Safe and Effective Surgery for Endometriosis Including Detection and Intervention for Ovarian Cancer

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Safe and Effective Surgery for Endometriosis Including Detection and Intervention for Ovarian Cancer Camran Nezhat,, MD, FACOG, FACS Stanford University Medical Center Center for Special Minimally Invasive Surgery Palo Alto, CA 94304 camran@nezhat.org

Introduction and Overview This talk aims to provide an overview of safer surgical techniques for the treatment of endometriosis as well as review the literature on ways to maximize the effectiveness of surgery for recurrence prevention and fertility. Included is a discussion of detection and intervention for ovarian cancer in the patient with endometriosis.

Outline Background on Surgery for Endometriosis Safer Surgical Technique Optimizing Effectiveness of Treatment Endometriosis and Infertiltiy Cancer Risk and Endometriosis

Surgical Treatment of Endometriosis Indications for surgery Diagnostic Severe endometriosis Failed medical management Infertility Options Definitive versus Conservative Surgery

Surgical Treatment of Endometriosis Definitive Surgery: Removal of uterus, ovaries, and tubes Conservative Surgery Ablation versus excision of implants and adhesions Resection of endometriomas

Conservative Surgery Excision, fulguration, or laser vaporization of endometriotic implants Removal of adhesions Resection of endometriomas including the cyst wall Restoration of normal pelvic anatomy

Conservative Surgery Ancillary procedures: Presacral neurectomy Uterosacral neurectomy

Maximizing Safety in Surgery Identifying Landmarks Ureterolysis Hydrodissection and CO2 Laser More precise and less penetrating

Maximizing Safety in Surgery Cystoscopy, Proctoscopy Check integrity if ablation/fulguration are done around bladder or bowel Recognizing when consultation is needed

Optimizing Effectiveness Recurrence risk Risk of recurrence is estimated to be as high as 40 percent at 10 year of follow up Pain control Pain relief is achieved in most patients who undergo ablation/resection of endometriosis Wheeler et al 1983

Optimizing Effectiveness Randomized trials Trial 1 LSC laser ablation of endometriotic implants plus uterine nerve ablation was more likely to result in improvement or resolution of symptoms at 6 months than expectant management (63 versus 23 %) Women with stage I disease were less likely to improve after their surgical procedure Sutton et al Oct 1994

Optimizing Effectiveness Trial 2 LSC excision of implants led to symptomatic improvement in 80% of patients at 6 months compared to 32% of controls undergoing diagnostic laparoscopy Most of these women had stage II-IV IV disease which may account for higher success rate Abbot et al Oct 2004

Optimizing Effectiveness Combining LSC laser ablation, adhesiolysis and uterine nerve ablation is likely to be beneficial treatment for pelvic pain associated with minimal, mild and moderate endometriosis Interpret with caution- only one trial in this Cochrane review Jacobson Cochrane 2005

Optimizing Effectiveness Presacral Neurectomy Insufficient evidence to recommend use of nerve interruption in the management of dysmenorrhea alone Our clinical experience: shows efficacy Proctor et al Cochrane 2005

Optimizing Effectiveness Barrier agents for preventing adhesions after surgery for subfertility Interceed reduces incidence of adhesion formation but insufficient data to support its use to improve pregnancy Seprafilm no evidence in prevention of adhesion formation Farquar et al Cochrane 2005

Optimizing Effectiveness Pre and post operative medical therapy for endometriosis surgery Cochrane Review showed insufficient evidence that hormonal suppression in association with surgery provides improvement of symptoms, pregnancy rates and overall tolerability but a significant improvement in disease recurrence Yap et al, Cochrane 2005

Treatment of Infertility Endometriosis can reduce fecundability Endometriosis does not usually completely prevent conception

Treatment of Infertility Achieving pregnancy following a surgical procedure depends on: stage of disease presence of other infertility factors Women with moderate to severe endometriosis who desire pregnancy benefit from surgical therapy

Treatment of Infertility Pregnancy rates after surgery: Moderate endometriosis 50% Severe endometriosis 39% Pregnancy rates with expectant management: Mild 50% Moderate <25% Severe disease 5% Evers 1989 Olive 1989

Cancer Risk and Endometriosis Epidemiologic evidence Large cohort studies suggest endometriosis is an independent risk factor for epithelial ovarian cancer (EOC) Risk of malignant transformation in ovarian endometriosis is approx 2.5% Van Gorp et al Apr 2004

Cancer Risk and Endometriosis Endometrioid and clear cell ovarian cancer can arise from endometriomas Erzen et al Oct 2001

Cancer Risk and Endometriosis Endometriosis associated ovarian cancer presents: Earlier stage Lower grade lesions Better overall survival 81% vs 54% Erzen et al Oct 2001 Ovarian endometrioid and clear cell cancer more commonly diagnosed in Stage 1 because of their frequent association with symptomatic endometriosis Nezhat, F 2005 abstract

Cancer Risk and Endometriosis Molecular studies detected common alterations in endometriosis and ovarian cancer Van Gorp et al Apr 2004 Nezhat, F 2005 abstract Risk of ovarian cancer is highest in women with endometriosis and primary infertility Brinton et al Aug 2004

Cancer Risk and Endometriosis Screening No Standardized Protocol Screening Routine annual exam Clinical symptoms Ultrasound if needed Tumor markers if indicated

Cancer Risk and Endometriosis Detection Consider washings Consider frozen section Prepare patient for full staging if index of suspicion is high

Thank you Camran Nezhat,, MD, FACOG, FACS Center for Special Minimally Invasive Surgery Stanford University

Bibliography Abbott, J et al. Laparoscopic excision of endometriosis: a randomized placebo-controlled controlled trial. Fertil Steril 2004; 82:878. Brinton,, LA, et al Ovarian cancer risk associate with varying causes of infertility. Fertil Steril 2004 Aug; 82(2): 405-14. Evers, JL. The pregnancy rate of the no-treatment group in randomized clinical trials of endometriosis therapy. Fertil Steril.. 1989; 52:906. Erzen,, M. Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case- control study. Gynecol Oncol 2001 Oct;83 (1): 100-8. Farquhar,, C et al. Barrier agents ffor preventing adhesions after surgery for subfertility.. Cochrane Database of Systematic Reviews. 3, 2005. Jacobson, TZ et al. Laparoscopic surgery for pelvic pain associated with endometriosis. Cochrane Database of Systematic Reviews. 3, 2005. Nezhat,, F, Deligdisch,, L et al. Stage 1 ovarian carcinoma. A different distribution of histologic pattern. The Mount Sinai School of Medicine, New York, NY. USA Abstract P-788 P 2005.

Bibliography Nezhat,, F. Schlosshauer,, P. Analysis of BRAF/ERK and P16 in ovarian endometrioid lesions. The Mount Sinai School of Medicine, New York, NY. USA Abstract O-237 O 2005. Olive, DL. Conservative Surgery. Endometirosis: : Contemporary Concepts in Clinical Management, Schenken,, RS Schenken (Ed), JB Lippincott Company, Philadelphia 1989. p. 213. Proctor, ML et al. Surgical interruption of pelvic nerve pathways s for primary and secondary dysmenorrhoea.. Cochrane Database of Systematic Reviews. 3, 2005. Sutton, CJ et al. Prospective, randomized, double-blind, blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mal, mild and moderate endometriosis. Fertil Steril 1994; 62:696. Van Gorp,, T. et al. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol 2004 Apr; 18(2): 349-71. Wheeler, JM et al. Recurrent endometriosis: Incidence, management t and prognosis. AmJ Obstet Gynecol 1983; 146: 247. Yap, C et al. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database of Systematic Reviews. 3, 2005.