Publication
Borghese B, Vaiman D, de Ziegler D, Chapron C
• 05/2010
Endometriosis is a very frequent and debilitating disease responsible for a considerable socio-economic toll. In spite of that, its pathogenesis remains enigmatic. Endometriosis is hold for a multifactorial pathology resulting from the mixed effects of environmental and genetic factors. To date, few susceptibility factors have been reported, with the exception of some polymorphisms in estrogen and progesterone receptors. Large-scale expressional studies have clearly demonstrated that endometriosis is a hormone-dependant disease, characterized by three main features: (i) inflammation, (ii) excessive production of estrogens, and (iii) progesterone resistance. Endometriosis is also considered as a benign metastatic disease, closely linked to cancer. However, the risk of malignant transformation appears to be very limited, likely by a systematic repression of the genes involved in cell cycle and a specific regulation of the HOX genes. Lastly, endometriosis might result from abnormalities of the eutopic endometrium, which show the same molecular alterations than the ectopic endometrium, to a lesser extent however. These alterations, possibly occurring during the embryonic life through epigenetic and genetic predisposition, could lead to an earlier and non-invasive diagnosis for endometriosis.
Publication
Dousset B, Leconte M, Borghese B, Millischer AE, Roseau G, Arkwright S, Chapron C
• 05/2010
OBJECTIVE: We conducted a prospective study to assess the long-term results of complete surgery for low rectal endometriosis (LRE), paying particular attention to surgical complications, functional results, and disease recurrence after a follow-up of at least 5 years. SUMMARY BACKGROUND DATA: Deep infiltrating endometriosis (DIE) may infiltrate the midlow rectum and lead to severe pelvic pain. Complete resection of LRE is reluctantly considered by young women of childbearing age. METHODS: From 1995 to 2003, 100 women with severe pelvic pain and previous incomplete surgery (n=82) underwent complete open surgery for LRE after thorough preoperative imaging work-up. This included total or subtotal rectal excision with combined resection of all extrarectal endometriotic lesions. Univariate analysis of predictive factors for transient neurogenic bladder and surgical complications was performed. Mean follow-up was 78+/-15 months. RESULTS: All patients underwent rectal resection with straight coloanal (n=16) or low colorectal anastomosis (n=84). A concomitant extrarectal procedure was required in all instances, including gynecologic procedures (n=100), additional intestinal (n=45), and urologic (n=23) resections. A fertility-preserving procedure was possible in 92% of the patients. Mean numbers of DIE and endometriotic lesions were 3.9+/-1.4 and 5.5+/-1.6 per patient, respectively. There were no deaths and the surgical morbidity rate was 16%. Sixteen patients developed a transient peripheral neurogenic bladder, which was more frequently observed after colonanal anastomosis (P<0.001) or concomitant hysterectomy (P<0.01) and in patients with more than 4 DIE lesions (P<0.05). At last follow-up, 94 patients had complete (n=83) or very satisfactory (n=11) relief of symptoms. Urine voiding and fecal continence was satisfactory in all cases. There was no recurrence of colorectal and/or urologic endometriosis and the overall DIE recurrence rate was 2%. CONCLUSIONS: Complete surgery for LRE provides excellent long-term functional results in 94% of the patients, provided all extraintestinal endometriotic lesions are resected during the same surgical procedure. In that setting, the overall 5-year recurrence rate is very low.
Publication
Chapron C, Chiodo I, Leconte M, AmsellemOuazana D, Chopin N, Borghese B, Dousset B
• 05/2010
OBJECTIVE: To evaluate the rate of intrinsic ureteral endometriosis in patients presenting with severe ureteral endometriosis. DESIGN: Observational study between June 1992 and December 2007. SETTING: University tertiary referral center. PATIENT(S): Twenty-nine patients presenting deeply infiltrating endometriosis (DIE) with severe ureteral endometriosis. Severe ureteral endometriosis was defined as DIE lesions causing significant obstruction to the urinary flow with ureteral stenosis. INTERVENTION(S): Complete surgical exeresis of DIE lesions. MAIN OUTCOME MEASURE(S): Pre- and peroperative evaluation associated with histologic analysis. Intrinsic ureteral endometriosis was defined as presence of DIE lesions infiltrating the ureteral muscularis. RESULT(S): In a series of 627 patients with histologic proved DIE, we observed 29 (4.6%) patients with severe ureteral endometriosis. Ureteral lesions (n = 34) were right sided in 7 (24.1%) patients, left sided in 17 (58.6%) patients, and bilateral in 5 (17.3%) patients. Eleven (37.9%) patients presented intrinsic lesions. Out of the 34 ureteral lesions 13 (38.2%) were intrinsic. In cases of radical ureteral surgery (n = 21 patients; n = 24 ureteral lesions) intrinsic ureteral DIE was observed in 52.4% (11 cases) of the patients and in 54.2% (13 cases) of the ureteral lesions. CONCLUSION(S): The prevalence of intrinsic ureteral endometriosis is underestimated. This result must be taken into account when specifying the surgical modalities for patients presenting with severe ureteral endometriosis.
Publication
Noël JC, Chapron C, Bucella D, Buxant F, Peny MO, Fayt I, Borghese B, Anaf V
• 04/2010
OBJECTIVE: To analyze the expression of estrogen (ER) and progesterone (PR) receptors in the smooth muscle component (SMC) of deep infiltrating endometriosis (DIE). DESIGN: A prospective clinical and pathologic study of 60 cases of DIE. SETTING: University Hospital Department of Gynacology. PATIENT(S): Sixty patients with symptomatic DIE (uterosacral endometriosis n = 14; bladder endometriosis n = 10; colonic endometriosis n = 16; rectovaginal endometriosis n = 20). INTERVENTION(S): Laparoscopic surgery. MAIN OUTCOME MEASURE(S): The expression of ER and PR was studied by immunohistochemistry in the SMC directly around endometriotic foci and at distance (at least >1.5 cm) from them in correlation with proliferative and secretory phases of cycle. RESULTS: The ER and PR were present in the SMC of DEI in each location excepting colonic endometriosis where ER were absent. Independently of cycle's phases the PR were more abundant than ER. With the exception of rectovaginal endometriosis, where the ER and PR were more abundant in the proliferative than in the secretory phase, in other locations the ER and PR did not differ significantly with cycle's phases. Last, if ER and PR were more abundant in SMC around endometriotic foci than at a distance from them. However, the difference was not significant. CONCLUSIONS: Our data substantially confirm for the first time that in various forms of DIE, ER and PR are present not only in glands and stroma but also in the smooth muscle major histologic component of this disease.
Publication
Chapron C, Bourret A, Chopin N, Dousset B, Leconte M, AmsellemOuazana D, de Ziegler D, Borghese B
• 04/2010
BACKGROUND: Deep infiltrating endometriosis (DIE) is presented as a disease with high recurrence risk. Bladder DIE is the most frequent location in cases of urinary endometriosis. Surgical removal has been recommended for bladder DIE but long-term outcomes remains unevaluated. The objectives of this study are to evaluate the rate of recurrence after partial cystectomy for patients presenting with bladder DIE and to outline the surgical modalities for handling associated posterior DIE nodules. METHODS: Seventy-five consecutive patients with histologically proved bladder DIE were enrolled at a single tertiary academic center between June 1992 and December 2007. A partial cystectomy was performed for each patient. Complete surgical exeresis of all associated symptomatic DIE lesions was carried out during the same surgical procedure. Bladder DIE patients were classified into three groups: patients with isolated bladder DIE (Group A); patients with associated symptomatic posterior DIE (Group B); patients with associated asymptomatic posterior DIE (Group C). Bladder DIE recurrence was defined as a clinical reappearance of the disease or radiological evidence that mandated a new surgical procedure. We assessed pelvic pain symptoms pre- and post-operatively using a 10-cm visual analogue scale. RESULTS: In a series of 627 patients with DIE, we observed 75 patients (12%) with bladder DIE. With a 50.9 +/- 44.6 months mean follow-up after partial cystectomy no patient presented evidence of bladder DIE recurrence. Post-operatively, we observed a significant improvement with respect to pain symptoms, with only two patients (2.7%) developing major complications during follow-up. Among patients with non-operated associated asymptomatic posterior DIE lesions (n = 15), a second surgical procedure indicated for pain symptoms was necessary in only one patient (6.7%). CONCLUSIONS: For patients presenting with bladder DIE, no patients required further surgery for bladder recurrence after radical surgery consisting in partial cystectomy. Exeresis of associated posterior DIE nodules is indicated only when they are symptomatic.
Publication
de Ziegler D, Streuli I, Vasilopoulos I, Decanter C, This P, Chapron C
• 02/2010
OBJECTIVE: To review the existing options for preserving fecundity in young cancer patients, outlining the differences that exist in each individual cancer situation and how these affect our choice of fecundity-preserving measures. DESIGN: Review the pathophysiology data on ovarian function that serve for outlining the advantages and/or drawbacks of certain fecundity-preserving measures such as ovarian freezing and emergency IVF. Provide support arguments for outlining the need for setting locally rooted cancer and fecundity task forces that throw the bases for a multidisciplinary approach in this field. SETTING: Review of literature data. PATIENT(S): Women of reproductive age affected with different types of cancer. MAIN OUTCOME MEASURE(S): Outcome of selected emergency fertility preserving measures such as ovarian tissue freezing followed by grafting or emergency IVF. RESULT(S): When performed in the 30s-the typical age for breast cancer, the most frequently encountered cancer in women of reproductive age, ovarian freezing hampers ovarian recovery and the chances for spontaneous pregnancy. CONCLUSION(S): Based on a review of the different situations encountered, we recommend that fecundity-preserving measures offered to young cancer patients, including ovarian freezing and emergency IVF, emanate from multidisciplinary approaches.
Publication
Podgaec S, Dias Junior JA, Chapron C, Oliveira RM, Baracat EC, Abrão MS
• 01/2010
OBJECTIVE: This study analyzed the relationship between clinical characteristics of endometriosis and Th1/Th2 immune response patterns. METHODS: A prospective study was performed with 65 patients with endometriosis (Group A) and 33 without the disease (Group B). Measurement of IL 2, 4 and 10, TNF-alpha and IFN-gamma was carried out in peripheral blood and peritoneal fluid. RESULTS: Serum TNF-alpha was higher in patients with endometriosis who had deep dyspareunia compared to controls (mean 4.5 pg/ml and 2.3 pg/ml, p<0.05). Among these patients (n=32), 65.5% had deep endometriosis. Patients with endometriosis and infertility had higher IL-2 concentrations in peritoneal fluid than controls (mean 5.9 pg/ml and 0.2 pg/ml, p<0.05). Among these patients (n=22), 63.5% (n=14) had deep endometriosis. A higher concentration of IL-10 was also observed in patients with ovarian endometriosis when compared to those without this type of disease, as well as when compared to control group patients (mean 50 pg/ml, 18.7 pg/ml and 25.7 pg/ml, p<0.05). CONCLUSIONS: These results suggest that when specific clinical data are associated with a higher production of certain cytokines, there is a Th1 response pattern that may be related to deep infiltrating endometriosis.
Publication
Chopin N, Malaret JM, LafayPillet MC, Fotso A, Foulot H, Chapron C
• 12/2009
BACKGROUND: This study was designed to investigate the intra-operative characteristics and the risk of intra- and post-operative complications in cases of total laparoscopic hysterectomy (TLH) in overweight, obese and non-obese patients. METHODS: This cohort study includes all patients undergoing TLH for benign pathologies between January 1993 and June 2007 in Cochin university hospital (Paris). Demographic and surgical data were analysed. A comparison between overweight and obese patients versus non-obese patients and multivariate analyses were performed. RESULTS: Of 1460 patients undergoing TLH, 101 patients (6.9%) had a BMI of 30 or higher and 338 (23.2%) were overweight. After adjustment with respect to the patients' characteristics and past history (age, parity, past history of laparotomies, previous Cesarean section, menopausal status), no significant difference was found whether in terms of intra-operative (haemorrhage, transfusion, thrombosis, ureter, bladder or bowel injuries) or post-operative complications (hyperthermia, infections, fistula). Concerning the intra- and post-operative characteristics of these patients, only a significantly longer operating time was noted in the case of obesity (RR = 1.80; CI 95%: 1.16-2.81). CONCLUSIONS: In our experience, provided that the operating technique is meticulous, the intra- and post-operative complications are not increased in the case of obesity, although the operating time is longer.
Publication
Chapron C, PietinVialle C, Borghese B, Davy C, Foulot H, Chopin N
• 08/2009
OBJECTIVE: To investigate whether an associated ovarian endometrioma is a marker for severity of deep infiltrating endometriosis (DIE). DESIGN: Observational study between June 1992 and December 2005. SETTING: University tertiary referral center. PATIENT(S): Five hundred patients with histologically assessed DIE. INTERVENTION(S): Complete surgical exeresis of deep endometriotic lesions. MAIN OUTCOME MEASURE(S): Severity of the disease was quantified according to the mean number of DIE lesions and the type of main lesion. RESULT(S): In patients with associated ovarian endometrioma, the number of single isolated DIE lesions was statistically significantly lower (41.9% vs. 61.1%). The mean number of DIE lesions was statistically significantly higher in patients presenting with an associated ovarian endometrioma (2.51 +/- 1.72 vs. 1.64 +/- 1.0). For patients with associated ovarian endometrioma DIE lesions were more severe with an increased rate of vaginal, intestinal, and ureteral lesions. CONCLUSION(S): Associated ovarian endometrioma is a marker for the severity of the DIE. In a clinical context suggestive of DIE, when there is an ovarian endometrioma, the practitioner should investigate the extent of the disease to check for severe and multifocal DIE lesions.
Publication
Ngô C, Chéreau C, Nicco C, Weill B, Chapron C, Batteux F
• 07/2009
Endometriosis is associated with chronic inflammation, and reactive oxygen species (ROS) are proinflammatory mediators that modulate cell proliferation. We have investigated whether the dysregulation of ROS production in endometriotic cells correlates with a pro-proliferative phenotype and can explain the spreading of this disease. Stromal and epithelial cells were purified from ovarian endometrioma and eutopic endometrium from 14 patients with endometriosis to produce four primary cell lines from each patient. ROS production, detoxification pathways, cell proliferation, and mitogen-activated protein kinase pathway activation were studied and compared with epithelial and stromal cell lines from 14 patients without endometriosis. Modulation of the proliferation of endometriosis by N-acetyl-cysteine, danazol, and mifepristone was tested in vitro and in 28 nude mice implanted with endometriotic tissue of human origin. Endometriotic cells displayed higher endogenous oxidative stress with an increase in ROS production, alterations in ROS detoxification pathways, and a drop in catalase levels, as observed for tumor cells. This increase in endogenous ROS correlated with increased cellular proliferation and activation of ERK1/2. These phenomena were abrogated by the antioxidant molecule N-acetyl-cysteine both in vitro and in a mouse model of endometriosis. Human endometriotic cells display activated pERK, enhanced ROS production, and proliferative capability. Our murine model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis.
