Surgical treatment of endometriosis: location and patterns of disease at reoperation Elizabeth Taylor, M.D., and Christina Williams, M.D. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, British Columbia Women s Hospital and Health Care Centre, Vancouver, British Columbia, Canada Objective: To assess the behavior of revised American Fertility Society stages I and II endometriosis after surgical treatment, by observation of location of pelvic involvement at reoperation. Design: Prospective study. Setting: Tertiary referral center at a university-based hospital. Patient(s): Thirty-nine women with persistent or recurrent chronic pelvic pain after laparoscopic excision or ablation of histologically confirmed endometriosis who underwent a second laparoscopy. Intervention(s): Laparoscopic pelvic mapping and surgical treatment of endometriosis, followed by repeat laparoscopic pelvic mapping of endometriosis at a second laparoscopy. Result(s): Superficial peritoneal endometriosis (revised American Fertility Society stage I II) endometriosis recurred in 37% of pelvic regions after surgical treatment. Endometriosis was more likely to recur in a treated pelvic region than an adjacent or distant pelvic region (relative risk 2.54; 95% confidence interval 1.63-3.97). A region adjacent to a previously affected pelvic region that was unaffected by endometriosis at the initial laparoscopy was more likely to have endometriosis at the second laparoscopy than a pelvic region distant from the treated pelvic region (relative risk 1.29; 95% confidence interval 0.84-2.0). Unaffected regions at initial laparoscopy had a low probability of having new endometriosis (11%) in the second laparoscopy. Conclusion(s): Recurrence of histologically proven endometriosis after surgical excision is more likely to cluster close to the original area of involvement, reflecting either incomplete excision at the initial surgery or a nonrandom favored implantation of new endometrial implants in adjacent peritoneum. Further studies are needed to elucidate the pathophysiology and mechanisms of recurrence of endometriosis. (Fertil Steril Ò 2010;93:57 61. Ó2010 by American Society for Reproductive Medicine.) Key Words: Endometriosis, laparoscopy, recurrent Endometriosis is an intriguing disease in which tissue resembling endometrium is found outside the uterine cavity. Endometriosis is associated with subfertility, dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Chronic pelvic pain affects 14.7% of women of reproductive age (1) and is attributable to endometriosis in more than one third of cases (2). The pain associated with endometriosis may be treated surgically, medically, or both. Failure to provide adequate longterm pain relief and adverse effects of currently available medical therapies are an indication for surgical treatment of endometriosis. Endometriosis can be ablated, excised, or both. Laparoscopic excision of endometriosis results in improved pain relief and improved quality of life after 6 months compared with diagnostic laparoscopy alone (3), but endometriosis can recur. Six months after laparoscopic excision of endometriosis, endometriosis was present at laparoscopy in 44% of Received April 18, 2008; revised September 3, 2008; accepted September 29, 2008; published online November 11, 2008. E.T. has nothing to disclose. C.W. has nothing to disclose. Reprint requests: Christina Williams, M.D., Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, British Columbia Women s Hospital and Health Care Centre, D600, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada (FAX: 604-875-2569; E-mail: cwilliams3@cw.bc.ca). women (3). Two other studies have demonstrated similar recurrence rates. In the first, Redwine (4) reported a series of 359 women with laparoscopic excision of endometriosis. Forty-three percent of women (35 of 81) who required reoperation for pelvic pain had recurrent or persistent endometriosis (4). In the second study, Wheeler and Malinak (5) reported a series of 423 women with endometriosis treated through a laparotomy incision and observed a 33% rate of recurrent endometriosis in the 62 women who required reoperation. These studies included patients at all revised American Fertility Society (rafs) stages, and the findings suggest that endometriosis recurs in 33% 44% of women after surgical treatment. This is surprising, given that endometriosis is considered incurable. Furthermore, Redwine (3) found that in reoperated women with endometriosis, there were fewer pelvic areas of involvement than at initial excisional surgery. In the subset of women who have persistent CPP after laparoscopic laser ablation of endometriosis, 29% have progressive disease, 29% have disease regression, and 42% have static disease 1 year after laparoscopic ablation of endometriosis (6). The reason for the frequent recurrence of endometriosis is postulated to be the continuous implantation of uterine endometrial fragments deposited by retrograde menstruation in pelvic peritoneum (7). As such, endometriosis is often 0015-0282/10/$36.00 Fertility and Sterility â Vol. 93, No. 1, January 2010 57 doi:10.1016/j.fertnstert.2008.09.085 Copyright ª2010 American Society for Reproductive Medicine, Published by Elsevier Inc.
considered to be a surgically incurable disease, and hormonal induction of amenorrhea or hysterectomy and bilateral salpingo-oophorectomy is performed on women with CPP and endometriosis. Knowledge of the location and pattern of recurrent endometriosis may clarify whether such disease represents incomplete treatment or de novo disease. We sought to assess the location of recurrent endometriosis in women with CPP and to examine whether the pelvic region of recurrent endometriosis is related to the region of previously treated disease and whether recurrence is more likely in a particular pelvic region. MATERIALS AND METHODS We reviewed the medical records of 600 women who underwent laparoscopy performed by a single surgeon (C.W.) between January 1999 and December 2005. All of these women had CPP and localized tenderness on pelvic pain mapping suggestive of endometriosis. Of the women, 61 (10%) had persistent or recurrent pelvic pain and localized tenderness after the initial laparoscopy, necessitating a second laparoscopy. We included women who had two laparoscopies at our center (by C.W.) with visual and histologic evidence of endometriosis at the initial laparoscopy and who had persistent CPP or dyspareunia and localized tenderness on pelvic examination resistant to medical therapy. Repeat laparoscopy was not performed for dysmenorrhea alone without lateral pain or localized tenderness on pelvic examination. Endometriosis was diagnosed at the second laparoscopy if proven by histologic evidence in the excised tissue. Women were excluded from the study if they had previously undergone hysterectomy, bilateral salpingo-oophorectomy, or if the pelvis could not be visualized at both laparoscopies. Thirty-nine women were included in this study. The initial surgery was performed in a standardized fashion under general anesthesia. All procedures included inspection of pelvic and peritoneal organs, and sharp adhesiolysis. All visible endometriosis was ablated or excised. Excision was used exclusively during the second procedure. Ablation was performed using monopolar diathermy at a coagulation current of 40 W using a needle-tip instrument. Only superficial lesions less than 2 to 3 mm in diameter and 1 to 2 mm in depth were ablated. Complete whitening and desiccation of the lesion, leaving normal surrounding peritoneum, was achieved. Excision was carried out using a needle-tip instrument with a blend of 50 W cutting and 40 W coagulation. Excision was performed by grasping the peritoneum harboring the endometriosis and excising the normal peritoneum around the implants with a monopolar needle-tip instrument until the base and surrounding areas were free of visible endometriosis. The stage of disease, as defined by the rafs classification system, was recorded (8). The pelvis was visually divided FIGURE 1 Map of pelvis. The presence or absence of endometriosis was recorded for each pelvic region at the initial and second laparoscopy. L ¼ left; R ¼ right; CDS ¼ cul-de-sac. into 12 regions (Fig. 1). The presence of disease, treatment administered (ablation or excision), and histology were documented for each region. An adjacent pelvic region was defined as a pelvic region immediately medial or lateral to the region of interest. The ovarian regions did not have laterally adjacent regions. A distant pelvic region was defined as a pelvic region not adjacent to the pelvic region of interest. Statistical Analysis At each of the 12 pelvic regions the change from the initial laparoscopy to the second regarding presence (1) or absence (0) of endometriosis was recorded as 1 (from 1 to 0), 0 (from 0 to 0), 1 (from 0 to 1), or 9 (from 1 to 1). These transitions were tested against the treatment given (0, no treatment; 1, cautery; 2, excision) by means of contingency table c 2 tests, and significant results were localized by means of adjusted standardized deviations. Similar analyses were performed by totaling across all regions, including as well as excluding the bladder. Kappa coefficients of agreement were also derived for each case. The probability of a new diagnosis of endometriosis at the second laparoscopy was derived in each region that was immediately adjacent to an index region at the initial laparoscopy. The corresponding standard errors of the estimated probabilities were also calculated, allowing for comparisons under different treatments. RESULTS Thirty-nine women with an average age of 30 years (range, 18 45 years) were included. Before referral to our center, 58 Taylor and Williams Location of recurrent endometriosis Vol. 93, No. 1, January 2010
44% of women (17 of 39) had undergone one previous laparoscopy, 20% (8 of 39) had two previous laparoscopies, and 10% (4 of 39) had three previous laparoscopies. Fifty-three percent of women who had undergone one previous laparoscopy had ablation of endometriosis performed, whereas in the remaining 47% the endometriosis was not treated. Women undergoing two or more procedures had ablation of endometriosis on at least one occasion. No patient had undergone previous excision of endometriosis. The average time between the initial and second laparoscopy included in this study was 18.4 months (range, 2 52 months; SD 13.0). Hormonal treatment was used between the two study laparoscopies in 16 of 39 women (5 received an estrogen progestogen combination, 7 received progestogen only, 3 received GnRH agonists, and 1 received danazol). Hormonal treatment was discontinued in all women at least 2 months before the second laparoscopy. All women had rafs stage I or II endometriosis at the initial laparoscopy. Of the 468 regions in 39 women, 108 regions (23%) had endometriosis present at the initial laparoscopy (median 2.5 regions per woman) and 76 regions (16%) at the second laparoscopy (median 1.0 regions per woman). Sixty-one percent of women (24 of 39) had less disease at the second laparoscopy than at the initial laparoscopy, and 33% (13 of 39) had no endometriosis at the second laparoscopy. The frequency of endometriosis by pelvic region was similar (P>.05) at both laparoscopies (Fig. 2). Endometriosis was excised from 85% of regions and ablated in 15% of regions with endometriosis at the initial laparoscopy. New Endometriosis: Disease Found in a Previously Disease-Free Pelvic Area Thirty-eight percent of women (15 of 39) had new endometriosis at the second laparoscopy. In those 360 regions (77%) with no endometriosis at the initial laparoscopy, endometriosis was present in 41 (11%) at the second laparoscopy. Recurrent Endometriosis: Disease Found Again in a Treated Pelvic Region The probability of recurrent endometriosis was 37%. There was no recurrent endometriosis in any anterior peritoneal region. The probability of recurrent endometriosis by pelvic region (excluding anterior peritoneal regions) is shown in Figure 3. There was no difference in the rate of recurrent endometriosis between areas that were excised or ablated. Endometriosis was more likely to recur in the treated pelvic region than in an adjacent or distant pelvic region (relative risk 2.54; 95% confidence interval 1.63-3.97). If a pelvic region adjacent to a region with endometriosis was free of endometriosis at the initial laparoscopy the probability that endometriosis was present in that region at the second laparoscopy was 20%, compared with 16% for a nonadjacent pelvic regions (relative risk 1.29; 95% confidence interval 0.84-2.0). The intersurgery interval when endometriosis was present in the same region at both laparoscopies was shorter (mean, 10 months) than if endometriosis was present only at the initial laparoscopy, treated with excision or ablation, and had no endometriosis at the second laparoscopy (mean, 15 months) (P¼.001). DISCUSSION In this study we observed that the distribution of endometriosis in women with recurrent or persistent pain after laparoscopic ablation or excision of endometriosis is similar to that observed at the initial laparoscopy. We also confirmed that not all persistent or recurrent pelvic pain is due to endometriosis in women who have undergone surgical treatment, because not all reoperated patients had endometriosis. This FIGURE 2 Distribution of endometriosis by pelvic region at the initial and second laparoscopy. R ¼ right; L ¼ left. Fertility and Sterility â 59
FIGURE 3 Probability of recurrent endometriosis by pelvic region. R ¼ right; L ¼ left. is consistent with previously published work that examined the relationship between the location of endometriosis at reoperation and the location of the primary lesion. Two previous studies have demonstrated that endometriosis is more often localized on the left hemipelvis, and recurrent disease after surgical treatment is more likely to occur on the left hemipelvis, suggesting a similar distribution of endometriosis before and after surgical treatment (9, 10). Our observation that endometriosis is most likely to recur in the treated region may reflect incomplete excision or ablation of endometriosis. Endometriosis is known to extend beyond the margins visible under white light at laparoscopy (11). Such occult disease might explain recurrent disease being more often located at the site of original, albeit treated, disease and the finding that previously unaffected adjacent pelvic regions are more likely to have endometriosis than distant pelvic regions. Another explanation is that endometriosis has a propensity to occur and recur in a specific pelvic region if embryologic tracts of retroperitoneal susceptible substrate tissue are incompletely treated and subsequently undergo metaplasia, perhaps aided by the tissue growth factors associated with wound healing (12). Such tracts need not have an identical ability to develop endometriosis at the same time in the future or disease of the same virulence. Several works have shown that endometriosis is most often located in the posterior compartment of the pelvis (13 15) and on the left side (16, 17). Furthermore, ovarian endometriomas are located significantly more frequently on the left ovary than on the right (9, 10, 16). We observed that 94% of women with persistent or recurrent CPP after laparoscopic excision or ablation of endometriosis had less or no endometriosis at the second laparoscopy. Indeed, 33% of women in our study were cured of endometriosis after surgical treatment. This rate is less than the cure rate of 56% 66% reported previously. This difference may be attributed to patient selection. Women were selected for reoperation if they had failed medical treatment and had lateral pelvic pain and localized pelvic tenderness. This might explain our low reoperation rate (61 of 600). Interestingly, despite use of these strict criteria for reoperation, 33% of the women had no histologic endometriosis identified. It is possible that CPP after surgical treatment of endometriosis may be a consequence of up-regulation of pain signals and not recurrent disease. Our low reoperation rate may also be attributed to the nutrition advice, pain management, counseling, and education provided at our center. This study provides insight into the natural history of surgically treated endometriosis in CPP patients. After surgical treatment of rafs stage I and II endometriosis, recurrent disease occurs most frequently at the site of treated disease. Moreover, regions that are adjacent and nonadjacent have a similar risk of developing endometriosis by the time of second laparoscopy. The probability that a previously uninvolved region develops disease is low (11%). This knowledge enhances our understanding of the pathogenesis of endometriosis and improves our ability to counsel patients undergoing surgical treatment of endometriosis. REFERENCES 1. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates. Obstet Gynecol 1996;87:321 7. 2. Guo SW, Wang Y. The prevalence of endometriosis in women with chronic pelvic pain. Gynecol Obstet Invest 2006;62:121 30. 3. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril 2004;82:878 84. 4. Redwine DB. Conservative laparoscopic excision of endometriosis by sharp dissection: life table analysis of reoperation and persistent or recurrent disease. Fertil Steril 1991;56:628 34. 5. Wheeler JM, Malinak LR. Recurrent endometriosis: incidence, management, and prognosis. Am J Obstet Gynecol 1983;146:247 53. 6. Sutton CJG, Pooley AS, Ewen SP, Haines P. Follow-up report on a randomized controlled trial of laser laparoscopy in the treatment of pelvic 60 Taylor and Williams Location of recurrent endometriosis Vol. 93, No. 1, January 2010
pain associated with minimal to moderate endometriosis. Fertil Steril 1997;68:1070 4. 7. Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:442 69. 8. American Fertility Society. The American Fertility Society classification of endometriosis. Fertil Steril 1997;67:817 21. 9. Vercellini P, Aimi G, de Giorgi O, Maddalena S, Carinelli S, Crosignani PG. Is cystic ovarian endometriosis an asymmetric disease? Br J Obstet Gynaecol 1998;105:1018 21. 10. Ghezzi F, Beretta P, Franchi M, Parissis M, Bolis P. Recurrence of ovarian endometriosis and anatomical location of the primary lesion. Fertil Steril 2001;75:136 40. 11. Buchweitz O, Staebler A, Tio J, Kiesel L. Detection of peritoneal endometriotic lesions by autofluorescence laparoscopy. Am J Obstet Gynecol 2006;195:949 54. 12. Gaetje R, Holtrich U, Engels K, Kissler S, Rody A, Karn T, et al. Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract. Fertil Steril 2007;87:651 6. 13. Ishimaru T, Masuzaki H. Peritoneal endometriosis: endometrial tissue implantation as its primary etiologic mechanism. Am J Obstet Gynecol 1991;165:210 4. 14. Chapron C, Chopin N, Borghese B, Foulot H, Dousset B, Vacher- Lavenu MC, et al. Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution. Hum Reprod 2006;21: 1839 45. 15. Redwine DB. Ovarian endometriosis: a marker for more severe pelvic and intestinal disease. Fertil Steril 1999;73:310 5. 16. Al-Fozan H, Tulandi T. Left lateral predisposition of endometriosis and endometrioma. Obstet Gynecol 2003;20:630 4. 17. Parazzini F. Left:right side ratio of endometriotic implants in the pelvis. Eur J Obstet Gynecol Reprod Biol 2003;111:65 7. Fertility and Sterility â 61