed. nurse wishing to understand endometriosis. The section on rectovaginal endometriosis excellently I thank the authors for the honor and privilege of writing describes a once misunderstood and avoided area of this foreword and commend them for performing an out- endometriosis surgery, which often resulted in prolonged standing service in the education of their readers on poor quality of life because of inadequate treatment. The endometriosis. authors’ attitude mirror the recent immense interest among the foremost practitioners of radical endometriosis surgery Charles Koh MDFACOGFRCOG in laparoscopically excising the disease completely, including Reproductive Specialty Center bowel resection, urinary resection and repair if necessary. Milwaukee, WI, USA viii Preface Endometriosis is arguably the most frequent problem The first Atlas of Endometriosiswas published in 1993 and encountered in gynaecology. It affects women in their a second edition in 2002. A third edition is required to reproductive years and has been described as second only update the atlas. Imaging, particularly magnetic resonance to uterine fibroids as the most common reason for surgery and ultrasound imaging, have developed, and new images in premenopausal women. The true incidence is unknown, are included. Advances in camera technology have result- but the study that came closest to identifying the fre- ed in greater clarity of the laparoscopic images, and images quency of the disease in the general population estimates are now placed throughout the text making the atlas easier that6% of all premenopausal women have endometriosis. to read. Endometriosis affects women in the reproductive years, is There have been significant contributions to the medical associated with pelvic pain and infertility and, although not literature about existing medical treatments. A section has life threatening, can seriously impair health. It has huge eco- been added on new and potential medical treatments, as nomic and social consequences. The economic cost can be well as complementary therapies. A section has also been calculated directly in terms of health care resources con- added on the natural progression of the disease, fertility sumed, and indirectly in terms of lost work capacity. The cost and pregnancy. This remains the definitive Atlas of of intangibles such as suffering and reduced quality of life Endometriosis, covering all aspects of the disease and every is impossible to quantify. The estimated total annual cost to question asked by patients. society for all women with pelvic pain was calculated in 1992 to be £158.4 million (direct) and £24 million (indirect). CO, CD, LM, RWS ix Acknowledgements The authors would like to acknowledge the following Professor J Scott†, kindly supplied Figure 3.24. contributions; Dr Basil Shepstone, Consultant Radiologist at the John Dr Heather Andrews, Consultant Radiologist at the Radcliffe Hospital, Oxford, kindly supplied Figures Bristol Royal Infirmary, kindly supplied Figures 4.19–4.24. 4.18(a,b). Mr Bill Smith, of Clinical Diagnostic Ultrasound Mr David Bromham†, kindly supplied Figures 3.8 and Services, London, kindly supplied Chapter 10. 3.23–3.25. Professor Chris Sutton, Professor of Gynaecological Mr Alpesh Doshi, Chief Embryologist at the Assisted Surgery, University of Surrey, kindly suppled Figure 9.64. Conception Unit, University College Hospital, London, Figures 2.1, 5.1 and 5.10 are reproduced by courtesy kindly supplied Figures 7.8–7.13. of Fertility and Sterility and The American Society for Dr Marilyn Glenville (www.marilynglenville.com) Reproductive Medicine. kindly supplied Chapter 11. Dr Joya Pawade, Consultant Histopathologist at the Bristol Royal Infirmary, kindly supplied Figures 5.11–5.18, 7.14 and 7.15. xi CHAPTER 1 Aetiology INTRODUCTION and biologically similar to normal endometrium. This ectopic endometrial tissue responds to ovarian hormones undergoing Endometriosis is one of the most common problems en- cyclical changes similar to those seen in eutopic endo- countered in gynaecology. It affects women in their repro- metrium. The cyclical bleeding from endometriotic deposits ductive years and has been described as second only to appears to contribute to the induction of an inflammatory uterine fibroids as the most common reason for surgery in reaction and fibrous adhesion formation, and in the case of premenopausal women1. Its true incidence is unknown, deep ovarian implants, leads to the formation of endome- but the study that came closest to identifying the frequency triomas or chocolate cysts. of the disease in the general population estimated that 6% The symptoms of endometriosis are variable and may be of all premenopausal women have endometriosis2. unrelated to the extent of the disease. The most extensive Endometriosis affects women in the reproductive years, endometriosis can be asymptomatic and be discovered ac- is associated with pelvic pain and infertility and, although cidentally. Conversely, small lesions may produce marked not life threatening, can seriously impair health. It has huge symptoms. Pelvic pain related to the menstrual cycle, dys- economic and social consequences. The economic cost can menorrhoea and infertility are the major complaints of women be calculated directly in terms of health care resources con- with endometriosis, while menstrual irregularities and dys- sumed, and indirectly in terms of lost work capacity. The pareunia are also commonly associated with the disease. cost of intangibles such as suffering and reduced quality of The clinical diagnosis of endometriosis is primarily made life, is impossible to quantify. The estimated total annual cost at the time of laparoscopy, although there is increasing to society for all women with pelvic pain was calculated to support for empirical treatment with laparoscopy if symp- be £158.4 million (direct) and £24 million (indirect). The toms persist. The classic appearance is of blue-black lesions, estimated total lifetime treatment costs for a 1-year inci- but many subtler appearances are now recognised. dence cohort of women with pelvic pain is £10.5 million The term endometriosis was first used by Sampson in the (direct) and £2.6 million (indirect)3. 1920s10,11. He and Meyer spent their medical careers argu- Endometriosis affects 45–70% of adolescents with chron- ing their theories of pathophysiology. More than 80 years have ic pelvic pain4. In a large survey of over 70000 adolescent passed, but endometriosis remains a perplexing and poorly women, dysmenorrhoea was a common cause of reported understood disease. school absence5. In the United States, chronic pelvic pain affects approximately one in seven women, with very high EPIDEMIOLOGY associated annual health costs6. A Norwegian study dem- onstrated that 2% of women had been treated for this con- Endometriosis is primarily a disease of the reproductive dition by the age of 407. Endometriosis-associated pain may years, and is only rarely described in adolescents (when it is be found in up to 60% of women with dysmenorrhoea and associated with obstructing genital tract abnormalities) and 40–50% of women with pelvic pain and dyspareunia8. postmenopausal women (when it is associated with obesity Despite the identification of symptoms there is often a and exogenous hormones). No differences in the incidence delay in establishing a diagnosis of endometriosis and hence of the disease between races have been found except for a delay in ensuring effective treatment. This delay is on Japanese women, who have been reported to have twice the average between 6 and 7 years, and a consistent feature of incidence of Caucasian women12. most female populations9. The exact prevalence of endometriosis in the general Endometriosis is characterised by the presence, outside female population is unknown. Diagnosis depends on the the endometrial cavity, of tissue that is morphologically observation of implants, at the time of either laparoscopy 1 AN ATLAS OF ENDOMETRIOSIS Table 1.1 Prevalence of endometriosis by presentation elsewhere, it should occur with increasing frequency with advancing age. The clinical pattern of endometriosis is Women undergoing tubal sterilisation6 2% distinctly different, with an abrupt halt in the disease at Women with affected first-degree relatives7 7% Infertile women8 15–25% the cessation of menstruation. Women with surgically removed ovaries9 17% At diagnostic laparoscopy10 0–53% Menstrual regurgitation and implantation At gynaecologic laparoscopy10 0.1–50% The most popular theory is that proposed by Sampson in Unexplained infertility8 70–80% 1921. He postulated that fragments of the uterine endo- metrium, transported through the fallopian tubes in a retrograde manner at the time of menstruation, implant in or laparotomy (Table 1.1), and until a simple screening test the peritoneal cavity, giving rise to endometriosis10. is developed, the true incidence will remain unknown. The following evidence exists to support the theory of ret- There has been only one population-based study, which rograde menstruation being the prime mechanism for the showed a prevalence of 6.2% for the disease2. Most preva- development of endometriosis: viable endometrial cells lence studies have reported women presenting with one of have been demonstrated in menstrual effluent15 and have several symptoms justifying laparoscopy, e.g. pelvic pain, been grown in vitro16and even within the peritoneal cavity dysmenorrhoea and infertility. (in monkeys) if the menstrual flow is diverted to permit Delayed childbearing, either by choice or due to infertil- intraperitoneal menstruation17. Endometrial cells obtained ity, has been implicated as a risk factor for the development from the menstrual effluent have been demonstrated to be of endometriosis. The risk of developing the disease corre- transplantable to abdominal wall fascia18. The tubal ostia sponds with the cumulative menstruation (menstrual are located near the uterosacral ligaments in the pouch frequency and volume over time)13. Women with shorter of Douglas, which are one of the most common sites of menstrual cycles (fewer than 27 days) and longer duration endometrial cell implantation19. of flow (more than 7 days) are twice as likely to develop Several studies have confirmed a high incidence of retro- endometriosis than those with longer cycles and shorter flow. grade menstruation (90–99%) and the presence of endome- trial cells in peritoneal fluid in women of reproductive age, PATHOGENESIS and yet, only 1–6% of these women have endometrio- The precise aetiology of endometriosis still remains unknown. sis20,21. This suggests that retrograde menstruation alone does It has often been called the disease of theories, because of not give rise to endometriosis, but that some other factor(s) the many postulated theories to explain its pathogenesis. must be involved in its development. Those factors could The major theories of causation of endometriosis are the include some alteration in the uterine endometrium of metaplasia of coelomic epithelium14or the implantation of women with endometriosis, an altered immune response to endometrial fragments which reach the pelvic cavity by retrograde menstruation or, alternatively, a more favourable retrograde menstruation10. peritoneal environment that may stimulate the growth and implantation of ectopic endometrium in the peritoneal cavity. Transformation of coelomic epithelium Dr Robert Meyer postulated the theory of coelomic meta- Genetic and immunological factors plasia in 191914. He proposed that endometriosis develops Several clinical studies indicate that there may be a genetic from metaplasia of cells lining the pelvic peritoneum. This factor related to endometriosis. The disease is more preva- theory is based on embryological studies demonstrating lent in certain families; the risk of developing endometrio- that Müllerian ducts, germinal epithelium of the ovary and sis is seven times higher and more likely to be severe in pelvic peritoneum are all derived from the epithelium of women with an affected first-degree relative22,23. Endo- the coelomic wall. If this theory is correct, peritoneum metriosis is more common in monozygotic than in dizygotic must contain either undifferentiated cells capable of trans- twin sisters, but no association was found with particular formation into endometrial cells, or differentiated cells that human leukocyte antigen (HLA) tissue types24. maintain the capacity for further differentiation. The rare Dmowski and colleagues25 suggested that genetic and case reports of endometriosis in men are taken as evidence immunological factors may alter the susceptibility of a woman for the theory of coelomic metaplasia. However, if the to allow her to develop endometriosis. They demonstrated theory is correct, metaplasia should occur wherever coelom- a decreased cellular immunity to endometriotic tissue in ic membranes are present. Although there is embryological women with endometriosis. No clinically significant immune evidence that the coelomic membranes cover the abdominal system abnormalities have been observed in women with and thoracic cavities, endometriosis is rare outside the endometriosis, and there are no differences in individual pelvis. Lastly, if coelomic metaplasia is similar to metaplasia subsets of circulating lymphocyte populations26. 2

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