Expression of CD44s, vascular endothelial growth factor, matrix metalloproteinase-2 and Ki-67 in peritoneal, rectovaginal and ovarian endometriosis

OBJECTIVE: To understand the pathogenetic mechanisms of endometriosis by examining the expression of adhesion molecules (CD44s), angiogenic factor (VEGF) and matrix protease and to perform Ki-67 labeling for evaluation of proliferative activity. STUDY DESIGN: Twenty-nine peritoneal endometriosis lesions (9 red, 12 black and 8 white), 11 rectovaginal and 22 ovarian were obtained. Immunohistochemical staining was performed with antibodies for CD44, VEGF, MMP-2 and Ki-67. RESULTS: CD44s were expressed mainly in stroma and showed higher expression in glandular epithelium of peritoneal endometriosis than in rectovaginal and ovarian endometriosis. The stroma in red and white lesions showed higher MMP-2 expression than in black lesions. The stromal cells in rectovaginal endometriosis showed significantly lower expression of Ki-67 (p = 0.002) than in peritoneal and ovarian endometriosis. When endometriosis was analyzed according to the revised American Fertility Society classification, Ki-67 expression was high in glandular epithelium in stages I and II (p = 0.025), whereas MMP-2 expression in stromal cells was significantly high (p < 0.001) in stages III and IV. CONCLUSION: CD44, VEGF and MMP-2 were consistently expressed in endometriotic epithelial and stromal cells. White lesions of peritoneal endometriosis should not be regarded as an inactive state, and MMP-2 in stromal cells may be responsible for the progression of endometriosis. The macroscopic appearance of endometriotic lesions should not be used as a criterion to define the degree of activity.     

Routine clinical examination is not sufficient for diagnosing and locating deeply infiltrating endometriosis

STUDY OBJECTIVE: To determine whether routine clinical examination is sufficient for the diagnosis and establishing the location of deeply infiltrating endometriosis (DIE). DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. Patients. One hundred sixty women with histologically proved deeply infiltrating endometriosis. MEASUREMENTS AND MAIN RESULTS: Speculum examination allowed endometriotic lesions to be viewed in only 14.4% (23) of patients, and a classic, painful, spheric nodule was palpated in only 43.1% (69). Results of routine clinical examination varied significantly with location of DIE. Whereas a nodule was found in 80.0% (24) of patients with vaginal endometriosis, this rate dropped to only 35.3% (6) and 33.3% (34) in those with DIE of the digestive tract and uterosacral ligaments, respectively (p <0.0001). CONCLUSION: High locations of DIE lesions at the level of uterosacral ligaments, bottom of the pouch of Douglas, and upper one-third of the posterior vaginal wall explain why results of routine clinical examination are so poor. The term "deep endometriosis infiltrating the rectovaginal septum" is generally incorrect in the true anatomic sense.     

Diagnosis of endometriosis

Endometriosis is a common disorder of women of reproductive age, yet diagnosis of this condition is often problematic. The most frequent clinical presentations of endometriosis include dysmenorrhea, pelvic pain, dyspareunia, infertility, and pelvic mass. However, the correlation between these symptoms and the stage of endometriosis is poor. Currently available laboratory markers are of limited value. At present, the best marker, serum CA-125, is usually elevated only in advanced stages and therefore not suitable for routine screening. Transvaginal ultrasound and magnetic resonance imaging are often helpful, particularly in detection of endometriotic cysts. Recently, transrectal ultrasound and magnetic resonance imaging were shown to be valuable in detection of deep infiltrating lesions, especially in the rectovaginal septum. Although direct assessment of endometriotic foci at laparoscopy may be viewed as a "gold standard" for identifying endometriosis, the correlation of laparoscopic observations with histological findings is often low. Ultimately, diagnosis of endometriosis requires a careful clinical evaluation in combination with judicious use and critical interpretation of laboratory tests, imaging techniques, and, in most instances, surgical staging combined with histological examination of excised lesions.     

Recto vaginal septum adenomyotic nodules: a series of 500 cases

Objective Laparoscopic procedure with excision of deep fibrotic endometriotic nodules of the rectovaginal septum and histological study of the lesions.
Setting An academic teaching hospital.
Participants A series of 500 women undergoing laparoscopy for pelvic pain or infertility.
Results Laparoscopic ( n = 497) and laparotomic ( n = 3) excision of endometriotic nodules resulted in considerable pain relief. Histologically the rectovaginal nodule was similar to an adenomyoma as it was a circumscribed nodular aggregate of smooth muscle and endometrial glands and stroma. The variations in oestrogen receptor and progesterone receptor content suggested a regulatory mechanism different from that of eutopic endometrium.
Conclusion This form of disease should be considered as an entity distinct from peritoneal and ovarian endometriosis, and originating from the Miillerian rests present in the rectovaginal septum.     

Surgical outcome of deep infiltrating colorectal endometriosis in a multidisciplinary setting

Background

Endometriosis as a benign disease appears frequently in premenopausal women with highly variable symptoms. In advanced stages bowel involvement is common. In symptomatic disease the adequate treatment requires complete resection of all residues. Indications of colorectal resection for endometriosis remain controversial because of the risk of major complications. The purpose of this study was to show the feasibility of planned complete laparoscopic management of symptomatic deep pelvic endometriosis with bowel involvement performing segmental colorectal resection in a center of excellence.

Methods

Between 2007 and 2012 all patients treated for symptomatic colorectal endometriosis in our institution were included and retrospectively evaluated. Laparoscopic excision of all visible disease was planned. Data analysis included age, previous history of endometriosis, intraoperative findings, operative procedure and intra- and postoperative complications.

Results

In this time period 35 patients with bowel infiltrating endometriosis were treated. Affected locations were the rectovaginal space in 31 patients (89 %), the rectum in 32 patients (91 %), the sigmoid colon in 10 patients (29 %), the coecum in 2 patients (5.7 %), the appendix in 3 patients (8.6 %) and the terminal ileum in 1 patient (2.9 %). In the majority of patients (85.7 %) the resection was achieved laparoscopically, in 3 patients a conversion to laparotomy was necessary and in 2 patients a primary laparotomia was performed. Complications occurred in 2 cases with anastomotic leakage in 1 patient (2.8 %) and a rectovaginal fistula in another patient. Radical resection was achieved in almost all patients (97 %).

Conclusions

A well-trained interdisciplinary team can perform treatment of deep infiltrating endometriosis laparoscopically with low incidence of major complications as anastomotic leakage or rectovaginal fistula. Criteria of complete endometriosis restoration of the rectum can be achieved by total or subtotal rectal excision.     

Endometriosis of Bladder: Outcomes after Laparoscopic Surgery

Study ObjectiveTo describe outcomes after laparoscopic excision of deep bladder endometriosis.DesignRetrospective study (Canadian Task Force classification II-3).SettingUniversity hospitals.PatientsTwenty-one consecutive patients with endometriotic nodule on the bladder (infiltrating detrusor muscle) from a series of 169 patients were included in the study. The primary outcome studied was resolution of bladder symptoms. Secondary outcomes included complication rates, recurrence rates, and pregnancy rates after laparoscopic surgery.InterventionsLaparoscopic excision of bladder endometriosis.Measurements and Main ResultsLaparoscopy was feasible in all cases without the need for conversion. Median follow-up was 20 months. Ten patients (47.6%) underwent partial cystectomy, and the remaining patients underwent partial-thickness excision of the detrusor muscle. Sixteen patients (76%) had associated deep lesions in the pelvis. The most common associated lesions were rectovaginal nodules (38%) and ureteric lesions (14%), with signs of obstruction. Major complications developed in 3 patients (14%), primarily related to bowel resection. Six patients became pregnant (60%). No patients experienced disease recurrence.ConclusionLaparoscopic excision is feasible in all types of bladder endometriosis but often involves multiple procedures to manage associated lesions, especially rectovaginal nodules and ureteric lesions. Previous reports have suggested that ureteric lesions are not associated with bladder endometriosis; however, this was not true in our series. Complications are primarily related to severity of the disease and associated procedures. Partial cystectomy is not required in all cases to achieve adequate clearance. Complete excision of the disease is associated with resolution of bladder symptoms and low recurrence rates.     

Abdominal radical trachelectomy for treatment of deep infiltrating endometriosis of the cervix

Surgical management of deep infiltrating endometriosis can be very challenging even for experienced gynecologists. Radical procedures like bowel resection and nephrectomy have been reported for treatment of the disease. Our aim is to report abdominal radical trachelectomy for treatment of deep infiltrating endometriosis of the cervix causing obstructive uropathy and diminished kidney function. We present a 38-year-old woman who was treated in our department for cervical endometriosis involving the vagina and left parametrium. Abdominal radical trachelectomy, insertion of a pig-tail catheter in the left ureter and end-to-end anastomosis of the uterus with the vagina was performed to remove the endometriotic lesion. Cooperation between gynecologists, urologists and nephrologists enabled fertility preservation as well as improvement of renal function. Deep infiltrating endometriosis is a complex disease that requires a multidisciplinary approach. Abdominal radical trachelectomy for cervical lesions seems feasible in this setting and helps preserve fertility.     

Peritoneal Retraction Pocket Defects and Their Important Relationship with Pelvic Pain and Endometriosis

ObjectiveThe objective of this video is to demonstrate different clinical presentations of peritoneal defects (peritoneal retraction pockets) and their anatomic relationships with the pelvic innervation, justifying the occurrence of some neurologic symptoms in association with these diseases.DesignSurgical demonstration of complete excision of different types of peritoneal retraction pockets and a comparison with a laparoscopic retroperitoneal cadaveric dissection of the pelvic innervation.SettingPrivate hospital in Curitiba, Paraná, Brazil.InterventionsA pelvic peritoneal pocket is a retraction defect in the surface of the peritoneum of variable size and shapes [1]. The origin of defects in the pelvic peritoneum is still unknown [2]. It has been postulated that it is the result of peritoneal irritation or invasion by endometriosis, with resultant scarring and retraction of the peritoneum [3,4]. It has also been suggested that a retraction pocket may be a cause of endometriosis, where the disease presumably settles in a previously altered peritoneal surface [5]. These defects are shown in many studies to be associated with pelvic pain, dyspareunia, and secondary dysmenorrhea 1, 2, 3, 4. Some studies have shown that the excision of these peritoneal defect improves pain symptoms and quality of life [5]. It is important to recognize peritoneal pockets as a potential manifestation of endometriosis because in some cases, the only evidence of endometriosis may be the presence of these peritoneal defects [6].In this video, we demonstrate different types of peritoneal pockets and their close relationship with pelvic anatomic structures.Case 1 is a 29-year-old woman, gravida 0, with severe dysmenorrhea and catamenial bowel symptoms (bowel distension and diarrhea/constipation) that were unresponsive to medical treatment. Imaging studies were reported as normal, and a laparoscopy showed a posterior cul-de-sac peritoneal pocket infiltrating the pararectal fossa, with extension to the lateral border of the rectum.Case 2 is a cadaveric dissection of a posterior cul-de-sac peritoneal pocket infiltrating the pararectal fossa, with extension to the pelvic sidewall. After dissection of the obturator fossa, we can observe that the pocket is close to the sacrospinous ligament, pudendal nerve, and some sacral roots.Case 3 is a 31-year-old woman, gravida 1, para 1, with severe dysmenorrhea that was unresponsive to medical treatment and catamenial bowel symptoms (catamenial bowel distention and diarrhea). Imaging studies were reported as normal and a laparoscopy showed left uterosacral peritoneal pocket infiltrating the pararectal fossa in close proximity to the rectal wall.Case 4 is a cadaveric dissection of the ovarian fossa and the obturator fossa showing the proximity between these structures.Case 5 is a 35-year-old woman, gravida 0, with severe dysmenorrhea that was unresponsive to medical treatment, referring difficulty, and pain when walking only during menstruation. A neurologic physical examination revealed weakness in thigh adduction, and the magnetic resonance imaging showed no signs of endometriosis. During laparoscopy, we found a peritoneal pocket infiltrating the ovarian fossa, with involvement in the area between the umbilical ligament and the uterine artery. This type of pocket can easily reach the obturator nerve. Because the obturator nerve and its branches supply the muscle and skin of the medial thigh [7,8], patients may present with thigh adduction weakness or difficulty ambulating [9,10].Case 6 is a cadaveric dissection of the sacrospinous ligament and the pudendal nerve from a medial approach, between the umbilical artery and the iliac vessels.Case 7 is a 34-year-old woman, gravida 1, para 1, with severe dysmenorrhea and catamenial bowel symptoms as well as deep dyspareunia. The transvaginal ultrasound showed focal adenomyosis and a 2-cm nodule, 9-cm apart from the anal verge, affecting 30% of the bowel circumference. In the laparoscopy, we found a posterior cul-de-sac retraction pocket associated with a large deep endometriosis nodule affecting the vagina and the rectum.In all cases, endometriosis was confirmed by histopathology, and in a 6-month follow-up, all patients showed improvement of bowel, pain, and neurologic symptoms.ConclusionPeritoneal pockets can have different clinical presentations. Depending on the topography and deepness of infiltration, they can be the cause of some neurologic symptoms associated with endometriosis pain.With this video, we try to encourage surgeons to totally excise these lesions and raise awareness about the adjacent key anatomic structures that can be affected.     

Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis

OBJECTIVE: To evaluate the effectiveness of a levonorgestrel-releasing IUD as therapy for endometriosis of the rectovaginal septum. DESIGN: Prospective therapeutic non-randomized, self-controlled clinical trial analyzing changes in pain symptoms and size of lesions induced by the levonorgestrel-releasing IUD over 12 months. SETTING: Tertiary referral center for treatment of deep endometriosis. PATIENT(S): Eleven symptomatic patients with rectovaginal endometriosis. INTERVENTION(S): A levonorgestrel-releasing IUD was inserted and maintained for 12 months. MAIN OUTCOME MEASURE(S): Severity of dysmenorrhea, pelvic pain, and deep dyspareunia were assessed before insertion of the IUD and throughout treatment. The size of rectovaginal endometriotic lesions were evaluated by using transrectal and transvaginal ultrasonography. RESULT(S): Dysmenorrhea, pelvic pain, and deep dyspareunia greatly improved and the size of the endometriotic lesions was significantly reduced by treatment. CONCLUSION(S): Insertion of a levonorgestrel-releasing IUD alleviates pain and reduces the size of lesions in patients with endometriosis of the rectovaginal septum.     

The “neurologic hypothesis”: a new concept in the pathogenesis of the endometriosis?

To cartograph the retroperitoneal infiltration of deep-infiltrating endometriosis of the rectovaginal space, we report on 467 patients who underwent laparoscopic/vaginal surgery for deep-infiltrating adenomyosis of the rectovaginal space. Exact localisation of the locoregional extension and of secondary infiltrating localisation where noted. The cervix and the rectovaginal ligament were mostly involved, while isolated lesions of the rectovaginal space were very rare. Comparisons of the most involved sites show an absolute correlation with the anatomical repartition of the pelvic sympathetic nervous system. We postulate a new neurologic theory which could be one more explanation for the development of adenomyosis of the rectovaginal space and maybe the peritoneum.No financial support was received for this study.     

Deep endometriosis conundrum: evidence in favor of a peritoneal origin

OBJECTIVE: To determine whether the depth and volume of the pouch of Douglas differs in patients with endometriosis with and without deep lesions and to compare them with subjects with a healthy pelvis or with diseases other than endometriosis. DESIGN: Prospective, comparative study. SETTING: Tertiary care and referral center for patients with endometriosis. PATIENT(s): Women undergoing laparoscopy for infertility, pelvic pain, or adnexal anomalies (deep endometriotic rectovaginal lesions in 16 cases, endometriosis without deep lesions in 127 cases, miscellaneous anomalies in 35 cases, and normal pelvis in 26 cases). INTERVENTION(s): Douglas pouch depth measurement from the upper border of uterosacral ligaments to its base with a calibrated probe and volume assessment by a fluid-filling technique. MAIN OUTCOME MEASURE(s): Douglas pouch depth and volume. RESULT(s): Mean (+/-SD) Douglas pouch depth and volume measurements were 3.6 +/- 1.6 cm and 41.6 +/- 19.3 mL in women with deep endometriosis, 5.3 +/- 0.8 cm and 67.2 +/- 18.1 mL in those with peritoneal and ovarian lesions only, 5.2 +/- 0.9 cm and 67.6 +/- 12.6 mL in those with miscellaneous conditions, and 5.5 +/- 0.8 cm and 65.8 +/- 10.9 mL in those with normal pelvis. CONCLUSION(s): Reduced Douglas pouch depth and volume in women with deep endometriosis suggest that such lesions develop not in the rectovaginal septum but intraperitoneally and that burial by anterior rectal wall adhesions creates a false bottom, giving an erroneous impression of extraperitoneal origin.     

Transrectal ultrasonography in the assessment of rectovaginal endometriosis

Objective: To evaluate the validity of transrectal ultrasonography in the assessment of rectovaginal endometriosis.Methods: We compared the findings of transrectal ultrasonographic examination performed before surgery with the operative and pathologic findings in 140 women who underwent laparoscopy or laparotomy for suspected endometriosis. The ultrasonographer was asked to investigate whether any deep endometriotic lesions were present in the rectovaginal septum and to define the lateral extension on the basis of involvement of the uterosacral ligaments. In addition, infiltration of the rectal and vaginal walls was evaluated.Results: Thirty-four women had endometriosis infiltrating the rectovaginal septum confirmed by combined operative and pathologic findings. Ultrasonography showed a sensitivity and specificity of 97% and 96%, respectively, in the diagnosis of the presence of rectovaginal endometriosis. The sonographer identified infiltration of the rectal and vaginal walls correctly in all cases in whom it was present, but also reported rectal infiltration in three cases not confirmed by the surgeon and pathologist. The sensitivity and specificity in the diagnosis of uterosacral ligament infiltration were 80% and 97%, respectively.Conclusion: If our preliminary results are confirmed by a larger series, transrectal ultrasonography will be considered a valid diagnostic tool in the evaluation of rectovaginal endometriosis.     

Endometriose und Nervenfasern

Nerve fibers could be detected in eutopic endometrium of patients with endometriosis and in ectopic endometriotic lesions such as peritoneal, deep infiltrating, and ovarian endometriotic lesions. The pathophysiological explanation for the occurrence of nerve fibers in endometrium and ectopic lesions is controversially discussed. There are two hypotheses: the occurrence of nerve fibers is induced by endometriosis or depends on pain mediators. Nerve fibers are only found in endometrium of patients with endometriosis and their presence is independent of the severity of pelvic pain. On the other hand, nerve fibers are found in endometrium of patients with chronic pelvic pain and with gynecological disorders like fibroids or endometriosis. It has to be clarified if the occurrence of endometrial nerve fibers can be used as a noninvasive test to diagnose endometriosis. However, endometriosis shows neuromodulatory properties. The nerve fiber invasion in endometriotic lesions may be a possible explanation for pain generation in endometriosis.     

Follow-up of dysfunctional bladder and rectum after surgery of a deep infiltrating rectovaginal endometriosis

Purpose  

The radical surgery of the deep infiltrating endometriosis of the rectovaginal septum and the uterosacral ligaments with or without bowel resection can cause a serious damage of the pelvic autonomic nerves with urinary retention and the need of self-catheterization. Major goal of this review article is to compare different surgical techniques of deep infiltrating endometriosis and their follow-up results.     

Peritoneal endometriosis. Morphologic appearance in women with chronic pelvic pain.

A prospective study analyzed the prevalence and severity of dysmenorrhea, intermenstrual pain and deep dyspareunia in relation to morphologic features of peritoneal disease in 73 consecutive women with endometriosis but no associated pelvic pathology, previous pelvic surgery or hormonal treatment. All underwent their first laparoscopy for chronic pelvic pain at the First Department of Obstetrics and Gynecology, University of Milan, Milan, Italy, between 1986 and 1989. Gynecologic pain symptoms were evaluated with a verbal score and visual analog scale. Peritoneal lesions were classified as typical (black nodules, yellow-brown patches, stellate scars), atypical (clear vesicles, clear or red papules, red polypoid lesions) or mixed. When the three types of lesions were considered together, a statistically significant association was observed only with deep dyspareunia (P less than .01). Moreover, a significantly higher prevalence of deep dyspareunia was revealed in patients with typical versus atypical lesions (P less than .01) and in those with mixed versus atypical lesions (P less than .05). Fresh, papular, atypical lesions exposed to peritoneal fluid might cause functional pain, whereas "old," black nodules immersed in infiltrating scars might provoke mainly organic pain.     

Enterocele as a consequence of laparoscopic resection of deeply infiltrating endometriosis

Laparoscopic excision of deeply infiltrating endometriosis in the cul-de-sac or the rectovaginal septum by means of electrosurgery or laser is performed frequently. Little is known about the long-term results or complications of this surgery. We suggest that enterocele could be a complication of the procedure. A patient developed a large enterocele 3 years a laparoscopic excision of a deep endometriotic nodule with resection of the uterosacral ligaments. We question whether routine preventive measures should not be taken after excision of a deep endometriotic nodule from the rectovaginal septum.     

Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis

In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFβ1), and Interferon-gamma (IFN-γ). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFβ1, IFNγ, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings. Received: 5 January 2000 / Accepted: 14 August 2000