- Email: [email protected]
Histopathologic features of endometriotic rectal nodules and the implications for management by rectal nodule excision
Histopathologic features of endometriotic rectal nodules and the implications for management by rectal nodule excision Using data from 27 women with deep rectal endometriosis, managed by segmental resection, we observed that in 89% of cases active glandular endometrial foci were responsible for a deeper infiltration of rectal layers than that of fibrosis and smooth fibers by 5 mm on average. These data might be useful for surgeons performing rectal nodule excision, suggesting the benefits of administrating postoperative medical treatment to reduce the risk of rectal recurrences caused by remaining active endometriotic foci. (Fertil Steril 2009;92:1250–2. 2009 by American Society for Reproductive Medicine.) Key Words: Rectal endometriosis, deep endometriosis, rectal resection, excision, medical treatment
Despite a myriad of scientific articles reported over the last two decades, there is no definitive answer to the question, ‘‘Which surgical procedure should be recommended in the management of rectal endometriosis?’’ To date, surgeons perform either rectal segmental resection or rectal nodule excision, with or without opening the rectum. The choice of technique, both of which are performed by experienced teams, depends on the particular idea each surgeon has about the disease. Those who perform mainly rectal segmental resection emphasize the significant postoperative improvement of pain (1–4) and strongly believe that the radical removal of digestive endometriotic foci is the most effective way of avoiding the risk of recurrence. This conviction was recently supported by the study of Remorgida et al., showing that disc resection of rectal nodules was microscopically incomplete in 40% of cases (5). Alternatively, surgeons who perform primarily nodule excision offered several arguments: surgical morbidity appears to be higher in women undergoing segmental resection (6), postoperative digestive symptoms seem to be less satisfactory after rectal removal, microscopic digestive endometriotic foci are to be found on the limits of the segmental resection (7), there is evidence of a high rate of postoperative recurrence of pain despite rectal resection (8), and postoperative continuous medical treatment might be able to halt the progression of the endometriotic implants left out and to decrease the risk of recurrences (9). Before December 2007, our department generally managed women with rectal endometriosis by performing segmental rectal resections, whereas we now perform threeReceived February 18, 2009; revised March 6, 2009; accepted March 18, 2009; published online May 5, 2009. H.R. has nothing to disclose. I.O. has nothing to disclose. B.R. has nothing to disclose. J.J.T. has nothing to disclose. J-C.S. has nothing to disclose. L.M. has nothing to disclose. Reprint requests: Horace Roman, M.D., Ph.D., Department of Gynecology and Obstetrics, Rouen University Hospital, 1 rue de Germont, 76031 Rouen, France (TEL: þ33 232 888 745; FAX: þ33 235 981 149; E-mail: [email protected]).
1250
fold more nodule excisions than resections, accompanied by a systematic recommendation of postoperative continuous contraceptive pill intake. This new orientation is based on the evaluation of midterm postoperative digestive functional symptoms of women treated by segmental rectal resection in our department and on reports from other experienced surgical teams. Our technique of rectal nodule excision is similar to that described by other surgical teams (10, 11). Both pararectal spaces are opened to isolate the endometriotic nodules. By this means, the rectovaginal space is reached under the inferior limit of the nodule. The nodule is then dissected away from the rectal wall, using the Ultracision Harmonic Scalpel (Ethicon Endosurgery, Cincinnati, OH). The dissection is made into the thickness of the rectal wall, to remove all abnormal fibrous lesions involving the rectal layers, using a high-magnification endoscopic view. Partial- rectal wall defects are closed laparoscopically for one or two layers using resorbable sutures. At the end of the procedure, the site of rectal dissection is recovered by an omentum flap, which is fixed by resorbable sutures. As a majority of endometriotic lesions involve rectal serosa, muscularis propria, or submucosal layers, we mainly perform partial excision of the nodule until reaching rectal muscular fibers that appear to be free of endometriotic lesions. Although the removal of endometriotic lesions may seem to be macroscopically complete, it is apparent that the dissection is more likely to identify fibrosis dependant on the nodule than to differentiate endometriotic glandular lesions from red rectal muscular fibers. Subsequently, our investigation focused on whether inside the endometriotic rectal nodules, glandular lesions remain surrounded by fibroconjunctive tissue and smooth fibers, and whether they are systematically removed by macroscopically complete excision of the fibrosis. We performed a retrospective study to include women with rectal endometriosis and who benefited from rectal segmental resection in our department from February
Fertility and Sterility Vol. 92, No. 4, October 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2009.03.073
2005 to July 2008. Women who had only full-thickness or partial resection of the rectal wall were excluded, to allow accurate checking of the depth of rectal wall infiltration by endometriotic lesions. In each case, lesions in serial sections were stained in hematoxylin and eosin, and with the use of a digital scanner, both the depth of infiltration by active endometriotic glands and stroma and that of fibroconjunctive tissue and smooth fibers were investigated (Fig. 1). The distance between the deepest point of active glandular and stromal infiltration and the deepest fibrotic lesion was then measured in micrometers (Fig. 1). In accordance with French regulations, this retrospective study was exempted from institutional review board approval.
FIGURE 1 Distance between the deepest point of active endometriotic glands and stroma infiltration and the deepest fibrotic lesion (7,621 mm; dotted line).
Twenty-seven women with histologically confirmed rectal endometriosis and managed by rectal segmental resection were included in the study. The age range was 23–45 years, with a mean (SD) age of 34.3 6.3 years. In 14 of 27 cases, both active endometriotic tissue (glandular epithelium surrounded by scanty stroma) and fibrosis (fibroconjunctive tissue and smooth fibers) had infiltrated the same rectal layer: muscularis propria (12 cases) and submucosa (two cases). In other cases, infiltrations of active endometriotic foci and fibrosis had respectively reached muscularis propria and subserosa (five cases), submucosa and subserosa (three cases), submucosa and muscularis propria (four cases), and mucosa and muscularis propria (one case). The depth of rectal infiltration by the glandular epithelium and stroma was superior to that of the fibrosis in 24 of 27 cases (89%), whereas fibrosis was responsible for the deepest infiltration in only three women (11%). In 24 women with deep infiltration of the active glandular epithelium and stroma, the distance from the deepest gland to the deepest point of the fibrosis ranged from 388–9,777 mm (mean [SD], 5,313 2,436 mm). In three cases in which fibrosis infiltration was deeper than that of glandular and stromal invasion, the distance between the deepest point of the fibrosis and that of the endometriotic glands and stroma was 626, 705, and 2,323 mm, respectively. Our data show that for the majority of rectal endometriosis nodules, the fibrosis does not surround but follows behind glandular epithelium and stroma foci. The distance between the deepest glandular and the deepest fibrosis foci can be as large as 5 mm; therefore, surgical excision of all macroscopic fibrosis may result in leaving active endometriotic lesions outside the deepest limit of the excision. Whereas surgeons use a harmonic scalpel with short thermal effect diffusion, these foci may be neither removed nor destroyed, and might therefore continue their natural evolution. Although further research is required to support the hypothesis that remaining active endometrium foci are responsible for clinical recurrence, our observation merits consideration by surgeons who use partial excision to manage rectal nodules. Fertility and Sterility
Roman. Histopathology of rectal endometriosis. Fertil Steril 2009.
Interpretations of our observations may vary, depending on the reader’s previous conviction. Surgeons who mainly perform rectal segmental resection may think that our study supports their choice not to perform nodule excision. Similar to the report of Remorgida et al. (5), our data confirms that segmental resection appears to be microscopically more complete than nodule excision, even if the latter would seem to remove all endometriotic fibrotic lesions from the rectal wall. Alternatively, surgeons who generally perform nodule excision might conclude that our data justify a systematic use of postoperative medical treatment to prevent clinical recurrences caused by remnant active endometrial foci. A recent trial by Seracchioli et al. (9) clearly stated that 2-year postoperative medical treatment by continuous
1251
intake of the contraceptive pill resulted in a threefold decrease in the risk of clinical recurrences, first level of evidence (LE-1). Although the trial included only women with ovarian endometriotic cysts and the outcome focused on endometrioma recurrences, it is probable that similar results might be obtained in a large trial recruiting exclusively women with deep endometriosis. Because endometriosis is a disease that progresses by cyclic bleeding (12), and clinical symptoms usually worsen after stopping use of contraceptive pills (13), we believe that long-term postoperative contraceptive pill intake might be efficient in preventing both the progression of remaining endometriotic foci and clinical recurrences. Sufficient data exist to suggest that surgical procedures of pelvic endometriosis rarely lead to a microscopically complete removal of endometriotic implants. On the basis of our observations, it is apparent that macroscopically complete excision of rectal nodules, without opening the rectum, probably does not remove glandular and stromal foci surrounding the fibrous nodule. Remorgida et al. (5) also reported that full thickness disc excision of the rectal nodule fails to be microscopically complete in 40% of cases. We also previously showed that even where rectal segmental resection is performed, endometriotic foci may be found on and outside the limits of the digestive resection (7). Incomplete resection of endometriotic implants is probably responsible for the high rate of pain recurrence observed a few years following surgery for deep endometriosis (8). All of these results suggest that long-term postoperative medical treatment could be required to inhibit recurrences. Not surprisingly, trials evaluating short-term postoperative treatments have failed to reveal an improvement at midterm (14), contrary to those studying the efficacy of prolonged continuous amenorrhea (9). In conclusion, we do not believe that our results contraindicate the use of partial rectal nodule excision in the management of rectal endometriosis, but rather support the recommendation of prolonged postoperative medical treatment to prevent the progression of persistent endometriotic implants. Horace Roman, M.D., Ph.D.a Ioana Opris, M.D.b Benoit Resch, M.D.a Jean Jacques Tuech, M.D., Ph.D.c
1252
Roman et al.
Correspondence
Jean-Christophe Sabourin, M.D., Ph.D.b Loı¨c Marpeau, M.D., Ph.D.a a Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France; b Department of Pathology, Rouen University Hospital, Rouen, France; and the c Department of Surgery, Rouen University Hospital, Rouen, France REFERENCES 1. Dubernard G, Piketty M, Rouzier R, Houry S, Bazot M, Darai E. Quality of life after laparoscopic colorectal resection for endometriosis. Hum Reprod 2006;21:1243–7. 2. Thomassin I, Bazot M, Detchev R, Barranger E, Cortez A, Darai E. Symptoms before and after surgical removal of colorectal endometriosis that are assessed by magnetic resonance imaging and rectal endoscopic sonography. Am J Obstet Gynecol 2004;190:1264–71. 3. Benbara A, Fortin A, Martin B, Palazzo L, Le Tohic A, Madelenat P, et al. Surgical and functional results of rectosigmoidal resection for rectal endometriosis. Gynecol Obstet Fertil 2008;36:1191–201. 4. Landi S, Ceccaroni M, Perutelli A, Allodi C, Barbieri F, Fiaccavento A, et al. Laparoscopic nerve-sparing complete excision of deep endometriosis: is it feasible? Hum Reprod 2006;21:774–81. 5. Remorgida V, Ragni N, Ferrero S, Anserini P, Torelli P, Fulcheri E. How complete is full thickness disc resection of bowel endometriotic lesions? A prospective surgical and histological study. Hum Reprod 2005;20:2317–20. 6. Daraı¨ E, Bazot M, Rouzier R, Houry S, Dubernard G. Outcome of laparoscopic colorectal resection for endometriosis. Curr Opin Obstet Gynecol 2007;19:308–13. 7. Roman H, Puscasiu L, Kouteich K, Gromez A, Resch B, MarouteauPasquier N, et al. Laparoscopic management of deep endometriosis with rectal affect. Chirurgia 2007;102:421–8. 8. Vercellini P, Crosignani PG, Abbiati A, Somigliana E, Vigano P, Fedele L. The effect of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod Update 2009;15:177–88. 9. Seracchioli R, Mabrouk M, Frasca C, Manuzzi L, Montanari G, Keramyda A, et al. Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial. Fertil Steril. Published online October 28, 2008 [Epub ahead of print]. 10. Slack A, Child T, Lindsey I, Kennedy S, Cunningham C, Mortensen N, et al. Urological and colorectal complications following surgery for rectovaginal. BJOG 2007;114:1278–82. 11. Donnez J, Squifflet J. Laparoscopic excision of deep endometriosis. Obstet Gynecol Clin N Am 2004;31:567–80. 12. Brosens IA. Endometriosis—a disease because it is characterized by bleeding. Am J Obstet Gynecol 1997;176:263–7. 13. Roman H, Gromez A, Hochain P, Marouteau-Pasquier N, Tuech JJ, Resch B, et al. Is painful rectovaginal endometriosis an intermediate stage of rectal endometriosis? Fertil Steril 2008;90:1014–8. 14. Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev 2004;(3): CD003678.
Vol. 92, No. 4, October 2009
Despite a myriad of scientific articles reported over the last two decades, there is no definitive answer to the question, ‘‘Which surgical procedure should be recommended in the management of rectal endometriosis?’’ To date, surgeons perform either rectal segmental resection or rectal nodule excision, with or without opening the rectum. The choice of technique, both of which are performed by experienced teams, depends on the particular idea each surgeon has about the disease. Those who perform mainly rectal segmental resection emphasize the significant postoperative improvement of pain (1–4) and strongly believe that the radical removal of digestive endometriotic foci is the most effective way of avoiding the risk of recurrence. This conviction was recently supported by the study of Remorgida et al., showing that disc resection of rectal nodules was microscopically incomplete in 40% of cases (5). Alternatively, surgeons who perform primarily nodule excision offered several arguments: surgical morbidity appears to be higher in women undergoing segmental resection (6), postoperative digestive symptoms seem to be less satisfactory after rectal removal, microscopic digestive endometriotic foci are to be found on the limits of the segmental resection (7), there is evidence of a high rate of postoperative recurrence of pain despite rectal resection (8), and postoperative continuous medical treatment might be able to halt the progression of the endometriotic implants left out and to decrease the risk of recurrences (9). Before December 2007, our department generally managed women with rectal endometriosis by performing segmental rectal resections, whereas we now perform threeReceived February 18, 2009; revised March 6, 2009; accepted March 18, 2009; published online May 5, 2009. H.R. has nothing to disclose. I.O. has nothing to disclose. B.R. has nothing to disclose. J.J.T. has nothing to disclose. J-C.S. has nothing to disclose. L.M. has nothing to disclose. Reprint requests: Horace Roman, M.D., Ph.D., Department of Gynecology and Obstetrics, Rouen University Hospital, 1 rue de Germont, 76031 Rouen, France (TEL: þ33 232 888 745; FAX: þ33 235 981 149; E-mail: [email protected]).
1250
fold more nodule excisions than resections, accompanied by a systematic recommendation of postoperative continuous contraceptive pill intake. This new orientation is based on the evaluation of midterm postoperative digestive functional symptoms of women treated by segmental rectal resection in our department and on reports from other experienced surgical teams. Our technique of rectal nodule excision is similar to that described by other surgical teams (10, 11). Both pararectal spaces are opened to isolate the endometriotic nodules. By this means, the rectovaginal space is reached under the inferior limit of the nodule. The nodule is then dissected away from the rectal wall, using the Ultracision Harmonic Scalpel (Ethicon Endosurgery, Cincinnati, OH). The dissection is made into the thickness of the rectal wall, to remove all abnormal fibrous lesions involving the rectal layers, using a high-magnification endoscopic view. Partial- rectal wall defects are closed laparoscopically for one or two layers using resorbable sutures. At the end of the procedure, the site of rectal dissection is recovered by an omentum flap, which is fixed by resorbable sutures. As a majority of endometriotic lesions involve rectal serosa, muscularis propria, or submucosal layers, we mainly perform partial excision of the nodule until reaching rectal muscular fibers that appear to be free of endometriotic lesions. Although the removal of endometriotic lesions may seem to be macroscopically complete, it is apparent that the dissection is more likely to identify fibrosis dependant on the nodule than to differentiate endometriotic glandular lesions from red rectal muscular fibers. Subsequently, our investigation focused on whether inside the endometriotic rectal nodules, glandular lesions remain surrounded by fibroconjunctive tissue and smooth fibers, and whether they are systematically removed by macroscopically complete excision of the fibrosis. We performed a retrospective study to include women with rectal endometriosis and who benefited from rectal segmental resection in our department from February
Fertility and Sterility Vol. 92, No. 4, October 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2009.03.073
2005 to July 2008. Women who had only full-thickness or partial resection of the rectal wall were excluded, to allow accurate checking of the depth of rectal wall infiltration by endometriotic lesions. In each case, lesions in serial sections were stained in hematoxylin and eosin, and with the use of a digital scanner, both the depth of infiltration by active endometriotic glands and stroma and that of fibroconjunctive tissue and smooth fibers were investigated (Fig. 1). The distance between the deepest point of active glandular and stromal infiltration and the deepest fibrotic lesion was then measured in micrometers (Fig. 1). In accordance with French regulations, this retrospective study was exempted from institutional review board approval.
FIGURE 1 Distance between the deepest point of active endometriotic glands and stroma infiltration and the deepest fibrotic lesion (7,621 mm; dotted line).
Twenty-seven women with histologically confirmed rectal endometriosis and managed by rectal segmental resection were included in the study. The age range was 23–45 years, with a mean (SD) age of 34.3 6.3 years. In 14 of 27 cases, both active endometriotic tissue (glandular epithelium surrounded by scanty stroma) and fibrosis (fibroconjunctive tissue and smooth fibers) had infiltrated the same rectal layer: muscularis propria (12 cases) and submucosa (two cases). In other cases, infiltrations of active endometriotic foci and fibrosis had respectively reached muscularis propria and subserosa (five cases), submucosa and subserosa (three cases), submucosa and muscularis propria (four cases), and mucosa and muscularis propria (one case). The depth of rectal infiltration by the glandular epithelium and stroma was superior to that of the fibrosis in 24 of 27 cases (89%), whereas fibrosis was responsible for the deepest infiltration in only three women (11%). In 24 women with deep infiltration of the active glandular epithelium and stroma, the distance from the deepest gland to the deepest point of the fibrosis ranged from 388–9,777 mm (mean [SD], 5,313 2,436 mm). In three cases in which fibrosis infiltration was deeper than that of glandular and stromal invasion, the distance between the deepest point of the fibrosis and that of the endometriotic glands and stroma was 626, 705, and 2,323 mm, respectively. Our data show that for the majority of rectal endometriosis nodules, the fibrosis does not surround but follows behind glandular epithelium and stroma foci. The distance between the deepest glandular and the deepest fibrosis foci can be as large as 5 mm; therefore, surgical excision of all macroscopic fibrosis may result in leaving active endometriotic lesions outside the deepest limit of the excision. Whereas surgeons use a harmonic scalpel with short thermal effect diffusion, these foci may be neither removed nor destroyed, and might therefore continue their natural evolution. Although further research is required to support the hypothesis that remaining active endometrium foci are responsible for clinical recurrence, our observation merits consideration by surgeons who use partial excision to manage rectal nodules. Fertility and Sterility
Roman. Histopathology of rectal endometriosis. Fertil Steril 2009.
Interpretations of our observations may vary, depending on the reader’s previous conviction. Surgeons who mainly perform rectal segmental resection may think that our study supports their choice not to perform nodule excision. Similar to the report of Remorgida et al. (5), our data confirms that segmental resection appears to be microscopically more complete than nodule excision, even if the latter would seem to remove all endometriotic fibrotic lesions from the rectal wall. Alternatively, surgeons who generally perform nodule excision might conclude that our data justify a systematic use of postoperative medical treatment to prevent clinical recurrences caused by remnant active endometrial foci. A recent trial by Seracchioli et al. (9) clearly stated that 2-year postoperative medical treatment by continuous
1251
intake of the contraceptive pill resulted in a threefold decrease in the risk of clinical recurrences, first level of evidence (LE-1). Although the trial included only women with ovarian endometriotic cysts and the outcome focused on endometrioma recurrences, it is probable that similar results might be obtained in a large trial recruiting exclusively women with deep endometriosis. Because endometriosis is a disease that progresses by cyclic bleeding (12), and clinical symptoms usually worsen after stopping use of contraceptive pills (13), we believe that long-term postoperative contraceptive pill intake might be efficient in preventing both the progression of remaining endometriotic foci and clinical recurrences. Sufficient data exist to suggest that surgical procedures of pelvic endometriosis rarely lead to a microscopically complete removal of endometriotic implants. On the basis of our observations, it is apparent that macroscopically complete excision of rectal nodules, without opening the rectum, probably does not remove glandular and stromal foci surrounding the fibrous nodule. Remorgida et al. (5) also reported that full thickness disc excision of the rectal nodule fails to be microscopically complete in 40% of cases. We also previously showed that even where rectal segmental resection is performed, endometriotic foci may be found on and outside the limits of the digestive resection (7). Incomplete resection of endometriotic implants is probably responsible for the high rate of pain recurrence observed a few years following surgery for deep endometriosis (8). All of these results suggest that long-term postoperative medical treatment could be required to inhibit recurrences. Not surprisingly, trials evaluating short-term postoperative treatments have failed to reveal an improvement at midterm (14), contrary to those studying the efficacy of prolonged continuous amenorrhea (9). In conclusion, we do not believe that our results contraindicate the use of partial rectal nodule excision in the management of rectal endometriosis, but rather support the recommendation of prolonged postoperative medical treatment to prevent the progression of persistent endometriotic implants. Horace Roman, M.D., Ph.D.a Ioana Opris, M.D.b Benoit Resch, M.D.a Jean Jacques Tuech, M.D., Ph.D.c
1252
Roman et al.
Correspondence
Jean-Christophe Sabourin, M.D., Ph.D.b Loı¨c Marpeau, M.D., Ph.D.a a Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France; b Department of Pathology, Rouen University Hospital, Rouen, France; and the c Department of Surgery, Rouen University Hospital, Rouen, France REFERENCES 1. Dubernard G, Piketty M, Rouzier R, Houry S, Bazot M, Darai E. Quality of life after laparoscopic colorectal resection for endometriosis. Hum Reprod 2006;21:1243–7. 2. Thomassin I, Bazot M, Detchev R, Barranger E, Cortez A, Darai E. Symptoms before and after surgical removal of colorectal endometriosis that are assessed by magnetic resonance imaging and rectal endoscopic sonography. Am J Obstet Gynecol 2004;190:1264–71. 3. Benbara A, Fortin A, Martin B, Palazzo L, Le Tohic A, Madelenat P, et al. Surgical and functional results of rectosigmoidal resection for rectal endometriosis. Gynecol Obstet Fertil 2008;36:1191–201. 4. Landi S, Ceccaroni M, Perutelli A, Allodi C, Barbieri F, Fiaccavento A, et al. Laparoscopic nerve-sparing complete excision of deep endometriosis: is it feasible? Hum Reprod 2006;21:774–81. 5. Remorgida V, Ragni N, Ferrero S, Anserini P, Torelli P, Fulcheri E. How complete is full thickness disc resection of bowel endometriotic lesions? A prospective surgical and histological study. Hum Reprod 2005;20:2317–20. 6. Daraı¨ E, Bazot M, Rouzier R, Houry S, Dubernard G. Outcome of laparoscopic colorectal resection for endometriosis. Curr Opin Obstet Gynecol 2007;19:308–13. 7. Roman H, Puscasiu L, Kouteich K, Gromez A, Resch B, MarouteauPasquier N, et al. Laparoscopic management of deep endometriosis with rectal affect. Chirurgia 2007;102:421–8. 8. Vercellini P, Crosignani PG, Abbiati A, Somigliana E, Vigano P, Fedele L. The effect of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod Update 2009;15:177–88. 9. Seracchioli R, Mabrouk M, Frasca C, Manuzzi L, Montanari G, Keramyda A, et al. Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial. Fertil Steril. Published online October 28, 2008 [Epub ahead of print]. 10. Slack A, Child T, Lindsey I, Kennedy S, Cunningham C, Mortensen N, et al. Urological and colorectal complications following surgery for rectovaginal. BJOG 2007;114:1278–82. 11. Donnez J, Squifflet J. Laparoscopic excision of deep endometriosis. Obstet Gynecol Clin N Am 2004;31:567–80. 12. Brosens IA. Endometriosis—a disease because it is characterized by bleeding. Am J Obstet Gynecol 1997;176:263–7. 13. Roman H, Gromez A, Hochain P, Marouteau-Pasquier N, Tuech JJ, Resch B, et al. Is painful rectovaginal endometriosis an intermediate stage of rectal endometriosis? Fertil Steril 2008;90:1014–8. 14. Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev 2004;(3): CD003678.
Vol. 92, No. 4, October 2009