Surgery versus hormonal therapy for deep endometriosis : is it a choice of the physician?

Deep endometriosis, occurring approximately in 1% of women of reproductive age, represents the most severe form of endometriosis. It causes severe pain in the vast majority of affected women and it can affect the bowel and the urinary tract. Hormonal treatment of deep endometriosis with progestins, such as norethindrone acetate or dienogest, or estroprogestins is effective in relieving pain in more than 90% of women at one year follow up. Progestins and estroprogestins can be safely administered in the long-term, may be not expensive and are usually well tolerated. Therefore, they should represent the first-line treatment of deep endometriosis associated pain in women not seeking natural conception. However, hormonal treatment is ineffective or not tolerated in about 30% of women, the most common side effects being erratic bleeding, weight gain, decreased libido and headache. Surgical excision of deep endometriosis is mandatory in presence of symptomatic bowel stenosis, ureteral stenosis with secondary hydronephrosis, and when hormonal treatments fail. Surgical treatment is similarly effective as compared to hormonal treatment in relieving dismenorhea, dyspareunia and dyschezia at one year follow up in more than 90% of women with deep endometriosis. Surgical removal of the nodules may require resection of the bowel, ureter or bladder, with possible severe complications such as rectovaginal or ureterovaginal fistula and anastomotic leakage. A thorough counsel with the patient is necessary in order to pursue a therapeutic plan centered not on the endometriotic lesions, but on the patient's symptoms, priorities and expectations

Advances in the medical management of bowel endometriosis

Endometriosis infiltrating the bowel can be treated medically in accurately selected women not seeking conception and without overt obstructive symptomatology. When the rectosigmoid junction is involved, the probabilities of intestinal symptoms relief, undergoing surgery after treatment failure, and developing bowel obstruction during hormonal treatment are around 70%, 10%, and 1-2%, respectively. When the lesion infiltrates exclusively the mid-rectum, thus in cases of true rectovaginal endometriosis, the probabilities of intestinal symptoms relief and undergoing surgery are about 80% and 3%, respectively. Endometriotic obstructions of the rectal ampulla have not been reported. A rectosigmoidoscopy or colonoscopy should be performed systematically before starting medical therapies, also to rule out malignant tumours arising from the intestinal mucosa. Progestogens are safe, generally effective, well-tolerated, inexpensive, and should be considered as first-line medications for bowel endometriosis. Independently of symptom relief, intestinal lesions should be checked periodically to exclude nodule progression during hormonal treatment

The impact of IVF on deep invasive endometriosis

Objective: Ovarian hyper-stimulation during IVF is associated with a significant raise in serum estrogens and one may expect detrimental effects on estrogen-dependent diseases such as endometriosis. However, available evidence from large case series of affected women performing IVF is generally reassuring with the possible exception of women carrying deep invasive lesions. On this basis we deemed important investigating more in depth whether women with deep invasive endometriosis could be a subgroup at higher risk of recurrence or disease progression during IVF. Study design: Women with endometriosis who underwent IVF and who had a second evaluation after 3\u20136 months from a failed cycle were retrospectively reviewed. The main inclusion criteria were the presence of deep invasive endometriosis and/or a history of surgery for this form of the disease. The primary aim of the study was to determine the frequency of endometriosis-related complications in the interval between the two evaluations. Secondary aims were pain symptoms and lesion size modifications. Results: Eighty-four women were ultimately selected: baseline ultrasound documented deep invasive lesions in 60 of them. One case of possible endometriosis-related complication was recorded, corresponding to a rate of 1.2% (95%: 0.05%\u20135.5%) for the whole cohort and 1.7% (95%CI: 0.08\u20137.6%) for the subgroup of women with ultrasound detected lesions. This rate appears similar to the reported frequency of endometriosis progression in women not receiving IVF. No significant modifications in pain symptoms or lesions size occurred. Conclusions: Women with deep invasive endometriosis who underwent IVF do not seem to be exposed to a substantially increased risk of recurrence/disease progression. Larger evidence from independent groups is however required for a definitive conclusion

"Per vaginam" topical use of hormonal drugs in women with symptomatic deep endometriosis : a narrative literature review

PURPOSE: We aim to provide a comprehensive overview of the role of the vagina as a route for drug delivery and absorption, with a particular focus on the use of vaginal hormonal compounds for the treatment of deep infiltrating symptomatic endometriosis. METHODS: A MEDLINE search through PubMed was performed to identify all published studies in English language on vaginal hormonal treatments for symptomatic endometriosis. RESULTS: Main advantages of the vaginal route include avoidance of the hepatic-first pass metabolic effect, the possibility of using lower therapeutic dosages, and the reduction of side effects compared with the oral administration. Studies on endometriosis treatment mainly focused on the use of vaginal danazol (n = 6) and the contraceptive vaginal ring (n = 2). One pilot study evaluated the efficacy of vaginal anastrozole in women with rectovaginal endometriosis. Most investigations evaluated the vaginal use of hormonal agents in women with deep infiltrating endometriosis/rectovaginal endometriosis. Overall, a substantial amelioration of pelvic pain symptoms associated with endometriosis was observed, particularly of dysmenorrhea. A significant reduction in rectovaginal endometriotic nodule dimensions measured at ultrasound examination was detected by some but not all authors. CONCLUSIONS: The vaginal route represents a scarcely explored modality for drug administration. High local hormonal concentrations might achieve a greater effect on endometriotic lesions compared with alternative routes. Future studies should focus on the use of the vagina for delivering target therapies particularly in patients with deeply infiltrating rectovaginal lesions

When love hurts : A systematic review on the effects of endometriosis surgical and pharmacological treatments on female sexual functioning

INTRODUCTION: Endometriosis is associated with an increased risk of dyspareunia, therefore this chronic gynaecologic disease should be considered as a major cause of sexual dysfunctions. The aims of this study were to review the literature on the effects of endometriosis surgical and pharmacological treatments on female sexual functioning, and to provide suggestions for future treatment strategies. MATERIAL AND METHODS: We followed the PRISMA guidelines to conduct this systematic review, which involved an electronic database search of studies on the association between endometriosis and sexuality published between 2000 and 2016. RESULTS: As a result of the screening process, 22 studies were included in this systematic review. The 22 studies included were divided in 2 categories: 1) surgical intervention studies (n = 17), examining postoperative sexual outcomes of surgery for endometriosis; 2) pharmacological intervention studies (n = 5), evaluating the effects of pharmacological endometriosis treatments on sexual functioning. The studies considered showed that overall surgical and pharmacological interventions for endometriosis can lead to medium-/long-term improvement, but not necessarily to a definitive resolution of female sexual dysfunctions due to endometriosis. CONCLUSIONS: Sexual functioning is a multidimensional phenomenon and the ideal treatment for endometriosis related sexual dysfunctions should be conducted by a multidisciplinary team that involves not only gynaecologists, but also sexologists and psychologists/psychotherapists. Improving global sexual functioning, and not just reducing pain at intercourse, should be considered as a major clinical goal of endometriosis treatment

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study

Purpose To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. Methods Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. Results Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22–4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23–3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23–3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49–79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69–38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38–22.09). Conclusion Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. Trial registration Clinical trial registration number: NCT03354793

High Yield Production Process for Shigella Outer Membrane Particles

Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria

Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies

<p>Abstract</p> <p>Background</p> <p>Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation.</p> <p>Aim</p> <p>To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies.</p> <p>Materials and methods</p> <p>315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs.</p> <p>Results</p> <p>Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree.</p> <p>Discussion</p> <p>Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.</p

Mining unexpected patterns using decision trees and interestingness measures: a case study of endometriosis

[[abstract]]Because clinical research is carried out in complex environments, prior domain knowledge, constraints, and expert knowledge can enhance the capabilities and performance of data mining. In this paper we propose an unexpected pattern mining model that uses decision trees to compare recovery rates of two different treatments, and to find patterns that contrast with the prior knowledge of domain users. In the proposed model we define interestingness measures to determine whether the patterns found are interesting to the domain. By applying the concept of domain-driven data mining, we repeatedly utilize decision trees and interestingness measures in a closed-loop, in-depth mining process to find unexpected and interesting patterns. We use retrospective data from transvaginal ultrasound-guided aspirations to show that the proposed model can successfully compare different treatments using a decision tree, which is a new usage of that tool. We believe that unexpected, interesting patterns may provide clinical researchers with different perspectives for future research.[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]紙本[[booktype]]電子