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Objective: Two‐dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost‐effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D‐TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis. Methods: This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D‐TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D‐TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed. Results: A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D‐TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7–62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2–81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs. Conclusions: Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false‐positive and false‐negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The idea of quality improvement in the management of endometriosis has been brought to attention throughout Europe. This - first and foremost - includes the implementation of centers specialized in treating endometriosis. This leads to qualification of both physicians and other medical staff, enforcement of research efforts, and informing the patients, the public, politicians, healthcare providers, and industry. Given limited budgets, focusing on the existing national commitment may be the first step. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

As well as providing reliable contraception, modern low-dose oral contraceptives may offer some non-contraceptive advantages. Positive effects on problems such as edema with weight increase and breast tenderness, bloating, dysmenorrhea, and an improvement in skin and hair condition have been reported in several studies using an oral contraceptive containing drospirenone. If these disorders are cycle-dependent, use of the contraceptive in an extended regimen may be of additional benefit. The study reported in this paper followed 1433 women, 175 of whom took the drospirenone-containing pill continuously for between 42 and 126 days. Some symptoms of the premenstrual syndrome were influenced very satisfactorily by administration in an extended regimen. [ABSTRACT FROM AUTHOR]

Essential features of endometrial physiology involve the extracellular matrix (ECM). In the pathogenesis of endometriosis, interactions of endometriosis cells with ECM can be postulated. Two systems of secreted proteases in the endometrium, the plasmin(ogen) activator/inhibitor and the matrix metalloproteinases and their inhibitors were examined in cell cultures of uterine endometrial cells from women with and without endometriosis. Soluble urokinase receptor secretion is increased, and mRNA transcription of tissue inhibitor of metalloproteinases-2 (TIMP-2) is upregulated by progestin in endometriosis. These findings are compatible with an altered ECM turnover in the endometrium of these patients that may explain a higher invasive potential of retrogradely menstruated endometrial fragments. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the influence of activated autologous blood therapy on immunological parameters and on the clinical outcome in patients with recurrent spontaneous abortion. In a prospective trial, 36 women with recurrent spontaneous abortion were treated with intramuscular reinjections of extracorporally haemolysed and ultraviolet irradiated autologous blood. A comprehensive immunological investigation revealed significant changes in lymphocyte subpopulations, plasma complement levels, mitogen stimulation and immunoglobulin levels during the treatment period. No side-effects were reported by the patients. From June 1994 to November 1995, 22 intrauterine and one extrauterine pregnancies occurred, resulting in 19 (86%) live births, two (9%) spontaneous abortions and one (4%) artificial abortion compared with a 64% live birth rate in the historical control group. We conclude that activated autologous blood therapy has detectable effects on the immune system, and seems to be promising for further investigation concerning the treatment of idiopathic recurrent spontaneous abortion. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: The aim of the current study was to evaluate the prevalence and the impact of sexual dysfunction, sexual distress and interpersonal relationships in patients with endometriosis. Study design: A questionnaire-based multicentre cohort study was conducted in eight tertiary referral centres in Austria and Germany. One hundred and twenty-five patients with histologically proven endometriosis and dyspareunia were included. The Female Sexual Function Index and the Female Sexual Distress Scale were used to screen women's sexuality. Additionally, we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered questionnaire. Results: Female sexual distress and sexual dysfunction were observed in 97/125 and 40/125 patients. Statistically significant correlations were found between sexual dysfunction and pain intensity during/after sexual intercourse (p <0.01/p <0.01), a lower number of episodes of sexual intercourse per month (p <0.01), greater feelings of guilt towards the partner (p <0.01) and fewer feelings of feminity (p <0.01). Thirty-eight out of 125 women agreed that the primary motivation for sexual intercourse was to conceive and nearly half of women (46%) included stated that satisfying the partner acted as primary motivation for sexual contact. Conclusion: Overall, our findings demonstrate that dyspareunia as a common complaint in patients with endometriosis causes a severe impairment of sexual function, relationship and psychological wellbeing. [Copyright &y& Elsevier]

Introduction: The description of a salivary miRNA signature for endometriosis has led to the development of a non-invasive diagnostic test. Current healthcare provider practices regarding the test remain uncaptured. The application of this test in practice was examined in a web-based survey, with the aim to provide their opinions on it., Methods: We conducted an open web-based survey study between November 2023 and January 2024. Members of the German society of gynecologic endoscopy (Arbeitsgemeinschaft gynäkologische Endoskopie, AGE), society of endometriosis (Arbeitsgemeinschaft Endometriose, AGEM), and the endometriosis research foundation (Stiftung Endometriose Forschung, SEF) were contacted per e-mail twice. Participants' data were anonymized. Differences in responses based on self-reported expertise in the field (basic knowledge, specialized knowledge, expert) were assessed using the χ 2 -test or Fisher's exact test. Statistical significance was set as p < 0.05., Results: In total 141 of 190 respondents completely responded to the survey (> 75% of the questions of the survey). Twenty-one physicians reported having experience with the test, while most participants had at least specialized knowledge on the field (112/141). In terms of specific questions, more than 90% found the costs high; almost 85% did not believe that the test replaces standard diagnostic tools (histology, clinical examination, and sonography). Eighty-six providers supported the use of the test in adolescents. Gynecologists with basic knowledge had a more positive attitude compared with more experienced ones in terms of usefulness (Fisher's exact test, p < 0.001). Significant differences were demonstrated between expertise groups regarding (not only) applicability in adolescents (Fisher's exact test, p = 0.004), and using the test for screening purposes (χ 2 -test, p = 0.002)., Discussion: Despite the promising benefits of a salivary test for endometriosis, German healthcare providers would not change current practices. Nevertheless, less experienced colleagues were more positive towards the test., (© 2024. The Author(s).)

Introduction After puberty, at least 10% of all women and girls suffer from endometriosis. Surgery is useful for both the diagnosis and therapy. To date, quality indicators for the surgical treatment of endometriosis are lacking. QS ENDO aims to record the quality of care provided in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis. In the first phase of the study, QS ENDO real, the reality of care was recorded using a questionnaire. The second phase, QS ENDO pilot, investigated the treatment of patients who underwent surgery in certified endometriosis centers in a defined time-period. Material and Methods The surgical data of 10 patients from each of the 44 endometriosis centers in the DACH region was recorded using an online tool. Collected data included the approach used, the endometriosis phenotype, a description of the surgical site, resection status, histological confirmation, the use of a classification, and any complications. All operations were carried out in October 2016 as the defined time-period. The surgical approaches used were compared with the recommendations in the current guidelines. Results The data of 435 patients with a median age of 34 years were evaluated. 315 (72.4%) were nulliparous. 120 patients had given birth to at least one child and 42.5% (51) of them had delivered their child by caesarean section. About 50% of all patients also had deep infiltrating endometriosis in addition to ovarian endometriosis, and the median NAS score was 7.5. With regards to the surgical treatment, endometriomas were completely resected in 81% (94) of patients. 87.3% of patients underwent resection of peritoneal endometriosis. Forty-one patients had a hysterectomy, with a total hysterectomy carried out in 26 (63.4%) and a supracervical hysterectomy in 15 (36.6%) patients. Of the 59 patients with bowel endometriosis, half had segmental resection and half had shaving of the anterior rectal wall. Complications requiring revision occurred in 0.9% of cases. Conclusion The surgical procedures carried out in the certified endometriosis centers of the DACH region are largely in line with the recommendations for appropriate surgical approaches in the current standard guidelines., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Purpose: Adenomyosis is a common disease of females during their reproductive age. As of today, histologic examination of the uterus after hysterectomy constitutes the gold standard for diagnosis. The aim of this study was to determine the validity of sonographic, hysteroscopic, and laparoscopic criteria for the diagnosis of the disease., Methods: This study included data collected from 50 women in the reproductive age of 18-45 years, who underwent a laparoscopic hysterectomy in the gynecology department of the Saarland University Hospital in Homburg between 2017 and 2018. The patients with adenomyosis were compared with a healthy control group., Results: We collected data of anamnesis, sonographic criteria, hysteroscopic criteria and laparoscopic criteria and compared it with the postoperative histological results. A total 25 patients were diagnosed with adenomyosis postoperatively. For each of these; at least three sonographic diagnostical criteria for adenomyosis were found compared with a maximum of two for the control group., Conclusion: This study demonstrated an association between pre- and intraoperative signs of adenomyosis. In this way, it shows a high diagnostic accuracy of the sonographic examination as a pre-operative diagnostic method of the adenomyosis., (© 2023. The Author(s).)

Introduction Endometriosis significantly reduces patients' quality of life and is additionally a burden on healthcare and social security systems. There are currently no quality indicators for the treatment of endometriosis. The care of patients with endometriosis must be considered inadequate. QS ENDO aims to record the quality of care available in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis as part of providing quality assurance in endometriosis care. The first phase, QS ENDO Real, recorded the reality of current care using a questionnaire. The second phase, QS ENDO Pilot, investigated the treatment of 435 patients who underwent surgical treatment within a defined one month period in certified endometriosis centers. Material and Methods An online tool was used to gather information about 9 points which covered both prior patient history and the process of clinical diagnosis. Surgery reports were reviewed to obtain information about the surgical approach, the investigated sites, findings of any histological examinations, the use of classification systems, and information about resection status. Results 85.3% of patients were asked all 4 questions about their prior medical history. All 5 diagnostic steps were carried out in 34.5% of patients. The 3 areas needed to describe potential sites of disease were recorded in 67.1% of patients. Samples for histological examination were taken in 84.1% of patients. The endometriosis stage was classified in 94.7% of surgeries. A combination of the rASRM and the ENZIAN classifications, which is needed for complex cases, was used in 46.1% of patients. Complete resection was achieved in 81.6% of surgical procedures. Conclusion For the first time, the quality of care in certified endometriosis centers has been recorded using QS ENDO Pilot. Despite the high certification standards, a substantial number of required indicators were omitted., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Importance: Pain is a silent global epidemic impacting approximately a third of the population. Pharmacological and surgical interventions are primary modes of treatment. Cognitive/behavioural management approaches and interventional pain management strategies are approaches that have been used to assist with the management of chronic pain. Accurate data collection and reporting treatment outcomes are vital to addressing the challenges faced. In light of this, we conducted a systematic evaluation of the current digital application landscape within chronic pain medicine., Objective: The primary objective was to consider the prevalence of digital application usage for chronic pain management. These digital applications included mobile apps, web apps, and chatbots., Data Sources: We conducted searches on PubMed and ScienceDirect for studies that were published between 1st January 1990 and 1st January 2021., Study Selection: Our review included studies that involved the use of digital applications for chronic pain conditions. There were no restrictions on the country in which the study was conducted. Only studies that were peer-reviewed and published in English were included. Four reviewers had assessed the eligibility of each study against the inclusion/exclusion criteria. Out of the 84 studies that were initially identified, 38 were included in the systematic review., Data Extraction and Synthesis: The AMSTAR guidelines were used to assess data quality. This assessment was carried out by 3 reviewers. The data were pooled using a random-effects model., Main Outcomes and Measures: Before data collection began, the primary outcome was to report on the standard mean difference of digital application usage for chronic pain conditions. We also recorded the type of digital application studied (e.g., mobile application, web application) and, where the data was available, the standard mean difference of pain intensity, pain inferences, depression, anxiety, and fatigue., Results: 38 studies were included in the systematic review and 22 studies were included in the meta-analysis. The digital interventions were categorised to web and mobile applications and chatbots, with pooled standard mean difference of 0.22 (95% CI: -0.16, 0.60), 0.30 (95% CI: 0.00, 0.60) and -0.02 (95% CI: -0.47, 0.42) respectively. Pooled standard mean differences for symptomatologies of pain intensity, depression, and anxiety symptoms were 0.25 (95% CI: 0.03, 0.46), 0.30 (95% CI: 0.17, 0.43) and 0.37 (95% CI: 0.05, 0.69), respectively. A sub-group analysis was conducted on pain intensity due to the heterogeneity of the results ( I 2  = 82.86%; p  = 0.02). After stratifying by country, we found that digital applications were more likely to be effective in some countries (e.g., United States, China) than others (e.g., Ireland, Norway)., Conclusions and Relevance: The use of digital applications in improving pain-related symptoms shows promise, but further clinical studies would be needed to develop more robust applications., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343., Competing Interests: PP has received research grant from Novo Nordisk, and other, educational from Queen Mary University of London, other from John Wiley & Sons, other from Otsuka, outside the submitted work. All other authors report no conflict of interest. TF has received funding from Boston Scientific. AS is the Chief Medical Officer for Nurokor Medical Systems. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health and Social Care or the Academic institutions., (© 2022 Shetty, Delanerolle, Zeng, Shi, Ebrahim, Pang, Hapangama, Sillem, Shetty, Shetty, Hirsch, Raymont, Majumder, Chong, Goodison, O'hara, Hull, Pluchino, Shetty, Elneil, Fernandez, Brownstone and Phiri.)

Introduction: Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries., Material and Methods: This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared., Results: The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (r Spearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups., Conclusions: A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Advances in preoperative diagnostics as well as in surgical techniques for the treatment of endometriosis, especially for deep endometriosis, call for a classification system, that includes all aspects of the disease such as peritoneal endometriosis, ovarian endometriosis, deep endometriosis, and secondary adhesions. The widely accepted revised American Society for Reproductive Medicine classification (rASRM) has certain limitations because of its incomplete description of deep endometriosis. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable tool for staging deep endometriosis, but does not include peritoneal or ovarian disease or adhesions. To overcome these limitations, a comprehensive classification system for complete mapping of endometriosis, including anatomical location, size of the lesions, adhesions and degree of involvement of the adjacent organs, that can be used with both diagnostic and surgical methods, has been created through a consensus process and will be described in detail-the #Enzian classification., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Endometriosis affects a significant number of young premenopausal women. Quite apart from the medical challenges, endometriosis is a relevant burden for healthcare and social security systems. Standardized quality indicators for the treatment of endometriosis have not previously been systematically verified. The three-stage study QS ENDO was initiated to record and improve the reality and quality of care. One of its aims is to create quality indicators for the diagnosis and treatment of endometriosis. For the first stage of QS ENDO Real, letters were sent to all 1014 gynecological departments in the German-speaking area of Europe (the DACH region) which included a questionnaire as a means of surveying the current state of care. A total of 296 (29.2%) of the centers which received the questionnaire participated in the survey. The subsequent evaluation of the completed questionnaires showed that the majority of patients with endometriosis (around 60%, based on estimates from the data) are not treated in hospitals which have been certified by the SEF. The guidelines recommend the use of specific classification systems (rASRM, ENZIAN) but, depending on the level of care offered by the hospital, only around 44.4 to 66.4% of departments used the rASRM score and only 27% of hospitals used the ENZIAN classification system to describe deep-infiltrating endometriosis. When taking patients' medical history, some centers (6.6 - 17.9%) considered questions about leading symptoms such as dyschezia, dysuria and dyspareunia to be unimportant. QS ENDO Real has made it possible, for the first time, to get an overview of the reality of care provided to patients with endometriosis in the German-speaking areas of Europe. The findings indicate that several of the measures recommended in international guidelines as the gold standard of care are only used to treat some of the patients. In this respect, more efforts will be needed to provide more advanced training. The approach used for treatment must be guideline-based, also in not-certified centers, to improve the quality of care in the treatment of patients with endometriosis., Competing Interests: Conflict of Interest/Interessenkonflikt No conflicts of interest reported. Several authors are leaders of SEF-certified Endometriosis centers. Klaus Bühler, Karl-Werner Schweppe and Martin Sillem are members of the SEF board./Kein Interessenkonflikt angegeben. Einige der Autoren sind Leiter SEF-zertifizierter Endometriosezentren. Klaus Bühler, Karl-Werner Schweppe und Martin Sillem sind Mitglieder des SEF-Vorstandes.

Purpose: Superficial peritoneal endometriotic (pEM) lesions are composed of endometrial glands and stroma, in addition to a third component-myofibroblasts and smooth muscles (SM)-like cells. The latter develops secondary to a metaplasia. In this study, we characterised the third component cells in pEM according to differentiation markers in different micro-compartments. Furthermore, a possible effect of TGFβ1 on myofibroblastic metaplasia in endometriotic epithelial cells was studied., Methods: Seventy-six premenopausal patients were included. Peritoneal biopsies were excised from EM patients (n = 23), unaffected peritoneum (peritoneum from EM patients but without EM components, n = 5/23) and non-EM patients (n = 10). All peritoneal biopsies were immunolabeled for ASMA, calponin, collagen I, desmin, TGFß receptor 1 (R1), R2 and R3 in addition to ultrastructure examination by transmission electron microscopy (TEM) (n = 1). TGFß1 level was measured in peritoneal fluid (PF) (EM, n = 19 and non-EM, n = 13) collected during laparoscopy. Furthermore, TGFß1 effect on myofibroblastic metaplasia was studied in vitro., Results: At the centre of pEM lesions, calponin immunolabeling outweighs the collagen I while in the periphery the reverse occurs. SM-like cells expressing desmin predominate at the periphery, while ASMA immunolabeling was detectable in all micro-compartments. Both indicate an abundance of myofibroblasts at the centre of pEM lesions and SM-like cells in the periphery. Although activated TGFß1 in PF did not differ between EM and non-EM, it inhibited the cell proliferation of the endometriotic epithelial cells and induced an upregulation in ASMA and collagen IA2 expression as well., Conclusion: The abundance of the myofibroblasts and SM-like cells points to a myofibroblastic metaplasia in pEM. Both cells are differentially arranged in the different micro-compartments of pEM lesions, with increasing cell maturity towards the periphery of the lesion. Furthermore, TGFß1 may play a role in the myofibroblastic metaplasia of the endometriotic epithelial cells. These findings provide a better insight in the micro-milieu in EM lesions, where most of the disease dynamics occur.

Background: Adenomyosis (AM) uteri exhibit hyperperistalsis. The latter causes a chronic tissue trauma at the endometrial-myometrial junctional zone (EMJZ). Upon tissue trauma, microdehiscences in the myometrium facilitate the translocation of basal endometrial fragments into the myometrium. There, a metaplasia (mediated by transforming growth factor β1 [TGFβ1] and connective tissue growth factor [CTGF]) occurs and AM lesions develop. The abundance of myofibroblasts in a tissue hallmarks metaplasia and points to a tissue microtrauma., Materials and Methods: To study if myofibroblasts-as an evidence of tissue microtrauma-are more abundant at EMJZ in AM-uteri, a case-control experimental study was carried out at Charité University Hospital-Endometriosis Research Centre. In all, 18 uteri with AM and 14 uteri without AM were obtained during laparoscopy-assisted vaginal hysterectomy. The immunolabeling of myofibroblastic metaplasia (alpha smooth muscle actin [ASMA] and collagen I), differentiated smooth muscle marker (desmin) and metaplasia mediators (TGF-β receptors 1, 2, 3 and CTGF) was investigated. The ultrastructure of myofibroblasts at EMJZ of AM uterus was characterized by transmission electron microscopy, in addition to an in vitro study to characterize myofibroblasts in the endometrium of non-AM uterus., Results: Immunolabeling of ASMA and collagen I was significantly higher at EMJZ of AM uteri versus non-AM uteri. Furthermore, myofibroblasts were ultrastructurally characterized at EMJZ of AM. Endometrium of non-AM uterus exhibited 5% to 8% of its cells, expressing ASMA and collagen I. No difference was noted regarding metaplasia mediators immunolabeling between both the groups., Conclusion: The abundant and persistent myofibroblasts (expressing ASMA/collagen I) at EMJZ in AM uteri are ultra-/microscopic evidence of chronic tissue trauma. They are of nonmyometrial origin, as they lack desmin immunolabeling.

Background: We evaluated breast cancer (BC) core biopsies taken before neoadjuvant chemotherapy (NACT) by immunohistochemistry using anti-phosphohistone H3 (PHH3) antibody to determine mitosis, and correlated the results to clinicopathological data and histopathological regression of resected tumor specimens after NACT., Methods: 72 patients with either triple-negative (TN) or luminal type BC received NACT with epirubicin/cyclophosphamide (EC) and Taxotere®. Tumor regression was analyzed in resected specimens; pathological complete response (pCR) was achieved in 22.2%. Immunohistochemistry with PHH3 was performed on biopsy samples taken before treatment, and mitotic figures were evaluated in 10 high-power fields (HPF)., Results: PHH3-detected mitoses correlated significantly with tumor grading (p = 0.001). TNBC showed > 10 PHH3-positive mitoses/10 HPF significantly more frequently than luminal type BC (p = 0.003). Tumors with > 10 PHH3-positive mitoses/10 HPF achieved pCR significantly more often than those with ≤ 10 PHH3-positive mitoses/10 HPF (p = 0.031). Even luminal type BC with > 10 PHH3-positive mitoses/10 HPF was associated significantly with pCR compared to luminal type BC with ≤ 10 PHH3-positive mitoses/10 HPF (p = 0.016)., Conclusion: NACT with EC and Taxotere is suitable for strong proliferating TNBC and luminal BC (> 10 PHH3-positive mitoses/10 HPF). Immunohistochemical determination of mitoses using anti-PHH3 antibody is a simple and robust method for predicting therapy response to NACT in BC tissue.

Introduction Minimally invasive operative techniques are being used increasingly in gynaecological surgery. The expansion of the laparoscopic operation spectrum is in part the result of improved imaging. This study investigates the practical advantages of using 3D cameras in routine surgical practice. Materials and Methods Two different 3-dimensional camera systems were compared with a 2-dimensional HD system; the operating surgeon's experiences were documented immediately postoperatively using a questionnaire. Results Significant advantages were reported for suturing and cutting of anatomical structures when using the 3D compared to 2D camera systems. There was only a slight advantage for coagulating. The use of 3D cameras significantly improved the general operative visibility and in particular the representation of spacial depth compared to 2-dimensional images. There was not a significant advantage for image width. Depiction of adhesions and retroperitoneal neural structures was significantly improved by the stereoscopic cameras, though this did not apply to blood vessels, ureter, uterus or ovaries. Conclusion 3-dimensional cameras were particularly advantageous for the depiction of fine anatomical structures due to improved spacial depth representation compared to 2D systems. 3D cameras provide the operating surgeon with a monitor image that more closely resembles actual anatomy, thus simplifying laparoscopic procedures.

Introduction: Our aim was to assess the practicability and reliability of a novel labeling regime for axillary sentinel lymph nodes (SLNs) in early breast cancer., Methods: 362 patients with early breast cancer (bilateral in 9 cases, giving a total of 371 cases) underwent intradermal radio tracer injection with simultaneous manual lymphatic drainage. SLN biopsy was performed within 24 h. For retrospective analysis, data were extracted from patient's records., Results: At least 1 SLN was detected intraoperatively in 369 cases (99.5%, range 1-9 nodes). This node was metastatic in 88 and unaffected in 281 cases. Coincidentally removed but unlabeled lymph nodes were affected in 3 cases in which the SLN was unaffected (3/153 = 2%). In all cases, on histological evaluation, tissue removed as SLN contained lymph nodes. After a period of 69.5 months (median 1.7-115.8 months), no axillary recurrences were observed in 213 patients., Conclusion: Manual lymphatic drainage is a simple technique that leads to an extremely high pick-up rate of axillary SLNs after subepidermal radio tracer injection. If unaffected, this node correctly predicts nodal-negative disease in 98% of cases studied.

BACKGROUND: Psychosocial treatment is an integral component in today's comprehensive breast cancer care. The main goal of this study was to test the feasibility (benefits and acceptance) of supportive-expressive group psychotherapy (SEGT), a short-term breast cancer-specific group therapy developed and tested in Anglo-American countries, within breast centers in Germany. PATIENTS AND METHODS: The study was realized as a single-group pre-post design. Data were analyzed by combining quantitative and qualitative research methods. The sample consisted of 49 women with breast cancer stage 1 or 2 according to TNM classification (tumor, node, metastasis). RESULTS: The results indicate positive acceptance of the group intervention. Quality of life, tumor-related fatigue and coping strategies improved after SEGT. 1 year after the intervention, the patients report lasting positive results from the group intervention. CONCLUSIONS: This pilot study illustrates the importance of psychooncological group interventions for breast cancer patients and indicates that this form of outpatient psychooncological care is feasible within the German health care system, and breast centers in particular. Effectiveness has to be investigated in randomized controlled trials.

Yasminelle((R)) is a newly developed combined oral contraceptive that contains ethinyl estradiol 20 microg and drospirenone 3 mg. Yasminelle is unlike other low-dose ethinyl estradiol combined oral contraceptives, since drospirenone produces antiandrogenic and antimineralocorticoid effects that offer various benefits including a reduced potential for estrogen-induced water retention. Pharmacological and pharmacokinetic data have been derived from clinical experience with ethinyl estradiol 30 microg and drospirenone 3 mg (Yasmin((R))). Clinical studies with Yasminelle have shown a high degree of contraceptive efficacy, similar to that of combined oral contraceptives that contain a low dose of ethinyl estradiol combined with other progestins. These studies have also demonstrated that Yasminelle produces excellent cycle control and has a good tolerability profile, similar to that of other low-dose ethinyl estradiol combined oral contraceptives.

Laparoscopy holds a key role in daignosing and treating endometriosis. The present paper aims at clarifying the correct indication for this procedure. To this end, relevant guidelines as well as considerations regarding incidence, pathogenesis as well as diagnostic and therapeutic alternatives are presented. An algorithm for clinical practice is presented.

The ENZIAN-Score is presented as a new instrument to classify the deep infiltrating endometriosis. Especially the retroperitoneal part of the severe endometriosis is focussed on. In analogy to an oncological staging four different stages are pronounced. The localisation and the expansion of the endometriosis nodule was indicated to different subgroups. The still used rAFS-score is of no clinical evidence, as we pointed out in a retrospective study of our patients with severe intestinal endometriosis.

Numerous medical, surgical, and combined therapies have been proposed in the management of endometriosis. This range of treatment options contrasts remarkably with the evidence regarding their respective proven success rates. An exact preoperative differential diagnosis as well as adherence to operative recommendations that have been established meanwhile are essential for optimal results of surgery.

Malignant tumors arising from endometriosis are rare. A frequency of about 1% has been reported with in 80% the ovary, and in 20% extragonadal sites being affected. The most common extragonadal manifestations are the rectosigmoid and the rectovaginal septum. For extragonadal malignant tumors arising from endometriosis, complete resection followed by post-operative radiotherapy, possibly plus adjuvant progestin therapy, is the treatment of choice. Endometriosis-associated ovarian carcinomas are likely to present with lower stage disease and predominantly lower grade tumors. While their treatment follows that of common ovarian cancer, a poorer response to chemotherapy must be considered. As unopposed estrogen replacement therapy has been identified as a risk factor for the development of endometriosis-associated cancer, it is not recommended for hormone replacement therapy in women with a history of endometriosis. Loss of heterozygosity and mutations of the PTEN tumor suppressor gene may be early events of tumorigenesis. Endometriosis and its malignant transformation, perhaps, may serve as a suitable model in this regard. According to recent studies, endometriosis is associated with an increased relative risk of non-Hodgkin lymphoma.

Objective: To determine whether alterations in the secretion and regulation of matrix metalloproteinases (MMPs) and their inhibitors are present in uterine endometrial cells from endometriosis patients., Study Design: In an in vitro study, uterine endometrial cells from 19 regularly cycling women with and 32 without endometriosis were treated with diethyl stilbestrol, promegestone (R5020), interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha). Culture supernatants were assayed for MMPs 1, 2, 3, and 9, and for tissue inhibitors of MMP (TIMP-1 and TIMP-2) by ELISA., Results: MMP-3 was secreted in high concentrations, moderate concentrations were seen for MMP-1 and MMP-2, and very low concentrations for MMP-9. Substantially more TIMP-1 than TIMP-2 was secreted. MMP-1 and MMP-3 were uniformly attenuated by R5020, while MMP-2 was not influenced by hormone treatment. MMP-3 was upregulated by TNF-alpha in all samples while IL-1 only increased secretion in cells from endometriosis patients., Conclusion: The upregulation of MMP-3 by IL-1 may contribute to an increased invasiveness of uterine endometrial fragments in endometriosis patients.

Objectives: (1) to demonstrate specificity of integrin function in endometrial cell adhesion; (2) to investigate their regulation by tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1); and (3) to detect differences between cells from patients with and without endometriosis., Study Design: Endometrial cell cultures from ten patients with and 13 without endometriosis were tested for their expression of integrins alpha2beta1, alpha5beta1, alpha(v)beta3, and alpha4beta1 by immunocytochemistry and for their adhesion to collagen type IV, laminin, and fibronectin., Results: Integrin expression was independent of cytokine treatment. Addition of antiintegrin antibodies inhibited adhesion. A significant increase in adhesion to laminin and fibronectin was seen in endometriosis after IL-1 treatment and additionally to collagen after TNF alpha. Cells from women without endometriosis showed a significant increase only to fibronectin., Conclusions: Human endometrial cells express functional integrins in vitro. TNF alpha and IL-1 had more pronounced effects on adhesion in endometriosis. Inflammatory cytokines in the peritoneal cavity may facilitate adhesion of retrogradely menstruated endometrial fragments in endometriosis.

Local invasiveness is an important prognostic factor in endometrial carcinoma. To study the role of two groups of secreted proteinases (serine proteinases and matrix metalloproteinases) in this process, we examined three endometrial cancer cell lines (Ishikawa HEC 1A, AN3CA) for their invasiveness in vitro. Additionally, we considered the secretion of urokinase type plasminogen activator (uPA), plasminogen activator inhibitor 1 and 2 (PAI-1 and PAI-2), as well as matrix metalloproteinases (MMP) 1, 2, 3, and 9, and their inhibitors TIMP-1 and TIMP-2. Compared to the highly invasive fibrosarcoma cell line HT 1080, Ishikawa displayed low and AN3CA moderate invasiveness, while HEC 1A cells were almost as invasive as HT 1080 cells. Ishikawa cells secreted the highest amounts of proteinases. Cytokine and steroid treatments upregulated MMP-1 in all cell lines while the effects were heterogeneous regarding other proteinases and inhibitors. No effect of these treatments on invasiveness could be detected. Both basal secretion and regulation of the proteinases tested in this set of experiments seem to be markers of differentiation rather than of invasiveness.

Objective: To examine the regulation of endometrial integrin expression by estrogens and progestins in vitro., Design: Immunocytochemical study., Setting: Academic research unit., Patient(s): Twenty-five regularly cycling women without endometrial pathology, of whom seven had endometriosis., Intervention(s): Endometrial cells obtained by aspiration curettage were treated with diethylstilbestrol, promegestone, and antiprogestin. Immunocytochemistry was performed with antibodies directed against integrins alpha 1 beta 1, alpha 2 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha v beta 3, and beta 3 integrin subunit., Main Outcome Measure(s): Semiquantitative staining score., Result(s): Endometrial cells express several integrins in vitro in a consistent and cell specific pattern. Neither differences between treated and untreated cells nor an effect of treatment duration or dosage were observed. Cells from patients with and without endometriosis showed similar patterns., Conclusion(s): The cellular distribution of integrin expression was similar to that described in vivo. In contrast, a steroid regulated expression could not be detected in vitro. Rather, a derepression by a factor not included in our model could be responsible for the cyclic appearance of some integrins. In endometriosis, no fundamental difference of integrin expression was detected.

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

Add-back hormone replacement therapy has been shown to alleviate some of the hypo-oestrogenic side effects associated with gonadotrophin-releasing hormone agonists, including demineralisation of bone. Studies on patients with uterine fibroids have shown that concomitant add-back therapy reduced the efficacy of these agents, but that deferred administration was less detrimental. This trial set out to investigate if deferred add-back therapy could offer any advantages to patients with endometriosis compared with immediate therapy. Zoladex [goserelin acetate (3.6 mg every 4 weeks)] was given for 24 weeks either with placebo, with medrogestone (10 mg/day) for 24 weeks (immediate add-back therapy), or with placebo for 12 weeks followed by medrogestone (10 mg/day) for 12 weeks (deferred add-back therapy) to 123 patients. The number of responders measured using the Revised American Fertility Society score (decrease in this score of > or = 50%) was greatest in the immediate add-back therapy group, although there were no significant differences between groups. All three treatment groups showed significant decreases in bone mineral density compared with baseline but smaller losses were generally observed in the add-back groups. A significantly smaller number of patients in the immediate add-back group reported hot flushes during the first 12 weeks of treatment compared with the deferred add-back group. In conclusion, it appears that there is no extra advantage to patients with endometriosis being treated with goserelin in delaying the start of add-back therapy.

Objective: To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis., Design: Prospective, comparative study., Setting: Animal research unit., Subjects: Thirty regularly cycling cynomolgus monkeys in three groups of 10 each., Interventions: Endometrium was minced and spilled into the cul-de-sac in group 1. In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor., Main Outcome Measures: Staging laparotomies after 3 weeks and 3 months., Results: In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3 weeks and in eight, three, and two monkeys, respectively, at 3 months., Conclusions: An intact structure leads to ectopic implantation of endometrial fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.