ClinicalTrials.gov (www.clinicaltrials.gov) registration numbers NCT01156857 (PEARL III) and NCT01252069 (PEARL III extension).

NCT01629563 (PEARL IV).

Deep endometriosis (DE) remains the most difficult endometriotic entity to treat. Medical treatment for DE can reduce symptoms but does not cure the disease, and surgical removal of the lesion is required when lesions are symptomatic, impairing bowel, urinary, sexual, and reproductive functions. Although several surgical techniques such as laparoscopic bowel resection, disc excision, and rectal shaving have been described, there is no consensus regarding the choice of technique or the timing of surgery. Our review of publications reporting results and complications of surgery for rectovaginal DE reveals a relatively higher complication rate after bowel resection compared with shaving and disc excision, especially for rectovaginal fistulas, anastomotic leakage, delayed hemorrhage, and long-term bladder catheterization. Data show that shaving is feasible even in advanced disease. The risk of immediate complications after shaving and disc excision is probably lower than after colorectal resection, allowing for better functional outcomes. The presumed higher risk of recurrence related to shaving has not been demonstrated. For these reasons, surgeons should consider rectal shaving as a first-line surgical treatment of rectovaginal DE, regardless of nodule size or association with other digestive localizations. When the result of rectal shaving is unsatisfactory (rare cases), disc excision may be performed either exclusively by laparoscopy or by using transanal staplers. Segmental resection may ultimately be reserved for advanced lesions responsible for major stenosis or for several cases of multiple nodules infiltrating the rectosigmoid junction or sigmoid colon.

Adenomyosis is a commonly diagnosed estrogen-dependent gynecological disorder that causes pelvic pain, abnormal uterine bleeding, and infertility. Despite its prevalence and severity of symptoms, its pathogenesis and etiology have not yet been elucidated. The aim of this manuscript is to review the different hypotheses on the origin of adenomyotic lesions and the mechanisms involved in the evolution and progression of the disease. Two main theories have been proposed to explain the origin of adenomyosis. The most common suggests involvement of tissue injury and the repair mechanism and claims that adenomyosis results from invagination of the endometrial basalis into the myometrium. An alternative theory maintains that adenomyotic lesions result from metaplasia of displaced embryonic pluripotent Müllerian remnants or differentiation of adult stem cells. Previous investigations performed in human adenomyotic lesions and corroborated by studies in mice supported the involvement of the epithelial-mesenchymal transition process in the early stages of progression and spread of adenomyosis. However, studies conducted in a recently developed baboon model indicate that collective cell migration may be implicated in the later events of invasion. This suggests that the invasiveness of this complex uterine disorder is not driven by a single mechanism of migration but by a time-dependent combination of two processes.

In symptomatic women with residual myometrial thickness of less than 3 mm who wish to conceive, laparoscopic repair could be considered an appropriate approach.

Endometriosis is a disorder associated with a general inflammatory response in the peritoneal cavity. Oxidative stress is a potential factor involved in the pathophysiology of this disease, and reactive oxygen species (ROS) are implicated in this process. Indeed, in healthy individuals, ROS and antioxidants are in balance, but when balance is tipped toward an overabundance of ROS, oxidative stress occurs and can impact the entire reproductive lifespan of a woman. Reactive oxygen species are intermediaries produced by normal oxygen metabolism but are known to have deleterious effects. Excessive release of ROS induces cellular damage and alters cellular function by regulating protein activity and gene expression, leading to harmful effects. To protect themselves, cells have developed antioxidant systems to limit production of ROS, inactivate them, and repair cell damage. Understanding of the control of hemoglobin, heme, and iron-induced redox balance in endometriosis led us to propose a number of hypotheses to explain why oxidative stress is induced in case of pelvic endometriosis. Erythrocytes, apoptotic endometrial tissue, and cell debris transplanted into the peritoneal cavity by menstrual reflux and macrophages have all been cited as potential inducers of oxidative stress. Erythrocytes are likely to release pro-oxidant and proinflammatory factors, such as hemoglobin and its highly toxic by-products heme and iron, into the peritoneal environment. Iron and heme are essential to living cells, but unless appropriately chelated, free iron, and to a lesser extent heme, play a key role in the formation of deleterious ROS.

NCT01629563.

No abstract