Laparoscopic treatment of deep endometriosis located on the uterosacral ligaments

The goal of this study was to assess the efficiency of laparoscopicsurgical treatment of pain for patients presenting deep endometriosislocated on the uterosacral ligaments. To this end we analyseda continuous series of 21 patients treated by laparoscopic surgerybetween January 1993 and June 1994. In all these cases treatmentconsisted of resection of all the uterosacral ligament(s) presentingdeep endometriotic lesions together with exeresis of all otherendometriotic lesions. No complications were observed per- orpost-operatively. The results were assessed for all the patientswith a minimnm follow-up of one year. The efficiency of thetreatment varied according to the symptoms. Patients who presenteddysmenorrhoea (19 cases) improved in 84.2% of cases (16 patients).Out of the 17 patients who presented deep dyspareunia, improvementwas evident for 94.1% of cases (16 patients). The chronic pelvicpain suffered improved in seven out of nine cases (77.7%). Patientswho benefited from an improvement rated it excellent or satisfactoryin over 80% of cases. These results demonstrate that, providedthe surgeon is highly skilled in laparoscopy, laparoscopic surgeryis efficient for the treatment of patients presenting painfulsymptoms related to deep endometriotic implants located on theuterosacral ligaments.     

Endometriosis: Evaluation of endometriosis in uterosacral ligaments by transrectal ultrasonography

Uterosacral ligaments are one of the common targets of pelvicendometriosis, which is usually clinically rather than surgicallydiagnosed. This study was performed to determine if uterosacralligaments infiltrated by endometriosis could be detected bytransrectal ultrasonography. Uterosacral ligaments in non-endometriosissubjects (n±64) were observed as low echoic homogeneousarcs in both sides of the uterine cervix. Patients who had endometriosis(n±29) on the ligaments showed thick and irregularly-shapeduterosacral ligaments by the transrectal ultrasound examination.The results also suggested that the thickness of uterosacralligaments was associated with the clinical symptoms. Transrectalultrasonography may provide quantitative information to managepatients with inilitrat ing endometriosis.     

Surgical management of deep infiltrating endometriosis of the rectum: pleading for a symptom-guided approach

Two surgical approaches are usually employed in the treatment of deep infiltrating endometriosis of the rectum (DIER): colorectal resection removing the rectal segment affected by the disease, and nodule excision either without opening the rectum (shaving) or by removing the nodule along with the surrounding rectal wall (full thickness or disc excision). Although the present available data are from retrospective series reported by surgeons who generally perform only one technique, there is no evidence to support the risk of recurrences as a valid argument in favour of colorectal resection over rectal nodule excision. The advantage of a lower morbidity associated with nodule excision is not necessarily at the cost of an increased rate of pain recurrences, especially in women benefiting from post-operative medical treatment. The symptom-guided surgical approach in DIER primarily focuses on the relief of digestive symptoms and pelvic pains, rather than on mandatory 'carcinologic' resection of lesions. In addition, the risk of new post-operative unpleasant symptoms as a result of a compulsory and systematic excision of all endometriotic foci may be avoided. In a majority of cases, pelvic anatomy and digestive function can be restored by shaving or disc excision, as well as by colorectal resection; thus digestive complaints can be resolved even when the rectum is conserved. The most accurate evaluation of the results of DIER surgery should be provided by post-operative evolution in digestive function. Even though quality of life is improved for the majority of patients managed by colorectal resection, the question is whether or not a greater health improvement can be achieved by performing nodule excision, which avoids various post-operative and functional digestive complications. In addition, continuous medical treatment leads to a decrease in endometriotic nodules and prevents post-operative pain recurrences. Instead of choosing between medical and surgical management in the treatment of DIER, it is most likely that the two therapies should be associated.     

Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis

Deep infiltrating endometriosis (DIE) is characterized by chronic pain, hyperproliferation of endometriotic cells and fibrosis. Since cannabinoids are endowed with antiproliferative and antifibrotic properties, in addition to their psychogenic and analgesic effects, cannabinoid agonists have been evaluated in DIE both in vitro and in vivo. The in vitro effects of the cannabinoid agonist WIN 55212-2 were evaluated on primary endometriotic and endometrial stromal and epithelial cell lines extracted from patients with or without DIE. Cell proliferation was determined by thymidine incorporation and production of reactive oxygen species by spectrofluorometry. ERK and Akt pathways were studied by immunoblotting. Immunoblotting of α-smooth muscle actin was studied as evidence of myofibroblastic transformation. The in vivo effects of WIN 55212-2 were evaluated on Nude mice implanted with human deep infiltrating endometriotic nodules. The in vitro treatment of stromal endometriotic cells by WIN 55212-2 decreased cell proliferation, reactive oxygen species production, and α-smooth muscle actin expression. The decrease in cell proliferation induced by WIN 55212-2 was not associated with a decrease in ERK activation, but was associated with the inhibition of Akt activation. WIN 55212-2 abrogated the growth of endometriotic tissue implanted in Nude mice. Cannabinoid agonists exert anti-proliferative effects on stromal endometriotic cells linked to the inhibition of the Akt pathway. These beneficial effects of cannabinoid agonists on DIE have been confirmed in vivo.     

Presurgical diagnosis of posterior deep infiltrating endometriosis based on a standardized questionnaire

BACKGROUND: To derive a diagnostic model based on symptoms and history as assessed by a standardized questionnaire to predict posterior deep infiltrating endometriosis (DIE) among women with chronic pelvic pain symptoms. METHODS: 134 women scheduled for laparoscopy for chronic pelvic pain symptoms completed a standardized self-administered questionnaire, specifically designed for the study. We compared the symptoms of the women with posterior DIE diagnosed at laparoscopy with those of the women with other disorders, and used multiple logistic regression analysis to select the best combination of symptoms for predicting posterior DIE. Cross-validation was performed with the jackknife method. RESULTS: 51 women (38.1%) were diagnosed with posterior DIE and 83 with other disorders (61.9%). The following variables were independent predictors for posterior DIE: painful defecation during menses, severe dyspareunia (visual analogic scale > or =8), pain other than noncyclic, and previous surgery for endometriosis. The cross-validation procedure leads to a simplified diagnostic model that uses two independent predictors: painful defecation during menses and severe dyspareunia. The sensitivity of this model for diagnosing posterior DIE was 74.5%, its specificity was 68.7%, its positive likelihood ratio was 2.4, and its negative likelihood ratio was 0.4. It correctly classified 70.9% of our sample into a high-risk (with either severe dyspareunia or painful defecation during menses) and a low-risk (neither symptom) group. CONCLUSIONS: Standardized evaluation of painful symptoms is useful for screening women so that they may have adequate exploration and counselling before laparoscopic surgery for pelvic pain symptoms.     

The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice

Deep infiltrating endometriosis (DIE) is a particular clinical and histological entity of endometriosis responsible for chronic pelvic pain and infertility. Here we characterize the proliferative phenotype of DIE cells, to explore the cellular and molecular mechanisms that could explain their aggressive potential. In addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment of DIE. Included were 22 patients with DIE and 12 control patients without endometriosis. Epithelial and stromal cells were extracted from biopsies of eutopic endometrium and deep infiltrating endometriotic nodules from patients with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE. The proliferation rate of eutopic endometrial cells and of deep infiltrating endometriotic cells from DIE patients was higher than that of endometrial cells from controls. The hyperproliferative phenotype of endometriotic cells was associated with an increase in endogenous oxidative stress, and with activation of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE.     

Fertility after laparoscopic myomectomy: preliminary results

We report the limits, complications, subsequent fertility and outcome of pregnancies after laparoscopic myomectomy. From January 1990 to October 1995, 143 patients underwent a first laparoscopic approach to myomectomy. A total of 41 patients (28.7%) had a laparoconversion (12 cases for a number of myomata >5, 15 cases for myoma diameter >7 cm, 12 cases for peroperative haemorrhage and two cases for adenomyosis). Seventy patients (49%) wished to conceive: 26 had undergone laparoconversion and 44 laparoscopic myomectomy. A total of 19 pregnancies were obtained in 17 patients after laparoscopic myomectomy (38.6%): eight vaginal deliveries, three Caesarean sections, four miscarriages, two abortions, one ectopic pregnancy and one therapeutic abortion. The pregnancy rate in patients with unexplained infertility and with multifactorial infertility was 48.2% and 20% respectively. The mean delay to conception was 11.3 months. No uterine rupture was noted. Pelvic adhesions were found in the four patients who underwent second- look procedure. Our preliminary results indicate that laparoscopic myomectomy is a useful technique.      

Fertility following laparoscopic management of benign adnexal cysts.

Fertility following laparoscopic treatment of benign adnexal cysts without ovarian suture was studied retrospectively. Patients with endometriomas or who were previously infertile were excluded. Thirty-eight patients treated conservatively were included, 10 after partial resection of functional cysts, 23 after an ovarian cystectomy and six after treatment of a paraovarian cyst. One patient had two cysts. The overall intrauterine pregnancy rate was 92%; one patient had an ectopic pregnancy (2.6%). From these results, we conclude that fertility following laparoscopic treatment of adnexal cysts appears to be normal. Technical guidelines to improve laparoscopic cystectomy are proposed.     

Pregnancy after laparoscopic partial cystectomy for bladder endometriosis

We report a case of partial laparoscopic cystectomy in a 31-year-oldinferile patient presenting vesical endometriosis. This patienthad suffered severe dysmenorrhoea for 10 years previously togetherwith repeated episodes of urinary infection, mostly occurringduring the menstrual period. A diagnostic laparoscopy performedin another centre diagnosed a stage IV endometriosis. Gonadotrophin-releasinghormone agonists were prescribed for 9 months. After failureof this treatment, the patient came to consult us. A solid massin the left supratrigone was detected by pelvic ultrasonographyand confirmed by cystoscopy. Transurethral resection was carriedout. A recurrence of the symptoms 9 months later prompted operativelaparoscopy under cystoscopic control. This confirmed recurrenceof a 3.5 cm endometriotic nodule. Laparoscopic partial cystectomywas performed using the monopolar electrode. The bladder wasthen sutured via laparoscopy. No complications occurred. Nopostoperative treatment was given. Second-look cystoscopy 2months later revealed that healing was perfect. Eight monthslater, the patient is well and has a normal intra-uterine pregnancy.     

Quality of life after laparoscopic colorectal resection for endometriosis

BACKGROUND: Indications of colorectal resection for endometriosis remain controversial because of the risk of major complications. Therefore, the aims of the current study were to evaluate the efficacy of laparoscopic segmental colorectal resection for endometriosis on quality of life and gynaecologic and digestive symptoms, and its complications. METHODS: After magnetic resonance imaging and rectal endoscopic sonographic evaluation of symptomatic colorectal endometriosis, 58 consecutive women requiring colorectal resection were included in this study. Symptom questionnaires and the short-form (SF)-36 Health Status and the quality of life score were completed. Linear intensity scores for several gynaecologic and digestive symptoms and perioperative complications were also recorded. RESULTS: Fifty-one women (88%) underwent laparoscopic segmental colorectal resection and seven required laparoconversion. Major complications occurred in nine cases (15.5%), including six rectovaginal fistulae (10.3%), and the three remaining complications corresponded to a haemoperitoneum, a uroperitoneum and a pelvic abscess. Median follow-up after colorectal resection was 22.5 months (2-55 months). A significant improvement in dysmenorrhoea (P < 0.0001), dysparaeunia (P < 0.0001), bowel movement pain or cramping (P < 0.0001), pain on defecation (P < 0.0001), diarrhoea (P < 0.016), lower back pain (P < 0.0001) and asthaenia (P < 0.0002) was observed. Tenesmus, rectorrhagia and constipation were not improved. All the items of the SF-36 Health Status and the quality of life score were improved after colorectal resection for endometriosis. CONCLUSION: Laparoscopic segmental colorectal resection for endometriosis significantly improves quality of life and gynaecologic and digestive symptoms. However, women have to be informed on the risk of complications including rectovaginal fistula.     

Deep dyspareunia and sex life after laparoscopic excision of endometriosis

BACKGROUND: Among subjects with endometriosis and deep dyspareunia (DD), those with endometriosis of the uterosacral ligament (USLE) have the most severe impairment of sexual function. This study examines the effect of laparoscopic excision of endometriosis on DD and quality of sex life. METHODS: This observational cohort prospective study included 68 women with endometriosis suffering DD (intensity of pain >or= 6 on a 10-cm visual analogue scale). Patients underwent laparoscopic full excision of endometriosis. Following surgery, they were asked to use nonhormonal contraception devices. Before surgery, at 6- and at 12-month follow-up, patients answered a self-administered questionnaire based on the Sexual Satisfaction Subscale of the Derogatis Sexual Functioning Inventory. RESULTS: At 6- and 12-month follow-up, women with and without USLE had significant improvement in DD. Subjects with USLE reported increased variety in sex life, increased frequency of intercourse, more satisfying orgasms with sex, relaxing more easily during sex and being more relaxed and fulfilled after sex. Similar improvements were observed among women without USLE; however, for some variables statistical significance was not reached. CONCLUSIONS: Surgical excision of endometriosis improves not only DD but also the quality of sex life.     

Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution

BACKGROUND: To investigate whether knowledge of the anatomical distribution of histologically proven deeply infiltrating endometriosis (DIE) lesions contributes to understanding the pathogenesis. METHODS: Observational study between June 1992 and December 2004 (retrospective study between 1992 and 2000; prospective study between 2001 and 2004). Continuous series of 426 patients suffering from pelvic pain who underwent complete surgical exeresis of DIE. DIE lesions were classified according to four different possibilities: (i) Firstly, DIE lesions were classified as located in the anterior or posterior pelvic compartment. (ii) Secondly, DIE were classified as left, median and right. (iii) Thirdly, DIE lesions were classified as pelvic or abdominal. (iv) Fourthly, DIE lesions that could present in a right and/or left location were classified as unilateral or bilateral. RESULTS: These 426 patients presented 759 histologically proven DIE lesions: bladder (48 lesions; 6.3%); uterosacral (USL) (400 lesions; 52.7%); vagina (123 lesions; 16.2%); ureter (16 lesions; 2.1%) and intestine (172, 22.7%). DIE lesions are significantly more often located in the pelvis (n=730 lesions) than in the abdomen (n=29 lesions) (P<0.0001). Pelvic DIE lesions are significantly more often located in the posterior compartment of the pelvis [682 DIE lesions (93.4%) versus 48 DIE lesions (6.6%); P<0.0001]. Pelvic DIE lesions are significantly more frequently located on the left side. For patients with unilateral pelvic DIE lesions, the anatomical distribution is significantly different in the three groups: left (172 lesions; 32.0%), median (284 lesions; 52.8%) and right (82 lesions; 15.2%) (P<0.0001). For patients with lateral lesions, left DIE lesions (172 lesions; 67.8%) were found significantly more frequently than right DIE lesions (82 lesions; 32.2%) (P<0.0001). A similar predisposition was observed when we included patients with bilateral pelvic DIE lesions (P=0.0031). The same significantly asymmetric distribution is observed for total (pelvic and abdominal) DIE lesions. CONCLUSIONS: Our results demonstrate that distribution of DIE lesions is asymmetric. It is possible that this is related to the anatomical difference between the left and right hemipelvis and to the flow of peritoneal fluid. These findings support the hypothesis that retrograde menstruation of regurgitated endometrial cells is implicated in the pathogenesis of DIE.     

Progesterone receptor polymorphism +331G/A is associated with a decreased risk of deep infiltrating endometriosis

BACKGROUND: Alterations in the progesterone receptor (PR) are considered a risk factor for the development of endometriosis. In this study, the frequencies of the PROGINS and +331G/A polymorphisms of the PR gene were determined in deep infiltrating endometriosis and correlated with the expression of the PR protein. METHODS AND RESULTS: The frequencies of the PR polymorphisms were determined in women with deep infiltrating endometriosis (n = 72), women with adenomyosis in the uterine wall (n = 40), gynaecological patients without symptomatic endometriosis (n = 102) and healthy females (n = 93). Detection of +331G/A and PROGINS polymorphisms was performed using PCR-restriction fragment length polymorphism (RFLP) analysis. Expression of PR-A and PR-B protein was assessed with immunohistochemistry. The allelic frequency of the polymorphic allele +331A was lower in women with endometriosis (P < 0.01) and adenomyosis (P < 0.02) compared with healthy females. The frequency of the PROGINS polymorphism did not differ between the groups. The mean staining index (SI) for PR-B in endometriotic epithelium was higher in the presence of the +331A polymorphic allele (n = 2) (P < 0.001) compared with +331G/G individuals (n = 61). The PROGINS polymorphism did not affect the SI for PR-A and PR-B. CONCLUSIONS: The presence of the PR gene polymorphic allele +331A is associated with a reduced risk of deep infiltrating endometriosis and adenomyosis compared with healthy population controls. The PROGINS polymorphism does not seem to modify the risk of deep infiltrating endometriosis.