Ileocecal endometriosis: clinical and pathogenetic implications of an underdiagnosed condition Luigi Fedele, M.D.,a,b Nicola Berlanda, M.D.,a,b Carlo Corsi, M.D.,d Giacomo Gazzano, M.D.,c,e Martina Morini, M.S.,a and Paolo Vercellini, M.D.a a Granda Ospedale Maggiore ‘‘Luigi Mangiagalli’’ Department of Obstetrics and Gynecology, IRCCS Fondazione Ca Policlinico, and b Department of Obstetrics and Gynecology, c Department of Pathology, and d Department of Colorectal Surgery, San Paolo Hospital, University of Milan; and e Department of Pathology, Mellino Mellini Hospital, Chiari (Brescia), Milan, Italy
Objective: To review our experience with surgical treatment of ileocecal endometriosis. Design: Observational study. Setting: Tertiary university hospital in Italy. Patient(s): Eight consecutive patients with infiltrating ileocecal endometriosis operated on between 2003 and 2005. Intervention(s): All of the women underwent laparotomic ileocecal or cecal resection and had radical treatment of rectovaginal endometriosis as well. Main Outcome Measure(s): Long-term relief of pelvic pain, constipation, and dyschezia. Result(s): There were no postoperative intestinal complications. At a mean SD follow-up of 106 10 months, all of the patients reported significant improvement of pelvic pain and bowel symptoms. Conclusion(s): Infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis, possibly reflecting a common pathogenesis. A thorough clinical evaluation of women with rectovaginal endometriosis might allow an improvement in the difficult preoperative diagnosis of ileocecal endometriosis. Our data support the long-term efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia. (Fertil SterilÒ 2014;101:750–3. Ó2014 by Use your smartphone American Society for Reproductive Medicine.) to scan this QR code Key Words: Bowel endometriosis, ileocecal endometriosis, pelvic pain, rectovaginal and connect to the endometriosis Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/fedelel-ileocecal-endometriosis-pelvic-pain/
B
owel endometriosis is estimated to be present in 5%–12% of women with genital endometriotic lesions (1). About 75% of intestinal lesions are located either in the rectum, the most common site, usually associated with vaginal endometriotic lesions, or in the sigmoid colon; the remaining 25% of intestinal endo-
metriotic lesions, proximal to the sigmoid colon, are almost invariably located in the ileocecal and appendix area (2–4). Symptoms of the different intestinal locations are different. Endometiosis of the rectum and sigmoid may be associated with specific symptoms allowing an early clinical suspicion,
Received August 27, 2013; revised November 23, 2013; accepted November 27, 2013; published online January 11, 2014. L.F. has nothing to disclose. N.B. has nothing to disclose. C.C. has nothing to disclose. G.G. has nothing to disclose. M.M. has nothing to disclose. P.V. reports payment of meeting/travel expenses by the American Society for Reproductive Medicine. Reprint requests: Nicola Berlanda, M.D., Clinica Ostetrica e Ginecologica I, Istituto Luigi Mangiagalli, Granda Ospedale Maggiore Policlinico, Via della Commenda 12, 20122 IRCCS Fondazione Ca Milano, Italy (E-mail: [email protected]). Fertility and Sterility® Vol. 101, No. 3, March 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2013.11.126 750
discussion forum for this article now.*
* Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
namely, deep dyspareunia, dyschezia, cathamenial diarrhea, and, in the most severe cases, ematochezia and narrowed stools. Conversely, ileocecal endometriosis may be asymptomatic or associated with aspecific symptoms, such as abdominal pain, nausea, vomiting, and diarrhea; therefore, it is a preoperatively underdiagnosed condition and the diagnosis is usually performed after an acute complication, such as appendicitis or acute bowel obstruction (5, 6). A reliable diagnosis of rectosigmoid endometriosis can often be obtained by means of a simple rectovaginal examination and a transvaginal or transrectal ultrasound (7). Conversely, the diagnosis of ileocecal endometriosis requires more VOL. 101 NO. 3 / MARCH 2014
Fertility and Sterility® advanced diagnostic procedures, such as colonoscopy, doublecontrast barium enema (8), magnetic resonance imaging, or multislice computerized tomographic enteroclysis (9). Because the number of patients with infiltrating ileocecal endometriosis reported in published series is limited, we sought to critically review our experience with a series of eight consecutive patients affected by this condition, with the aim of gaining insight on the pathogenesis, diagnosis, and management of this uncommon location of endometriosis.
MATERIALS AND METHODS The charts of 241 consecutive patients operated on for endometriosis over a 3-year period from 2003 to 2005 at the Department of Obstetrics and Gynecology, San Paolo Hospital, University of Milan, were reviewed. Among them, eight patients (3.3%) with infiltrating ileocecal endometriosis were found and included in the present descriptive study. Patients with superficial ileocecal endometriosis or endometriosis limited to the appendix were excluded from the study. Another patient who was not included in the study underwent rectosigmoid resection and stripping of bilateral endometrioma in 2004 and was subsequently diagnosed with asymptomatic ileocecal endometriosis by a follow-up colonoscopy performed in 2006 (Fig. 1). The preoperative work-up included rectovaginal examination as well as transvaginal and urinary tract ultrasonography in all patients; all patients underwent bowel evaluation with colonoscopy, rectosigmoidoscopy, or barium enema because of the diagnosis of rectovaginal endometriosis. At surgery, a radical treatment of endometriosis was performed, including ablation of all endometriotic lesions and resection of stenotic intestinal segments. All anastomoses were performed manually in double layer by laparotomy. The ileocecal valve was spared when not directly involved by endometriosis.
FIGURE 1
The patients underwent a 1-month postoperative evaluation in our outpatient clinic and then were followed by their referring gynecologists. In May 2013, all of the patients were available for a telephone follow-up interview. Institutional Review Board approval and patients’ informed consents were obtained.
RESULTS Characteristics of the Patients and the Surgical Procedures The eight patients were all premenopausal, ranging in age from 29 to 43 years, and were nulliparous; one patient had an ectopic pregnancy and one had previously undergone IVF-ET without success. Six patients had previous surgery for endometriosis: Five women had undergone at least one laparotomy, and one woman had undergone an operative laparoscopy. Primary indication for surgery in all patients was severe pelvic pain, in the form of dysmenorrhea, dyspareunia, or noncyclic pelvic pain. Six patients had symptoms related to bowel function, most frequently represented by constipation and dyschezia. A preoperative diagnosis of ileocecal endometriosis was suspected in one of six patients (17%) who underwent colonoscopy, owing to a hyperemic and edematous appendix, and in one of the two patients (50%) who had barium enema because of a filling defect of the cecum. Table 1 reports the intraoperative characteristics of the eight patients. All patients underwent radical treatment of endometriosis at laparotomy, including resection of cecal or ileocecal nodules. One patient required urgent laparotomy for acute bowel obstruction the day before the scheduled operation; this woman had an endometriotic nodule involving the ileocecal valve and underwent ileocecal resection. The remaining seven patients had nodules of the cecal fundus not involving the ileocecal valve and therefore underwent resection of the cecal fundus only. In addition, three of these patients required appendectomy and one required appendectomy and resection of terminal ileum. All patients had rectovaginal endometriosis as well: seven underwent resection of rectosigmoid, and one underwent excision of a rectovaginal nodule. The operating time ranged from 135 to 265 minutes and hospital stay from 8 to 16 days. In one patient, who had undergone total hysterectomy and bilateral salpingooophorectomy, a microinfiltrating endometriotic ovarian carcinoma was observed at pathologic evaluation. This patient underwent a staging laparotomy a few months later with no signs of malignancies, and she was free of disease 7 years after the procedure. The same patient had a permanent lesion of the right femoral nerve and required blood transfusion. No other complications were observed.
Follow-up
Colonoscopy view of an intussusception of the appendix (arrow). Fedele. Surgery for ileocecal endometriosis. Fertil Steril 2014.
VOL. 101 NO. 3 / MARCH 2014
Table 2 shows the long-term follow up of the eight patients. All of the patients reported significant improvement of pelvic pain and bowel symptoms. Three patients had mild to moderate pain that was controlled by medical treatment, namely, 751
ORIGINAL ARTICLE: ENDOMETRIOSIS
TABLE 1 Intraoperative details of eight patients who underwent surgery for ileocecal endometriosis, n (%). Ileocecal procedures Resection of cecum Appendectomy Ileocecal resection Resection of terminal ileum Protective ileostomy Associated procedures Resection of rectosigmoid Stripping of ovarian endometrioma Ureterolysis Hysterectomy and bilateral salpingo-oophorectomy Adenomyomectomy Excision of vaginal endometriosis Myomectomy Excision of rectal endometriotic nodule Surgical approach Midline laparotomy Pfannenstiel incision Operating time, min Blood loss, mL Hospital stay, d Complications Permanent right femoral nerve lesion Blood transfusion
7 (88) 3 (38) 1 (13) 1 (13) 1 (13) 7 (88) 6 (75) 3 (38) 1 (13) 2 (25) 2 (25) 1 (13) 1 (13) 5 (63) 3 (38) 204 47 (135–265) 500 250 (200–900) 10.8 3.3 (8–16) 1 (13) 1 (13)
Note: Data are presented as n (%) or mean SD (range). Fedele. Surgery for ileocecal endometriosis. Fertil Steril 2014.
low dose progestin, levonorgestrel-releasing intrauterine device, and nonsteroidal antiinflammatory drugs, respectively. No patients reported dyschezia or hematochezia. Among the five patients who had additional surgery, three had fertilityenhancing laparoscopies and two had late complications involving the abdominal wall, namely, the correction of an abdominal hernia 1 year after the operation and the removal of an endometriotic nodule of the laparotomic scar 7 years
TABLE 2 Follow-up data of eight women who underwent surgery for ileocecal endometriosis. Follow-up (mo) 106 10 Pelvic pain No pain 5 (63) Mild to moderate pain (NRS 1-5) 3 (38) Bowel symptoms No symptoms 3 (38) Constipation 2 (25) Alternating constipation and loose stool 2 (25) Bloating 1 (13) Reproductive outcome Patients seeking pregnancy 5 (63) Time of seeking pregnancy (years) 3.8 1.6 Patients undergoing IVF-ET 4 (50) Pregnancy 1 (13) Repeat surgery Staging laparotomy for ovarian cancer 1 (13) Laparoscopy for infertility 2 (25) Laparoscopy for infertility and myomectomy 1 (13) Correction of abdominal wall hernia 1 (13) Excision of endometriotic nodule of laparotomic scar 1 (13) Note: Data are presented as n (%) or mean SD. NRS ¼ numeric rating scale (0 ¼ no pain; 10 ¼ unbearable pain). Fedele. Surgery for ileocecal endometriosis. Fertil Steril 2014.
752
after surgery. Among the five patients seeking pregnancy, three underwent multiple IVF attempts. Owing to the severity of endometriosis, one patient was considered to be not eligible for IVF and another patient was allowed one IVF attempt only. Pregnancy was achieved by only one patient after 7 years of infertility at the fourth IVF attempt.
DISCUSSION The number of patients in the present series may appear to be limited. However, ileocecal endometriosis is rare, and information on the management and prognosis of this condition is scanty. We observed that infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis. This finding is in agreement with a recent larger series of patients reporting a prevalence of rectovaginal endometriosis of 94% among patients with ileocecal endometriosis (10). This must be kept in mind when discussing pathogenesis, symptoms, preoperative diagnosis, and treatment of ileocecal endometriosis. From a pathogenetic point of view, this association might be consistent with Sampson’s theory that endometriotic lesions originate from endometrial cells regurgitated through the fallopian tubes during menstruation (11). In fact, the cecum and the rectum are the less mobile intestinal sites, lower, and closer to the fallopian tubes; in these areas, there is the highest possibility that a significant amount of regurgitated endometrial cells might adhere to the intestinal wall for a prolonged period of time, eventually leading to the formation of an endometriotic nodule (4, 12–14). Superficial endometriosis of the cecal and appendicular region, which is more frequent than infiltrative disease, usually appears as multiple red-bluish superficial lesions on the peritoneum of the cecum and appendix, resembling those that are usually seen on the pelvic peritoneum. It is tempting to speculate that these superficial lesions might represent the first stage of the disease, followed by fibrosis and retraction of the cecal wall and the development of an infiltrating nodule. A clinical preoperative diagnosis of ileocecal endometriosis is difficult, because symptoms, when present, are aspecific and could mimic other conditions, such as inflammatory bowel disease, ischemic colitis, and neoplasms. In addition, when ileocecal endometriosis is associated with rectovaginal endometriosis, pelvic pain and gastrointestinal symptoms are justified by the latter condition and ileocecal endometriosis might be overlooked. Accordingly, in a recent series, preoperative diagnosis was not obtained in any of the 31 women operated for ileocecal endometriosis, and the condition was an intraoperative incidental finding in all of the patients (10). On the other hand, owing to the observed strong association between ileocecal and rectovaginal endometriosis, we think that a significant improvement in the diagnosis might be achieved at least among patients with the latter condition. In the present series, eight out of 32 patients (25%) operated for rectosigmoid endometriosis presented ileocecal lesions as well. These figures are consistent with the findings of Chapron et al., who reported a prevalence of multifocal bowel lesions of 39% (15). VOL. 101 NO. 3 / MARCH 2014
Fertility and Sterility® A thorough preoperative evaluation of patients with rectovaginal endometriosis presenting additional aspecific symptoms such as nausea, vomiting, and diffuse abdominal pain may help to identify those subjects with associated ileocecal endometriosis. The notion that a patient with suspected bowel endometriosis might be affected by multiple intestinal endometriotic lesions has to be taken into account when planning treatment. From this point of view, medical treatment has the advantages of treating the disease simultaneously at all sites, avoiding the risk of major surgical complications. As for the efficacy of medical treatment, the few available studies show that the use of either a combination of estrogen and progestin or progestin alone for rectovaginal or bowel endometriosis appears to be effective in many women, with 60%–90% of patients reporting considerable improvement or complete relief of pain symptoms (16–18). However, when an intestinal stenosis is present or when medical treatment has failed, surgery is indicated. In the present surgical series, most patients required multiple intestinal resections to achieve a radical treatment of endometriois. All intestinal anastomosis were performed manually in double layer at laparotomy. To avoid possible postoperative chronic diarrhoea (19), the ileocecal valve was spared in most women, because it was not directly involved by endometriosis. We did not observe any intestinal complications. Complication rate and hospital stay for the present series are in line with a previously published series of women who underwent rectosigmoid resection for endometriosis in our center (20). In agreement with available data (10), it seems that the additional resection of one or more ileocecal segments does not significantly alter the postoperative course of patients compared with rectosigmoid resection alone. After a mean follow-up of >8 years, three patients experienced a recurrence of mild to moderate pain, which was responsive to medical treatment, and five patients had minor intestinal symptoms. Therefore, our data support the longterm efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia. Unfortunately, no meaningful conclusion can be drawn about reproductive performance, because only five women in our series sought a pregnancy after surgery. In conclusion, infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis. This finding might reflect a common pathogenesis and might allow an improvement in the difficult preoperative diagnosis of ileocecal endometriosis, at least among women with rectovaginal lesions. In addition, our data support the long-term efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia.
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Weed JC, Ray JE. Endometriosis of the bowel. Obstet Gynecol 1987;69: 727–30. Bailey HR, Ott MT, Hartendorp P. Aggressive surgical management for advanced colorectal endometriosis. Dis Colon Rectum 1994;37: 747–53. Coronado C, Franklin RR, Lotze EC, Bailey HR, Valdes CT. Surgical treatment of symptomatic colorectal endometriosis. Fertil Steril 1990;53:411–6. Vercellini P, Chapron C, Fedele L, Gattei U, Daguati R, Crosignani PG. Evidence for asymmetric distribution of lower intestinal tract endometriosis. BJOG 2004;111:1213–7. Gindoff PR, Jewelewicz R. Ileal resection in the operative treatment of endometriosis. Obstet Gynecol 1987;69:511–3. Wickramasekera D, Hay DJ, Fayz M. Acute small bowel obstruction due to ileal endometriosis: a case report and literature review. J R Coll Surg Edinb 1999;44:59–60. Fedele L, Bianchi S, Portuese A, Borruto F, Dorta M. Transrectal ultrasonography in the assessment of rectovaginal endometriosis. Obstet Gynecol 1998;91:444–8. Faccioli N, Foti G, Manfredi R, Mainardi P, Spoto E, Ruffo G, et al. Evaluation of colonic involvement in endometriosis: double-contrast barium enema vs. magnetic resonance imaging. Abdom Imaging 2010;35: 414–21. Biscaldi E, Ferrero S, Fulcheri E, Ragni N, Remorgida V, Rollandi GA. Multislice CT enteroclysis in the diagnosis of bowel endometriosis. Eur Radiol 2007;17:211–9. Ruffo G, Stepniewska A, Crippa S, Serboli G, Zardini C, Steinkasserer M, et al. Laparoscopic ileocecal resection for bowel endometriosis. Surg Endosc 2011;25:1257–62. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422–69. Vercellini P, Aimi G, Panazza S, Vicentini S, Pisacreta A, Crosignani PG. Deep endometriosis conundrum: evidence in favor of a peritoneal origin. Fertil Steril 2000;73:1043–6. Somigliana E, Infantino M, Candiani M, Vignali M, Chiodini A, Busacca M, et al. Association rate between deep peritoneal endometriosis and other forms of the disease: pathogenetic implications. Hum Reprod 2004;19: 168–71. Parazzini F, Cipriani S, Bianchi S, Gotsch F, Zanconato G, Fedele L. Risk factors for deep endometriosis: a comparison with pelvic and ovarian endometriosis. Fertil Steril 2008;90:174–9. Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, et al. Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification. Hum Reprod 2003;18: 157–61. Vercellini P, Crosignani PG, Somigliana E, Berlanda N, Barbara G, Fedele L. Medical treatment for rectovaginal endometriosis: what is the evidence? Hum Reprod 2009;24:2504–14. Vercellini P, Pietropaolo G, de Giorgi O, Pasin R, Chiodini A, Crosignani PG. Treatment of symptomatic rectovaginal endometriosis with an estrogenprogestogen combination versus low-dose norethindrone acetate. Fertil Steril 2005;84:1375–87. Ferrero S, Camerini G, Ragni N, Venturini PL, Biscaldi E, Remorgida V. Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study. Hum Reprod 2010;25:94–100. Folaranmi S, Rakoczy G, Bruce J, Humphrey G, Bowen J, Morabito A, et al. Ileocaecal valve: how important is it? Pediatr Surg Int 2011;27:613–5. Fedele L, Bianchi S, Zanconato G, Bettoni G, Gotsch F. Long-term follow-up after conservative surgery for rectovaginal endometriosis. Am J Obstet Gynecol 2004;190:1020–4.
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Objective: To review our experience with surgical treatment of ileocecal endometriosis. Design: Observational study. Setting: Tertiary university hospital in Italy. Patient(s): Eight consecutive patients with infiltrating ileocecal endometriosis operated on between 2003 and 2005. Intervention(s): All of the women underwent laparotomic ileocecal or cecal resection and had radical treatment of rectovaginal endometriosis as well. Main Outcome Measure(s): Long-term relief of pelvic pain, constipation, and dyschezia. Result(s): There were no postoperative intestinal complications. At a mean SD follow-up of 106 10 months, all of the patients reported significant improvement of pelvic pain and bowel symptoms. Conclusion(s): Infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis, possibly reflecting a common pathogenesis. A thorough clinical evaluation of women with rectovaginal endometriosis might allow an improvement in the difficult preoperative diagnosis of ileocecal endometriosis. Our data support the long-term efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia. (Fertil SterilÒ 2014;101:750–3. Ó2014 by Use your smartphone American Society for Reproductive Medicine.) to scan this QR code Key Words: Bowel endometriosis, ileocecal endometriosis, pelvic pain, rectovaginal and connect to the endometriosis Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/fedelel-ileocecal-endometriosis-pelvic-pain/
B
owel endometriosis is estimated to be present in 5%–12% of women with genital endometriotic lesions (1). About 75% of intestinal lesions are located either in the rectum, the most common site, usually associated with vaginal endometriotic lesions, or in the sigmoid colon; the remaining 25% of intestinal endo-
metriotic lesions, proximal to the sigmoid colon, are almost invariably located in the ileocecal and appendix area (2–4). Symptoms of the different intestinal locations are different. Endometiosis of the rectum and sigmoid may be associated with specific symptoms allowing an early clinical suspicion,
Received August 27, 2013; revised November 23, 2013; accepted November 27, 2013; published online January 11, 2014. L.F. has nothing to disclose. N.B. has nothing to disclose. C.C. has nothing to disclose. G.G. has nothing to disclose. M.M. has nothing to disclose. P.V. reports payment of meeting/travel expenses by the American Society for Reproductive Medicine. Reprint requests: Nicola Berlanda, M.D., Clinica Ostetrica e Ginecologica I, Istituto Luigi Mangiagalli, Granda Ospedale Maggiore Policlinico, Via della Commenda 12, 20122 IRCCS Fondazione Ca Milano, Italy (E-mail: [email protected]). Fertility and Sterility® Vol. 101, No. 3, March 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2013.11.126 750
discussion forum for this article now.*
* Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
namely, deep dyspareunia, dyschezia, cathamenial diarrhea, and, in the most severe cases, ematochezia and narrowed stools. Conversely, ileocecal endometriosis may be asymptomatic or associated with aspecific symptoms, such as abdominal pain, nausea, vomiting, and diarrhea; therefore, it is a preoperatively underdiagnosed condition and the diagnosis is usually performed after an acute complication, such as appendicitis or acute bowel obstruction (5, 6). A reliable diagnosis of rectosigmoid endometriosis can often be obtained by means of a simple rectovaginal examination and a transvaginal or transrectal ultrasound (7). Conversely, the diagnosis of ileocecal endometriosis requires more VOL. 101 NO. 3 / MARCH 2014
Fertility and Sterility® advanced diagnostic procedures, such as colonoscopy, doublecontrast barium enema (8), magnetic resonance imaging, or multislice computerized tomographic enteroclysis (9). Because the number of patients with infiltrating ileocecal endometriosis reported in published series is limited, we sought to critically review our experience with a series of eight consecutive patients affected by this condition, with the aim of gaining insight on the pathogenesis, diagnosis, and management of this uncommon location of endometriosis.
MATERIALS AND METHODS The charts of 241 consecutive patients operated on for endometriosis over a 3-year period from 2003 to 2005 at the Department of Obstetrics and Gynecology, San Paolo Hospital, University of Milan, were reviewed. Among them, eight patients (3.3%) with infiltrating ileocecal endometriosis were found and included in the present descriptive study. Patients with superficial ileocecal endometriosis or endometriosis limited to the appendix were excluded from the study. Another patient who was not included in the study underwent rectosigmoid resection and stripping of bilateral endometrioma in 2004 and was subsequently diagnosed with asymptomatic ileocecal endometriosis by a follow-up colonoscopy performed in 2006 (Fig. 1). The preoperative work-up included rectovaginal examination as well as transvaginal and urinary tract ultrasonography in all patients; all patients underwent bowel evaluation with colonoscopy, rectosigmoidoscopy, or barium enema because of the diagnosis of rectovaginal endometriosis. At surgery, a radical treatment of endometriosis was performed, including ablation of all endometriotic lesions and resection of stenotic intestinal segments. All anastomoses were performed manually in double layer by laparotomy. The ileocecal valve was spared when not directly involved by endometriosis.
FIGURE 1
The patients underwent a 1-month postoperative evaluation in our outpatient clinic and then were followed by their referring gynecologists. In May 2013, all of the patients were available for a telephone follow-up interview. Institutional Review Board approval and patients’ informed consents were obtained.
RESULTS Characteristics of the Patients and the Surgical Procedures The eight patients were all premenopausal, ranging in age from 29 to 43 years, and were nulliparous; one patient had an ectopic pregnancy and one had previously undergone IVF-ET without success. Six patients had previous surgery for endometriosis: Five women had undergone at least one laparotomy, and one woman had undergone an operative laparoscopy. Primary indication for surgery in all patients was severe pelvic pain, in the form of dysmenorrhea, dyspareunia, or noncyclic pelvic pain. Six patients had symptoms related to bowel function, most frequently represented by constipation and dyschezia. A preoperative diagnosis of ileocecal endometriosis was suspected in one of six patients (17%) who underwent colonoscopy, owing to a hyperemic and edematous appendix, and in one of the two patients (50%) who had barium enema because of a filling defect of the cecum. Table 1 reports the intraoperative characteristics of the eight patients. All patients underwent radical treatment of endometriosis at laparotomy, including resection of cecal or ileocecal nodules. One patient required urgent laparotomy for acute bowel obstruction the day before the scheduled operation; this woman had an endometriotic nodule involving the ileocecal valve and underwent ileocecal resection. The remaining seven patients had nodules of the cecal fundus not involving the ileocecal valve and therefore underwent resection of the cecal fundus only. In addition, three of these patients required appendectomy and one required appendectomy and resection of terminal ileum. All patients had rectovaginal endometriosis as well: seven underwent resection of rectosigmoid, and one underwent excision of a rectovaginal nodule. The operating time ranged from 135 to 265 minutes and hospital stay from 8 to 16 days. In one patient, who had undergone total hysterectomy and bilateral salpingooophorectomy, a microinfiltrating endometriotic ovarian carcinoma was observed at pathologic evaluation. This patient underwent a staging laparotomy a few months later with no signs of malignancies, and she was free of disease 7 years after the procedure. The same patient had a permanent lesion of the right femoral nerve and required blood transfusion. No other complications were observed.
Follow-up
Colonoscopy view of an intussusception of the appendix (arrow). Fedele. Surgery for ileocecal endometriosis. Fertil Steril 2014.
VOL. 101 NO. 3 / MARCH 2014
Table 2 shows the long-term follow up of the eight patients. All of the patients reported significant improvement of pelvic pain and bowel symptoms. Three patients had mild to moderate pain that was controlled by medical treatment, namely, 751
ORIGINAL ARTICLE: ENDOMETRIOSIS
TABLE 1 Intraoperative details of eight patients who underwent surgery for ileocecal endometriosis, n (%). Ileocecal procedures Resection of cecum Appendectomy Ileocecal resection Resection of terminal ileum Protective ileostomy Associated procedures Resection of rectosigmoid Stripping of ovarian endometrioma Ureterolysis Hysterectomy and bilateral salpingo-oophorectomy Adenomyomectomy Excision of vaginal endometriosis Myomectomy Excision of rectal endometriotic nodule Surgical approach Midline laparotomy Pfannenstiel incision Operating time, min Blood loss, mL Hospital stay, d Complications Permanent right femoral nerve lesion Blood transfusion
7 (88) 3 (38) 1 (13) 1 (13) 1 (13) 7 (88) 6 (75) 3 (38) 1 (13) 2 (25) 2 (25) 1 (13) 1 (13) 5 (63) 3 (38) 204 47 (135–265) 500 250 (200–900) 10.8 3.3 (8–16) 1 (13) 1 (13)
Note: Data are presented as n (%) or mean SD (range). Fedele. Surgery for ileocecal endometriosis. Fertil Steril 2014.
low dose progestin, levonorgestrel-releasing intrauterine device, and nonsteroidal antiinflammatory drugs, respectively. No patients reported dyschezia or hematochezia. Among the five patients who had additional surgery, three had fertilityenhancing laparoscopies and two had late complications involving the abdominal wall, namely, the correction of an abdominal hernia 1 year after the operation and the removal of an endometriotic nodule of the laparotomic scar 7 years
TABLE 2 Follow-up data of eight women who underwent surgery for ileocecal endometriosis. Follow-up (mo) 106 10 Pelvic pain No pain 5 (63) Mild to moderate pain (NRS 1-5) 3 (38) Bowel symptoms No symptoms 3 (38) Constipation 2 (25) Alternating constipation and loose stool 2 (25) Bloating 1 (13) Reproductive outcome Patients seeking pregnancy 5 (63) Time of seeking pregnancy (years) 3.8 1.6 Patients undergoing IVF-ET 4 (50) Pregnancy 1 (13) Repeat surgery Staging laparotomy for ovarian cancer 1 (13) Laparoscopy for infertility 2 (25) Laparoscopy for infertility and myomectomy 1 (13) Correction of abdominal wall hernia 1 (13) Excision of endometriotic nodule of laparotomic scar 1 (13) Note: Data are presented as n (%) or mean SD. NRS ¼ numeric rating scale (0 ¼ no pain; 10 ¼ unbearable pain). Fedele. Surgery for ileocecal endometriosis. Fertil Steril 2014.
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after surgery. Among the five patients seeking pregnancy, three underwent multiple IVF attempts. Owing to the severity of endometriosis, one patient was considered to be not eligible for IVF and another patient was allowed one IVF attempt only. Pregnancy was achieved by only one patient after 7 years of infertility at the fourth IVF attempt.
DISCUSSION The number of patients in the present series may appear to be limited. However, ileocecal endometriosis is rare, and information on the management and prognosis of this condition is scanty. We observed that infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis. This finding is in agreement with a recent larger series of patients reporting a prevalence of rectovaginal endometriosis of 94% among patients with ileocecal endometriosis (10). This must be kept in mind when discussing pathogenesis, symptoms, preoperative diagnosis, and treatment of ileocecal endometriosis. From a pathogenetic point of view, this association might be consistent with Sampson’s theory that endometriotic lesions originate from endometrial cells regurgitated through the fallopian tubes during menstruation (11). In fact, the cecum and the rectum are the less mobile intestinal sites, lower, and closer to the fallopian tubes; in these areas, there is the highest possibility that a significant amount of regurgitated endometrial cells might adhere to the intestinal wall for a prolonged period of time, eventually leading to the formation of an endometriotic nodule (4, 12–14). Superficial endometriosis of the cecal and appendicular region, which is more frequent than infiltrative disease, usually appears as multiple red-bluish superficial lesions on the peritoneum of the cecum and appendix, resembling those that are usually seen on the pelvic peritoneum. It is tempting to speculate that these superficial lesions might represent the first stage of the disease, followed by fibrosis and retraction of the cecal wall and the development of an infiltrating nodule. A clinical preoperative diagnosis of ileocecal endometriosis is difficult, because symptoms, when present, are aspecific and could mimic other conditions, such as inflammatory bowel disease, ischemic colitis, and neoplasms. In addition, when ileocecal endometriosis is associated with rectovaginal endometriosis, pelvic pain and gastrointestinal symptoms are justified by the latter condition and ileocecal endometriosis might be overlooked. Accordingly, in a recent series, preoperative diagnosis was not obtained in any of the 31 women operated for ileocecal endometriosis, and the condition was an intraoperative incidental finding in all of the patients (10). On the other hand, owing to the observed strong association between ileocecal and rectovaginal endometriosis, we think that a significant improvement in the diagnosis might be achieved at least among patients with the latter condition. In the present series, eight out of 32 patients (25%) operated for rectosigmoid endometriosis presented ileocecal lesions as well. These figures are consistent with the findings of Chapron et al., who reported a prevalence of multifocal bowel lesions of 39% (15). VOL. 101 NO. 3 / MARCH 2014
Fertility and Sterility® A thorough preoperative evaluation of patients with rectovaginal endometriosis presenting additional aspecific symptoms such as nausea, vomiting, and diffuse abdominal pain may help to identify those subjects with associated ileocecal endometriosis. The notion that a patient with suspected bowel endometriosis might be affected by multiple intestinal endometriotic lesions has to be taken into account when planning treatment. From this point of view, medical treatment has the advantages of treating the disease simultaneously at all sites, avoiding the risk of major surgical complications. As for the efficacy of medical treatment, the few available studies show that the use of either a combination of estrogen and progestin or progestin alone for rectovaginal or bowel endometriosis appears to be effective in many women, with 60%–90% of patients reporting considerable improvement or complete relief of pain symptoms (16–18). However, when an intestinal stenosis is present or when medical treatment has failed, surgery is indicated. In the present surgical series, most patients required multiple intestinal resections to achieve a radical treatment of endometriois. All intestinal anastomosis were performed manually in double layer at laparotomy. To avoid possible postoperative chronic diarrhoea (19), the ileocecal valve was spared in most women, because it was not directly involved by endometriosis. We did not observe any intestinal complications. Complication rate and hospital stay for the present series are in line with a previously published series of women who underwent rectosigmoid resection for endometriosis in our center (20). In agreement with available data (10), it seems that the additional resection of one or more ileocecal segments does not significantly alter the postoperative course of patients compared with rectosigmoid resection alone. After a mean follow-up of >8 years, three patients experienced a recurrence of mild to moderate pain, which was responsive to medical treatment, and five patients had minor intestinal symptoms. Therefore, our data support the longterm efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia. Unfortunately, no meaningful conclusion can be drawn about reproductive performance, because only five women in our series sought a pregnancy after surgery. In conclusion, infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis. This finding might reflect a common pathogenesis and might allow an improvement in the difficult preoperative diagnosis of ileocecal endometriosis, at least among women with rectovaginal lesions. In addition, our data support the long-term efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia.
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