Medical treatment in the management of deep endometriosis infiltrating the proximal rectum and sigmoid colon : a comprehensive literature review

A comprehensive literature review was performed to evaluate the effect of various hormonal therapies, in terms of variations of intestinal and pain complaints and of patient satisfaction with treatment, in women with symptomatic, non-severely sub-occlusive endometriosis infiltrating the proximal rectum and sigmoid colon. A MEDLINE search through PubMed from 2000 to 2018 was conducted to identify all original English language articles published on medical treatment for colorectal endometriosis. Additional reports were identified by systematically reviewing reference lists and using the "similar articles" function in PubMed. A total of 420 women with colorectal endometriosis treated with combined oral contraceptives, progestins, gonadotropin releasing-hormone (GnRH) agonists, and aromatase inhibitors have been described in eight case series, two retrospective cohort studies, and four case reports. Published data consistently suggest that several hormonal medications can control most symptoms associated with intestinal endometriosis, provided the relative bowel lumen stenosis is less than 60%. Patients with irritative-type symptoms appear to respond better than those with constipation. Overall, about two thirds of women were satisfied with the treatment received, independently of the drug used. Progestins are the compound supported by the largest body of evidence. The addition of aromatase inhibitors or, alternatively, the use of GnRH agonists, do not seem to be associated with better outcomes. Long-term treatment with a progestin should be proposed as an alternative to surgery to patients with non-severely sub-occlusive endometriosis infiltrating the proximal rectum and sigmoid colon not seeking conception. The final decision should be shared together with the woman, respecting her preferences and priorities

COMPREHENSIVE ANALYSIS OF BASELINE OUTCOME BIOPREDICTORS IN YOUNGER PATIENTS WITH MANTLE CELL LYMPHOMA: THE ANCILLARY BIOLOGICAL STUDIES OF FONDAZIONE ITALIANA LINFOMI (FIL) MCL0208 CLINICAL TRIAL

Despite the improvement in therapeutic schedules, a relevant fraction of mantle cell lymphoma (MCL) patients still experience primary treatment failure. This is due to a deep biological heterogeneity, not adequately dissected by the clinical predictors alone, as the MIPI (MCL International Prognostic Index). The Fondazione Italiana Linfomi (FIL) MCL0208 trial (NCT02354313) is a prospective, randomized phase III trial comparing lenalidomide maintenance vs observation after an intensive citarabine containing chemo-immunotherapy followed by autologous transplantation in frontline MCL patients <66 years.[Ladetto, ASH 2018] Several biological ancillary studies were planned upfront, prospectively investigating the prognostic impact of putative biomarkers. Here we present a comprehensive analysis of the clinical impact of all the identified biopredictors

Transcriptomics and immunological analyses reveal a pro-angiogenic and anti-inflammatory phenotype for decidual endothelial cells

Copyright © 2019 by the authors. Background: In pregnancy, excessive inflammation and break down of immunologic tolerance can contribute to miscarriage. Endothelial cells (ECs) are able to orchestrate the inflammatory processes by secreting pro-inflammatory mediators and bactericidal factors by modulating leakiness and leukocyte trafficking, via the expression of adhesion molecules and chemokines. The aim of this study was to analyse the differences in the phenotype between microvascular ECs isolated from decidua (DECs) and ECs isolated from human skin (ADMECs). Methods: DECs and ADMECs were characterized for their basal expression of angiogenic factors and adhesion molecules. A range of immunological responses was evaluated, such as vessel leakage, reactive oxygen species (ROS) production in response to TNF-α stimulation, adhesion molecules expression and leukocyte migration in response to TNF-α and IFN-γ stimulation. Results: DECs produced higher levels of HGF, VEGF-A and IGFBP3 compared to ADMECs. DECs expressed adhesion molecules, ICAM-2 and ICAM-3, and a mild response to TNF-α was observed. Finally, DECs produced high levels of CXCL9/MIG and CXCL10/IP-10 in response to IFN-γ and selectively recruited Treg lymphocytes. Conclusion: DEC phenotype differs considerably from that of ADMECs, suggesting that DECs may play an active role in the control of immune response and angiogenesis at the foetal-maternal interface.This work was supported by grants from the Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” to G. Ricci, Trieste, Italy (RC 20/16, RC 23/18). Fondazione Cassa di Risparmio Trieste to R. Bulla

Adenomyosis: fertility and obstetric outcome : a comprehensive literature review

Adenomyosis is a benign condition characterized by the presence of endometrial glands and stroma deep within the myometrium. In recent years, the potential negative impact of adenomyosis on in vitro fertilization clinical outcomes has gained momentum, as well as, the possible link of this condition with obstetrical complications. The aim of this narrative review is to elucidate the possible association between uterine adenomyosis, infertility, and poor obstetrical outcomes. Several theories have been proposed to clarify the potential harmful impact of adenomyosis on fertility, such as a functional and structural defect of both the eutopic endometrium and the inner myometrium, an impairment of the uterine system of sperm transport, the presence of uterine dysperistalsis and of high levels of free radicals in the uterine milieu of women with the disease. Numerous studies have demonstrated that adenomyosis exerts a detrimental effect on in vitro fertilization outcomes, reducing pregnancy and live birth rates and increasing miscarriage rate. Regarding pregnancy outcomes data are scarce; however, epidemiological studies suggest that women with uterine adenomyosis could be at increased risk of numerous obstetrical complications, in particular, preterm birth and preterm premature rupture of membranes. These preliminary results are valuable for preconception and prenatal counseling of women with adenomyosis and suggest that this category of women necessitate a more cautious prenatal management than previously expected

Deep endometriosis: definition, pathogenesis, and clinical management

"Deep endometriosis" includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. The available evidence suggests the same pathogenesis for deep infiltrating vesical and rectovaginal endometriosis (i.e., intraperitoneal seeding of regurgitated endometrial cells, which collect and implant in the most dependent portions of the peritoneal cavity and the anterior and posterior cul-de-sac, and trigger an inflammatory process leading to adhesion of contiguous organs with creation of false peritoneal bottoms). According to anatomic, surgical, and pathologic findings, deep endometriotic lesions seem to originate intraperitoneally rather than extraperitoneally. Also the lateral asymmetry in the occurrence of ureteral endometriosis is compatible with the menstrual reflux theory and with the anatomic differences of the left and right hemipelvis. Peritoneal, ovarian, and deep endometriosis may be diverse manifestations of a disease with a single origin (i.e., regurgitated endometrium). Based on different pathogenetic hypotheses, several schemes have been proposed to classify deep endometriosis, but further data are needed to demonstrate their validity and reliability. Drugs induce temporary quiescence of active deep lesions and may be useful in selected circumstances. Progestins should be considered as first-line medical treatment for temporary pain relief. However, in most cases of severely infiltrating disease, surgery is the final solution. Great importance must be given to complete and balanced counseling, as awareness of the real possibilities of different treatments will enhance the patient's collaboration

Role of surgery in endometriosis-associated subfertility

Analysis of published series reveals that no more than a fourth of subfertile patients undergoing surgery for peritoneal endometriotic implants, rectovaginal endometriotic lesions, or recurrent endometriomas achieved conception spontaneously. First-line surgery for ovarian endometriotic cysts appears associated with a better reproductive performance, that is, a mean postoperative pregnancy rate of 3c50%. At the same time, excision of endometriomas paradoxically seems to induce gonadal damage. With the exception of peritoneal disease, no randomized trials are available to assess the effect of surgery in subfertile women with endometriosis. Therefore, it is not possible to define the absolute benefit increase of the treatment of ovarian and rectovaginal lesions. The decision to undergo surgery for endometriosis-associated subfertility must be shared with the woman after detailed information and taking into account several additional conditions, such as presence of pain, large or complex adnexal masses, bowel or ureteral stenosis, and coexisting infertility factors. When considering surgery, a therapeutic equipoise should be reached that includes demonstrated benefits, potential morbidity, and costs of treatment alternatives. Particularly in case of recurrent endometriosis, in vitro fertilization should generally be preferred to surgery. The role of surgery in endometriosis-associated subfertility includes temporary pain relief in symptomatic women desiring a spontaneous conceptio

A randomized comparison of tension-free vaginal tape and endopelvic fascia plication in women with genital prolapse and occult stress urinary incontinence

Objective: The purpose of this study was to compare 2 anti-incontinence procedures in women who had severe genital prolapse and potential stress incontinence. Study design: In addition to vaginal reconstructive surgery, 50 patients with stage II or higher anterior defect and a positive stress test result with prolapse reduction received either tension-free vaginal tape or plication of the endopelvic fascia. Preoperative evaluation included history, physical examination, stress test, and urodynamic assessment. Data were analyzed with the Student t test, the Fisher's exact test, and the Wilcoxon signed-rank test. Results: The median follow-up time was similar for both groups, 26 and 24 months. Subjective (96% vs 64%; P = .01) and objective (92% vs 56%; P < .01) continence rates were higher after the tension-free vaginal tape procedure. Time for the resumption of spontaneous voiding, rates of urinary retention, or de novo urge incontinence were similar in the 2 groups. Conclusion: Tension-free vaginal tape can be recommended for patients with prolapse and occult stress incontinence

Bladder endometriosis: getting closer and closer to the unifying metastatic hypothesis

Objective: It has been hypothesized that bladder endometriotic nodules are an independent form of endometriosis that should be considered a distinct clinical entity. If this is true, the frequency of nonvesical endometriotic lesions in affected patients should be similar to the prevalence of the disease in the general population (about 10%). The aim of the study was to evaluate the presence of other forms of endometriosis in patients with bladder endometriotic nodules. Design: Case series. Setting: Two gynecologic surgical units. Patient(s): Fifty-eight women with large bladder endometriotic nodules. Intervention(s): To evaluate the concomitant presence of other forms of endometriosis. Main Outcome Measure(s): Presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis. Result(s): The presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis was observed in 58.6% (95% confidence interval [CI]: 45.2-71.2), 44.8% (95% CI: 32.2-58.2), 81.0% (95% CI: 68.4-89.6), and 27.6% (95% CI: 16.7-40.8) of cases, respectively. The presence of at least one of them was documented in 87.9% of cases (95% CI: 76.7-94.3). Conclusion(s): Endometriotic nodules of the bladder are frequently associated with other forms of pelvic endometriosis. This result does not support the vision that bladder endometriotic nodules should be considered an independent form of the disease