Evaluating the safety of high-intensity focused ultrasound treatment for rectal endometriosis: results from a French prospective multicentre study including 60 patients.

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.

Correlation between endometriosis and migraine features: Results from a prospective case-control study.

BACKGROUND: Endometriosis and migraine frequently coexist, but only a limited number of studies have focused on their mutual association. The aim of our study was to investigate, in untreated women with comorbid endometriosis/adenomyosis and migraine, the correlation between headache features and endometriotic subtypes and their possible relationship with pain severity and disease disability. METHODS: Fifty women affected by endometriosis/adenomyosis and migraine matched (1:2) with 100 patients with endometriosis alone and 100 patients with only migraine were recruited and underwent pelvic ultrasound imaging and neurological examination. RESULTS: Severe adenomyosis, posterior and anterior deep infiltrating endometriosis (p = 0.027, p = 0.0031 and p = 0.029, respectively) occurred more frequently in women with migraine. Dysmenorrhea was the most commonly reported symptom in women with endometriosis and migraine and the mean VAS scores of all typical endometriotic symptoms were significantly higher in the presence of comorbidity. Women with both migraine and endometriosis reported significant higher pain intensity (p = 0.004), higher monthly migraine days (p = 0.042) and increased HIT 6-scores (p = 0.01), compared with those without endometriosis. CONCLUSIONS: Our results demonstrated that the co-occurrence of migraine in untreated women with endometriosis is associated with more severe gynecological infiltrations and correlated with increased pain intensity and disease disability.Trial Registration: Protocol number 119/21.

Single-cell profiling identifies distinct hormonal, immunologic, and inflammatory signatures of endometriosis-constituting cells.

Endometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis-constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single-cell RNA-sequencing (scRNA-seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B+ TFF3low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte-derived macrophages and IL1B expression in DIE. The scRNA-seq predicted NRG1 (macrophage)-ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types-endometrial, lymphoid, macrophage, fibroblast, and endothelial cells-are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis-specific findings of MUC5B+ EEECs, mesothelial cell-derived myofibroblasts, and NRG1-ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland.

Role of robot-assisted laparoscopy in deep infiltrating endometriosis with bowel involvement: a systematic review and application of the IDEAL framework.

AIMS: This review aims to evaluate the feasibility of robot-assisted laparoscopic surgery (RALS) as an alternative to standard laparoscopic surgery (SLS) for the treatment of bowel deep-infiltrative endometriosis. Additionally, it aims to provide guidance for future study design, by gaining insight into the current state of research, in accordance with the IDEAL framework. METHOD: A systematic review was conducted to identify relevant studies on RALS for bowel deep infiltrating endometriosis in Medline, Embase, Cochrane Library and PubMed databases up to August 2023 and reported in keeping with PRISMA guidelines. The study was registered with PROSPERO Registration: CRD42022308611 RESULTS: Eleven primary studies were identified, encompassing 364 RALS patients and 83 SLS patients, from which surgical details, operative and postoperative outcomes were extracted. In the RALS group, mean operating time was longer (235 ± 112 min) than in the standard laparoscopy group (171 ± 76 min) (p < 0.01). Patients in the RALS group experienced a shorter hospital stay (5.3 ± 3.5 days vs. 7.3 ± 4.1 days) (p < 0.01), and appeared to have fewer postoperative complications compared to standard laparoscopy. Research evidence for RALS in bowel DE is at an IDEAL Stage 2B of development. CONCLUSION: RALS is a safe and feasible alternative to standard laparoscopy for bowel endometriosis treatment, with a shorter overall length of stay despite longer operating times. Further robust randomized trials recommended to delineate other potential advantages of RALS.

Ultrasound appearance of decidualized non-ovarian endometriotic lesions during pregnancy and after delivery.

OBJECTIVE: To evaluate the changes in the ultrasound characteristics of decidualized non-ovarian endometriotic lesions that occur during pregnancy and after delivery. METHODS: This was a prospective observational cohort study carried out at a single tertiary center between December 2018 and October 2021. Pregnant women with endometriosis underwent a standardized transvaginal ultrasound examination with color Doppler imaging once in every trimester and after delivery. Non-ovarian endometriotic lesions were measured and evaluated by subjective semiquantitative assessment of blood flow. Lesions with moderate-to-marked blood flow were considered decidualized. The size and vascularization of decidualized and non-decidualized lesions were compared between the gravid state and after delivery. Only patients with non-ovarian endometriotic lesion(s) who underwent postpartum examination were included in the final analysis. RESULTS: Overall, 26 pregnant women with a surgical or sonographic diagnosis of endometriosis made prior to conception were invited to participate in the study, of whom 24 were recruited. Of those, 13 women with non-ovarian endometriosis who attended the postpartum examination were included. In 7/13 (54%) cases, the lesion(s) were decidualized. In 4/7 (57%) women with decidualized lesion(s), the size of the largest lesion increased during pregnancy, while in 3/7 (43%), the size was unchanged. The size of non-decidualized lesions did not change during pregnancy. On postpartum examination, only seven lesions were observed, of which three were formerly decidualized and four were formerly non-decidualized. Lesions that were detected after delivery appeared as typical endometriotic nodules and were smaller compared with during pregnancy. The difference in maximum diameter between the gravid and postpartum states was statistically significant in decidualized lesions (P < 0.01), but not in non-decidualized lesions (P = 0.09). The reduction in mean diameter was greater in decidualized compared with non-decidualized lesions (P = 0.03). CONCLUSIONS: Decidualization was observed in 54% of women with non-ovarian endometriotic lesion(s) and resolved after delivery. Our findings suggest that the sonographic features of decidualization, which might mimic malignancy, are pregnancy-related and that expectant management and careful monitoring should be applied in these cases. Clinicians should be aware of the changes observed during pregnancy to avoid misdiagnosing decidualized lesions as malignancy and performing unnecessary surgery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Robot-assisted laparoscopy does not have demonstrable advantages over conventional laparoscopy in endometriosis surgery: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is a chronic condition affecting 6-10% of women of reproductive age, with endometriosis-related pain and infertility being the leading symptoms. Currently, the gold standard treatment approach to surgery is conventional laparoscopy (CL); however, the increasing availability of robot-assisted surgery is projected as a competitor of CL. This study aimed to compare the perioperative outcomes of robot-assisted laparoscopy (RAL) and CL in endometriosis surgery. OBJECTIVES: We aimed to compare the effectiveness and safety of these two procedures. METHODS: A systematic search was conducted in three medical databases. Studies investigating different perioperative outcomes of endometriosis-related surgeries were included. Results are presented as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). RESULTS: Our search yielded 2,014 records, of which 13 were eligible for data extraction. No significant differences were detected between the CL and RAL groups in terms of intraoperative complications (OR = 1.07, CI 0.43-2.63), postoperative complications (OR = 1.3, CI 0.73-2.32), number of conversions to open surgery (OR = 1.34, CI 0.76-2.37), length of hospital stays (MD = 0.12, CI 0.33-0.57), blood loss (MD = 16.73, CI 4.18-37.63) or number of rehospitalizations (OR = 0.95, CI 0.13-6.75). In terms of operative times (MD = 28.09 min, CI 11.59-44.59) and operating room times (MD = 51.39 min, CI 15.07-87.72;), the RAL technique remained inferior. CONCLUSION: RAL does not have statistically demonstrable advantages over CL in terms of perioperative outcomes for endometriosis-related surgery.

Robotic Management of Recurrent Rectal Endometriosis After Previous Segmental Bowel Resection.

OBJECTIVE: To describe the management of recurrent bowel endometriosis after previous colorectal resection. DESIGN: Surgical video article. The local institutional board review was omitted due to the narration of surgical management. Patient consent was obtained. SETTING: A tertiary referral center. The patient first underwent segmental bowel resection for deep infiltrating endometriosis of the rectum in the ENDORE randomized controlled trial in 2012 and then received a total hysterectomy in 2018. Five years later, she presented with recurrent nodules in the rectovaginal, left parametrium, and abdominal wall after discontinuing medical suppressive treatment. INTERVENTION: Laparoscopic management using robotic assistance was employed to complete excision of the rectovaginal nodule. Disc excision was performed to remove rectal infiltration. The procedure started with rectal shaving and excision of vaginal infiltration . A traction stitch was placed over the limits of the rectal shaving area. The general surgeon placed a 28 mm circular anal stapler transanally and performed complete excision of the shaved rectal area. Anastomotic perfusion was checked with indocyanine green. A methylene blue enema test was conducted to rule out anastomotic leakage. Outcomes were favorable, with systematic self-catheterization during 5 postoperative weeks. No specific symptoms were related to the other 2 nodules, which were not removed. CONCLUSION: Rectal recurrences may occur long after colorectal resection and outside the limits of the previous surgery site. To accurately assess this risk, long-term follow-up of patients is mandatory.. Postoperative medical amenorrhea may play a role in recurrence prevention. Surgical management of recurrences may be challenging and focus on only those nodules responsible for symptoms so as to best preserve the organ's function and reduce postoperative morbidity.

Not All Bad Comes to Harm: Enhanced Recovery After Surgery for Rectosigmoid Endometriosis.

STUDY OBJECTIVE: To assess the impact of implementing an enhanced recovery after surgery (ERAS) protocol on the length of hospitalization in women undergoing laparoscopy for rectosigmoid deep infiltrating endometriosis (DIE). DESIGN: A retrospective cohort study. SETTING: An academic referral center for endometriosis and minimally invasive gynecologic surgery. PATIENTS: Women aged between 18 and 50 years scheduled for laparoscopic excision (shaving, full-thickness anterior wall resection, segmental resection) of rectosigmoid endometriosis between February 2017 and February 2023. INTERVENTIONS: We divided patients into 2 groups (non-ERAS and ERAS) based on the timing of surgery (before or after March 5, 2020). Starting from this day, restrictions were issued to limit the spread of the coronavirus disease 2019 pandemic, inducing our group to implement an ERAS protocol for patients hospitalized after surgery for posterior DIE. MEASUREMENTS AND MAIN RESULTS: We included 579 patients in the analysis, 316 (54.6%) in the non-ERAS group and 263 (45.4%) in the ERAS group. In the ERAS group, we observed a shorter length of hospital stay (5.8 ± 3.1 days vs 4.8 ± 2.9 days; p <.001) and lower complications rates (33, 12.5% vs 60, 19.0%; p = .04), despite a decreased frequency of conservative surgical approaches (shaving procedures 121 vs 196; p <.001). Repeated surgery or hospital readmissions owing to postdischarge complications were infrequent, with no significant differences between the 2 groups. The multiple linear regression analysis strengthened our results given the higher prevalence of bowel resection surgeries (both full-thickness anterior wall or segmental), showing that patients managed with a multimodal protocol had an overall reduction of hospital stay by 1.5 days. CONCLUSION: The implementation of an ERAS program in patients undergoing laparoscopic surgery for DIE is associated with a significant reduction in hospital stay, without an increase in perioperative or postoperative complication rates.

Transvaginal Sonography for the Preoperative Assessment of Parametrial Deep Infiltrating Endometriosis: A Diagnostic Accuracy Study.

OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy for parametria endometriosis (PE) of transvaginal sonography (TVS) performed following a systematic approach for the assessment of the lateral parametria. DESIGN: A diagnostic accuracy study was employed based on a prospective observational design. PARTICIPANTS: All consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020 were considered. SETTING: The study was conducted at endometriosis referral hospitals. METHODS: We prospectively collected clinical, imaging, and surgical data of all consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020. A standardized technique with a systematic approach for the assessment of the lateral parametria following specific anatomic landmarks was used for the TVS. The diagnostic accuracy for PE in TVS was assessed using the intraoperative and pathologic diagnosis of PE as the gold standard. RESULTS: In 476 patients who underwent surgery, PE was identified in 114 out of 476 patients (23.95%): 91 left and 54 right PE out of 476 surgical procedures were identified (19.12% vs. 11.34%; p = 0.001); bilateral involvement in 27.19% (31/114 patients) cases. The sensitivity of TVS for PE was 90.74% (79.70-96.92%, 95% CI) for the right side and 87.91% (79.40-93.81%, 95% CI) for the left side. The specificity was almost identical for both sides (98.58% vs. 98.18%). For the right parametrium, the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 63.82 (28.70-141.90, 95% CI) and 0.09 (0.04-0.22, 95% CI), respectively. On the left parametrium, the PLR and NLR were 48.35 (23.12-101.4, 95% CI) and 0.12 (0.07-0.21, 95% CI), respectively. The diagnostic accuracy for right and left PE was 97.69% (95.90-98.84%, 95% CI) and 96.22% (94.04-97.74%, 95% CI), respectively. LIMITATIONS: The principal limit is the high dependence of TVS on the operator experience. Therefore, although a standardized approach following precise definitions of anatomical landmarks was used, we cannot conclude that the observed accuracy of TVS for PE is the same for all sonographers. In this regard, the learning curve was not assessed. In the case of negative TVS for parametrial involvement with an absent intraoperative suspect, a complete dissection of the parametrium was not performed to avoid surgical complications; therefore, cases of minor PE may be missed, underestimating false negatives. CONCLUSIONS: TVS performed following a systematic approach for assessing the lateral parametria seems to have good diagnostic accuracy for PE with large changes in the posttest probability of parametrial involvement based on the TVS evaluation. Considering the clinical and surgical implications of PE, further studies implementing a standardized approach for assessing the parametrium by TVS are recommended to confirm our observations and implement a standardized protocol in clinical practice.

Robotic surgery for bowel endometriosis: a multidisciplinary management of a complex entity.

BACKGROUND: Bowel endometriosis impacts quality of life. Treatment requires complex surgical procedures with associated morbidity. Precision approach with robotic surgery leads to organ preservation. Bowel endometriosis requires a multidisciplinary management to improve patient outcomes. This study evaluates perioperative outcomes of bowel endometriosis undergoing multidisciplinary planning and robotic surgery. METHODS: Consecutive cases of multidisciplinary robotic bowel endometriosis procedures (January 2021-December 2022) were evaluated from a prospectively maintained database in a national endometriosis accredited centre. Patients were managed through a multidisciplinary setting including gynaecologists, colorectal robotic surgeons, and other specialists. Dyschezia (menstrual and non-cyclical) and quality of life were assessed pre- and postoperatively (6 months) through validated questionnaires. RESULTS: Sixty-eight consecutive cases of robotic bowel endometriosis were included. Median age was 35.0 (30.2-42.0) years. Median body mass index was 24.0 (21.0-26.7) kg/m2. Procedures performed were 48 (70.6%) shavings, 11 (16.2%) deep shavings, 3 (4.4%) disc excisions, and 6 (8.8%) segmental resections. One (1.5%) patient required temporary stoma. Median operating time was 150 (120-180) min. There were no conversions/return to theatre postoperatively. Median endometriotic nodule size was 25.0 (15.5-40.0) mm. Two (2.9%) patients developed postoperative complications. Median length of postoperative stay was 2 (2-4) days. Median follow-up was 12 (7-17) months. One (1.5%) patient recurred. Median menstrual dyschezia score improved from 5.0 (2.0-8.0) to 1.0 (0.0-5.7). Median non-cyclical dyschezia significantly improved (p < 0.001) from 1.0 (0.0-5.7) to 0.0 (0.0-2.0). Median quality of life score improved from 52.5 (35.0-70.0) to 74.5 (60.0-80.0). CONCLUSIONS: Robotic multidisciplinary approach to bowel endometriosis provides good perioperative outcomes with improvement of dyschezia and quality of life.

The implications of the anatomy of the nerves and vessels in the treatment of rectosigmoid endometriosis.

Endometriosis is a common benign gynecological disease characterized by the presence of endometrial glands and stroma outside the uterus. It can be defined as endometrioma, superficial peritoneal endometriosis or deep infiltrating endometriosis (DIE) depending on the location and the depth of infiltration of the organs. In 5%-12% of cases, DIE affects the digestive tract, frequently involving the distal part of the sigmoid colon and rectum. Surgery is generally recommended in cases of obstructive symptoms and in cases with pain that is non-responsive to medical treatment. Selection of the most optimal surgical technique for the treatment of bowel endometriosis must consider different variables, including the number of lesions, eventual multifocal lesions, as well as length, width and grade of infiltration into the bowel wall. Except for some major and widely accepted indications regarding bowel resection, established international guidelines are not clear on when to employ a more conservative approach like rectal shaving or discoid resection, and when, instead, to opt for bowel resection. Damage to the pelvic autonomic nervous system may be avoided by detection of the middle rectal artery, where its relationship with female pelvic nerve fibers allows its use as an anatomical landmark. To reduce the risk of potential vascular and nervous complications related to bowel resection, a less invasive approach such as shaving or discoid resection can be considered as potential treatment options. Additionally, the middle rectal artery can be used as a reference point in cases of upper bowel resection, where a trans mesorectal technique should be preferred to prevent devascularization and denervation of the bowel segments not affected by the disease.

Effect of Oral Contraceptive Use in Relation to Fertile Years on the Risk of Endometriosis in Women with Primary Infertility: A Ten-Year Single-Centre Retrospective Analysis.

Background and Objectives: Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. Materials and Methods: This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. Results: In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; p = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 [95% CI 0.87-1.29]). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 [95% CI 0.26-0.95]; p = 0.036) or superficial implants (aOR 0.88 [95% CI 0.58-0.95]; p = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. Conclusions: When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study's limitations.

Comparing gene expression in deep infiltrating endometriosis with adenomyosis uteri: evidence for dysregulation of oncogene pathways.

BACKGROUND: The pathogenesis of deep infiltrating endometriosis (DIE) is poorly understood. It is considered a benign disease but has histologic features of malignancy, such as local invasion or gene mutations. Moreover, it is not clear whether its invasive potential is comparable to that of adenomyosis uteri (FA), or whether it has a different biological background. Therefore, the aim of this study was to molecularly characterize the gene expression signatures of both diseases in order to gain insight into the common or different underlying pathomechanisms and to provide clues to pathomechanisms of tumor development based on these diseases. METHODS: In this study, we analyzed formalin-fixed and paraffin-embedded tissue samples from two independent cohorts. One cohort involved 7 female patients with histologically confirmed FA, the other cohort 19 female patients with histologically confirmed DIE. The epithelium of both entities was microdissected in a laser-guided fashion and RNA was extracted. We analyzed the expression of 770 genes using the nCounter expression assay human PanCancer (Nanostring Technology). RESULTS: In total, 162 genes were identified to be significantly down-regulated (n = 46) or up-regulated (n = 116) in DIE (for log2-fold changes of < 0.66 or > 1.5 and an adjusted p-value of < 0.05) compared to FA. Gene ontology and KEGG pathway analysis of increased gene expression in DIE compared to FA revealed significant overlap with genes upregulated in the PI3K pathway and focal adhesion signaling pathway as well as other solid cancer pathways. In FA, on the other hand, genes of the RAS pathway showed significant expression compared to DIE. CONCLUSION: DIE and FA differ significantly at the RNA expression level: in DIE the most expressed genes were those belonging to the PI3K pathway, and in FA those belonging to the RAS pathway.

High Frequency of Deep Infiltrating Endometriosis in Patients with Inflammatory Bowel Disease: A Nested Case-Control Study.

INTRODUCTION: Inflammatory bowel disease (IBD) and endometriosis are chronic inflammatory diseases occurring in young women, sharing some clinical manifestations. In a multidisciplinary approach, we aimed to investigate symptoms, type, and site of pelvic endometriosis in IBD patients versus non-IBD controls with endometriosis. METHODS: In a prospective nested case-control study, all female premenopausal IBD patients showing symptoms compatible with endometriosis were enrolled. Patients were referred to dedicated gynecologists for assessing pelvic endometriosis by transvaginal sonography (TVS). Each IBD patient with endometriosis (cases) was retrospectively matched for age (±5 years) and body mass index (±1) with 4 patients with endometriosis at TVS but no-IBD (controls). Data were expressed as median [range]; the Mann-Whitney or Student t and χ2 tests were used for comparisons. RESULTS: Endometriosis was diagnosed in 25 (71%) out of 35 IBD patients with compatible symptoms including 12 (52.6%) Crohn's disease and 13 (47.4%) ulcerative colitis patients. Dyspareunia and dyschezia were significantly more frequent in cases versus controls (25 [73.7%] vs. 26 [45.6%]; p = 0.03). At TVS, deep infiltrating endometriosis (DIE) and posterior adenomyosis were significantly more frequently observed in cases versus controls (25 [100%] vs. 80 [80%]; p = 0.03 and 19 [76%] vs. 48 [48%]; p = 0.02). CONCLUSIONS: Endometriosis was detected in two-thirds of IBD patients with compatible symptoms. The frequency of DIE and posterior adenomyosis was higher in IBD than in controls. A diagnosis of endometriosis, often mimicking IBD activity, should be considered in subgroups of female patients with IBD.

Lesion-to-anal-verge distance in rectosigmoid endometriosis on transvaginal sonography vs magnetic resonance imaging: prospective study.

OBJECTIVES: To compare transvaginal sonography (TVS) and magnetic resonance imaging (MRI) with intraoperative measurement (IOM) using a rectal probe in the estimation of the location of rectosigmoid endometriotic lesions, i.e. lesion-to-anal-verge distance (LAVD), and to compare two different MRI techniques for measuring LAVD. METHODS: This was a prospective single-center observational study that included women undergoing surgery for symptomatic rectosigmoid endometriosis by discoid (DR) or segmental (SR) resection from December 2018 to December 2019. TVS and MRI were performed presurgically for each participant to evaluate LAVD, and the measurements on imaging were compared with IOM using a rectal probe. Clinically acceptable difference and limits of agreement (LoA) between TVS and MRI compared with IOM were set at ± 20 mm. Two different measuring methods for MRI, MRICenter and MRIDirect , were proposed and evaluated, as there is currently no guideline to describe deep endometriosis on MRI. Bland-Altman plots and LoA were used to assess agreement of TVS and both MRI methods with IOM. Systematic and proportional biases were assessed using paired t-test and Bland-Altman plots. RESULTS: Seventy-five women were eligible for inclusion. Twenty-eight women were excluded, leaving 47 women for the analysis. Twenty-three DR and 26 SR procedures were performed, with both procedures performed in two women. The Bland-Altman plots showed that there were no systematic differences between TVS or MRICenter when compared with IOM for all included participants. MRIDirect systematically underestimated LAVD for lesions located further from the anal verge. TVS, MRICenter and MRIDirect had LoA outside the preset clinically acceptable difference when compared with IOM. LAVD was within the clinically acceptable difference from IOM of ± 20 mm in 70% (33/47) of women on TVS, 72% (34/47) of women on MRICenter and 47% (22/47) of women on MRIDirect . CONCLUSIONS: TVS should be the preferred method to estimate the location of a rectosigmoid endometriotic lesion, i.e. LAVD, as it is more available, less expensive and has a similar accuracy to that of MRI. Estimating LAVD can be relevant for planning colorectal surgery for rectosigmoid endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Robotic-assisted versus conventional laparoscopic approach in patients with large rectal endometriotic nodule: the evaluation of safety and complications.

AIM: The aim was to compare postoperative complications in patients undergoing the excision of a rectal endometriotic nodule over 3 cm by a robotic-assisted versus a conventional laparoscopic approach. METHODS: We conducted a retrospective cohort study evaluating prospectively collected data. The main interventions included rectal shaving, disc excision or colorectal resection. All the surgeries were performed in one endometriosis reference institute. To evaluate factors significantly associated with the risk of anastomosis leakage or fistula and bladder atony, we conducted a multivariate logistic regression model. RESULTS: A total of 548 patients with rectal endometriotic nodule over 3 cm in diameter (#ENZIAN C3) were included in the final analysis. The demography and clinical characteristics of women managed by the robotic-assisted (n = 97) approach were similar to those of patients who underwent conventional laparoscopy (n = 451). The multivariate logistic regression demonstrated that the surgical approach (robotic-assisted vs. laparoscopic) was not associated with the rate of anastomosis leakage or fistula (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.3-4.0) and bladder dysfunction (aOR 0.5, 95% CI 0.1-1.8). A rectal nodule located lower than 6 cm from the anal verge was significantly associated with anastomosis leakage (aOR 4.1, 95% CI 1.4-10.8) and bladder atony (aOR 4.3, 95% CI 1.5-12.3). Anastomosis leakage was also associated with smoking (aOR 3.2, 95% CI 1.4-7.4), significant vaginal infiltration (aOR 2.7, 95% CI 1.2-6.7) and excision of nodules involving sacral roots (aOR 5.6, 95% CI 1.7-15.5). CONCLUSION: The robotic-assisted approach was not associated with increased risk of main postoperative complications compared to conventional laparoscopy for the treatment of large rectal endometriotic nodules.

Prevalence of urinary dysfunction after minimally invasive surgery for deep rectosigmoid endometriosis.

PURPOSE: This study aimed to assess the prevalence and progression of lower urinary tract symptoms following laparoscopic surgery for deep-infiltrating endometriosis of the rectosigmoid and identify preoperative factors associated with worse postoperative outcomes. METHODS: Prospective, observational study. SETTINGS: single-center, referral hospital for endometriosis. Patients undergoing laparoscopic surgery for deep-infiltrating endometriosis of the rectosigmoid colon between October 2016 and October 2018. MAIN OUTCOME MEASURES: urinary function was assessed with the validated Portuguese language version of the International Prostate Symptom Score, which is also used in women. The score was collected before and after surgery. The Wilcoxon signed-rank test was used to compare pre and postoperative scores and the chi-square test compared symptoms categorized by severity. RESULTS: Fifty-three patients were assessed and 44 were included. Concerning urinary symptoms after surgery, the irritative symptoms prevailed over the obstructive ones. Additionally, 58.8% and 54.5% of the women reported moderate or severe symptoms at pre and postoperative, respectively. In at least one questionnaire category, the postoperative questionnaire scores increased in ten (22.7%) participants. A statistically significant difference was found comparing the changes from absent/mild to moderate/severe IPSS categories (P = 0.039). No significant changes were identified in any of the International Prostate Symptom Score pre and postoperatively (P = 0.876). CONCLUSIONS: There was a high prevalence of pre and postoperative urinary symptoms. Patients with preoperative moderate/severe International Prostate Symptom Score are at risk of persisting urinary dysfunction after surgery for rectosigmoid deep endometriosis.

Prevalence and Risk Factors of Central Sensitization in Women with Endometriosis.

STUDY OBJECTIVE: To assess prevalence of central sensitization (CS) and its association with demographic and clinical factors in patients with endometriosis. DESIGN: Single-center, observational, cross-sectional study. SETTING: Tertiary center. PATIENTS: Consecutive patients with endometriosis referred to the center from January 15, 2022, to April 30, 2022. INTERVENTIONS: For each enrolled patient, demographic and clinical data were collected, and the presence of CS was measured using the CS Inventory questionnaire (score ≥40). MEASUREMENTS AND MAIN RESULTS: Primary study outcome was CS prevalence, and secondary study outcomes were the associations between demographic and clinical factors and CS. The 95% confidence intervals for CS prevalence were obtained with Bayesian-derived Jeffreys method, and the associations between CS and demographic and clinical factors were evaluated with the chi-square test and Fisher's exact test, where appropriate. The variables significantly associated with CS were then included in a multivariable logistic regression model. The significance level was set at .05 for all analyses. During the study period, 285 eligible women were enrolled. CS prevalence was 41.4% (95% confidence interval, 35.8-47.2). At univariable analysis, infertility, moderate to severe pain symptoms (except for dyschezia), altered bowel movements, posterolateral parametrium involvement, hormonal therapy failure (HTF), and most of central sensitivity syndromes were significantly associated with CS occurrence. Multivariable analysis only confirmed the significant association of CS with moderate to severe chronic pelvic pain, posterolateral parametrium involvement, HTF, migraine or tension-type headache, irritable bowel syndrome, and anxiety or panic attacks. CONCLUSION: CS has a high prevalence in patients with endometriosis, especially in those with moderate to severe chronic pelvic pain, posterolateral parametrium involvement, HTF, and 3 central sensitivity syndromes (i.e. migraine or tension-type headache, irritable bowel syndrome, anxiety or panic attacks). Given the association with HTF, identifying CS through CS Inventory might be useful to counsel the patient and to choose multimodal treatment.

Outcomes after Laparoscopic Excision of Bladder Endometriosis Using a CO2 Laser: A Review of 207 Cases in a Single Center.

STUDY OBJECTIVE: Assess efficacy, safety, fertility outcomes and recurrence after laparoscopic resection of bladder endometriosis (BE) using a CO2 laser. DESIGN: Retrospective cohort study. SETTINGS: University gynecologic surgery unit, referral center for endometriosis. PATIENTS: A total of 207 women having undergone laparoscopic BE excision between January 1998 and January 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Intra- and postoperative complication rates. Disease recurrence and fertility outcomes in patients with a minimum 1-year follow-up (n = 176) for "isolated" and "non-isolated" BE groups. RESULTS: Forty-three patients presented with isolated BE. Bladder "shaving" without mucosae opening was performed in 50.7% cases. No intraoperative complications were noted. One postoperative grade 3 complication was related to BE excision: a bladder breach requiring closure by repeat laparoscopy. Mean (± SD) follow-up was 7.05 (± 4.65) years. In patients wishing to conceive (n = 132), the total pregnancy rate (PR) was 75% (48.5% spontaneous), 76.19% in the isolated BE group (56.3% spontaneous). Among the 94 patients with previous infertility, 74.5% conceived, 50% spontaneously. No statistical difference was found in PR and need for in vitro fertilization between isolated and nonisolated BE groups. BE recurrence rate was 3.4%. No difference was observed between groups with full-thickness bladder resection (4/88) and shaving (2/88) (p = .406). Age at surgery (hazard ratio 0.91 [0.84-0.98], p = .016) and postoperative pregnancy (hazard ratio 0.07 [0.01-0.91], p = .042) showed influence on disease recurrence. CONCLUSIONS: The study demonstrates that laparoscopic BE removal is feasible with very low complications rates and was associated with high PR (both spontaneous and in vitro fertilization), even in patients with previous infertility. BE recurrence is lower than for other endometriosis locations. Bladder endometriosis; Laparoscopy; Deep infiltrating endometriosis; Fertility; Partial bladder resection.

Ultrasound Characteristics and Scanning Techniques of Uterosacral Ligaments for the Diagnosis of Endometriosis: A Systematic Review.

Endometriosis is a common and painful gynaecological condition that takes an average of 6.4years to diagnose. While laparoscopic surgery is the recommend gold standard in diagnosis of endometriosis, transvaginal ultrasound (TVS) is able to assist surgeons in the planning and management of patients, especially when there is limited visualisation in the posterior compartment. Uterosacral ligaments (USL) are located in the posterior compartment and are one of the first and most common places that endometriosis deposits, The International Deep Endometriosis Analysis (IDEA) group consensus, which are the current guidelines for DE imaging, recommends a thorough ultrasound assessment to identify endometriotic disease. This includes an assessment of anatomic structures in the posterior compartment including the USLs. However, IDEA does not explicitly articulate specifics of USL imaging and measurements on ultrasound. The primary aim of this review is to determine is to identify ultrasound techniques and characteristics of USLs in the diagnosis of deep infiltrative endometriosis (DE). The secondary aim is to describe and summarise these findings into normal and pathological findings. A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A population, interventions, comparator, and outcome framework was used to define a search strategy. Articles were screened using Covidence review management system, and data was extracted by two authors using a standardised and piolet-tested form. Quality assessment was conducted using the Critical Appraisal Skills Programme (CASP). Medline, Embase and Scopus and Google Scholar were searched yielding 250 articles, with 22 being included in the review. Analysis of the data demonstrated inconsistent reporting of ultrasound techniques and characteristics of USLs. Most (20/22) papers described abnormal criteria of USLs, only 5/22 papers determined what the normal USL appearance is or what techniques (11/22) were applied. Even though reporting was heterogeneous, there was a high level of tertiary centre participation with gynaecological experienced operators, therefore was a high level of agreement. Through review of the current literature, this study has investigated ultrasound techniques and characteristics of USLs for the diagnosis of DE. All papers included in this review reported presence of pathological sonographic findings of the USLs when DE was presented therefore it is recommended that USL examination become a part of TVS exams when DE is clinically suspected. This study also demonstrated that there was lack of data and no agreement when it comes to measuring USLs with DE. Even so, the current evidence demonstrates that scanning the USLs, and locating, identifying, and describing USL thickening and endometriotic nodules in the various locations using the described techniques and characteristics in this review has clinical value in early diagnosis.