Search

Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.

to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features.This is a multicenter, retrospective case series. Patients under biologic therapy were included if they developed uveitis for the first time or experienced intraocular inflammation which was different in location or laterality to previous inflammation.Sixteen patients were identified. The underlying disorders included ankylosing spondylitis, juvenile idiopathic arthritis, rheumatoid arthritis, and Behçet's Disease. The biologic agents associated with a first episode of uveitis (n = 11) or with a new recurrence of uveitis (n = 5) were etanercept, adalimumab, abatacept, infliximab, and golimumab. Sarcoidosis based on bihilar lymphadenopathy, other computer tomography-findings, or biopsy was diagnosed in five patients under therapy with etanercep, adalimumab, and abatacept. Additionally, seven patients developed clinical changes in their uveitis pattern, suggesting sarcoid uveitis.Biologic treatment-induced uveitis often presents as granulomatous disease.

Purpose There is growing interest in low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case–control analysis, we compared the efficacy of LDMC and conventional chemotherapy (CCT) in MBC. Methods Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two controls who received CCT. Age, number of chemotherapy lines and metastatic sites as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate longer than 24 weeks (DCR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR) and subgroup analyses using the matching criteria. Results 40 cases and 80 controls entered the study. 30.0% patients with LDMC and 22.5% patients with CCT showed DCR (p = 0.380). The median PFS was 12.0 weeks in both groups (p = 0.218) and the median DoR was 31.0 vs. 20.5 weeks (p = 0.383), respectively. Among younger patients, DCR was 40.0% in LDMC vs. 25.0% in the CCT group (p = 0.249). DCR was achieved in 33.3% vs. 26.2% non-heavily pretreated patients (p = 0.568) and in 36.0% vs. 18.0% patients without multiple metastases (p = 0.096), respectively. In the HR-positive group, 30.0% LDMC vs. 28.3% CCT patients showed DCR (p = 1.000). Among triple-negative patients, DCR was achieved in 30.0% LDMC and 5.0% CCT patients (p = 0.095). Conclusions We demonstrated a similar efficacy of LDMC compared to CCT in the treatment of MBC. Thus, LDMC may be a valuable treatment option in selected MBC patients.

Purpose Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure. Methods A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719). Results Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p p p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC. Conclusion The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.

Introduction/Background* Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel lymphonodectomy (SNLD) successfully replaced inguinofemoral lymphadenectomy (IL) in patients with early vulvar cancer. Nevertheless, management of patients in special situations is not well studied or current data are inconclusive. Methodology To assess the current management of diagnostic and surgical procedures with respect to SNLD in early vulvar cancer, a web-based survey was mailed to 612 gynecological departments. Data are presented as frequencies of selected items. Result(s)* A total of 222 hospitals (36.27%) replied the questionnaire. Only 9.5% of hospitals did not offer the SNLD and 79.5% processed the evaluation of sentinel node (SN) by ultrastaging. After detection of isolated tumor cells (ITCs) or micrometastases, IL was performed in 28.1% and 60.5% of hospitals, respectively, and radiation without further surgical intervention was performed in 19.3% and 23.8% of hospitals, respectively. In 50.9% and 15.1% of cases, hospitals would not initiate any further therapy in patients with ITCs and micrometastases, respectively. In vulvar cancer of the midline with unilateral localized positive SN, 49.1% and 48.6% of hospitals performed ipsilateral or bilateral IF, respectively. Repeat SNLD was performed by 16.2% of hospitals. Conclusion* The vast majority of German hospitals are following current guidelines and are offering SNLD in patients with early vulvar cancer. Despite the fact that according to the GROINSS-V-I-study approximately 42% of positive SN were determined by ultrastaging, only 79.5% of German hospitals implemented this procedure. Our findings showed that hospitals would recommend expectant management in patients with ITCs or with micrometastases in 50.9% and 15.1% of cases, but current guidelines do not support this approach. Nevertheless, radiation is a good option in these patients, as shown by preliminary results of the GROINSS-V-II-study. Bilateral IL should be performed in patients with unilateral positive SN, as a SN positivity rate of 22.2% on the contralateral side was described by a current study and understaging of the groins might be fatal. Any deviation from current guidelines, as well as applying the SNLD in special situations, should be individually discussed with each patient.

Introduction/Background* We evaluated the prognostic impact of various global health assessment tools in accordance to conventional prognostic factors in patients with endometrial cancer (EC) older than 60 years. Methodology G-8 geriatric screening tool (G-8 geriatric score), Lee Schonberg prognostic index (Lee-Index), Charlson Comorbidity Index (CCI) and American Society of Anesthesiologists (ASA-PS) – Physical Status System were retrospectively determined in a consecutive cohort of elderly patients with EC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to determine the impact of the global health assessment tools on progression free survival (PFS) and overall survival (OS). Result(s)* 153 patients entered the study. In multivariate analysis adjusted for common clinical-pathological risk factors (e.g. histological type and stadium, histological grading, FIGO-stadium, tumor stadium and postoperative tumor burden) and different global health assessment tools (G-8 geriatric score, Lee-Index, CCI and ASA-PS) only the G-8 geriatric score retained its significance as a considerable and independent prognostic factor of 5-year OS rate (HR: 3.173; 95%-CI [1.436-7.010]; p=0.004) but not for univariate 5-year PFS rate (HR: 2.033; 95%-CI [0.925-4.468]; p=0.078). 92 patients (61.3%) were assigned to the G-8-non-frail cohort (cut-off value > 14 points) with an increased 5-year PFS and OS rate compared to the 58 patients (38.7%) classified as G-8-frail (PFS: 82.1% vs. 65.4%; p=0.071 and OS: 88.2% vs. 49.7%; p Conclusion* Preoperative G-8 geriatric score independently predicted 5-year OS in elderly EC patients irrespectively of the maximal surgical effort.

Introduction/Background* In the treatment of both platinum-resistant recurrent ovarian cancer (ROC) and metastatic breast cancer (MBC), symptom control and maintenance of quality of life (QoL) play a crucial role. In the advanced stage of disease, metronomic chemotherapy (MCT) may be a favourable treatment option. The aim of this study is to assess the QoL of heavily pretreated patients with ROC and MBC treated with MCT. Methodology PROmetronomic, FoR.UM 19-02193, is a monocentric, open-label, single-arm observational study to assess health-related patient-reported outcome data in ROC and MBC patients treated with MCT (cyclophosphamide 50 mg p.o. daily ± methotrexate 2.5 mg p.o. every other day). QoL data are evaluated using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0, EORTC QLQ-OV28 version 1.0 (ROC)/EORTC QLQ-BR23 version 1.0 (MBC), and Hospital anxiety and depression scale (HADS-D) questionnaires via an internet-based therapy support system CANKADO. Patients previously treated with at least 1 line of platinum-based and 1 platinum-free chemotherapy (ROC)/at least 2 lines of endocrine therapy (for hormone receptor-positive cancer) and at least 2 lines of chemotherapy (MBC) are included. Secondary endpoints are disease control rate at 12 and 24 weeks, duration of response, progression-free survival and overall survival. Assessment of safety and tolerability is conducted according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. As part of the translational research approach, potentially relevant anti-angiogenic and immunomodulatory biomarkers are being investigated. Result(s)* Until 2021-05-01, 4 ROC and 3 MBC patients have been enrolled. It is planned to include a total of 65 patients until 08/2023. Conclusion* Potentially toxic chemotherapy is often required to achieve disease control in patients with metastatic cancer. However, well-being and personal preferences must not be neglected. MCT could provide an efficacious treatment option with limited toxicities and positive impact on QoL.

Introduction/Background* Treatment of vulvar cancer contains surgery if applicable and often primary or neo-/adjuvant chemoradiation. Cisplatin and Mitomycin/5-FU are widely used radiosensitizers in vulvar cancer, although evidence is limited. We retrospectively investigated both radiosensitizers for outcome and toxicity. Methodology We screened the archive for patients treated with chemoradiation for pathologically-confirmed squamous cell cancer of the vulva between 01/2010 – 02/2021 at our institution. The impact of both radiosensitizers on prognosis was compared using Kaplan-Meier method and Cox-Regression analysis. Result(s)* 127 patients with vulvar cancer were screened. 24 patients received chemoradiation (Cisplatin n=11; Mitomycin/5-FU n=11; others n=2) as a neoadjuvant, primary or adjuvant treatment. Median follow-up was 17 months in both groups. Median age was 65 (35-91) years. Patients in the Cisplatin group were older than in the Mitomycin/5-FU group (Median age 73 vs. 55, p=0.007). Median radiation dose in total was 59.6 (41.4 – 85.0) Gy. 68.2% of the patients had FIGO stage III and 18.2% of the patients had FIGO stage IV before chemoradiation. Both groups showed no differences in terms of FIGO stage. 72.7% (8 out of 11) patients receiving Mitomycin/5-FU achieved clinical complete response compared to 45.5% (5 out of 11) receiving Cisplatin (p=0.309). One patient in each group was progressive during chemoradiation. Three patients stopped chemoradiation due to toxicity (Cisplatin n=2; Mitomycin/5-FU n=1) and one patient in the Cisplatin group died of treatment related sequelae. Radiodermatitis with epitheliolysis were the most common adverse events in both groups. Additionally, four patients in the Mitomycin/5-FU group required treatment for myelotoxicity. The 2 -year overall survival showed a numerical but not statistically significant difference in favour of the Mitomycin/5-FU group (59.7% vs. 30.7%; p= 0.306). The 2-year-recurrence-free-survival was comparable between Mitomycin/5-FU and Cisplatin (43.6% vs. 31.8%; p=0.829). Conclusion* Cisplatin and Mitomycin/5-FU showed a numerical but not statistically significant difference in overall survival in vulvar cancer. MitomycinC/5-FU tended to result in a clinical complete response more frequently but required more often a treatment for myelotoxicity. However, overall toxicity of Mitomycin/5-FU was acceptable and may be considered in the treatment of young, healthy patients with locally advanced vulvar cancer.

Introduction/Background* The aim of this study was to evaluate the impact of the preoperative global health status on the prognosis of patients with ovarian cancer (OC) older than 60 years, who received cytoreductive surgery. Methodology G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Result(s)* 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of PFS (HR: 2.009; 95%-CI [1.091-3.699]. 56 patients were classified as G-8 non-frail with an increased PFS compared to 50 G-8 frail patients (53.4% vs. 16.7%; p=0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p=0.012) but it did not influence the risk of recurrences or death (p=0.360; p=0.111, respectively). The Lee Schonberg prognostic index, the ECOG and mean age were not associated with survival. Conclusion* The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

The World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO 2017) included updated criteria for diagnosis and classification of post-transplant lymphoproliferative disorders (PTLDs). This study evaluated the clinicopathologic spectrum using WHO 2017 criteria and adult PTLD patients’ outcomes over 30 years between 1987 and 2017 at Mayo Clinic (Rochester, MN). Patients were retrospectively reviewed for clinical features, outcomes, and diagnostic pathology material and classified based on WHO 2017 criteria. A total of 227 patients were diagnosed with PTLD, with a median time from transplant to PTLD of 45 months. PTLD occurred >1 year after transplant in 149 (66%) patients. Monomorphic PTLD was the most common subtype (173, 76%), with diffuse large B cell lymphoma as the commonest morphology (n = 137). Epstein-Barr virus was positive in 61% of total cases and 90% of PTLD that developed within 1 year from transplant. The median event-free survival (EFS) and overall survival for the entire cohort were 21 months (95% confidence interval [CI]: 9–35) and 82 months (95% CI: 39–115), respectively. The EFS or overall survival was not impacted by Epstein-Barr virus status but differed based on WHO subtypes and year of diagnosis. Management changed over time with increased use of rituximab or chemotherapy + immunosuppression reduction as initial therapy. When compared to the matched general population and de novo diffuse large B cell lymphoma, patients not achieving EFS 24 status (no progression/treatment or death within 24 mo of diagnosis) had a worse standardized mortality ratio 16.75 (95% CI: 13.91–20) versus SMR 1.72 (95% CI: 1.26–2.28) in those who achieved EFS24. Cause of death was mostly attributed to non-lymphoma–related causes in those achieving EFS 24.

Introduction/Background* This study evaluated the impact of the global health status on the rate of postoperative clinical complications in patients with ovarian cancer (OC) older than 60 years. Methodology Selected global health status assessment tools were retrospectively determined in a cohort of OC patients older than 60 years, treated at our institution between 2008 and 2019. The primary outcome was the incidence and type of postoperative clinical complications in accordance with the Veteran Affairs’ National Surgical Quality Improvement Program (NSQIP). Differences in binary and ordinal variables between independent groups were analyzed by the chi-square test. Furthermore, rank correlations were examined with Spearman-Correlation. Result(s)* 116 patients entered the study. 54 patients (46.6%) were classified as G-8 frail and 56 patients (48.3%) as G-8 non-frail. CCI classified 24 patients (20.7%) into CCI-1, 63 patients (54.3%) into CCI-2 and 29 patients (25.0%) into CCI-3. The ASA PS allocated 48 patients (44.0%) as ASA-2 and 61 patients (56.0%) as ASA-3. The Lee-Index allocated 60 patients (61.9%) to a cohort with a four-year-mortality Conclusion* Preoperative evaluation of global health status with G-8 score and CCI were significantly associated with elevated rates of postoperative complications and the need of transfusions, in contrast to age alone in elderly patients with OC.

Study question The aim was to assess the prevalence of self-reported symptoms of depression and anxiety and the moderating factors influencing mental symptoms during the COVID–19 pandemic. Summary answer Endometriosis patients were at risk of developing mental disorders during the pandemic. Associated risk factors were: reduction of the social network and the employment status. What is known already Endometriosis is a disease affecting up to 10% of women of fertile age. The leading symptoms are sub- or infertility and chronic pain. Additionally, the psychological impact on womeńs life is enormous. Women with endometriosis show higher rates of depression, anxiety and emotional distress, and these alterations in mental health were associated with the presence of pain rather than with the diagnosis of endometriosis. Additionally, a higher level of depression was observed in women with endometriosis. Study design, size, duration To assess the impact of the government-imposed social distancing or quarantine on mental health, an online questionnaire was placed on internet platforms of endometriosis patients support groups between 6th and 27th April 2020. Data collection and analysis were performed anonymously. Recruitment was conducted via a direct link to the survey and an invitation to participate was distributed via the internet platforms of patients support groups. Participants/materials, setting, methods 274 participants answered the Patient Health Questionnaire for Depression and Anxiety (PHQ–4), which screens for depression (PHQ–2), anxiety (GAD–2) and the level of psychological distress (PHQ–4). PHQ–2 and GAD–2 scores ≥ 3 are cut-off points between normal range and probable cases of mental disorders. A PHQ–4 score above 6 is indicative for severe symptoms. We used descriptive statistics to describe the study population. Correlates of depression and anxiety were identified using multivariate logistic regressions. Main results and the role of chance We showed that depression and anxiety were highly prevalent in endometriosis patients during the pandemic: 46.7% and 48.2% of participants showed scale scores of ≥ 3 on the PHQ–2 and GAD–2 scales, respectively. The mean PHQ–4 score was 5.72 (SD = 3.21), thus endometriosis patients were achieving significantly higher PHQ–4 sores (p Risk factors for higher probability of depressive disorders were the employment status (being employed, OR 2.890, p Risk factors for higher probability of anxiety were the employment status (being employed, OR 2.697, p Endometriosis patients were at higher risk for developing mental health problems. The effective use of brief screening measures, such as PHQ–4, can be widely implemented even in the busy outpatient care of general practitioners and gynecologists and may help to reduce morbidity. Limitations, reasons for caution We used self-reports for assessment of anxiety and depression and those are susceptible to response bias, such as giving socially desirable responses. Moreover, as PHQ–4 is only a screening tool, the diagnosis must be confirmed in accordance to the appropriate DSM–V criteria. Wider implications of the findings: A better understanding of potential mental problems in endometriosis patients during stressful events, such as the COVID–19 pandemic or other comparable difficult environmental or social circumstances, is crucial for providing an optimal patient centered care in cases of upcoming stressful events. Trial registration number Not applicable

Background Endometriosis is a chronic pain condition in premenopausal women. Pain is mainly characterized by pain intensity and may induce disability in all areas of daily life. Nevertheless, pain is influenced by emotional and social factors as well. Social distancing measures or quarantine, as reaction to rapidly rising infections with the COVID-19 virus due to the SARS-CoV-2 pandemic, were implemented across Europe to prevent the spread of the virus and social distancing measures were imposed by the German government by beginning of March 2020 with initiation of the lockdown by the end of March 2020. The objective of this study was to assess, how social distancing measures during the lockdown impacted the various aspects of pain perception in a group of chronic pain patients, such as women suffering from endometriosis. Methods Between 6th to 27th April 2020, an online questionnaire was activated at internet platforms of endometriosis patients support groups. Participants were asked retrospectively at one time point about their visual pain intensity measured by the visual analogue scale (VAS) and pain disability via pain disability index (PDI) prior to initiation of social distancing measures in Germany (VASP, PDIP), as well as the pain intensity and pain disability since implementation of social distancing measures (VASI, PDII). Differences of VAS and PDI previous and after implementation of social distancing measures were displayed as ΔVAS and ΔPDI. Pain experience and social support were assessed by a 5-point Likert scale. Results 285 participants completed at least one question regarding pain intensity, disability, pain experience or social support. Dysmenorrhea, the symptom with the highest level of pain assessed by VAS, decreased significantly during the SARS-CoV-2 pandemic compared to the time period prior to social isolation (45.30% respondents experienced improvemenet vs 40.50% who experienced worsening; p = 0.025). The global physical impairment improved significantly (improvement of pain induced disability in 48.20% vs 40.90% with worsening of pain symptoms; p = 0.032) after the implementation of social distancing measures. Pain experience was negatively affected by social distancing measures, since frequency of pain awareness increased in 43.6% (p Conclusions Physical pain and disability on one hand and emotional and social pain experience on the other were differentially affected by the emerged emotional, social and health care constraints related to the SARS-CoV-2 pandemic.

Rationale: Cerebrovascular function is critical for brain health, and endogenous vascular protective pathways may provide therapeutic targets for neurological disorders. S1P (Sphingosine 1-phosphate) signaling coordinates vascular functions in other organs, and S1P 1 (S1P receptor-1) modulators including fingolimod show promise for the treatment of ischemic and hemorrhagic stroke. However, S1P 1 also coordinates lymphocyte trafficking, and lymphocytes are currently viewed as the principal therapeutic target for S1P 1 modulation in stroke. Objective: To address roles and mechanisms of engagement of endothelial cell S1P 1 in the naive and ischemic brain and its potential as a target for cerebrovascular therapy. Methods and Results: Using spatial modulation of S1P provision and signaling, we demonstrate a critical vascular protective role for endothelial S1P 1 in the mouse brain. With an S1P 1 signaling reporter, we reveal that abluminal polarization shields S1P 1 from circulating endogenous and synthetic ligands after maturation of the blood-neural barrier, restricting homeostatic signaling to a subset of arteriolar endothelial cells. S1P 1 signaling sustains hallmark endothelial functions in the naive brain and expands during ischemia by engagement of cell-autonomous S1P provision. Disrupting this pathway by endothelial cell-selective deficiency in S1P production, export, or the S1P 1 receptor substantially exacerbates brain injury in permanent and transient models of ischemic stroke. By contrast, profound lymphopenia induced by loss of lymphocyte S1P 1 provides modest protection only in the context of reperfusion. In the ischemic brain, endothelial cell S1P 1 supports blood-brain barrier function, microvascular patency, and the rerouting of blood to hypoperfused brain tissue through collateral anastomoses. Boosting these functions by supplemental pharmacological engagement of the endothelial receptor pool with a blood-brain barrier penetrating S1P 1 -selective agonist can further reduce cortical infarct expansion in a therapeutically relevant time frame and independent of reperfusion. Conclusions: This study provides genetic evidence to support a pivotal role for the endothelium in maintaining perfusion and microvascular patency in the ischemic penumbra that is coordinated by S1P signaling and can be harnessed for neuroprotection with blood-brain barrier-penetrating S1P 1 agonists.

Introduction/Background Premalignant or malignant disease of the vulva or vagina and require appropriate surgical oncological treatment. In these patients, wound breakdown occurs in 20–40% and, additionally, some patients might not be eligible for standard procedures of reconstructive surgery. In these cases, tissue engineered buccal mucosa might promote wound healing, reduce hospital days and improve satisfaction and long-term outcomes of patients. In this project we tested the use of collagen matrices for generation of engineered mucosa replacements. Methodology Primary buccal epithelial cells and fibroblasts were seeded on three commercially available (BioGide®, TissueFoil E®, Sugsisis ES®) and one non-commercially available (BioGide-Pro®) biodegradable membranes. After 21 days cultivation the tissue engineered oral mucosa (TEOM) equivalents were evaluated. Results Each examined TEOM displayed multi-layered epithelial cells on the bottom side of the membrane and mono-layered fibroblasts on the underside of each membrane. Immunohistochemical staining showed collagen IV as a marker of the basement membrane, detected in all TEOMs. Additionally, the BioGide® membrane enabled deep invasion of fibroblasts, whereas cells seeded on TissueFoil E® were not able to penetrate the membrane. Suboptimal invasion of fibroblasts was displayed by Sugsisis ES® and BioGide-Pro®. The BioGide® membrane showed a clear shrinkage during TEOM formation. Conclusion In summary, the BioGide® scaffold showed the best results regarding formation of TEOMs. We showed that tissue engineered oral mucosa equivalents can be engineered under in vitro conditions. This could enable surgeons to apply the engineered tissue for reconstructive purposes in patients with benign or malignant vulvar or vaginal conditions, who are not eligible for standard surgical approach but who may benefit from innovative procedures. Disclosure Roxana Schwab: I have received honoraria and expenses from Roche Pharma AG and AstraZeneca GmbH and funding by MacoPharma International GmbH and by Max Planck Institute for Polymer Research Mainz. BioGide-Pro® was kindly provided by Geistlich Biomaterials. Annette Hasenburg: I have received honoraria and expenses from AstraZeneca, FBA Frauenarzte BundesAkademie GmbH, KlarigoVerlag, MedConcept, Med public GmbH, Med update GmbH, Medicultus, Pfizer, Promedicis GmbH, Pierre Fabre Pharma GmbH, Softconsult, Roche Pharma AG, Streamedup! GmbH, Tesaro Bio Germany GmbH. I am consultant to PharmaMar, Promedicis GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG and Tesaro Bio Germany GmbH. I have received funded research from Celgene. Celine Pfeifer: I have no conflict of interest. Martin Heller: I have no conflict of interest. Walburgis Brenner: I have no conflict of interest.

Introduction/Background Oncological therapy may affect women in terms of future reproductive capabilities. The infertility resulting from the treatment of cancer has a great impact on the quality of life. Patients of reproductive age consider a risk for infertility one of the most difficult components of their illness and treatment. The aim of the EORTC module is the development of an international questionnaire to assess the individual unmet needs and concerns related to fertility issues in young cancer patients. Methodology We conducted interviews with 13 health care professionals and 12 young cancer patients regarding the topic of fertility preservation and related issues (phase I). The relevant issues were assessed by using thematic analysis of the interviews. Additionally, literature research and discussion with the collaborators at the autumn EORTC meeting 2018 helped to identify important missing topics (phase I). Results We developed a relevant list of 54 issues in 6 preliminary domains: psychoeducation and counseling; partnership, sexuality and family; financial aspects; quality of life; decision making and coping and global issues (phase I). This list of issues will be translated in national languages. For the next step interviews with young cancer patients and health care professionals during diagnosis and the survivorship continuum will be conducted in eight European countries (phase II and III) for identification of missing issues and to streamline the particular topics with the final goal to develop the international EORTC ‘fertility module’. Conclusion Identification of patients9 psychosocial needs is an important part of advanced onco-fertility care including sexual health, intimate relationships and the affordability of fertility preservation measures. This EORTC module will help health care providers to tailor and optimize the individual counseling regarding fertility related issues during cancer diagnosis, treatment and the survivorship continuum and thus to improve the quality of life of young cancer patients. Disclosure Roxana Schwab: I have received honoraria and expenses from Roche Pharma AG and AstraZeneca GmbH and funding by MacoPharma International GmbH, by Max Planck Institute for Polymer Research Mainz and by Geistlich Biomaterials. Annette Hasenburg: I have received honoraria and expenses from AstraZeneca, FBA Frauenarzte BundesAkademie GmbH, KlarigoVerlag, MedConcept, Med public GmbH, Med update GmbH, Medicultus, Pfizer, Promedicis GmbH, Pierre Fabre Pharma GmbH, Softconsult, Roche Pharma AG, Streamedup! GmbH, Tesaro Bio Germany GmbH. I am consultant to PharmaMar, Promedicis GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG and Tesaro Bio Germany GmbH. I have received funded research from Celgene. Andrea Kiemen: I have no conflict of interest. E. Greimel: I have no conflict of interest. V. Kesic: I have no conflict of interest. Joachim Weis: This study is supported by an EORTC grant.

Introduction/Background There is a growing importance of low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control-analysis we compared the efficacy of LDMC and conventional chemotherapy in MBC. Methodology Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two patients who received conventional chemotherapy. Age, number of chemotherapy lines and metastatic lesions as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate greater than 24 weeks (DCR). Secondary endpoints were DCR in subgroups (age at begin of therapy, number of chemotherapy lines, number of different metastatic lesions and HR status), progression-free survival (PFS) and duration of response (DoR). Results A total of 40 cases and 80 controls entered the study. 30% patients with LDMC and 23% patients with conventional chemotherapy showed DCR (p=0.380). Among younger patients DCR was 40% in LDMC vs. 25% in the control group (p=0.249). In addition, DCR was achieved in 33% vs. 26% patients with ≤ 2 chemotherapy lines (p=0.568) and in 36% vs. 18% patients with ≤ 2 different metastatic lesions (p=0.096), respectively. In the triple negative group 30% LDMC vs. 5% control patients showed DCR (p=0.095). The median PFS was 12.5 weeks in both groups (p=0.218). The median DoR was 31 weeks in LDMC and 21 weeks in the control group (p=0.383). Conclusion In this retrospective case-control study we demonstrated a similar efficacy of LDMC compared to conventional chemotherapy in the treatment of MBC. Moreover, no significant differences were found in the subgroups studied. Therefore, the concept of LDMC may also be a treatment option in both younger and non-heavily pre-treated MBC patients who do not need rapid remission. Disclosure Nothing to disclose.

Eine Krebserkrankung wahrend der Schwangerschaft ist eine besondere Belastung fur die Schwangere und ihren Partner sowie eine grose Herausforderung fur alle Beteiligten. Besonderheiten in der psychoonkologischen Betreuung krebserkrankter Schwangerer und ihrer Partner unter Berucksichtigung der Fertilitatsprotektion. Literaturrecherche und Diskussion der besonderen Belastung wahrend einer Krebserkrankung in der Schwangerschaft. Ein multidisziplinares Team aus Onkologen, Geburtshelfern, Neonatologen und Psychoonkologen ist notwendig, um das optimale Behandlungskonzept fur die Schwangere und den Fetus zu gewahrleisten. Die Prognose einer Tumorerkrankung in der Schwangerschaft unterscheidet sich bei gleicher Therapie nicht von derjenigen einer Nichtschwangeren. Die Prognose des Ungeborenen hangt entscheidend vom Entbindungszeitpunkt ab. Trotz bestehender Schwangerschaft sollten die Frage der Fertilitatsminderung als Langzeitnebenwirkung der onkologischen Therapie thematisiert und Moglichkeiten der Fertilitatsprotektion besprochen werden. Patientin und Partner benotigen eine sorgfaltige, routinemasige Uberprufung des psychischen Wohlergehens und das Angebot einer kontinuierlichen psychosozialen Unterstutzung wahrend der gesamten Behandlung. Ausfuhrliche und verstandliche Informationen uber jeden Behandlungsschritt und seine Auswirkungen auf die Schwangerschaft und das Kind sind unerlasslich. Sie verringern die Angst, dem Kind schaden zu konnen und reduzieren damit Sorgen und Schuldgefuhle.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients.

Terroranschlage kommen mittlerweile im westlichen Europa mit einer Haufigkeit vor, dass man davon ausgehen muss, von dieser Thematik weiter begleitet zu werden und man standig mit derartigen Szenarien rechnen muss. Dabei haben diese Szenarien in der Regel durch den Einsatz entsprechender Waffen oder Bomben meist eine grose Anzahl an verletzten Patienten im Sinne eines Massenanfalls von Verletzten (TerrorMANV) zur Folge. Dies ist nicht nur eine grose Herausforderung fur die Ersthelfer und Sicherheitskrafte am Ereignisort, sondern im unmittelbaren Nachgang auch fur die versorgenden Kliniken. Dies gilt insbesondere, da es sich bei den Verletzungen in vielen Fallen um unmittelbar vital bedrohliche Traumen mit nicht selten relevanten Blutungen handelt. Im Rahmen der vorliegenden Arbeit werden die chirurgischen Versorgungsstrategien im Terrorfall gegenubergestellt. Situationsabhangig muss dabei zwischen Masnahmen nach dem Damage-Control-Surgery(DCS)- vs. dem Tactical-Abrreviated-Surgical-Care(TASC)-Konzept unterschieden werden. Anhand einer entsprechenden Literaturaufarbeitung und mit Bezug zu beispielhaften klinischen Fallen werden die Versorgungskonzepte genauer vorgestellt und diskutiert. Besonders werden dabei die notwendigen Entscheidungspfade in derartigen Situationen beleuchtet. Versorgungsnotwendigkeiten beim TerrorMANV erzwingen ein Umdenken im chirurgischen Handeln. Ein Vorgehen nach den Prinzipen der DCS ist bekannt, hier jedoch durch den Patientenzustand bedingt. Der TerrorMANV erfordert dieses Umdenken jedoch aufgrund der Gesamtlage. Im Extremfall mussen die Masnahmen der DCS noch weiter eingeschrankt und es muss nach dem TASC-Konzept vorgegangen werden. TerrorMANV-Situationen erfordern im Extremfall ein anderes chirurgisches Vorgehen nach anderen chirurgischen Prioritaten in der Behandlung einzelner Patienten. Die notwendigen, v. a. taktisch-strategischen Uberlegungen sind dabei nicht vertraut und mussen vermittelt und geubt werden. Dazu konnte nun zuletzt ein neues Kurskonzept (Terror and Disaster Surgical Care, TDSC®) etabliert werden.

ZusammenfassungZiel dieser Studie war der Vergleich der Zufriedenheit und des Behandlungserfolgs bei Schmerzpatienten, die interdisziplinär (anästhesiologisch, psychosomatisch, neurologisch, orthopädisch) oder rein neurologisch betreut wurden. Methoden Es wurden 183 Patienten ausgewählt, die in unserer neurologischen Ambulanz und in unserem interdisziplinären Schmerztherapiezentrum (IST) behandelt wurden. Davon wurden 142 Patienten mit Polyneuropathie, Kopfschmerz oder muskuloskelettalen Schmerzen in die endgültige Analyse eingeschlossen. 39 Patienten (27,5 %) wurden im IST und 103 Patienten ausschließlich neurologisch behandelt. Diese Patienten wurden aufgefordert, einen Fragebogen auszufüllen, mit dem Zufriedenheits- und Schmerzparameter erfragt wurden. Ergebnisse Die neurologische und die multidisziplinäre Schmerzbehandlung führten zu einer vergleichbaren Besserung der Schmerzen (je p < 0,001). Dieser Effekt war unabhängig von der Grunderkrankung. Die interdisziplinäre ambulante Behandlung führte primär nicht zu vermehrter Patientenzufriedenheit. Schlussfolgerungen Die Schmerzreduktion und die Patientenzufriedenheit der neurologischen ambulanten Schmerzbehandlung waren vergleichbar mit denen einer interdisziplinären ambulanten Therapie. Der einzig signifikante Vorteil der interdisziplinären Behandlung war eine niedrigere stationäre Aufnahmerate nach der ambulanten Therapie. Dieses Ergebnis sagt nichts aus über die Effizienz stationärer oder tagesklinischer Schmerztherapie, es legt aber nahe, dass bei vielen ambulanten Fällen eine neurologische Schmerztherapie zumindest als primäre Maßnahme ausreichend ist. Neurologische Schmerzambulanzen sollten also gefördert werden.

Simple Summary The co-occurrence of cancer and pregnancy is fortunately a rare event. It is a challenging situation for all involved parties, as the risks and benefits of oncological treatments should be balanced for both the mother and the offspring. This work offers guidance to clinicians regarding the choice of diagnostic and therapeutic procedures, as well as regarding the management of the pregnancy. Abstract Cancer diagnosis and treatment in pregnant women is a challenging situation. A multidisciplinary network of specialists is required to guide both, the expecting mother and the unborn child through the diagnostic workup and the cytotoxic therapy, by balancing the respective risks and benefits. Tumor entity, stage, biology and gestational week at diagnosis determine the appropriate approach. As premature delivery emerged as one of the main risk factors for adverse long-term outcome of the progeny, it should be avoided, if reasonable from the oncological perspective. This article offers a comprehensive review with respect to the various aspects of cancer in pregnancy.

Introduction The incidence of radial nerve injury after humeral shaft fractures is on average 11.8% (Shao et al., J Bone Jt Surg Br 87(12):1647–1652, 2005) representing the most common peripheral nerve injury associated with long bone fractures (Korompilias et al., Injury, 2013). The purpose of this study was to analyze our current policy and long-term outcome, regarding surgically treated humeral shaft fractures in combination with radial nerve palsy. Materials and methods We retrospectively analyzed the data of patients with surgically treated humeral shaft fractures from 01/01/2003 to 28/02/2013. The analysis included fracture type, soft tissue injury regarding closed and open fractures, type of fixation, management, and outcome of radial nerve palsy. Results A total of 151 humeral shaft fractures were fixed in our hospital. In 20 (13%) cases, primary radial palsy was observed. Primary nerve exploration was performed in nine cases. Out of the 13 patients with follow-up, 10 showed a complete, 2 a partial, and 1 a minimal nerve recovery. Two of them underwent a revision procedure. Secondary radial nerve palsy occurred in 9 (6%) patients postoperatively. In five patients, the radial nerve was not exposed during the initial surgery and, therefore, underwent revision with nerve exploration. In all 5, a potential cause for the palsy was found and corrected as far as possible with full recovery in 3 and minimal recovery in one patient. In four patients with exposure of the nerve during the initial surgery, no revision was performed. All of these 4 showed a full recovery. Conclusion Our study showed an overall rate of 19% radial nerve palsy in surgically treated humeral shaft fractures. Most of the primary palsies (13%) recovered spontaneously, and therefore, nerve exploration was only exceptionally needed. The incidence of secondary palsy after surgery (6%) was high and mainly seen after plate fixation. In these cases, we recommend early nerve exploration, to detect and treat potential curable neural lesions.

Hintergrund Sexualitat ist ein wesentlicher Bestandteil der gesundheitsbezogenen Lebensqualitat (LQ) und kann durch eine Krebserkrankung und deren Therapie eingeschrankt werden. Bei gynakologischen Karzinomen spielt die Restriktion sexueller Funktionen durch Operation, Chemo- und/oder Strahlentherapie eine grose Rolle.

Purpose To determine the spectrum of retinal complications (RCs) in a cohort of eyes with a type 1 Boston keratoprosthesis (KPro). Methods All patients (36 eyes of 31 patients) who received a type 1 Boston KPro from January 2004 to December 2015 at the University of California, Davis, were included. Electronic medical records were reviewed for relevant clinical data. Demographic information, initial corneal diagnosis, postoperative course, posterior segment complications, preoperative and final visual acuity were tabulated and analyzed. Results Posterior segment complications after type 1 Boston KPro were identified in 56% of eyes (n = 20). They included retinal detachment (n = 11; 31%), retroprosthetic membrane (n = 10; 28%), endophthalmitis (n = 7; 19%), cystoid macular edema (n = 5; 14%), epiretinal membrane (n = 4; 11%), vitreous hemorrhage (n = 2; 6%), choroidal detachment (n = 2; 6%), retinal vein occlusion (n = 1; 3%), and macular hole (n = 1; 3%). During the average follow-up period of 53.8 months (median, 57.1 months; range, 1.8-108.7 months) after type 1 Boston KPro, final best-corrected visual acuity improved by a mean of 0.12 logarithm of the minimum angle of resolution (LogMAR) units (range, -2.26 to +2.26) overall. The proportion of eyes with final best-corrected visual acuity better than 20/200 was 2 of 20 (10%) in the group with RCs, in contrast to 7 of 16 eyes (44%) noted among eyes without RCs. Conclusions Long-term visual outcomes in eyes after type 1 Boston KPro may depend, in part, on maintaining a healthy posterior pole. Retinal detachment, in particular, may represent a threat to ultimate visual functioning. Regular examination of the peripheral fundus is recommended.

Das Konzept der „damage control surgery“ (DCS) hat sich heute, als lebensrettende Notfallchirurgie bei enger Indikationsstellung, etabliert und dient der Schadensminimierung. Der Ursprung der DCS liegt im Stoppen der Blutung und Kontrolle der Kontamination des schwer verletzten Abdomens. Dies ist ausschlaggebend bei der Entscheidung zur Anwendung oder Ablehnung eines derartigen Verfahrens, da das Uberleben nachweislich von der Blutstillung in der Korperhohle und den Extremitatenubergangen abhangt. Die Damage-control-Strategie stellt einen gezielten Versorgungsansatz bei Vorliegen bestimmter Auslosemechanismen dar. Die DCS ermoglich das Uberleben Schwerstverletzter durch schnelle Blutungs- und Kontaminationskontrolle. Sie gehort in das Gesamtkonzept der „damage control resuscitation“, als eine Form der blutstillenden Verfahren. Die DCS lasst sich nicht mit anderen Versorgungsstrategien vergleichen, denn sie geht einerseits mit erhohten Uberlebensraten, andererseits aber auch mit einer potenziell relevanten Komorbiditat einher. Ein hoher Evidenzgrad fur die einzelnen DCS-Verfahren steht weiterhin aus und wird, prospektiv randomisiert, vermutlich auch in Zukunft nur schwer erreichbar sein. Die Techniken der abdominellen und thorakalen DCS sind in der Literatur mittlerweile mehrfach beschrieben und finden verbreitet Anwendung. Umso wichtiger ist es, den differenzierten Einsatz der DCS anhand der entsprechenden Patientenauswahl zu gewahrleisten, und einen inflationaren Gebrauch zu verhindern, da die DCS dem geeigneten Patienten das Leben rettet, fur den anderen dagegen potenziell die Morbiditat erhoht.>

Study question What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? Summary answer In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. What is known already Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. Study design, size, duration Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. Participants/materials, setting, methods Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. Main results and the role of chance The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). Limitations, reasons for caution The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. Wider implications of the findings This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. Study funding/competing interest This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. Trial registration number None.

The New Zealand White rabbit has been widely used as a model of limbal stem cell deficiency (LSCD). Current techniques for experimental induction of LSCD utilize caustic chemicals, or organic solvents applied in conjunction with a surgical limbectomy. While generally successful in depleting epithelial progenitors, the depth and severity of injury is difficult to control using chemical-based methods. Moreover, the anterior chamber can be easily perforated while surgically excising the corneal limbus. In the interest of creating a safer and more defined LSCD model, we have therefore evaluated a mechanical debridement technique based upon use of the AlgerBrush II rotating burr. An initial comparison of debridement techniques was conducted in situ using 24 eyes in freshly acquired New Zealand White rabbit cadavers. Techniques for comparison (4 eyes each) included: (1) non-wounded control, (2) surgical limbectomy followed by treatment with 100% (v/v) n-heptanol to remove the corneal epithelium (1-2 min), (3) treatment of both limbus and cornea with n-heptanol alone, (4) treatment of both limbus and cornea with 20% (v/v) ethanol (2-3 min), (5) a 2.5-mm rounded burr applied to both the limbus and cornea, and (6) a 1-mm pointed burr applied to the limbus, followed by the 2.5-mm rounded burr applied to the cornea. All corneas were excised and processed for histology immediately following debridement. A panel of four assessors subsequently scored the degree of epithelial debridement within the cornea and limbus using masked slides. The 2.5-mm burr most consistently removed the corneal and limbal epithelia. Islands of limbal epithelial cells were occasionally retained following surgical limbectomy/heptanol treatment, or use of the 1-mm burr. Limbal epithelial cells were consistently retained following treatment with either ethanol or n-heptanol alone, with ethanol being the least effective treatment overall. The 2.5-mm burr method was subsequently evaluated in the right eye of 3 live rabbits by weekly clinical assessments (photography and slit lamp examination) for up to 5 weeks, followed by histological analyses (hematoxylin & eosin stain, periodic acid-Schiff stain and immunohistochemistry for keratin 3 and 13). All 3 eyes that had been completely debrided using the 2.5-mm burr displayed symptoms of ocular surface failure as defined by retention of a prominent epithelial defect (∼40% of corneal surface at 5 weeks), corneal neovascularization (2-3 quadrants), reduced corneal transparency and conjunctivalization of the corneal surface (demonstrated by the presence of goblet cells and/or staining for keratin 13). In conclusion, our findings indicate that the AlgerBrush II rotating burr is an effective method for the establishment of ocular surface failure in New Zealand White rabbits. In particular, we recommend use of the 2.5-mm rotating burr for improved efficiency of epithelial debridement and safety compared to surgical limbectomy.

Die Frage „Hat sich in Ihrer Partnerschaft etwas verandert?“ konnte der Einstieg fur das Gesprach mit ihrer Krebspatientin sein, um uber die Auswirkungen einer onkologischen Therapie auf die Sexualitat und Fertilitat zu sprechen. Die notwendige Beratung gewinnt im Rahmen der onkologischen Versorgung zunehmend an Bedeutung.

Im Verlauf einer Tumorerkrankung leiden bis zu 90% der Patienten an Schmerzen, die nozizeptiven, neuropathischen oder gemischt nozizeptiv/neuropathischen Charakter haben konnen. Psychische, soziale und existenzielle Belastungsfaktoren beeinflussen das Schmerzgeschehen zusatzlich („total pain“). Mit den Praparaten des WHO-Stufenschemas steht dem Therapeuten eine Vielzahl wirksamer Substanzen zur Verfugung, die entsprechend dem spezifischen Schmerzgeschehen differenziert einzusetzen sind. Parenterale und ruckenmarknahe Opioidtherapie sowie neurodestruktive Verfahren konnen im Einzelfall entscheidend zur Schmerzlinderung beitragen. Dieser CME-Artikel berucksichtigt in seiner aktualisierten Fassung die 2012 veroffentlichten evidenzbasierten Empfehlungen der Europaischen Gesellschaft fur Palliativmedizin sowie die im Mai 2015 publizierte S3-Leitlinie „Palliativmedizin fur Patienten mit einer nicht heilbaren Krebserkrankung“ und bietet somit auf der Basis der bestmoglichen Evidenz und klinischer Erfahrung eine Entscheidungshilfe fur die Praxis.

Since more and more hernia registries are being created and the number of patients included is increasing, knowledge of potential pitfalls in interpretation of registry data has to be known and dealt with. This invited commentary is to discuss some of these topics. The aim is to present and discuss the main shortcoming of register-based studies and how to deal with these problems, to contribute to more validated results and eventually improved surgical outcomes.

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.Die Kryokonservierung von Ovarialgewebe mit anschließender Transplantation des Gewebes stellt eine etablierte Methode der Fertilitätsprotektion für Patientinnen dar, die sich einer gonadotoxischen Therapie unterziehen müssen. Das Verfahren kann zu jedem Zykluszeitpunkt erfolgen und führt somit meistens zu keiner Verzögerung der onkologischen Therapie. Mithilfe dieses Verfahrens konnten bis dato mehr als 130 Geburten weltweit verzeichnet werden. Die Geburtenrate beträgt derzeit ca. 30% und es ist von einer Steigerung durch eine weitere Optimierung der Kryokonservierungs- und Operationstechnik auszugehen. Das hier vorgelegte Konzeptpapier soll Handlungsempfehlungen für den Umgang mit der Kryokonservierung und Transplantation von Ovarialgewebe an deutschsprachigen reproduktionsmedizinischen Zentren geben.

Aim The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline. Methods This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40). Recommendations The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patient's personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities. Ziel Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) publiziert und zusammen mit der Deutschen Gesellschaft für Urologie (DGU) sowie Deutschen Gesellschaft für Reproduktionsmedizin (DGRM) koordiniert wurde, ist es, durch die Evaluation der relevanten Literatur konsensbasierte Handlungsempfehlungen für die Beratung und den Einsatz von fertilitätserhaltenden Maßnahmen bei präpubertären Mädchen und Jungen sowie für Patienten/-innen im reproduktiven Alter zu geben. Im Folgendem werden die Statements und Empfehlungen für Mädchen und Frauen dargestellt. Die Statements und Empfehlungen für Jungen und Männer sind nicht Inhalt dieser Publikation. Methoden Diese S2k-Leitlinie wurde durch einen strukturierten Konsens von repräsentativen Mitgliedern verschiedener Fachgesellschaften (n = 40) im Auftrag der Leitlinienkommission der DGGG, DGU und DGRM entwickelt. Empfehlungen Es werden Empfehlungen zur Beratung und dem Einsatz von fertilitätserhaltenden Maßnahmen bei Patientinnen unter Berücksichtigung der Lebensumstände, der geplanten onkologischen Therapie und des individuellen Risikoprofils dargestellt sowie über das Vorgehen bei ausgewählten Tumorentitäten.

Diese Frage konnte der Einstieg fur die Krebspatientin sein, uber die Auswirkungen einer onkologischen Therapie auf ihre Sexualitat und Fertilitat zu sprechen. Denn diese gewinnen zunehmend an Bedeutung. Die notwendige Beratung stellt behandelnde Arzte vor eine Herausforderung.

Background One of the leading causes of death is out-of-hospital cardiac arrest (OHCA) with an in-hospital mortality of about 70%. To identify predictors for the high mortality of OHCA patients and especially for women, that are considered at high risk for in-hospital mortality, we evaluated one specific setting of in-hospital treatment after OHCA: the emergency department (ED). Methods Retrospective analysis of consecutive ED admissions with OHCA at the Inselspital Bern, Switzerland from 1st June 2012 to 31th Mai 2015. Demographic, preclinical and ED medical data were compared for patient groups with return of circulation (ROSC) and on-going resuscitation (CPR) on admission, as well as for subgroups with and without ED mortality. Predictors for ED mortality were investigated using univariate analysis with logistic regression. Results In 354 patients (228 (64.4%) with ROSC; 126 (35.6%) with on-going CPR) we found an overall ED mortality of 28.5% (5.7% ROSC group; 69.8% on-going CPR group). Female gender (OR 7.053 (CI 95% 2.085; 24.853), p = 0.002) and greater age (OR 1.052 (95% CI 1.006–1.101), p = 0.029) were associated with ED mortality in the ROSC but not in the on-going CPR group. Ventricular fibrillation as initially monitored rhythm (OR 0.126 (95% CI 0.027–0.582), p = 0.008) and shorter CPR duration (OR 1.055 (95% CI 1.024;1.088), p = 0.001) were associated with ED survival in patients with ROSC but not in patients with on-going CPR on admission. In ROSC patients a higher lactate and lower pH were associated with mortality (pH: OR 0.009 (CI95% 0.000;0.420), p = 0.016; lactate: OR 1.183 (95% CI 1.037; 1.349), p = 0.013); similar in on-going CPR patients (pH 0.061 (95% CI 0.007, 0.558), p = 0.013, lactate: 1.146 (95% CI 1.041;1.261), p = 0.005). Conclusion Patients with ROSC who died during ED care were predominantly women and older patients, as well as patients with non-shockable initial heart rhythm and long CPR durations. In patients with on-going CPR on admission, no clinical or demographic predictors for ED mortality were found. Higher lactate and lower pH were predictors in both OHCA groups.

Hintergrund Im Rahmen der vorliegenden Studie sollte untersucht werden, ob bei Patienten in der Fruhphase einer ambulant erworbenen Sepsis („community-acquired sepsis“, CAS) ein Zusammenhang zwischen der Leberfunktion, gemessen uber die Indocyaningrun(ICG)-Elimination, und dem klinischen Verlauf existiert.

e12578 Background: There is a growing importance of low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control-analysis we compared the efficacy of LDMC and conventional chemotherapy in MBC. Methods: Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two patients who received conventional chemotherapy. Age, number of chemotherapy lines and metastatic lesions as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate greater than 24 weeks (DCR). Secondary endpoints were DCR in subgroups (number of chemotherapy lines, number of different metastatic lesions and HR status), progression-free survival (PFS) and duration of response (DoR). Results: A total of 35 cases and 70 controls entered the study. 31% patients with LDMC and 26% patients with conventional chemotherapy showed DCR (p = 0.644). Among younger patients DCR was 41% in LDMC vs. 30% in the control group (p = 0.534). In addition, DCR was achieved in 35% vs. 27% patients with ≤ 2 chemotherapy lines (p = 0.560) and in 36% vs. 20% patients with ≤ 2 different metastatic lesions (p = 0.168), respectively. In the triple negative group 30% LDMC vs. 5% control patients showed DCR (p = 0.095). PFS was 12.0 vs. 13.5 weeks (p = 0.415), DoR was 26.5 vs. 20.5 weeks (p = 0.628), respectively. Conclusions: In this retrospective case-control study we demonstrated a similar efficacy of LDMC compared to conventional chemotherapy in the treatment of MBC. Moreover, no significant differences were found in the subgroups studied. Therefore, the concept of LDMC may also be a treatment option in both younger and non-heavily pre-treated MBC patients who do not need rapid remission.

An otherwise healthy 62-year-old woman developed necrotizing scleritis 23 years following pterygium excision with adjunctive beta-radiation. Surgically induced necrotizing scleritis (SINS) was diagnosed, but the scleritis progressed despite anti-inflammatory therapy, and 10 weeks after presentation the patient developed a hypopyon and decreased vision. After cultures revealed no growth at 72 hours, immunosuppressive therapy was escalated, with a subsequent deterioration in the patient's clinical course. Scedosporium superinfection was eventually cultured and found on histological examination of the enucleated globe. In reported cases, infectious scleral necrosis occurs most commonly following pterygium (71.4%) and scleral buckling (97.2%) surgery. Hypopyon is uncommon (10.0%) in patients with postoperative scleral necrosis, but when present is a strong predictor of infection (odds ratio, 21.2; 95% confidence interval, 2.9-157.5). Rates of underlying autoimmune disease are generally low (0.0-12.5%) except following cataract and lens procedures, where the occurence of SINS heralds systemic illness in 42.9% of cases.

Background Diffuse large B cell lymphoma post-transplant lymphoproliferative disorder (DLBCL-PTLD) represents a fatal complication after a solid organ transplant (SOT). Approximately 50% of DLBCL-PTLD can be related to Epstein Barr Virus (EBV) infection. However, the EBV status is not taken into account in the DLBCL-PTLD categorization, although increasing evidence suggests its critical role in biological, clinical and prognostic aspects of the disease. In this single center retrospective study, we compared clinical and histological features, as well as outcomes of DLBCL-PTLDs by EBV status. Methods This study focused on patients with SOT who were diagnosed with DLBCL-PTLD at Mayo Clinic (Rochester, MN). Patients were identified through the Mayo Clinic Lymphoma Data base and the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), between 1989 and 2017. The histology was re-reviewed (RLK) and classified according to the WHO Classification or Tumours of Haematopoietic and Lymphoid Tissues 2017. Cell of origin (COO) was performed by Hans algorithm. EBV RNA in situ hybridization (EBER) was performed. Cox proportional hazards models were used to assess the association of clinical factors in overall survival (OS). Results 148 DLBCL-PTLD were identified. The median age at SOT and at the time of PTLD diagnosis were 50 years (range: 15-71) and 56 years (range: 18-82), respectively. The median time to PTLD diagnosis from SOT was 38 months (range: 1-499). The types of SOT included renal (44%), liver (36%), cardiac (9%), renal/pancreas (5%), pancreas (8%), lung (7%) and multiorgan (4%). 62% were stage III-IV, 30% had elevated LDH and 67% had an IPI >1. 88% of patients presented with extranodal disease, and 16% had involvement of the grafted organ. Eighty-three (56%) cases were EBV positive. The COO information was available on 35 cases. The non-GCB subtype was identified in 24 cases and GCB subtype in 11 cases. The initial treatment was as follows: reduction in immunosuppression (12%), immunosuppression reduction with rituximab (26%), rituximab alone (5%), chemotherapy with or without rituximab (35%). Patients with EBV positive PTLD were more likely to have grafted organ involvement (20% vs. 8%, p=0.047) and late PTLD (occurring after 12 months from SOT - 60% vs. 8%, p Conclusion Our study assessed the impact of EBV status on the presentation and clinical outcome of DLBCL-PTLD in a 148-patient single-institution cohort. 56% of cases were EBV positive. EBV positivity was associated with grafted organ involvement and late PTLD diagnosis. Patients with EBV-negative and EBV-positive disease had similar survival from PTLD diagnosis. Disclosures Maurer: Celgene: Research Funding; Morphosys: Research Funding; Nanostring: Research Funding. Cerhan:Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding.

Background: PTLD is the most common malignancy, other than non-melanoma skin cancer, complicating solid organ transplantation (SOT) and has been one of the most commonly observed fatal consequences in SOT. The clinical presentations, management strategies, histologies, causes of death and outcomes are diverse (Dierickx D, Habermann TM. N Engl J Med 2018;378:549-62). The 2017 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues has redefined the categories as non-destructive PTLDs (plasmacytic hyperplasia, infectious mononucleosis, and florid follicular hyperplasia), polymorphic PTLD, monomorphic PTLD: B-cell neoplasms (diffuse large B-cell lymphoma, Burkitt lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, plasma cell myeloma, plasmacytoma, and other) and T-cell neoplasms (peripheral T-cell lymphoma NOS, hepatosplenic T-cell lymphoma, other), and classic Hodgkin lymphoma (CHL) PTLD. We report the outcomes and long-term follow-up of patients from a single institution based on these categories whose pathology was retrospectively reviewed and reclassified based on the WHO 2017 classification. Methods: Patients with SOT who were diagnosed with PTLD at Mayo Clinic (Rochester, MN) were identified through the Mayo Clinic Lymphoma Data base and the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER). The histology was re-reviewed in 80% of the cases (RLK) and classified according to the WHO Classification of Tumours of Haematopoietic an Lymphoid Tissues 2017. Cases were considered "PTLD, unclassified" if the histology could not be confidently classified based on pathology material available for review. Indolent small B-cell lymphomas were not included among the PTLDs except for EBV-positive marginal zone lymphoma. Cox proportional hazards models were used to assess the association of clinical factors in overall survival (OS). Results: 233 patients diagnosed with PTLD between 1987 and 2017 were identified. The median age at the time of diagnosis of PTLD was 54 years (range 16 to 84) with 85 patients (36%) over the age of 60. 156 (67%) were male. The transplanted organs were kidney (41%), kidney/pancreas (5%), liver (29%), heart (9%), lung (7%), and other (8%). PTLD occurred late (more than one year after transplantation) in 66%. There were 69 stage I, 19 stage II, 8 stage III, and 128 stage IV patients. 84% presented with extranodal disease. 21% had involvement of the engrafted organ. 64% of the patients developed a PTLD that was EBV positive by in situ hybridization. Initial approaches to management included reduction of immunosuppression (N=55), chemotherapy/immunochemotherapy (N=71), reduction in immunosuppression with rituximab (N=58), single agent rituximab (N=14), and radiation therapy (N=5). At a median follow-up of 87 months (range 9-289), 139 (60%) patients had died. All six CHL-PTLD patients are alive, two of whom had an event. The median overall survival (OS) was 85 months (95% CI: 39-144) in 177 monomorphic B-cell lymphoma PTLD, 95.5 months (95% CI: 40-not reached) in 24 polymorphic PTLD, and 60 months in 8 non-destructive PTLD cases. In contrast, the median overall survival was 12 months (95% CI: 4-200) in 8 monomorphic T cell and 3 months (95% CI: 1-unreached) in 9 unclassified PTLD cases. Conclusion: PTLD is a heterogeneous group of immunodeficiency-associated lymphoproliferative disorders. The overall survival in non-destructive, polymorphic, and monomorphic PTLD were similar. Monomorphic T/NK cell types had inferior outcomes. Figure. Figure. Disclosures Maurer: Morphosys: Research Funding; Nanostring: Research Funding; Celgene: Research Funding. Ansell:Celldex: Research Funding; Merck & Co: Research Funding; Takeda: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Pfizer: Research Funding. Cerhan:Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.

Objectives To characterize the clinical presentations, features, and outcomes of eyelash alopecia areata. Design Retrospective chart review of patients evaluated for eyelash loss and found to have eyelash alopecia areata. A 3-year follow-up was required. Participants The study involved 15 patients. Methods Patients who presented at a tertiary care eye clinic for evaluation of eyelash loss and were found to have eyelash alopecia areata were reviewed. Demographic considerations were categorized; they included age at presentation, areas of other hair loss, other relevant history, and treatment responses. Results Patients were young (mean age 18 years) and had a large female predominance (female-to-male ratio, 14:1). Concurrent scalp and brow involvement, either in isolation (20% and 13%, respectively) or together (13%), were seen in half of the patients (46%). Upper eyelid involvement was more common and severe than lower eyelid involvement, and 40% of patients experienced complete regrowth of lashes, with a mean time to regrowth of 28 months (range, 6 to 60 months). Of these, 13% experienced partial regrowth. Younger age at presentation was associated with regrowth, whereas presence or absence of other involved sites, personal or family histories of atopy, family history of alopecia, other autoimmune diseases, or the use of topical steroids did not appear to affect prognosis. Conclusions Eyelash alopecia areata is a unique entity, although it remains potentially underdiagnosed. The key differential diagnosis is trichotillomania, which is commonly associated with obsessive-compulsive disorders. The presence of exclamation-mark hairs in alopecia areata plays an important role in differentiating the 2 diagnoses.