Recurrent endometriosis

Endometriosis is known to have a remarkably negative effect on the Quality of Life of the women. Surgery is considered when medical therapy is unsuccessful or in the setting of infertility. A high recurrence rate is reported in advanced stages of endometriosis. Thus, Complete excision and prevention of recurrence is particularly important.

1. recurrent ENDOMETRIOSIS DR. NIRANJAN CHAVAN

2. He Who Knows Endometriosis Knows Gynaecology Sir William Osler

3. INTRODUCTION It’s a clinical entity characterised by presence of tissue resembling functioning endometrium outside uterine cavity . Characteristics of disease was described at least as far back as 1600 BCE Schrön described a “female disorder in which ulcers appear[ ed ] in the abdominal, the bladder, intestines and outside the uterus and cervix, causing adhesions” 1 ST described by Von Rokintansky in 1860.

4. SITES OF ENDOMETRIOSIS

5. PREVALENCE Endometriosis affects 6% to 10% of reproductive age women Prevalence can be as high as 50% infertile women

6. HISTIOGENESIS Reflux and Direct Implantation theory Coelomic Metaplasia Theory Vascular Dissemination Theory Autoimmune Disease Theory PROMOTING FACTORS Estradiol >60pg/ml Platelet-derived growth factor Macrophage derived growth factors Increased expression of P-450 Overexpression of metalloproteinase

7. RECURRENCE IN ENDOMETRIOSIS The recurrence rate at 3 and 5 years after initial conservative surgery is 13.5% and 40.3 % ACOG practice bulletin 2010 says the most common site of recurrence are large and small bowel after hysterectomy

8. RECURRENCE IN ENDOMETRIOSIS Neither the initial staging or the ability to conceive after the initial surgery affect the recurrence rate Repeat conservative surgery for recurrent endometriosis has similar efficacy and limitations and a similar cumulative recurrence rate ranging from 20% to 40% Laparoscopic cystectomy of ovarian endometriomas >3cm has a cumulative rate of ultra sonographic recurrence of 11.7% and 57 % over 48 months and 60 months respectively

9. SYMPTOMS OF RECURRENCE Chronic pelvic pain Dyspareunia Vaginal or rectal bleed Rectal pain Low back pain Painful defecation

10. CAUSES OF RECURRENCE Deep endometriotic lesion left behind especially in sub peritoneal spaces

11. CAUSES OF RECURRENCE Atypical or non – pigmented lesions difficult to recognize i.e. clear or white endometriotic spot

12. CAUSES OF RECURRENCE Lesions hidden by peritoneal adhesions of the Pouch Of Douglas

13. CAUSES OF RECURRENCE Hormone replacement therapy According to ACOG practice bulletin 2010, in the current era of HRT, it has become increasingly important to make an effort to remove all deep lesions as they carry a risk for symptomatic recurrence and rarely malignant transformation.

14. CAUSES OF RECURRENCE Microscopic foci of disease (invisible at the time of surgery) could progress to clinically significant disease. * Pelvic peritoneal biopsy shows characteristic features of endometriosis, with endometrioid glands surrounded by stroma ( hematoxylin and eosin stain * Redwine D. Evidence for asymmetric distribution of sciatic nerve endometriosis. Obstet Gynecol. 2003 Dec;102(6):1416; author reply 1416-7. PubMed PMID: 14662240.

15. CAUSES OF RECURRENCE Lymphatic spread may contribute to recurrence : Lymph node involvement is reportedly involved in 25-40% of rectosigmoid endometriosis * * Abrao MS, Podgaec S, Dias JA Jr, Averbach M, Garry R, Ferraz Silva LF, Carvalho FM. Deeply infiltrating endometriosis affecting the rectum and lymph nodes. Fertil Steril . 2006 Sep;86(3):543-7. Epub 2006 Jul 28. PubMed PMID: 16876165

16. CAUSES OF RECURRENCE Ovarian preservation surgery: women undergoing hysterectomy for symptomatic endometriosis with ovarian conservation carries a 6.1 fold risk of recurrent pain and 8.1 fold risk of re-operation.* Peritoneal endometriosis visualized along the course of left ureter causing persistent pain after laparoscopic hysterectomy. * Namnoum AB, Hickman TN, Goodman SB, Gehlbach DL, Rock JA. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril . 1995 Nov;64(5):898-902. PubMed PMID: 7589631

17. CAUSES OF RECURRENCE Ovarian remnant syndrome : recurrent endometriosis has been associated with the presence of residual tissue after oophorectomy. * * Kho RM, Abrao MS. Ovarian remnant syndrome: etiology , diagnosis, treatment and impact of endometriosis. Curr Opin Obstet Gynecol. 2012 Aug;24(4):210-4. doi : 10.1097/GCO.0b013e3283558539. Review. PubMed PMID: 22729094.

18. DIAGNOSIS: CLINICAL The ESHRE GUIDELINES 2014 recommends diagnosis of endometriosis, in the presence of : Gynaecological symptoms: Dysmenorrhoea Non-cyclical pelvic pain Deep dyspareunia Infertility Fatigue Non-gynaecological cyclical symptoms: Dyschezia Dysuria Haematuria Rectal bleeding Shoulder pain

19. DIAGNOSIS: CLINICAL Physical examination has poor sensitivity, specificity, and predictive value in the diagnosis of endometriosis “Pain mapping” may help isolate location-specific disease such as nodular masses in posterior rectovaginal septum Absence of evidence during examination is not evidence of disease absence

20. DIAGNOSIS: IMAGING ULTRASOUND Transvaginal sonography (TVS) is useful for identifying or ruling out rectal endometriosis Diagnosis of ovarian endometrioma is based on the following ultrasound characteristics: ground glass echogenicity and one to four compartments and no papillary structures with detectable blood flow

21. DIAGNOSIS: IMAGING MRI MRI may detect even smallest of lesions and distinguish hemorrhagic signal of endometriotic implants; superior to CT scan in detecting limits between muscles and abdominal subcutaneous tissues Clinicians can assess ureter, bladder and bowel involvement by additional imaging like Barium enema, transvaginal sonography (TVS) and transrectal sonography

22. DIAGNOSIS: LAPAROSCOPY The combination of laparoscopy and the histological verification of endometrial glands and/or stroma is considered to be the GOLD STANDARD for the diagnosis of the disease. Clinically visualized findings may represent “tip of the iceberg” ; thus emphasizing the importance of diagnostic laparoscopy for diagnosis and staging

23. CLASSIFICATION “The American Society for Reproductive Medicine’s current classification of endometriosis in stages 1−4 is the most widely used and accepted staging system; however, it does not correspond well to pain and dyspareunia, and fecundity rates cannot be predicted accurately”

24. ASRM CLASSIFICATION

25. SURGICAL MANAGEMENT DEFINITIVE SURGERY : Total abdominal hysterectomy with bilateral salphingo -oophorectomy, excision of peritoneal surface lesions or endometriomas and lysis of adhesions A “SEMIDEFINITIVE” procedure that preserves an uninvolved ovary increases 6 times the risk of recurrence and 8 times reoperation rate

26. SURGICAL MANAGEMENT SEE AND TREAT : When endometriosis is identified at laparoscopy, it is recommended to surgically treat endometriosis, either by ablation or excision CYSTECTOMY for ovarian endometriomas SURGICAL INTERRUPTION OF PELVIC NERVE PATHWAYS e.g LUNA, Presacral neurectomy LAPAROTOMY for deep endometriosis Laparoscopic Uterosacral Nerve Ablation

27. CASE REPORT A 28 years old nulliparous woman, married since 9 years complains of chronic pelvic pain and severe dysmenorrhoea. Patient has a history of laparotomy with right ovarian cystectomy done 4 years back. USG pelvis is suggestive of 7cm x 6cm x 4.5cm right ovarian complex cyst with ground glass echogenicity , most likely to be chocolate cyst

28. An endometrioma or "Chocolate Cyst" on ultrasound and On laparoscopy

29. LAPAROSCOPY IN RECURRENT ENDOMETRIOSIS VIDEO

30. MEDICAL MANAGEMENT Rationale is to induce amenorrhea and create hypoestrogenic environment, by suppressing the hypothalamic ovarian axis, theoretically inhibiting growths and promoting temporary regression Agents used: DINOGEST: 2 mg od for 3 months, causes symptomatic relief OCPs The recommended dose is 20 -30 µg ethinyl estradial pill . It causes symptomatic relief in 65-90 % of cases.

31. MEDICAL MANAGEMENT GnRH Agonists Suppresses hypothalamic –pituitary – ovarian axis to produce a ‘medical oophorectomy’ or ‘ pseudomenopause state ’. It causes osteoporosis on prolonged use . So Add back therapy is needed for long term use of GnRh agonist therapy Danazol Aromatase Inhibitors- preferred drug in deep infiltrating endometriosis in pod Progestin like Medroxyprogesterone acetate, Mirena NSAIDS may be used for pain management

32. PRE OPERATIVE MEDICAL MANAGEMENT Combined hormonal contraceptive, Progestins like Medroxyprogesterone acetate, Mirena GnRH Agonists as it reduces endometriosis-associated dyspareunia, dysmenorrhoea and non-menstrual pain There are no trials that compares hormonal suppression of endometriosis before and/or after surgery with surgery alone

33. POST OPERATIVE MEDICAL TREATMENT Post surgical hormonal suppression of endometriosis compared to surgery alone (either no medical therapy or placebo) showed no benefit for the outcomes of pain or pregnancy rates but a significant improvement in disease recurrence (AFS scores (WMD -2.30, 95% CI -4.02 to -0.58)). * The available literature strongly supports the benefits of prolonged administration of estroprogestins after surgery in preventing recurrence of endometriomas . ** * Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev. 2004;(3):CD003678. Review. PubMed PMID: 15266496. ** Somigliana E, Vercellini P, Vigano P, Benaglia L, Busnelli A, Fedele L. Postoperative medical therapy after surgical treatment of endometriosis: from adjuvant therapy to tertiary prevention. J Minim Invasive Gynecol. 2014 May-Jun;21(3):328-34. doi : 10.1016/j.jmig.2013.10.007. Epub 2013 Oct 22. Review. PubMed PMID: 24157566.

34. SECONDARY PREVENTION Secondary prevention is defined as interventions to prevent the recurrence of pain symptoms or the recurrence of disease in the long-term, defined as more than 6 months after surgery. The choice of intervention depends on patient preferences, costs, availability and side effects.

35. SECONDARY PREVENTION European society guidelines 2014 for secondary prevention: In women operated on for an endometrioma (≥4cm), clinicians should perform ovarian cystectomy, instead of drainage and electrocoagulation, for the secondary prevention of endometriosis-associated dysmenorrhoea, dyspareunia and non-menstrual pelvic pain. * * Mircea O, Bartha E, Gheorghe M, Irimia T, Vlădăreanu R, Puşcaşiu L. Ovarian Damage after Laparoscopic Cystectomy for Endometrioma . Chirurgia ( Bucur ). 2016Jan-Feb;111(1):54-7. PubMed PMID: 26988540.

36. SECONDARY PREVENTION After cystectomy for ovarian endometrioma in women not immediately seeking conception, clinicians are recommended to prescribe combined hormonal contraceptives for the secondary prevention of endometrioma . * * Vercellini P, Meana M, Hummelshoj L, Somigliana E, Viganò P, Fedele L. Priorities for endometriosis research: a proposed focus on deep dyspareunia. Reprod Sci. 2011 Feb;18(2):114-8. doi : 10.1177/1933719110382921. E pub 2010 Oct26. Review. PubMed PMID:20978182.

37. SECONDARY PREVENTION In women operated on for endometriosis, clinicians are recommended to prescribe post-operative use of a LNG-IUS or a combined hormonal contraceptive for at least 18–24 months , as one of the options for the secondary prevention of endometriosis-associated dysmenorrhoea, but not for non-menstrual pelvic pain or dyspareunia. * * Seracchioli R, Manuzzi L, Mabrouk M, Solfrini S, Frascà C, Manferrari F, Pierangeli F, Paradisi R, Venturoli S. A multidisciplinary, minimally invasive approach for complicated deep infiltrating endometriosis. Fertil Steril . 2010 Feb;93(3):1007.e1-3. doi:10.1016/j.fertnstert.2009.09.058. Epub 2009 Nov 25. PubMed PMID: 19939374.

38. NATURAL HISTORY OF ENDOMETRIOSIS According to Falcone and Lebovic’s analysis of findings of follow – up laparoscopies performed 6 to 39 months following initial diagnostic procedure among 162 patients : There was almost equal distribution of those with progressive disease(31%), unchanged (31%) and improvent in extent of lesions (38%).

39. ENDOMETRIOSIS AND INFERTILITY Approximately 20 to 40% of women with endometriosis are infertile.

40. RECURRENT ENDOMETRIOSIS AND INFERTILITY

41. ENDOMETRIOSIS AND INFERTILITY MANAGEMENT ESHRE GUIDELINES 2014 makes following recommendations In infertile women with AFS/ASRM Stage I/II endometriosis, it is better perform operative laparoscopy(excision or ablation of the endometriosis lesions) including adhesiolysis , rather than performing diagnostic laparoscopy only, to increase on going pregnancy rates Clinicians may consider Co2 laser vaporisation of endometriosis instead of monopolar electrocoagulation as former is associated with better cumulative spontaneous pregnancy rates In infertile women with ovarian endometrioma undergoing surgery, clinicians should perform excision of the endometrioma capsule, instead of drainage and electrocoagulation of the endometrioma wall, to increase spontaneous pregnancy rates

42. Clinicians may consider Co2 laser vaporisation of endometriosis instead of monopolar electrocoagulation as former is associated with better cumulative spontaneous pregnancy rates - Chang et al

43. Approximately 0.7% to 1.0% of patients with endometriosis have lesions that undergo malignant transformation with most common histological type being Endometrioid Adenocarcinoma

44. CONCLUSION Recurrence of endometriosis is fairly common; some studies suggest the rate of recurrence to be as high as 40%. Most common cause of recurrence is incomplete resection in primary surgery and microscopic foci which escapes detection. Laparoscopy remains the GOLD STANDARD for diagnosis of endometriosis

45. CONCLUSION The combined surgical approach (of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation) is beneficial for pelvic pain associated with minimal, mild and moderate endometriosis. Medical management only acts adjuvant to surgical management which may help in reducing to recurrence. Interventions to prevent the recurrence of pain symptoms or the recurrence of disease in the long-term used for more than 6 months after surgery may be used for secondary prevention

46. REFERENCES Rizk B, Fischer AS, Lotfy HA, et al. Recurrence of endometriosis after hysterectomy.  Facts, Views & Vision in ObGyn . 2014;6(4):219-227. Vercellini P, Barbara G, Abbiati A, Somigliana E, Viganò P, Fedele L. Repetitive surgery for recurrent symptomatic endometriosis: what to do? Eur J Obstet Gynecol Reprod Biol. 2009 Sep;146(1):15-21. doi:10.1016/j.ejogrb.2009.05.007. Epub 2009 May 30. Review. PubMed PMID: 19482404. Vercellini P, Abbiati A, Aimi G, Amicarelli F, De Giorgi O, Uglietti A. Gynecological endoscopy for symptomatic endometriosis. Minerva Ginecol . 2009 Jun;61(3):215-26. Review. PubMed PMID: 19415065 Vercellini P, De Giorgi O, Pisacreta A, Pesole AP, Vicentini S, Crosignani PG.Surgical management of endometriosis. Baillieres Best Pract Res Clin Obstet Gynaecol . 2000 Jun;14(3):501-23. Review. PubMed PMID: 10962639. Shakiba K, Bena JF, McGill KM, Minger J, Falcone T. Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol. 2008 Jun;111(6):1285-92. doi : 10.1097/AOG.0b013e3181758ec6. Erratum in: Obstet Gynecol. 2008 Sep;112(3):710. PubMed PMID: 18515510. Namnoum AB, Hickman TN, Goodman SB, Gehlbach DL, Rock JA. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril . 1995 Nov;64(5):898-902. PubMed PMID: 7589631 Kho RM, Abrao MS. Ovarian remnant syndrome: etiology , diagnosis, treatment and impact of endometriosis. Curr Opin Obstet Gynecol. 2012 Aug;24(4):210-4. doi : 10.1097/GCO.0b013e3283558539. Review. PubMed PMID: 22729094 Abrao MS, Podgaec S, Dias JA Jr, Averbach M, Garry R, Ferraz Silva LF, Carvalho FM. Deeply infiltrating endometriosis affecting the rectum and lymph nodes. Fertil Steril . 2006 Sep;86(3):543-7. Epub 2006 Jul 28. PubMed PMID: 16876165

47. SYMPTOMS