Endometriosis after menopause: physiopathology and management of an uncommon condition.

Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause. Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be used in cases of pain recurrence after surgery. Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions. The evidence is currently insufficient to support a conclusion about the optimal hormone replacement therapy for women with endometriosis. The question of malignant transformation of endometriosis in response to hormone replacement therapy in women with a history of endometriosis remains unanswered and needs a long-term follow-up study to evaluate the risk of an adverse outcome. Further studies should be performed to determine the optimal management of menopausal women with endometriosis.

Advances in neurosteroids: role in clinical practice.

The steroidogenic endocrine glands and local synthesis both contribute to the pool of steroids present in the central nervous system and peripheral nervous system. Although the synthesis of neurosteroids in the nervous system is now well established, the spectrum of respective functions in regulating neuronal and glial functions remains to be fully elucidated. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids during fertile life and reproductive aging and their relationship with endogenous and exogenous sex steroids. The brain metabolism of synthetic progestins and the implications of DHEA treatment in postmenopausal women will also be discussed.

Immunohistochemical evaluation of epithelial antigen Ber-Ep4 and CD10: new markers for endometriosis?

BACKGROUND: Early and certain diagnoses of endometriosis are mandatory to begin the correct treatment and to exclude the risk of endometriosis-associated ovarian carcinoma (EOC) and endometrial stromal sarcoma (ESS). PURPOSE OF THE STUDY: To assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and CD10 in endometriosis. MATERIALS AND METHODS: Forty-eight women underwent laparoscopic surgery for endometriosis and endometriotic samples were recovered for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an immnohistochemical method. The authors evaluated the correlations among the immunohistochemical positivity and the location of endometriosis. RESULTS: Most cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%, 100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and CD10 for endometriosis diagnosis were 87.50% and 95.83%, respectively. Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical case. CONCLUSION: Immunohistochemical expression of Ber-Ep4 and CD10 was positive in most cases of endometriosis and was useful in differential diagnosis with mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or cytological atypia; these cases are not well-differentiated and could be optimally treated by surgery and not by hormonal therapy because of the risk of cancer degeneration.

P16 immunostaining and HPV testing in histological specimens from the uterine cervix.

BACKGROUND: The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression. PURPOSE OF THE STUDY: To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix. MATERIALS AND METHODS: The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. RESULTS: In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%. CONCLUSIONS: These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.

[LESS, NOTES and robotic surgery in gynecology: an update and upcoming perspectives]. / Chirurgie LESS, NOTES et robotique en gynécologie: mise au point et perspectives.

Laparoscopy revolutionized the gynecological surgical world during the 1980's and 1990's and has changed the approach to surgical procedures ever since. Minimal invasive surgery procedures are now the standard of care for many gynecological operations. At the beginning of the 21st century, robotic gynecological surgery, laparo-endoscopic single site surgery (LESS) and natural orifice transluminal endoscopic surgery (NOTES) may be on the threshold of another such revolutionary breakthrough. In this article, we review the present place of these new techniques in gynecological surgery and discuss their future perspective.

[Endometriosis: review of the literature and clinical management]. / Prise en charge de l'endométriose.

Despite numerous studies, endometriosis remains unclear concerning the etiopathogenesis, the natural history and optimal treatment. It occurs preferentially in young women and may be associated with a series of painful symptoms very disabling, together with infertility and significant psychological problems. Because of the multiple consultations, operations and disability it can cause, endometriosis takes an increasing part in health costs. Delays between onset and diagnosis are still long, and it is important to diagnose as early as possible to stop this disease so as to maintain or restore fertility and quality of life for patients. That is why a careful listening and clinical examination with appropriate investigations will improve our global care.

[Laparoscopic lateral suspension, another way to treat genital prolapse]. / La suspension latérale cœlioscopique, une autre façon de traiter les prolapsus génitaux.

The laparoscopic sacrocolpopexy is the treatment of choice of pelvic organ prolapses since more than twenty years. The laparoscopic lateral suspension with mesh is an alternative technique. Its originality is the subperitoneal passing of the lateral arm of the mesh in the lateral abdominal wall, leaving the skin above the iliac crest, in a place without risks of vascular, nerve, bowel injuries. We report in this article the results of the three main publications on the subject. The indications are cystocele and apical descent. It can be envisaged when the access of the promontory is difficult; for instance in the presence of obesity, adhesions, sigmoid megacolon, or low position of the left common iliac vein, partially covering the promontory. It is also a practical technique for surgeons having a moderate experience of the promontory access.

[Practice guidelines: conservative treatment of fibroids]. / Traitement conservateur des fibromes: recommandations pour la pratique.

The conservative treatment of uterine fibroids is essentially based on symptomatology and patient's choice of treatment. The gynaecologist must develop a clear therapeutic protocol based on clinical examination, available test results and consideration of patient preference. The therapeutic options include close surveillance, hormonal treatments, conservative operative endoscopy and arterial embolization.

Neurobiology of DHEA and effects on sexuality, mood and cognition.

Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the most abundant steroid hormones in the humans. However, their physiological significance, their mechanisms of action and their possible roles as treatment are not fully clarified. Biological actions of DHEA(S) in the brain involve neuroprotection, neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion, as well as anti-oxidant, anti-inflammatory and antiglucocorticoid effects. In addition, DHEA affects neurosteroidogenis and endorphin synthesis/release. We also demonstrated in a model of ovariectomized rats that DHEA therapy increases proceptive behaviors, already after 1 week of treatment, affecting central function of sexual drive. In women, the analyses of clinical outcomes are far from being conclusive and many issues should still be addressed. Although DHEA preparations have been available in the market since the 1990s, there are very few definitive reports on the biological functions of this steroid. We demonstrate that 1 year DHEA administration at the dose of 10mg provided a significant improvement in comparison with vitamin D in sexual function and in frequency of sexual intercourse in early postmenopausal women. Among symptomatic women, the spectrum of symptoms responding to DHEA requires further investigation, to define the type of sexual symptoms (e.g. decreased sexual function or hypoactive sexual desire disorder) and the degree of mood/cognitive symptoms that could be responsive to hormonal treatment. In this regard, our findings are promising, although they need further exploration with a larger and more representative sample size. This article is part of a Special Issue entitled: Essential role of DHEA.

Environment and Endometriosis: a toxic relationship.

Endometriosis is a common, benign, estrogen-dependent gynecological disease that represents one of the main causes of hospitalization in industrialized countries. It is well established that a large amount of natural and man-made chemicals are present in the environment and both humans and animals are exposed to them. Dioxin and dioxin-like compounds have long biological half-life, can accumulate within the organism and could negatively affect several physiological processes. The purpose of this review is to provide an overview of the possible relationship between these chemicals and the pathogenesis of endometriosis.

Tubal endometrioma within a twisted fallopian tube: a clinically complex diagnosis.

BACKGROUND: Endometriotic lesions affect the fallopian tubes in 6% of patients with endometriosis and adhesions involve the salpinges in 26%. Different studies report that 45%-70% of adolescents with chronic pelvic pain have endometriosis diagnosed at the time of laparoscopy. CASE: We report a case of an 18-year-old girl with a tubal torsion due to a tubal endometrioma. The endometriotic nodule before laparoscopy appeared to be located in the rectovaginal septum. At laparoscopy, a right fallopian tube torsion was visible and several adhesions were connecting the lesion to the pouch of Douglas' walls. SUMMARY AND CONCLUSION: The tenacious adhesions, which welded the nodule to the walls of the pouch of Douglas, did not allow to distinguish at the MRI a tubal endometrioma from a rectovaginal endometriotic mass, justifying the false diagnosis.

[Laparoscopic repair of pelvic organ prolapse by lateral suspension with mesh: a continuous series of 218 patients]. / Réparation cœlioscopique des prolapsus des organes pelviens par suspension prothétique latérale: une série continue de 218 patientes.

OBJECTIVES: To evaluate the technique of laparoscopic lateral colpo-uterine suspension using a mesh to treat pelvic organ prolapse, with a sufficient follow-up. PATIENTS AND METHODS: The technique consists of two steps. First, the lateral suspension of the vaginal vault and of the uterus is performed using a polypropylene mesh placed in the vesicovaginal septum as a transversal hammock. The second step is the application of a polypropylene patch to the posterior surface of the vagina and the rectovaginal septum. The transversal hammock is placed laterally by the tension-free fixation of the mesh to the lateral abdominal wall above the iliac crests. Between January 2004 and December 2007, 218 patients were treated. It is a continuous series including all the patients needing a surgical procedure to treat a genital prolapse. We excluded, from the study, the patients with a severe cardiorespiratory disease and the cases of isolated rectocele. RESULTS: We observed a recurrence of the prolapse in thirty patients (13.76%). A reoperation was performed in 10 patients (4.6%). One complication was related to the technique of lateral suspension (bladder injury immediately sutured 0.46%). A mesh erosion was noted in 13 cases (5.96%), nine were treated by vaginal excision of the mesh (4.12%). CONCLUSIONS: The laparoscopic lateral colpo-uterine suspension using a mesh corrects the pelvic organ prolapse with a predominant cystocele or rectocele. It is an interesting alternative to the other procedures because of the low risk of complications and the satisfactory results.

Radical splenopancreatectomy with duodenal loop conservation in rats.

In an attempt to find a reproducible method of total splenopancreatectomy (TSP) with duodenal loop conservation in rats, we used the technique recently described by S. Houry and M. Huguier (Eur. Surg. Res. 15: 328, 1983) but were not able to induce a true diabetes. We therefore developed a more radical splenopancreatectomy (RSP) in rats and compared this technique with the TSP. RSP involves a more extensive dissection of the common bile duct, a short choledocoduodenal anastomosis, and total excision of the retroportal pancreatic lobules with the aid of a dissecting microscope. In rats who had undergone the TSP technique, blood glucose levels were maximal 8 hr after operation (270 +/- 16 mg/dl), and thereafter recovered baseline values. In contrast, after the RSP technique all the rats became diabetic as documented by persistent hyperglycemia (347 +/- 20 mg/dl at 8 hr, P = 0.01 compared to TSP; 500 +/- 20 mg/dl at 8 hr, P less than 0.0001). Eight hours after the operation, blood lipase levels increased more significantly after TSP than after RSP (847 +/- 247 IU/liter and 130 +/- 37 IU/liter, respectively, P = 0.01), and then decreased to 92 +/- 19 IU/liter at 24 hr in the TSP group and less than or equal to 30 IU/liter in the RSP group (P = 0.003), suggesting a more radical dissection of pancreatic tissue with the RSP technique. At sacrifice at 48 hr, no complications were found with either technique on macroscopic and microscopic examination, except for marked gastric distension with RSP. A third group of rats underwent RSP and were followed until natural death.(ABSTRACT TRUNCATED AT 250 WORDS)

[Full-contact and dissecting aneurysm of the thrombosed left internal carotid artery associated with encephalomalacia]. / Full-contact et anévrysme disséquant de l'artère carotide interne gauche thrombosée avec ramollissement cérébral. Etude d'un cas.

Full-contact, a sport which is becoming more and more popular in our society as a means of self-defence, is not without its hazards. We describe the case of a 32-year-old man who, shortly after an intensive practice match, presented symptoms consistent with cerebral damage which resulted in his death within three days. The main pathological findings were confined to the left internal carotid artery, which presented a dissecting aneurysm as a result of rupture of its intima with thrombosis of its lumen. The thrombus extended as far as the intracranial portion of the artery, resulting in massive cerebral infarction as cause of death. Furthermore, there were histological modifications of both main carotid arteries and their branches which suggested repeated microtraumatic events. The causal relation between the lesions observed and the practice of full-contact are discussed.