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Introduction: As part of the development of the evidence-based (S3) clinical practice guidelines for kidney and bladder cancer by the German Guideline Program in Oncology, quality indicators (QIs) were defined to measure the quality of care. Based on these guidelines and QIs, the German Cancer Society (DKG) developed two new certification systems. The aim of this article is to show the process of development and implementation of QIs in certified cancer centres., Methods: Based on strong recommendations of each guideline and an additional systematic literature review for national and international QIs, two sets of QIs were derived in a multistep standardized approach. These QIs were implemented in the centres in certification data sheets to measure their outcomes. First results of treatment years 2018 and 2019 are available., Results: The final sets include 9 QIs for kidney cancer and 12 QIs for bladder cancer. Two-thirds of the QIs were transferred to the data sheets. In 2018 and 2019, the results of all but one QI are within the plausibility limits. From 2020 on, they are replaced by stricter target values that will challenge centres to improve their outcomes., Conclusions: Guideline-derived QIs make relevant aspects of patient care measurable and consequently improvable. The first QI results are encouraging. However, the DKG certification system and the methods of measuring quality are under ongoing development. Systematic QI implementation and evaluation may help to generate broader databases and thus expand knowledge., (© 2021 S. Karger AG, Basel.)

Objectives: Mammography screening is generally accepted in women aged 50-69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines., Methods: We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (<50, 50-69 and 70-74). GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the certainty of evidence., Results: We identified 10 RCTs including 616,641 women aged 38-75. Mammography reduced BC mortality in women aged 50-69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66-0.90, high certainty ) and 70-74 (RR 0.77, 95%CI 0.54-1.09, high certainty ), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76-1.02, moderate certainty ). Mammography reduced stage IIA+ in women 50-69 (RR 0.80, 95%CI 0.64-1.00, very low certainty ) but resulted in an overdiagnosis probability of 23% (95%CI 18-27%) and 17% (95%CI 15-20%) in under 50s and 50-69, respectively ( moderate certainty ). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes ( low certainty )., Conclusions: For women 50-69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.

Background: Approximately half of all patients with cancer use at least one method of complementary medicine during or after tumor treatment. The substances most commonly taken are micronutrients, food supplements, and plant extracts., Methods: This guideline is based on pertinent articles retrieved by a systematic search in the Medline, Cochrane Library, Embase, PsycInfo, and Cinahl databases., Results: The evidence is offen scant for any effect of a complementary method on patient-relevant endpoints such as relief of disease symptoms, reduction of treatment side effects, or prolonged survival. Micronutrients are available in different compositions, and their dosages vary. In most studies on the use of vitamins and trace elements by cancer patients, the blood level of the substance in question was not measured before its administration, so that it remains unknown whether a deficiency was present. For this reason, no well-founded conclusion on the effects of these substances can be drawn, and their use cannot be recommended in most cases. On the other hand, there is high-level evidence supporting physical exercise by cancer patients during and after their treatment. For patients with any type of cancer, mortality is lower among those who perform more physical exercise, whether before or after they receive the diagnosis of cancer (exercise before diagnosis, hazard ratio [HR] 0.82, 95% confidence interval [CI] [0.79; 0.86]; exercise after diagnosis, HR 0.63, 95% CI [0.53; 0.75]). Physical exercise during and after treatment for cancer should, therefore, be recommended to all cancer patients., Conclusion: The inherent positive attribute of complementary medicine is patient empowerment: it enables patients to help themselves in an active way even while undergoing cancer treatment, as well as afterward. To avoid risks to health, patients should be instructed about unsafe methods, asked repeatedly about their use of complementary medicine, and informed specifically about potential interactions between such interventions and their cancer treatment.

Malignancies are among the most common diseases, especially in old age, and are responsible for 25% of all deaths in Germany. Especially carcinomas of the gastrointestinal tract can be cured in most cases only through extensive surgery with significant morbidity. About 25 years ago, the multimodal, perioperative Fast Track (FT) concept for reducing postoperative complications was introduced and additional elements were added in the following years. Meanwhile, there is growing evidence that adherence to the key elements of more than 70% leads to reduction in postoperative adverse events as well as a shorter hospital stay and could be associated with an improved oncological outcome. Despite the high level of awareness and the proven advantages of the FT concept, the implementation and maintenance of the measures is difficult and results in an adherence of only 20 - 40%. There are many reasons for this: In addition to a lack of interdisciplinary and interprofessional cooperation and the time consuming and extended logistical efforts, limited human resources are often listed as one of the main causes. We took these aspects as an opportunity and started to develop a S3 guideline for perioperative treatment to accelerate the recovery of patients with gastrointestinal malignancies. By creating a consensus- and evidence-based, multidisciplinary guideline, many of the problems listed above could probably be solved by optimising and standardising interdisciplinary care, which is particularly important in a setting with many different disciplines and their competing interests. Furthermore, the standardisation of the perioperative procedures will reduce the time and logistical effort. The presentation of the evidence allows increased transparency and justifies the additional personnel expenditure on hospital medicine and health insurance companies. In addition, the evidence-based quality indicators generated during the development of the guideline make it possible to include perioperative standards in certification systems and thus to measure and check the quality of perioperative care., Competing Interests: Wolfgang Schwenk: Geschäftsführer GOPOM GmbH (Gesellschaft für Optimiertes PeriOperatives Management) in Düsseldorf seit 01.03.2021. Advisory Board: Coloplast, Dänemark. Beratertätigkeit: Johnson & Johnson Medical, Norderstedt. Vorträge gegen Honorar: Johnson & Johnson Medical, Norderstedt; Medtronic, Meerbusch; Dr. Falk Pharma bzw. Falk-Foundation, Freiburg; B.Braun/Aesculap, Melsungen/Tuttlingen; Karl-Storz GmbH, Tuttlingen, (Thieme. All rights reserved.)

Introduction : In 2013, riociguat a potent and specific stimulator of the soluble guanylyl cyclase (sGC) was approved as first in class sGC stimulator which reflected a first culmination of intense research and development efforts starting in the mid 1990ies. In the meantime, it turned out that triggering cGMP production by sGC stimulators could have a broad treatment potential. In consequence, various pharmaceutical companies are still very active in identifying novel chemistry for sGC stimulators. After the first generation of sGC stimulators like riociguat or lificiguat, new compound classes with different physicochemical and kinetic profiles were identified, like the sGC stimulators vericiguat or praliciguat. Area covered : Patent literature on sGC stimulators with a focus on recent compounds of the years 2014-2019 as on claimed use and formulations of these compounds. The information was collected from publicly available data sources only (MedLine, EmBase, Chemical Abstracts, Orbit, Dolphin). Expert Opinion : With the recent advancements reported in the patent literature, sGC stimulators might be differentiated due to tissue selectivity or route of application although exhibiting the same molecular mode of action. The indication space of these compounds is potentially very broad and multiple indications in cardiovascular diseases and beyond are under investigation.

Background: In 2017, the European Commission's Joint Research Centre (JRC) started developing a methodological framework for a guideline-based quality assurance (QA) scheme to improve cancer quality of care. During the first phase of the work, inconsistency emerged about the use of terminology for the definition, the conceptual underpinnings and the way QA relates to health questions that are answered in guidelines. The objective of this final of three articles is to propose a conceptual framework for an integrated approach to guideline and QA development and clarify terms and definitions for key elements. This work will inform the upcoming European Commission Initiative on Colorectal Cancer (ECICC)., Methods: A multidisciplinary group of 23 experts from key organizations in the fields of guideline development, performance measurement and quality assurance participated in a mixed method approach including face-to-face dialogue and several rounds of virtual meetings. Informed by results of a systematic literature review that indicated absence of an existing framework and practical examples, we first identified the relations of key elements in guideline-based QA and then developed appropriate concepts and terminology to provide guidance., Results: Our framework connects the three key concepts of quality indicators, performance measures and performance indicators integrated with guideline development. Quality indicators are constructs used as a guide to monitor, evaluate, and improve the quality of the structure, process and outcomes of healthcare services; performance measures are tools that quantify or describe measurable elements of practice performance; and performance indicators are quantifiable and measurable units or scores of practice, which should be guided by guideline recommendations., Conclusions: The inconsistency in the way key terms of QA are used and defined has confused the field. Our conceptual framework defines the role, meaning and interactions of the key elements for improving quality in healthcare. It directly builds on the questions asked in guidelines and answered through recommendations. These findings will be applied in the forthcoming ECICC and for the future updates of ECIBC. These are large-scale integrated projects aimed at improving healthcare quality across Europe through the development of guideline-based QA schemes; this will help in implementing and improving our approach.

Background: Although quality indicators are frequently derived from guidelines, there is a substantial gap in collaboration between the corresponding parties. To optimise workflow, guideline recommendations and quality assurance should be aligned methodologically and practically. Learning from the European Commission Initiative on Breast Cancer (ECIBC), our objective was to bring the key knowledge and most important considerations from both worlds together to inform European Commission future initiatives., Methods: We undertook several steps to address the problem. First, we conducted a feasibility study that included a survey, interviews and a review of manuals for an integrated guideline and quality assurance (QA) scheme that would support the European Commission. The feasibility study drew from an assessment of the ECIBC experience that followed commonly applied strategies leading to separation of the guideline and QA development processes. Secondly, we used results of a systematic review to inform our understanding of methodologies for integrating guideline and QA development. We then, in a third step, used the findings to prepare an evidence brief and identify key aspects of a methodological framework for integrating guidelines QA through meetings with key informants., Results: Seven key themes emerged to be taken into account for integrating guidelines and QA schemes: (1) evidence-based integrated guideline and QA frameworks are possible, (2) transparency is key in clearly documenting the source and rationale for quality indicators, (3) intellectual and financial interests should be declared and managed appropriately, (4) selection processes and criteria for quality indicators need further refinement, (5) clear guidance on retirement of quality indicators should be included, (6) risks of an integrated guideline and QA Group can be mitigated, and (7) an extension of the GIN-McMaster Guideline Development Checklist should incorporate QA considerations., Discussion: We concluded that the work of guideline and QA developers can be integrated under a common methodological framework and we provided key findings and recommendations. These two worlds, that are fundamental to improving health, can both benefit from integration.

Background: Recommendations of evidence- and formally consensus-based clinical practice guidelines (CPGs) represent a valuable source of quality indicators (QIs). Nevertheless, a standardized methodological procedure for developing QIs in the context of CPGs does not yet exist in Germany for all CPGs. For this reason, a methodological standard for the guideline-based development of QIs (QI Standard) was developed based on a structured consensus process involving multiple key stakeholders., Methods: The proposed content of the QI Standard was derived from evidence, drawing upon results of reviews and qualitative studies, and considered German manuals for guideline-based QI development of two guideline programs. A multi-perspective consensus panel, broadly representing key stakeholders from the German healthcare system with expertise in CPGs and/or quality management, was nominated to vote on recommendations for guideline-based development of QIs. The iterative, structured consensus process included a two-stage online survey based on the Delphi method ("preliminary voting") and a moderated final stakeholder conference where all those recommendations were definitely included in the QI Standard that received approval of more than 75 % (consensus criterion) of the consensus panel., Results: Based on the agreed QI Standard, the QI development process starts with a criteria-based selection of "potential" QIs which - in case of adoption - are published in CPGs as "preliminary" QIs and can achieve the status "final" after successful testing. The QI Standard is composed of a total of 30 recommendations, which are allocated to six areas: A) preparatory work steps for the guideline-based recommendation of QIs, B) QI development group and cooperation with the CPG group, C) development of potential QIs, D) critical appraisal of potential QIs, E) formal adoption and publication as well as F) piloting/testing of preliminary QIs and conversion into final QIs., Discussion: Before the QI Standard can be recommended for implementation in future CPGs, it should have been successfully tested in selected German CPG projects. In addition to methodological requirements for the QI development, it must be ensured that guideline groups have adequate resources for the implementation of the QI Standard., Conclusion: By using the QI Standard, scientifically sound and healthcare-relevant QIs can be expected., (Copyright © 2021. Published by Elsevier GmbH.)

Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer. Diagnostic vaginal biopsies should be examined by step sections on H&E. Sentinel lymph nodes should be processed completely using ultrastaging. Morphology-based prognostic factors with good clinical evidence are tumour stage and lymph node status. Molecular markers are not currently relevant for treatment decision and prognosis.

When Furchgott, Murad, and Ignarro were honored with the Nobel prize for the identification of nitric oxide (NO) in 1998, the therapeutic implications of this discovery could not be fully anticipated. This was due to the fact that available therapeutics like NO donors did not allow a constant and long-lasting cyclic guanylyl monophosphate (cGMP) stimulation and had a narrow therapeutic window. Now, 20 years later, the stimulator of soluble guanylate cyclase (sGC), riociguat, is on the market and is the only drug approved for the treatment of two forms of pulmonary hypertension (PAH/CTEPH), and a variety of other sGC stimulators and sGC activators are in preclinical and clinical development for additional indications. The discovery of sGC stimulators and sGC activators is a milestone in the field of NO/sGC/cGMP pharmacology. The sGC stimulators and sGC activators bind directly to reduced, heme-containing and oxidized, heme-free sGC, respectively, which results in an increase in cGMP production. The action of sGC stimulators at the heme-containing enzyme is independent of NO but is enhanced in the presence of NO whereas the sGC activators interact with the heme-free form of sGC. These highly innovative pharmacological principles of sGC stimulation and activation seem to have a very broad therapeutic potential. Therefore, in both academia and industry, intensive research and development efforts have been undertaken to fully exploit the therapeutic benefit of these new compound classes. Here we summarize the discovery of sGC stimulators and sGC activators and the current developments in both compound classes, including the mode of action, the chemical structures, and the genesis of the terminology and nomenclature. In addition, preclinical studies exploring multiple aspects of their in vitro, ex vivo, and in vivo pharmacology are reviewed, providing an overview of multiple potential applications. Finally, the clinical developments, investigating the treatment potential of these compounds in various diseases like heart failure, diabetic kidney disease, fibrotic diseases, and hypertension, are reported. In summary, sGC stimulators and sGC activators have a unique mode of action with a broad treatment potential in cardiovascular diseases and beyond.

Following the rapid spread of a new type of coronavirus (SARS-CoV-2), nearly all countries have introduced temporary restrictions affecting daily life, with "social distancing" as a key intervention for slowing the spread of the virus. Despite the pandemic, the development or actualization of medical guidelines, especially in the rapidly changing field of oncology, needs to be continued to provide up-to-date evidence- and consensus-based recommendations for shared decision making and maintaining the treatment quality for patients. In this viewpoint, we describe the potential strengths and limitations of online conferences for medical guideline development. This viewpoint will assist guideline developers in evaluating whether online conferences are an appropriate tool for their guideline conference and audience., (©Theresa Steeb, Markus Follmann, Ralf Matthias Hagen, Carola Berking, Markus Vincent Heppt. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 29.12.2020.)

Uterine sarcomas represent a heterogeneous group of rare malignancies, derived from the myometrium, the endometrial stroma, and very rarely from the nonspecialized uterine soft tissue. The actual incidence is about 1.5 for Caucasian and 3.0 for Afro-American women. There is no grading system for leimoysarcoma defined by the WHO classification; however, if clinicians request, the FNCLCC grading can be specified in analogy to soft tissue sarcomas. Adenosarcomas must be distinguished from adenofibromas (the existence of which is questionable)-with the vast majority of these tumors being uterine adenosarcomas. Within adenosarcomas, deep myometrial invasion (>50%), sarcomatous overgrowth, and a high-grade heterologous component are associated with a higher recurrence rate and poor survival. The immunohistochemical panel represents a very helpful tool for distinguishing low-grade from high grade endometrial stromal sarcomas (ESS) and may be supplemented by molecular analyses. Steroid hormone receptor analysis should be performed for all ESS due to the possible therapeutic relevance. Undifferentiated uterine sarcomas represent a diagnosis of exclusion and have a very poor prognosis. Carcinosarcomas represent a special subtype of endometrial carcinomas and are in fact not uterine sarcomas. Uterine sarcomas may present substantial intratumoral heterogeneity and adequate embedding is mandatory. Lesions ≤2 cm in the largest dimension should be processed completely and larger tumors should be processed with one block per centimeter for the largest tumor dimension.

Background: Guidelines and quality indicators (for example as part of a quality assurance scheme) aim to improve health care delivery and health outcomes. Ideally, the development of quality indicators should be grounded in evidence-based, trustworthy guideline recommendations. However, anecdotally, guidelines and quality assurance schemes are developed independently, by different groups of experts who employ different methodologies. We conducted an extension and update of a previous systematic review to identify, describe and evaluate approaches to the integrated development of guidelines and related quality indicators., Methods: On May 24th, 2019 we searched in Medline, Embase and CINAHL and included studies if they reported a methodological approach to guideline-based quality indicator development and were published in English, French, or German., Results: Out of 16,034 identified records, we included 17 articles that described a method to integrate guideline recommendations development and quality indicator development. Added to the 13 method articles from original systematic review we included a total 30 method articles. We did not find any evaluation studies. In most approaches, guidelines were a source of evidence to inform the quality indicator development. The criteria to select recommendations (e.g. level of evidence or strength of the recommendation) and to generate, select and assess quality indicators varied widely. We found methodological approaches that linked guidelines and quality indicator development explicitly, however none of the articles reported a conceptual framework that fully integrated quality indicator development into the guideline process or where quality indicator development was part of the question formulation for developing the guideline recommendations., Conclusions: In our systematic review we found approaches which explicitly linked guidelines with quality indicator development, nevertheless none of the articles reported a comprehensive and well-defined conceptual framework which integrated quality indicator development fully into the guideline development process.

Background: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection., Methods: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries., Results: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate., Conclusion: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Background: In 2018, an update of the German evidence-based (S3) guidelines "Diagnosis, Therapy and Follow-up of Melanoma" first issued in 2013 was published under the auspices of the German Guideline Program in Oncology. The update also included a revision of existing guideline-based quality indicators (QIs)., Patients and Methods: Using a standardized multi-step process, the guideline-derived QIs were revised by a multidisciplinary, interprofessional working group based on the strong (level A) recommendations contained in the guideline update as well as on a systematic literature search for international indicators and on the outcomes of existing QIs as reported by certified German skin cancer centers., Results: Based on the original set of twelve guideline-based QIs agreed upon in 2013, the working group developed an updated set containing nine indicators. Four QIs were kept unchanged; two were modified; two were removed; and three new QIs were added. Unlike 2013, the working group was now able to incorporate the outcomes of QIs previously implemented at the various skin cancer centers., Conclusions: Close cooperation between guideline group and certification commission allows for the implementation of guideline-based QIs in cancer care. Measured outcomes form the basis for updating both the guidelines and the QI development process. They provide information about the care of cancer patients in a real-world setting as well as on guideline adherence and the feasibility of QIs themselves. This is a dynamic process that can be described in a transparent manner and that requires regular updating., (© 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers., Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence., Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Aims This is an official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of how they should be managed clinically, and treatment requires a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is the result of the consensus of a representative interdisciplinary group of experts who carried out a systematic search of the literature on uterine sarcomas in the context of the guidelines program of the DGGG, OEGGG and SGGG. Members of the participating professional societies achieved a formal consensus after a moderated structured consensus process. Recommendations The consensus-based recommendations and statements include the epidemiology, classification, staging, symptoms, general diagnostic work-up and general pathology of uterine sarcomas as well as the genetic predisposition to develop uterine sarcomas. Also included are statements on the management of leiomyosarcomas, (low and high-grade) endometrial stromal sarcomas and undifferentiated uterine sarcomas and adenosarcomas. Finally, the guideline considers the follow-up and morcellation of uterine sarcomas and the information provided to patients., (© Thieme Medical Publishers.)

Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission (EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.

Pharmaceutical companies often refer to 'screening their library' when performing high-throughput screening (HTS) on a corporate compound collection to identify lead structures for small-molecule drug discovery programs. Characteristics of such a library, including the size, chemical space covered, and physicochemical properties, often determine the success of a screening campaign. Therefore, strategies to maintain and enhance the overall quality of screening collections are crucial to stay competitive and to cope with the 'novelty erosion' that is observed gradually. The Next Generation Library Initiative (NGLI), the enhancement of Bayer's HTS collection by 500000 newly designed compounds within 5 years, is addressing exactly this challenge. Here, we describe this collaborative project, which involves all internal medicinal chemists in a crowd-sourcing approach, as well as selected external partners, to reach this ambitious goal., (Copyright © 2018 Bayer AG. Published by Elsevier Ltd.. All rights reserved.)

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma., (© 2019 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.)

Aims Annual opportunistic screening for cervical carcinoma has been done in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as this guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The second part of this short summary deals with the triage, treatment and follow-up care of cervical dysplasia. With regard to those women who do not participate in screening, the guideline authors recommend sending out repeat invitation letters or an HPV self-collection kit. Colposcopy should be carried out for further investigation if cytology findings are Pap II-p and HPV test results are positive or if the results of an HPV 16 or HPV 18 screening test are positive. A single abnormal Pap smear should be triaged and investigated using HPV testing or p16/Ki67 dual staining.

Aims Annual opportunistic screening for cervical carcinoma has been carried out in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as the guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The first part of this short summary presents the pathological basis and considers various questions related to screening for cervical cancer. As also reported in earlier reviews, the meta-analysis by Kleijnen Systematic Reviews showed that HPV-based screening offers better protection against invasive cervical cancer compared to cytology-based screening. The authors of this guideline therefore recommend - in accordance with the guideline of the Joint National Committee of Germany (Gemeinsamer Bundesauschuss, G-BA) - that women aged 35 and above should be examined at regular intervals (at least every 3 years) and undergo HPV-based screening. Co-testing can also be carried out. Women between the ages of 20 and 35 should have cytological screening every 2 years.

The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology., (© 2018 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.)

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.

Background: Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy usually lead to cure. Finding ways to lessen the treatment- associated morbidity and mortality is a major goal of current research., Methods: For the creation of an updated guideline (DKH grant number 111778), a systematic literature search was carried out in medical databases (MEDLINE, CENTRAL) and guideline databases (GIN) (search dates: January 2012 to June 2017)., Results: Results from 10 meta-analyses, 89 randomized and controlled trials, and 81 prospective or retrospective trials were evaluated. The use of positron emission tomography (PET) is strongly recommended in the initial diagnostic evaluation, as well as for the guidance of treatment in advanced stages. In early stages, two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-site radiotherapy (IS-RT) at a dose of 20 Gy are recommended. For the treatment of intermedi- ate stages, two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) + two cycles of ABVD and 30 Gy IS-RT are recommended. In advanced stages, two cycles of escalated BEACOPP are administered, and then PET is performed for the guidance of further treatment: two further cycles of escalated BEACOPP are recommended if the PET is negative and four further cycles if it is positive, followed by radiotherapy of PET- positive residual tumor tissue. The five-year survival of patients with Hodgkin lymphoma is 95%. In case of disease recurrence, high-dose chemotherapy followed by autologous stem-cell transplantation is performed, and targeted drugs including brentuxi- mab vedotin, nivolumab, and pembrolizuab are used., Conclusion: The highly favorable long-term prognosis of HL necessitates careful consideration of the intensity of treatment as well as thorough follow-up to enable the detection of late sequelae, such as second tumors or organ damage.

Competing Interests: Interessenkonflikt: Alle Interessenkonflikterklärungen liegen gemäß AWMF-Regelwerk leitlinienkonform vor.

The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.