Changes of breast and axillary surgery patterns in patients with primary breast cancer during the past decade.

PURPOSE: Breast-conserving therapy (BCT) is the standard procedure for most patients with primary breast cancer (BC). By contrast, axillary management is still under transition to find the right balance between avoiding of morbidity, maintaining oncological safety, and performing a staging procedure. The rising rate of primary systemic therapy creates further challenges for surgical management. METHODS: Patients with primary, non-metastatic BC treated between 01.01.2003 and 31.12.2016 under guideline-adherent conditions were included in this study. For this prospectively followed cohort, breast and axillary surgery patterns are presented in a time-trend analysis as annual rate data (%) for several subgroups. RESULTS: Overall, 6700 patients were included in the analysis. While BCT rates remained high (mean 2003-2016: 70.4%), the proportion of axillary lymph node dissection has declined considerably from 80.1% in 2003 to 16.0% in 2016, while the proportion for sentinel lymph node biopsy (SLND) has increased correspondingly from 10.3 to 76.4%. Among patients with cT1-2, cN0 breast cancer receiving BCT with positive SLND, the rate of axillary completion has decreased from 100% in 2008 to 24.4% in 2016. CONCLUSIONS: In the past decade, SLNB has been established as the standard procedure for axillary staging of clinically node-negative patients. Surgical morbidity has been further reduced by the rapid implementation of new evidence from the ACOSOG Z0011 trial into clinical routine. The results reflect the transition towards more individually tailored, less invasive treatment for selected patient subgroups, especially in regards to axillary lymph node management.

Does knowledge of fetal outcome influence the interpretation of intrapartum cardiotocography and subsequent clinical management? A multicentre European study.

OBJECTIVE: To investigate whether knowledge of fetal outcome influences retrospective interpretation of cardiotocographic tracings and subsequent management recommendations. DESIGN: Prospective online study. SETTING: Seven university hospitals in five European countries. POPULATION: Forty-two intrapartum tracings from women with singleton pregnancies and uneventful antepartum courses. METHODS: Using an online questionnaire, 123 healthcare professionals interpreted 42 tracings without any knowledge of fetal outcome and provided management recommendations according to the National Institute of Clinical Excellence guidelines (intrapartum care). Two months later, 93 of the 123 participants re-interpreted the same re-ordered tracings, this time with information on the newborn's umbilical artery pH. OUTCOME MEASURES: Comparison of the evaluation of tracing features, overall tracing classification, and management recommendations between the initial analysis and re-interpretation. RESULTS: In newborns with umbilical artery pH ≤ 7.05, knowledge of the pH value led to significant changes in the evaluation of all basic tracing features. In this group, classification of tracings as 'normal' decreased 76% (8.8-2.1%, P < 0.001), whereas classification as 'pathologic' increased 51% (44.7-67.5%, P < 0.001). In newborns with pH 7.06-7.19, classification of tracings as 'normal' decreased 36% (22.4-14.4%, P < 0.001), and in those with pH ≥ 7.20, classification of tracings as 'pathologic' decreased 40% (23.4-14.1%, P < 0.001). In the group of newborns with umbilical artery pH ≤ 7.05, the recommendations 'no attention needed' decreased 75% (10.2-2.6%, P < 0.001), and the number of recommendations 'rapid reversal of hypoxic cause or immediate delivery' increased 70.3% (42.1-71.7%, P < 0.001). CONCLUSIONS: When provided with information on adverse fetal outcome, healthcare professionals provide a more pessimistic evaluation of basic tracing features, overall classification, and clinical management recommendations. TWEETABLE ABSTRACT: Knowledge of adverse fetal outcome leads to more pessimistic CTG evaluation and management recommendations.

Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans development.

Cellular identity during metazoan development is maintained by epigenetic modifications of chromatin structure brought about by the activity of specific proteins which mediate histone variant incorporation, histone modifications, and nucleosome remodeling. HP1 proteins directly influence gene expression by modifying chromatin structure. We previously showed that the Caenorhabditis elegans HP1 proteins HPL-1 and HPL-2 are required for several aspects of post-embryonic development. To gain insight into how HPL proteins influence gene expression in a developmental context, we carried out a candidate RNAi screen to identify suppressors of hpl-1 and hpl-2 phenotypes. We identified SET-2, the homologue of yeast and mammalian SET1, as an antagonist of HPL-1 and HPL-2 activity in growth and somatic gonad development. Yeast Set1 and its mammalian counterparts SET1/MLL are H3 lysine 4 (H3K4) histone methyltransferases associated with gene activation as part of large multisubunit complexes. We show that the nematode counterparts of SET1/MLL complex subunits also antagonize HPL function in post-embryonic development. Genetic analysis is consistent with SET1/MLL complex subunits having both shared and unique functions in development. Furthermore, as observed in other species, we find that SET1/MLL complex homologues differentially affect global H3K4 methylation. Our results suggest that HP1 and a SET1/MLL-related complex may play antagonistic roles in the epigenetic regulation of specific developmental programs.

Severe Fournier's gangrene-a conjoint challenge of gynaecology and plastic surgery.

Necrotizing fasciitis (NF) is a rare soft tissue infection characterized by rapidly progressing necroses and a high mortality. Prompt diagnosis and immediate medical treatment including radical debridement and broad spectrum antibiotics are the key to successful management. We report on a 46-year-old diabetic female who developed extensive, deep necroses in the perineal area and proximal thighs within a few days. After initial gynaecological consultation, she was transferred directly to our department. Due to the suspicion of NF, an immediate radical debridement was performed. Two more debridements were necessary to control the infection. After stabilization, the extensive soft tissue defect was reconstructed using a combination of plastic reconstructive procedures. Due to early diagnosis, direct referral and immediate surgical treatment, the patient survived.

Senology in Gynaecology Specialist Training: a Baseline Survey from 2014.

Introduction: Qualified training in senology is essential for maintaining adequate, high quality patient care. In order to meet the needs of doctors in training and those of the medical infrastructure it is necessary to assess the quality of training regularly, to enable its adaption and optimisation. Methods: We developed a comprehensive, 10 item online questionnaire to assess the quality of specialised training in senology. This questionnaire was sent to 4000 speciality trainees and young specialists countrywide via the DGGG newsletter and was accessible for over four weeks. Results: 111 obstetrics and gynaecology speciality trainees participated in this national survey, 79 % of whom were female. 33 % of participants were working at university hospitals, 29 % at hospitals offering maximal level care without an associated medical faculty, 37 % at hospitals offering primary and secondary level care and 2 % at gynaecology practices. 25 % of participants could imagine working in the field of senology in future. On average the current perception of general specialist training was satisfactory. Specialist trainees at university hospitals rated training in senology highest (score: 2.95) compared to those at other hospitals. A fixed rotation through a breast centre offering comprehensive advanced training was seen as a potential improvement to senology training. Conclusions: This is the first survey of specialised training in senology to be conducted in Germany. Results showed that there is significant potential for young doctors to enter the speciality in future. There are also significant differences in the perceived quality of senology training between training facilities. This survey aimed to determine the quality of specialised training at senology centres and hopes to contribute to a sustainable improvement in training. The intention is to continue to make senology attractive to gynaecologists and to ensure well-grounded training.

Expectations for Endoscopic Training During Gynaecological Specialty Training - Results of a Germany-wide Survey.

Question: Endoscopy is an integral part of surgical gynaecology and is playing an increasingly important role in ensuring adequate gynaecological training in the context of specialty training in general. At present, little is known about the expectations and notions of young junior doctors with respect to endoscopic training. For this reason, junior doctors throughout Germany were surveyed on this topic and asked to share their opinions. Methods: Using an anonymized standardized survey, the following information was elicited: importance of endoscopic training, willingness to take courses, expectations for instructors and the hospital, ideas about the number of required operations, both as a surgical assistant and as a surgeon, as well as satisfaction with the current status of training. The questionnaires were sent via the Young Forum (Junges Forum) of the German Society of Gynaecology and Obstetrics (DGGG) and the newsletter of the Working Group for Gynaecological Endoscopy (AGE). Results: The evaluation of the study was based on 109 completed questionnaires. The resident junior doctors were 31 years old on average and were in their third to fourth year of their specialty training on average. The majority of the participants (87 %) considered the learning of endoscopic techniques to be very important and advocated regular participation in endoscopy training courses. Among the participants, 48 % were prepared to invest up to €1500 of their own funds to attend courses up to twice a year during the entire specialty training period. The expectations of the instructors and institutions focused on technical expertise, the willingness and time for teaching and on the number and range of surgical procedures, followed by being granted leave for the courses and having costs covered for the courses. Thirty-eight per cent stated that their expectations had been completely or mostly met and 62 % said they had been met in part or inadequately. Eighty-three per cent of the respondents reported that they would change specialty training institutions in order to achieve their own goals in the context of specialty training. Conclusions: This study presents data for the first time on the satisfaction of young junior doctors and their expectations for endoscopic specialty training. The residents exhibited a high level of interest in endoscopy and a high level of willingness to actively shape the specialty training, including course participation. However, there appears to be a great deal of room for improvement for endoscopic specialty training, independent of the current training institution, training year or sex of the junior doctors.

[Urogynaecological training situation in Germany : Gap between demand and reality]. / Urogynäkologische Aus- und Weiterbildungssituation in Deutschland : Kluft zwischen Anspruch und Realität.

BACKGROUND: With increasing life expectancy, progressive demographic change and decreasing societal stigmatization of incontinence urologists and gynaecologists are increasingly faced with urogynaecological challenges. To date however, urogynaecology is a poorly standardized area of expertise in both disciplines. Therefore, the urogynaecology training, especially in Germany, is very heterogeneous and requires evaluation as well as improvement. MATERIALS AND METHODS: The GeSRU-Academics research group "Functional urology and LUTS" evaluated this subject nationwide among urological and gynecological trainees and their chief physicians by using a comprehensive questionnaire (34/38 multiple-choice items) between April 2015 and May 2016. RESULTS: 336 urological residents and 190 chief physicians as well as 171 gynaecological residents and 175 chief physicians participated in the survey. Of all trainees, 70.0 % stated a personal interest in urogynaecology, but 45.4 % (gynaecological residents) and 52.9 % (urological residents) mention not to receive a standardized training in their own department. The chief physicians' survey resulted in discrepancies concerning the same question, <10 % of all residents do not receive a standardized urogynaecological training from their point of view. However, standardized urogynaecological training is of importance for those chief physicians. CONCLUSIONS: There is a discrepancy between expectations and reality of urogynaecological education and training. To enable a well-structured and standardized urogynaecological education and training, it is compulsory to focus on an interdisciplinary cooperation and to promote multidisciplinary development. A broad-based, well-designed training network and curricula should be established and used consistently.

The time course, localization and quantitation of T- and B-cell mitogen-driven apoptosis in vivo.

Apoptosis has very recently been visualized in situ in a mammalian thymus and spleen. We report here the first in situ visualization, localization and quantitation of the time course of mitogen-altered basal levels of apoptosis within the thymus and spleen of a vertebrate. Adult Xenopus leavis, South African clawed toads, were injected intraperitoneally with either the T-cell mitogen, Concanavalin (Con) A, or the B-cell mitogen, lipopolysaccharide (LPS). Controls, reflecting the basal level of apoptosis of both organs, were injected with isotonic phosphate-buffered saline for amphibians (APBS). ConA and LPS failed to enhance the nearly 2% apoptotic rate in the thymic cortex, which is made up largely of immature lymphocytes, but it did double the base level of 2% apoptosis in the mature lymphocytes of the medulla, particularly along the corticomedullary boundary. In the lymphoid splenic white pulp, the 2% basal level was exceeded slightly after ConA treatment, while the 6% basal lymphoid apoptotic rate in the red pulp was enhanced 7-fold in 12 h. LPS induced lymphocytic apoptosis in the partly erythropoietic red pulp of the spleen after 12 h but did not effect the white pulp. Extensive macrophage engulfment of apoptotic cells was apparent in both the thymus and the spleen.

Psychosomatic Primary Care in Gynecology-Assessment and Acceptance by Residents for Obstetrics and Gynecology in Germany.

Background: The course "Psychosomatic Primary Care" has been part of the training curriculum of obstetrics and gynecology in Germany since 2003. The aim of the course is to train up physicians, whose prior training primarily focussed on somatic care, to enable them to offer care also taking into account biopsychosocial aspects. Taking the guidelines for psychotherapy as a template, the aim of psychosomatic primary care is to recognize the etiological links between psychological and somatic factors which contribute to diseases. The necessity for a compulsory course as part of training in gynecology was recently critically discussed. Major points discussed included the question whether the current forms of teaching, consisting of courses, are outdated and whether the required skills should be part of regular daily training. Method: A 3-part online questionnaire consisting of 30 items was developed and sent to 2431 residents in the period from September to December 2012 through the online mailing list of the DGGG. Results: The 540 residents who responded to the questionnaire were predominantly female (83.3 %) with an average age of 30 years; 50.3 % were in their 1st to their 4th year of training. Over the longer term, the majority of respondents (56.1 %) hoped to continue working in a hospital and regularly (84.6 %) attended teaching courses voluntarily. 70.9 % of them had already attended the course "Psychosomatic Primary Care". Of the group who had completed the course, 29.4 % were satisfied with the offer. The main criticism directed against the course was its scope which 24.1 % considered completely inadequate. 24.5 % considered the course to be an important part of training, while 16.5 % would have preferred that the course be abolished. 18 % of respondents reported that psychosomatic medicine did not feature regularly in their daily clinical routine. Perspective: Because of the huge gap between what is currently offered and the experiences reported by the respondents, the Young Forum of the DGGG and the DGPFG have expanded the program of courses offered by the DGPFG, which will offer practice-oriented courses to future gynecologists across Germany in cooperation with the DAGG. The first courses are held in Heidelberg and Erlangen in 2014.

Multigene Assays for Classification, Prognosis, and Prediction in Breast Cancer: a Critical Review on the Background and Clinical Utility.

Gene signatures which are based on multigene profiling assays have been developed for the purpose to better define the prognosis and prediction of therapy results in early-stage breast cancer. These assays were designed to be more specific than conventional clinico-pathologic parameters in the selection of patients for (neo-)adjuvant treatment and in effect help to avoid unnecessary cytotoxic treatment. In this review we describe molecular risk scores, for which tests are commercially available (PAM50®, MammaTyper®, MammaPrint®, Oncotype DX®, Endopredict®, Genomic Grade Index®) and IHC risk scores (Mammostrat® and IHC4), and discuss the current evidence of their clinical use.

Change of aesthetic and functional outcome over time and their relationship to quality of life after breast conserving therapy.

PURPOSE: We analyzed changes in aesthetic and functional outcome over time after breast conserving therapy. Our special interest resides in the question of whether these aspects gain or loose their influence on quality of life (QoL) with temporal progress. PATIENTS AND METHODS: This prospective single centre cohort study included 138 patients, treated with breast conserving surgery and consecutive radiotherapy. Patients completed two questionnaires one week and one year after surgery: the BCTOS (Breast Cancer Treatment Outcome Scale) to measure Functional, Aesthetic, and Breast Sensitivity Status and the EORTC (European Organisation for Research and Treatment of Cancer) C30-BR23 to assess QoL. We applied correlation and multiple regression analysis as statistical methods. RESULTS: Aesthetic and Functional Status did not change significantly over one year, whereas Breast Sensitivity Status and several QoL subscales showed significant improvement (p < 0.0001). Correlations between BCTOS scales and EORTC subscales remain similar over time. Functional and Aesthetic Status kept a strong impact on global health (Spearman's Rho = -0.28 to -0.45 depending on time of assessment). Increasing age and poorer Functional Status shortly after surgery are predictors of a decline in global health over one year (p < 0.001). CONCLUSION: Functional and aesthetic outcome after breast conserving surgery maintain their impact on QoL over a one year follow-up period and are valuable predictors of QoL.

Breast cancer and diabetes mellitus.

Breast cancer is the leading neoplastic malignancy among females worldwide. Another major health problem in industrial countries is diabetes mellitus type 2, both with a raising tendency. Up to 16% of the elderly breast cancer patients additionally suffer from diabetes. Epidemiologic studies suggest that type 2 diabetes increases breast cancer risk and goes along with an increased mortality however, there has been limited experimental evidence supporting this association. In the present review we summarized epidemiological data on a correlation between diabetes and breast cancer. Further, the diverse hypothesized molecular investigations and purposed mechanisms are recapitulated. The latest discussions on insulin and its enhancement of cancer rates among patients with diabetes have also toughed the breast cancer sector. In contrary, recent data indicate a benefit of breast cancer treatment due to metformin therapy. A large amount of literature is available and provides concepts for future research that is needed to rule out possible overlapping pathomechanism, prognostic factors, therapy interactions as well as possible synergistic or additive or even controversial interaction of chemotherapy and diabetes medication.

[Two autopsy cases with systemic amyloidosis--case 11/2010]. / Zwei Autopsiefälle mit systemischer Amyloidose--Fall 11/2010.

HISTORY AND ADMISSION FINDINGS: A 37-year old patient was admitted with upper abdominal pain, vomiting and diarrhea. A 38-year-old patient was admitted for liver failure. INVESTIGATIONS: Case 1 was diagnosed with an AL amyloidosis due to deposition of the immunoglobulin light chain kappa in all tissues analyzed. In the bone marrow plasma cells were increased to 20-30%. Case 2 suffered from AA amlyoidosis secondary to familial mediterranean fever and underwent dialysis treatment for years. He was positive for hepatitis B and C. DIAGNOSIS, TREATMENT AND COURSE: Patient 1 developed refractory nephrotic syndrome and low blood pressure. During hemodialysis circulatory failure occured and she died during resuscitation. In patient 2 a flare of chronic hepatitis B was found and treated with antiviral therapy. He was referred to ICU for rectal bleeding and developed pulmonary arrest. After resuscitation he died because of lactate acidosis and refractory circulatory failure. Both cases were subjected to autopsy. CONCLUSIONS: The vast majority (90%) of amyloidoses are due to acquired AA or AL amyloidosis. Prognosis remains poor, in particular when cardiac and vascular involvement occurs.

[Secondary adrenal insufficiency after local injections of triamcinolone acetonide]. / Sekundäre Nebennierenrindeninsuffizienz nach lokaler Triamcinolonacetonid-Gabe.

HISTORY AND ADMISSION FINDINGS: Two women, aged 74 and 57 years, were admitted for endocrinological work-up. The 74-year-old women had clinical signs of adrenal insufficiency after she had been given one triamcinolone acetonide intra-articular injection 3 months before. The 57-year-old women who had over several years been repeatedly received local triamcinolone acetonide injections for degenerative changes in her cervical spine for several years and needed reoperative investigation. Physical examination was unremarkable in both patients: they had no signs of Cushing's syndrome. INVESTIGATIONS: Serum cortisol and plasma adrenocorticotropic hormone (ACTH) were reduced in both patients. Endocrinological tests in the 74-year-old patient showed reduced free cortisol excretion in the urine, normal cortisol response in the ACTH test and subnormal cortisol stimulation during the corticotropin-releasing-hormone test and the insulin tolerance test. Magnetic resonance imaging of the sella was normal. The 57-year-old patient had a reduced cortisol response. DIAGNOSIS, TREATMENT AND COURSE: The results of endocrinological tests in both patients were consistent with secondary adrenal insufficiency after local injection of triamcinolone acetonide. In the 74-year-old patient substitution treatment with hydrocortisone was started and resulted in rapid improvement of the symptoms. Perioperative intravenous substitution was advised for the 57-year-old patient . CONCLUSIONS: Locally administered synthetic glucocorticoids can be associated with systemic adverse effects, such as secondary adrenal insufficiency. Clinically significant secondary adrenal failure can be produced not only by long-term administration of triamcinolone acetonide, but possibly also if it is injected just once.

[A rare cause of hypoglycaemia in a patient with type 2 diabetes]. / Seltene Ursache für eine Hypoglykämie bei einem Patienten mit Typ-2-Diabetes mellitus.

BACKGROUND: Insulinomas are rare neuroendocrine tumours with an incidence of four cases per million a year. Only few cases of insulinoma in patients with preexisting diabetes mellitus have been reported. CASE: We present a 50-year-old male with type 2 diabetes mellitus who suffered from recurring hypoglycemia. He had gained 20 kilograms of weight in five years. 72-hour fast revealed hypoglycaemia in the presence of inadequately high C-peptide and insulin levels. Magnetic resonance imaging and selective arterial calcium stimulation test confirmed a mass in the body of the pancreas. The tumor was removed surgically. Pathological examination demonstrated a benign insulinoma. Postoperatively, blood glucose levels were within the therapeutic range. The HbA (1c) value was 6.8 % three months after the intervention. CONCLUSION: Clinicians should be alert to insulinoma as a, though rare, differential diagnosis of hypoglycaemia in diabetes, in particular in patients with recurrent, otherwise unexplained hypoglycaemia.

[7-fluoro-4-chromone-3-sulfur compounds]. / 7-Fluor-4-chromon-3-Schwefel-Verbindungen.

The novel 7-fluoro-4-chromone-3-sulfur compounds 5-12 were synthesized from the sulfinic acid 4, which can be obtained from the enaminone 3 and thionyl chloride. Especially the Flosequinane-like sulfoxide 12 was prepared and the vasodilating activity was evaluated in isolated ring segments of rat aorta.

Spermine and spermidine, modulators of the cell surface enzyme adenylate cyclase.

Adenylate cyclase activity was measured in membrane preparations of cultured fibroblasts from controls and patients with cystic fibrosis. Enzyme activity increased as the transition from exponential growth to confluence occurred; sodium fluoride-stimulated activity more markedly displayed this relationship than basal cyclase activity. The in vitro addition of spermine (1 X 10(-6) to 2 X 10(-3) M) to membrane preparations caused inhibition of basal and sodium fluoride-stimulated enzyme activity, with 50% inhibition of basal activity occurring at 10(-6) M spermine. Spermidine (10(-4) M) caused 15--25% inhibition of adenylate cyclase activity. The increase in fibroblast adenylate cyclase activity during the transition from exponential growth was comparable in cells obtained from cystic fibrosis patients and control subjects. Basal and sodium-fluoride stimulated adenylate cyclase activity as well as inhibition of this enzyme activity by spermidine and spermine were undistinguishable between the different cell genotypes. A potential modulation of cellular proliferative activity through polyamine interaction with the adenylate cyclase system is postulated.

Ornithine decarboxylase and S-adenosyl methionine decarboxylase in skin fibroblasts of normal and cystic fibrosis patients.

The key enzymes in the synthesis of the naturally occurring polyamines, ornithine decarboxylase (ODC) and S-adenosyl methionine (SAM) decarboxylase, were investigated during cell growth and aging in fibroblast cultures from normal patients and patients with cystic fibrosis. A linear correlation between increased S-adenosyl methionine activity and putrescine concentration was apparent in all cell lines. A putrescine concentration of 0.8 mM was optimal for enhancement of SAM decarboxylase activity. The passage number of the cell line correlated inversely with maximal putrescine-stimulated SAM decarboxylase activity, earlier passage numbers having the highest specific activity (Fig. 1). No significant differences in basal or putrescine-stimulated SAM decarboxylase activity were noted between normal fibroblast cultures and cells from patients with cystic fibrosis (Fig. 2). SAM decarboxylase activity increased as the cell lines approached confluence. Activity was lowest during exponential growth (Fig. 3). ODC activity was increased during early exponential growth and fell as cells reached confluence (Fig. 4). No differences in ODC activity and putrescine inhibition between the normal and cystic fibrosis cell cultures at equivalent points of exponential growth were noted.

[Assessing health-related quality of life data of building trade workers by means of the SF-36 questionnaire]. / Die Erfassung der gesundheitsbezogenen Lebensqualität von Beschäftigten der Bauwirtschaft mit dem SF-36-Fragebogen.

The Lower Saxony statutory medical service of the building trade, the building trade association in Hanover and the statutory health insurance body of Lower Saxony have co-operated in the "ArGO" model project. The objective was to focus on the main areas of work-dependent health hazards and disorders. The SF-36 questionnaire was employed to ascertain how far the results obtained concerning health-related quality of life were suitable for this purpose. Hence, the data from industrial medical check-ups were compared with the additional findings for 4,334 building trade workers. Additional unfitness for work and medication data were available from the health insurance schemes for about one half of the group. The analyses revealed clear relationships between the subjectively experienced disorders on the one hand, and the stress and illness data on the other. In addition to age and the conventional stresses, e. g. strenuous physical work, the influence of psychosocial stress was also reflected in the assessment of the quality of life. The results obtained confirm the value of the SF-36 questionnaire for preventive medicine at an industrial level. It is suitable for identifying focal points of stress and can be employed for assessing preventative measures.