Accuracy of ultrasound signs on two-dimensional transvaginal ultrasound in prediction of adenomyosis: prospective multicenter study.

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.

The cost-effective, but forgotten, medical endometriosis therapy: a prospective, quasi-randomized study on progestin therapy.

Endometriosis represents nowadays a real burden for the patients as well as for the physicians, as it requires surgical and/or medical treatment, often long - termed and repeated. Moreover, the high costs necessary to diagnose and treat endometriosis represent a real economic burden, being comparable to other chronic diseases like diabetes or rheumatoid arthritis. Therefore, the physicians dealing with this disease should take into account not only the efficacy of the treatment, but also the economic aspects and patients compliance. The present paper analyses the efficiency of progestins (lynestrenol and medrogestone) in endometriosis as a cost - effective, but forgotten medical therapy of the disease. Our study underlines the good tolerability of progestins, as they have limited side effects, the compliance of patients being high. They are also low-cost medications, which could represent an effective alternative method in the endometriosis treatment, especially in less - developed countries that cannot afford the higher therapeutic costs.

Diagnostics and Therapy for Malignant (Degenerate) Colon Endometriosis - Three Case Reports.

Malignant degeneration of colon endometriosis is a very rare event. We report here on three cases. A 48-year-old woman with a 10-year history of endometriosis was treated for a rectal adenocarcinoma, a 61-year-old G1P1, who was operated at the age of 40 years for ovarian endometriosis and again at the age of 53 years for an endometriosis-associated endometroid ovarian carcinoma, presented for therapy for a lymph node recurrence of the ovarian cancer and, secondly, due to a malignantly degenerated rectum-sigmoid colon endometriosis; furthermore a 54-year old woman with a 21-year history of endometriosis was operated for malignant colon endometriosis. The tumour occurred during an adjuvant anti-oestrogen treatment with an aromatase inhibitor following surgical and radiotherapy for breast cancer. In all cases a radical cancer operation was followed by adjuvant chemotherapy and in one case with an additional radiotherapy. In the follow-up periods of 18 months, 2 and 5 years, respectively, all women remained free of recurrences. Although this is not a randomised controlled study due to the rare occurrence of such cases, a radical operation followed by individualised adjuvant therapy appears to be the treatment of choice.

National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis: Long Version - AWMF Registry No. 015-045.

In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic.

Implementation of certified endometriosis centers: 5-year experience in German-speaking Europe.

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.

Surgical Therapy of Endometriosis: Challenges and Controversies.

Endometriosis is one of the most common disorders encountered in surgical gynaecology. The laparoscopic technique, the planning of the surgical intervention, the extent of information provided to patients and the interdisciplinary coordination make it a challenging intervention. Complete resection of all visible foci of disease offers the best control of symptoms. However, the possibility of achieving this goal is limited by the difficulty of detecting all foci and the risks associated with radical surgical strategies. Thus, the excision of ovarian endometrioma can result in a significant impairment of ovarian function, while damage to nerve structures during resection of the uterosacral ligaments, the parametrium, the rectovaginal septum or the vaginal cuff to treat deep infiltrating endometriosis can lead to serious functional impairments such as voiding disorders. A detailed risk-benefit analysis is therefore necessary, and patients must be treated using an individual approach.

[ENZIAN-score, a classification of deep infiltrating endometriosis]. / ENZIAN-Score, eine Klassifikation der tief infiltrierenden Endometriose.

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.

[Guidelines for the use of GnRH-analogues in the treatment of endometriosis]. / Leitlinien für den Einsatz der GnRH-Agonisten zur Behandlung der Endometriose.

Today GnRH-Analogues are the most effective substances for the regression of endometriosis and endometriosis related complaints. In combination with add-back medication the treatment is effective with only few tolerable side effects. The different types of GnRH-Analogues are equally effective, but depot preparation have the best compliance. The tailored application of GnRH-Analogues preoperatively, postoperatively or instead of surgery is dependent on the individual situation of the patient and dependent on the proliferative activity, localisation, type and stage of the disease.

[Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis]. / Aromatasehemmer--theoretisches Konzept und bisherige Erfahrungen in der Endometriosetherapie.

The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies of endometriosis-associated pain or recurrent disease is primarily aimed at downregulating the ovarian function or at antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is delivering powerful tools for the possible development of new, specific treatment modalities. Recently, aromatase overexpression has been detected in endometriotic tissue. Aromatase (p450arom) is responsible for conversion of C19 androgens to estrogen in several human tissues. Aromatase activity gives rise to local estrogen biosynthesis, which, in turn, stimulates prostaglandin E(2) production by upregulation of cyclooxygenase-2 (COX-2), thus establishing a positive feedback cycle. Another abnormality in endometriosis, i. e. the deficiency in 17 beta-hydroxysteroiddehydrogenase type-II (17 beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations collectively favour accumulation of increasing amounts of local estradiol and prostaglandin E(2) in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance, and even invasiveness. Consequently, aromatase and COX-2 are promising new therapeutic targets. In summary, specific aromatase inhibitors (such as Letrozole, Anastrozol or Exemestan) or selective COX-2 inhibitors (e.g. Celecoxib, Rofecoxib) are of great interest to be studied in clinical trials in premenopausal woman with endometriosis to extend the spectrum of currently available treatment options.

[The ranking of the gestagens in the treatment of pain caused by endometriosis--an overview]. / Stellenwert der Gestagene in der Behandlung endometriosebedingter Beschwerden---eine Ubersicht.

Progestins are used for the treatment of endometriosis and endometriosis related complains in low dosages since more than four decades. Progestins induce incomplete regression of endometriotic implants only, they have a high recurrence rate, and they cause side effects--depending of the type of progestin and doses used--therefore GnRH-Agonist induced reversible ovarian suppression has become the standard in medical therapy for endometriosis prior and after surgery during the last ten years. New follow up studies have demonstrated the this new therapeutic principle is associated with relevant recurrence rates also and we have learned, that endometriosis is a chronic disease. For this background a medical therapy, which has low subjective and objective side effects, which can be used repeatedly or over a long time period, and which is cost effective becomes more important. This means that the place of progestins in the treatment of endometriosis has to be defined again and prospective randomised studies with the different substances are necessary.

Current place of progestins in the treatment of endometriosis-related complaints.

Oral progestins have been used for the treatment of endometriosis and endometriosis-associated complaints for more than 40 years. The mechanism of action on the menstrual cycle is well understood; however, the mechanism of action on endometriosis is still a matter of debate. The different progestins are able to stop proliferation in endometriotic implants and to induce regressive change to certain degrees; they are not able to heal endometriosis because endometriosis is a chronic and recurrent disease. For this reason, no medical treatment can heal endometriosis and repeat medication is necessary in the medical management of this disease. Progestins--especially non-androgenic progestins--are well tolerated and have only few side-effects; they can be used repeatedly or continuously over a long period of time.

Diagnostic errors in interactive telepathology.

Telepathology (TP) as a service in pathology at a distance is now widely used. It is integrated in the daily workflow of numerous pathologists. Meanwhile, in Germany 15 departments of pathology are using the telepathology technique for frozen section service; however, a common recognised quality standard in diagnostic accuracy is still missing. In a first step, the working group Aurich uses a TP system for frozen section service in order to analyse the frequency and sources of errors in TP frozen section diagnoses for evaluating the quality of frozen section slides, the important components of image quality and their influences an diagnostic accuracy. The authors point to the necessity of an optimal training program for all participants in this service in order to reduce the risk of diagnostic errors. In addition, there is need for optimal cooperation of all partners involved in TP service.

Progestins and uterine leiomyoma.

Myomas are the most frequent benign gynecological tumors and are responsible for several symptoms and complaints. Their etiology is unknown and their pathology and proliferation is poorly understood. Besides the importance of estrogens for development and growth of the myoma, progesterone seems to play an important role in the modulation of mitotic activity, local growth factors and growth factor receptors, as well as other paracrine mechanisms.

Recommendations for estrogen and progestin replacement in the climacteric and postmenopause. European Progestin Club.

The diversity of function that sex steroids have proven to have in the female body, gives them a position of central importance in gynaecology. Scientific research demonstrates not only the well known genital functions of sexual steroids, furthermore, various extragenital organs are influenced and modulated by ovarian hormones. Therefore, the general benefit of HRT for the female organism becomes clearer and the clinical management of menopause is developing to a broad new discipline, the gender specific medicine. In clinical practise, phytosteroids are claimed by the patient and therefore, also of high interest for the scientific research. Also, tissue specificity of the endocrine treatment and the biological relevance of different steroid receptors of HRT are discussed, leading to the development of new HrT preparations. Individualisation, the tailoring of HRT, according to the patients needs, and low dose steroids management, will also become an important aspect in the recommendations for estrogen and progestin replacement therapy.

Impact of maternal body build characteristics on newborn size in two different European populations.

The association patterns between maternal anthropometric characteristics (stature, prepregnancy weight, prepregnancy body mass index, pregnancy weight gain) and newborn size (birth weight, length, head circumference) were tested with 10,240 single births taking place between 1985 and 1995 in Vienna, Austria, and 3,452 single births taking place between 1989 and 1995 in Westerstede-Ammerland (Friesland), northern Germany. Maternal size and newborn size differed highly significantly (p < 0.001) between the two genetically and socioeconomically different population groups. Furthermore, the incidence of macrosomia among newborns (birth weight greater than 4000 g) was extraordinarily high (17.9%) in the Frisian group from northern Germany. In both populations taller and heavier women with a higher weight gain during pregnancy gave birth to heavier offspring. Nevertheless, the pregnancy weight gain, which indicates environmental conditions of the mother, had only a minor impact on newborn size compared with stature and prepregnancy weight, which reflect the maternal genetic potential to a higher degree.

Aspects of progestin activity on the breast. European Progestin Club.

On 9-11 May 1997, the second Meeting of the European Progestin Club was held in Turin, Italy. Aspects of progestin use on the breast were discussed, based on the currently available scientific data. The paper covers topics addressed at the meeting and summarizes the recommendations which could be agreed on by the participants.

[The significance of gestagens in treatment of mastopathy]. / Die Bedeutung der Gestagene zur Behandlung der Mastopathie.

The term "mastopathy" has yet to receive a common accepted definition. 70% of all mastopathies do not demonstrate, morphologically speaking, a proliferation, where as less than 10% show an atypical proliferation that suggests an increased risk for cancer development. The indication for the treatment of a mastopathy without proliferative processes is the existence of pain. The concurrent development of Hyperprolactinemia, Hyperandrogenemia, or Hypothyreosis and the resulting metabolic disorders that accompany such should be treated in a causal manner. Progestins have proved to be effective in cases where a progesterone deficit and/or a relative hyperestrogenism exist. An evaluation of progestins as a prophylaxis for breast carcinoma development in women with an atypical proliferation, however, can first be completed when a deeper knowledge of the local hormone situation in the breast tissue exists. Suitable in this case, are the 17-Hydroxyprogesterone derivatives, because the 19-Nortestosterone derivatives produce a negative influence on the Lipid metabolism due to their partial androgenic effect and in addition, antagonise the hepatocellular estrogen effect (IGF1-reduction and SHBG-increase), which may indirectly offer protection for the breast.