To the Editor:
We read with great interest “Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary?” (1). The study evaluated 17 teens – aged 12-19 when they presented with pelvic pain – who underwent a laparoscopic procedure and were found to have biopsy-proven endometriosis. Seven of these patients (41.2%) had, in fact, been treated by ablation or fulguration previous to the “index” laparoscopy for this study, with a total of 13 of the 17 patients having at least one prior laparoscopy. The surgeons state that at this index laparoscopy “all” endometriosis was excised, and postoperatively the teens were not specifically asked to utilize suppressive hormonal therapy. However, 6 (35.1%) patients were on combination hormones and 1 was on GnRH agonist. Among the 17 patients, the study reports 47% return of pain to a level where subsequent laparoscopy was performed within an average of 23.1 months (maximum 66 months). We believe that this finding supports established data that with aggressive surgical therapy alone pain symptoms return (2).
The authors state that, among the 8 patients who underwent a second laparoscopy, the lack of appreciation of the disease on repeat laparoscopy is evidence of complete eradication of the disease. We are perplexed by this conclusion, since the presenting symptom of endometriosis-related pain returned or remained present and thus it does not follow that the patients were “cured.” It has been demonstrated that endometriosis can be present microscopically (3) without visual appearance and thus with the present symptom of pain, the lack of the surgeon’s visual appreciation of endometriosis does not support a statement of disease eradication. The authors also promote excision for Stage I or II disease, while other reports have shown no difference of excision versus destruction of disease (4,5).
In addition to concern regarding the interpretation of these data, we also wish to highlight several design and analytic issues. The sample size is small, with only 8 patients undergoing two laparoscopies. While it is appropriate to account for repeated measures via generalized estimating equations, the data in table 1 are proportions, while the statistical tests are for continuous variables. It is unlikely that these data are normally distributed, making the paired-t-tests and Pearson correlations invalid. More importantly, these analyses do not adjust or account for the influence of time of follow-up nor differences between patients during follow-up that may influence symptoms or disease progression, with the most critical being hormonal treatment.
We suggest caution on accepting the recommendation proposed by this study and look forward to future studies on endometriosis so that one day the disease and its associated pain can be eradicated.
Marc R. Laufer, M.D.a,b
Stacey A. Missmer, Sc.D.b,c,d
aDivision of Gynecology
Department of Surgery
Children’s Hospital Boston
bDivision of Reproductive Medicine
Department of Obstetrics, Gynecology, and Reproductive Biology
Brigham and Women’s Hospital and Harvard Medical School
Department of Medicine
Brigham and Women’s Hospital and Harvard Medical School
dDepartment of Epidemiology
Harvard School of Public Health
1. Yeung P, Sinervo K, Winer W, Albee RB. Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary? Fertil Steril 2011; 95:1909-12 e1.
2. Sutton J, Ewen SP, Whitelaw N, et al. Prospective, randomized, double blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild and moderate endometriosis. Fertil Steril 1994;64:696.
3. Murphy AA, Green WR, Bobbie D, et al. Unsuspected endometriosis documented by scanning electron microscopy in visually normal peritoneum. Fertil Steril 1986;46:522.
4. Wright J, Lotfallah H, Jones K, Lovell D. A randomized trial of excision versus ablation for mild endometriosis. Fertil Steril 2005;83:1830-6.
5. Healey M, Ang C, Cheng C. Surgical treatment of endometriosis: a prospective randomized double-blinded trial comparing excision and ablation. Fertil Steril 2010; 94:2536-40.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.06.025
The Authors Respond:
We would like to thank Drs. Laufer and Missmer for their interest in our article. The main concern is that the high rate of repeat surgery due to pain (8/17 or 47.1% in up to 66 months) is evidence: (1) “in support of established data that with aggressive surgical therapy alone pain symptoms return”, (2) that the post-operative pain is “endometriosis-related”, due to (3) that microscopic, non-visible endometriosis exists.
First, post-operative hormonal suppression has not been shown to be superior to complete excision of endometriosis alone at preventing pain. In the present study, of the patients who needed a repeat surgery due to pain, 5/8 (62.5%) were actually on some form of postoperative hormonal suppression (of between 10-22 months), even without a specific recommendation to do so. This is dramatically higher than the 6/17 (35.3%) of patients who took hormonal suppression postoperatively in the entire cohort.
Second, persistent pelvic pain does not necessarily equate to actual disease, and should not be presumed to be from endometriosis. ACOG recommends that the diagnosis of endometriosis can only be confirmed by the visual appearance of endometriotic lesions (1) at laparoscopy. Similar to at the index or primary surgery, neither response to empiric hormonal suppression (2,3), nor recurrent or persistent pain symptoms equate to actual disease at repeat surgery.
Third, and the fundamental basis for the objections made, is the belief that non-visible endometriosis causing pain is a pervasive entity. An article from 25 years ago (4) was cited suggesting that microscopic endometriosis exists in up to 25% of cases of ‘normal’ peritoneum. This study was performed at laparotomy, and well before the magnification and high definition laparoscopes that are currently in use, and before the spectrum of atypical endometriosis and the definition of normal peritoneum were fully recognized (5, 6). Redwine (7), in a review of more recent, more convincing, studies looking at non-visible endometriosis, elegantly shows that the presence of biopsy-proven endometriosis in visually ‘normal’ peritoneum is inversely proportional to the power of magnification (see the Figure below, used with permission), and approaches zero especially by experienced surgeons. Significant non-visible endometriosis in our study cohort is unlikely, and should not be used to discount our findings. Using different statistical tests for small sample sizes would not change the results of the study.
We would like to draw attention to a recent study by Doyle in 2009 (8) that evaluated the effect of a combination surgical-medical regimen without complete surgical excision of disease in adolescents. Stabilization of disease was found in 70% of patients, and 10% of patients even showed progression of disease, despite all the patients having been treated with postoperative continuous hormonal suppression.
Overall, we would like to reiterate that the present study data suggests that complete excision of endometriosis by experienced surgeons results in a high rate of complete eradication of disease, without the need for postoperative hormonal suppression. We agree and recommend that larger, comparative trials are needed to verify these results.
Patrick P Yeung, M.D.a
Ken Sinervo, M.D.b
Wendy Winer, R.N.b
Robert Jr. B Albee, M.D..b
aDepartment of Obstetrics & Gynecology
Durham, North Carolina
b Center for Endometriosis Care
1. ACOG Committee Opinion. Number 310, April 2005. Endometriosis in adolescents. Obstet Gynecol, 2005. 105(4): p. 921-7.
2. Jenkins, T.R., C.Y. Liu, and J. White, Does response to hormonal therapy predict presence or absence of endometriosis? J Minim Invasive Gynecol, 2008. 15(1): p. 82-6.
3. ACOG Practice Bulletin No. 51. Chronic pelvic pain. Obstetrics and Gynecology, 2004. 103(3): p. 589-605.
4. Murphy, A.A., W.R. Green, D. Bobbie, Z.C. dela Cruz, and J.A. Rock, Unsuspected endometriosis documented by scanning electron microscopy in visually normal peritoneum. Fertil Steril, 1986. 46(3): p. 522-4.
5. Albee, R.B., Jr., K. Sinervo, and D.T. Fisher, Laparoscopic excision of lesions suggestive of endometriosis or otherwise atypical in appearance: relationship between visual findings and final histologic diagnosis. J Minim Invasive Gynecol, 2008. 15(1): p. 32-7.
6. Redwine, D.B., Age-related evolution in color appearance of endometriosis. Fertil Steril, 1987. 48(6): p. 1062-3.
7. Redwine, D.B., ‘Invisible’ microscopic endometriosis: a review. Gynecol Obstet Invest, 2003. 55(2): p. 63-7.
8. Doyle, J.O., S.A. Missmer, and M.R. Laufer, The effect of combined surgical-medical intervention on the progression of endometriosis in an adolescent and young adult population. J Pediatr Adolesc Gynecol, 2009. 22(4): p. 257-63.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.06.027