Advances and Concepts in Management of Endometriosis

Educational Objectives

The goal of this program is to improve diagnosis and treatment of endometriosis. After hearing and assimilating this program, the clinician will be better able to:

1. Explain the advantages of using indocyanine green when operating on a patient with suspected endometriosis.

2. Manage a patient with endometriosis.

Summary

Etiology of endometriosis: pathogenesis is complex; theory of retrograde menstruation cannot fully explain endometriosis; disorder may be seen in girls before menarche; endometriosis may be associated with immunologic and autoimmune disorders such as systemic lupus erythematosus and genetic factors

Diagnosis: on average, time from first painful menstrual period to diagnosis of endometriosis >10 yr; goal should be to establish diagnosis when patient first reports chronic pelvic pain; cyclic symptoms with menses (pain or other findings) should lead to diagnosis of endometriosis; endometriosis often presents with dysmenorrhea and cyclic pelvic pain; younger patients with endometriosis often have chronic (rather than cyclic) pelvic pain; women may have pain with intercourse or bowel movements, other gastrointestinal problems, symptoms in urinary tract, infertility, heavy menstrual bleeding, and chronic fatigue; laparoscopy gold standard for diagnosis; surgical goals to remove all visible disease, restore anatomy, improve fertility, and rule out occult malignancy; early lesions may be clear or white and difficult to detect

Lesions of endometriosis: classic red lesions may be seen on peritoneal lining; defect in peritoneum may be only manifestation; other findings may include endometrioma, deeply infiltrative endometriosis (DIE), and obliterated cul-de-sac, which may be associated with nodules >5 mm; among patients with endometriosis, 97% of teens and women in 20s have typical lesions; during laparoscopy, clinician should zoom in and wipe away any bubbles to avoid missing lesions in younger patients

Identifying hypervascular areas: in some cases, increased vascularity only sign of endometriosis; endometriosis causes neovascularization or angiogenesis; hypervascular areas of peritoneum indicate endometriosis; ablation or excision of surrounding areas of peritoneum may be required to remove microscopic disease

Indocyanine green (ICG): may be used on robotic platform (Firefly) or laparoscopic platform; infrared camera required; ICG binds albumin and thereby identifies areas of high blood flow; endometriosis shows as hazy concentration of green

Deeply infiltrative lesions: also difficult to detect; entire lesion should be excised; sensitivity and specificity of magnetic resonance imaging and ultrasonography similar; protocols should be established; these include thin cuts, intravenous contrast, and application of rectal and vaginal gel when rectovaginal disease suspected; sensitivity 70% and specificity 95% when such protocols employed; preoperative imaging to look for DIE especially important in patients with dyschezia, palpable rectovaginal nodule, or bilateral endometrioma; incomplete resection results in recurrent pain

Surgical management of superficial peritoneal disease: excision provides tissue (definitive diagnosis needed to allow patient to receive medical or integrative treatment) and reduces risk for leaving DIE behind; review of excision vs ablation reported no difference between these approaches at 6 mo to 1 yr; however, in meta-analysis that included several studies with ≈5-yr follow-up, almost all favored excision; advantages of excision include lower chance for incomplete treatment of DIE, decreased pain, and less recurrence

Treating obliterated cul-de-sac: effective uterine manipulator and experienced operator required; 30° scope improves visualization; “pexy everything” to prevent ovary, bowel, or uterus from obscuring surgical field; T-lift devices may be used; alternatively, needle may be inserted through abdominal wall and into structure of interest, then clamped with snap; monofilament suture should be used on uterus to reduce bleeding

Restoring anatomy: surgeon should begin laterally, identify ureters, and push them laterally; pushing rectum medially aids dissection; retroperitoneal dissection may be required

Retroperitoneal dissection: entry of ureter into pelvis may be identified near bifurcation of common iliac vessels at level of pelvic brim; surgeon should identify triangle formed by anterior leaf of broad ligament, external iliac vessels, and infundibulopelvic (IP) ligament, and open space parallel to IP ligament; ureter found in medial leaf of broad ligament; ureterolysis performed with blunt dissection in superior to inferior direction; by pulling on obliterated umbilical artery, surgeon may see superior vesical artery; uterine vessels should be skeletonized; following course of ureter leads to origin of uterine artery; most dissection may be done bluntly, with occasional use of harmonic scalpel

Additional dissection: at this point, if patient undergoing hysterectomy or does not desire future fertility, uterine artery should be clipped where it crosses ureter; this improves visualization and reduces bleeding; if fertility desired, clip may be removed at end of procedure; clinician may adopt lateral approach to dissect rectum off posterior uterus; to restore anatomy of cul-de-sac, rectovaginal septum should be dissected and endometriosis removed from posterior uterus and rectum

Medical management: hysterectomy and oophorectomy not curative but decrease recurrence of disease; hormonal suppression after surgery decreases risk for recurrent pain; endometriosis may return after treatment with gonadotropin releasing-hormone (GnRH) agonist; in patients with milder endometriosis, long-term suppression with progestin-releasing intrauterine device (Mirena IUD) or oral contraceptives (OCs) well tolerated and should be continued until pregnancy desired; for severe disease or DIE, GnRH agonist may be given for 6 mo along with add-back therapy; OCs then continued until pregnancy desired or until menopause

Definitive surgery: hysterectomy and oophorectomy may be offered; for patients nearing menopause, oophorectomy alone reasonable

Medical options: most methods prevent menstruation and oppose estrogen; among progestin-based therapies, IUD supported by strongest evidence; GnRH agonists effective and should be given with add-back therapy; oral danazol (Danocrine) not often used at speaker’s center because of side effects

New medical approaches: include new GnRH antagonist; vaginal or rectal danazol associated with fewer side effects than oral route; aromatase inhibitors experimental and must be given with suppression of ovulation to prevent ovarian cysts; GnRH agonists may be used safely ≤3 yr with add-back therapy; bone density should be evaluated during prolonged use; for pain, first-line therapies include gabapentin, pregabalin (Lyrica), and low-dose antidepressants; other options include hypogastric nerve block and injection of onabotulinumtoxinA (Botox) in pelvic floor; opioids should be avoided, as they may lead to development of tolerance and centralized pain; unmanageable pain should be referred to pain service

New GnRH antagonist (elagolix): randomized controlled trial tested 150 mg daily vs 200 mg twice daily vs placebo; study reported significant, dose-dependent improvement in cyclic pelvic and nonpelvic pain in patients on elagolix; only higher dose associated with reduced need for rescue analgesia and relief of dyspareunia; side effects similar to those of other GnRH agonists (hot flashes, headache, insomnia, mood swings, night sweats, arthralgia); drug may cause increase in cholesterol and triglycerides and decrease in bone mineral density; 8 pregnancies observed in treated patients; elagolix is oral alternative that allows dose to be stopped or titrated

Comprehensive treatment: relies on multimodal approach that includes complementary and alternative treatments such as yoga, acupuncture, and anti-inflammatory diet; at University of California, San Francisco, multidisciplinary network includes patient navigator, gynecologist, psychologist, reproductive endocrinologist, pain service, physical therapist, integrated medicine personnel, specialist in sexual health, urologist, radiologist, and others

Summary: interdisciplinary and holistic approach emphasized; early diagnosis and complete surgical excision important

Readings

Bazot M et al: European Society of Urogenital Radiology (ESUR) guidelines: MR imaging of pelvic endometriosis. Eur Radiol 2017 Jul;27(7):2765-2775; Cosentino F et al: Near-infrared imaging with indocyanine green for detection of endometriosis lesions (Gre-Endo Trial): a pilot study. J Minim Invasive Gynecol 2018 Nov - Dec;25(7):1249-1254; de Paula Andres M et al: The current management of deep endometriosis: a systematic review. Minerva Ginecol 2017 Dec;69(6):587-596; Healey M et al: To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. J Minim Invasive Gynecol 2014 Nov-Dec;21(6):999-1004; Jayakumaran J et al: Robotic single-site endometriosis resection using near-infrared fluorescence imaging with indocyanine green: a prospective case series and review of literature. J Robot Surg 2019 Apr 1 [Epub ahead of print]; Muzii L et al: Management of endometriosis from diagnosis to treatment: roadmap for the future. Minerva Ginecol 2019 Feb;71(1):54-61; Pundir J et al: Laparoscopic excision versus ablation for endometriosis-associated pain: an updated systematic review and meta-analysis. J Minim Invasive Gynecol 2017 Jul - Aug;24(5):747-756; Taylor HS et al: Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med 2017 Jul 6;377(1):28-40.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. Dr. Opoku-Anane presents information in her lecture related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Opoku-Anane spoke at the 2018 Obstetrics and Gynecology Update: What Does the Evidence Tell Us?, presented by the University of California, San Francisco, School of Medicine, and held October 17-19, 2018, in San Francisco, CA. For information on upcoming CME meetings presented by the University of California, San Francisco, please visit meded.ucsf.edu. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OB661801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.