Angehörige Sterbender sind einerseits Teil des Versorgungssystems der Sterbenden, andererseits sind sie auch Betroffene mit eigenen Sorgen und Ängsten. Die Probleme, Bedürfnisse und Aufgaben der ...Angehörigen variieren dabei auch in Anhängigkeit vom Versorgungsort der Sterbenden. Zudem unterscheiden sich die Erwartungen der Angehörigen daran, was eine „gute“ Sterbesituation ausmacht, je nach Versorgungsform, ob Zuhause, im Hospiz, auf Palliativstationen, im Krankenhaus oder Pflegeheim.
Zusammenfassung
Angehörige Sterbender sind einerseits Teil des Versorgungssystems der Sterbenden, andererseits sind sie auch Betroffene mit eigenen Sorgen und Ängsten. Die Probleme, Bedürfnisse und ...Aufgaben der Angehörigen variieren dabei auch in Anhängigkeit vom Versorgungsort der Sterbenden. Zudem unterscheiden sich die Erwartungen der Angehörigen daran, was eine „gute“ Sterbesituation ausmacht, je nach Versorgungsform, ob Zuhause, im Hospiz, auf Palliativstationen, im Krankenhaus oder Pflegeheim.
Mismatch repair (MMR) deficiency and microsatellite instability (MSI) are associated with cisplatin resistance in human germ cell tumors (GCTs). BRAF mutation (V600E) is found in MSI colorectal ...cancers. The role of RAS/RAF pathway mutations in GCT treatment response is unknown.
Two patient cohorts were investigated: 100 control GCTs (50 seminomas and 50 nonseminomas) and 35 cisplatin-based chemotherapy-resistant GCTs. MMR proteins were analyzed by immunohistochemistry, and eight microsatellite loci were examined for MSI. Tumors were assessed for specific BRAF and KRAS mutations.
Resistant tumors showed a higher incidence of MSI than controls: 26% versus 0% in two or more loci (P < .0001). All resistant tumors were wild-type KRAS, and two controls (2%) contained a KRAS mutation. There was a significantly higher incidence of BRAF V600E mutation in resistant tumors compared with controls: 26% versus 1% (P < .0001). BRAF mutations were highly correlated with MSI (P = .006), and MSI and mutated BRAF were correlated with weak or absent staining for hMLH1 (P = .017 and P = .008). Low or absent staining of hMLH1 was correlated with promoter hypermethylation (P < .001). Tumors lacking expression of hMLH1 or MSH6 were significantly more frequent in resistant GCTs than in controls (P = .001 and 0.0036, respectively). Within the subgroup of resistant tumors, patients with MSI showed a trend to longer progression-free survival (P = .068).
We report for the first time a correlation between a gene mutation--BRAF V600E--and cisplatin resistance in nonseminomatous GCTs. Furthermore, a correlation between MMR deficiency, MSI, and treatment failure is confirmed.
During humanitarian crises, such as a pandemic, healthcare systems worldwide face unknown challenges. This study aimed to explore and describe the effect of the SARS-CoV-2 pandemic on the needs of ...non-infected patients and family caregivers in specialist palliative care, using qualitative, semi-structured interviews. Data were analyzed using inductive content analysis, following the framework approach. Thirty-one interviews were conducted with patients/family caregivers (15/16) in palliative care units/specialist palliative home care (21/10) from June 2020 to January 2021. Well-known needs of patients and family caregivers at the end of life remained during the pandemic. Pandemic- dependent themes were (1) implications of the risk of contagion, (2) impact of the restriction of social interactions, (3) effects on the delivery of healthcare, and (4) changes in the relative’s role as family caregiver. Restriction on visits limited family caregivers’ ability to be present in palliative care units. In specialist palliative home care, family caregivers were concerned about the balance between preserving social contacts at the end of life and preventing infection. Specialist palliative care during a pandemic needs to meet both the well-known needs at the end of life and additional needs in the pandemic context. In particular, attention should be given to the needs and burden of family caregivers, which became more multifaceted with regards to the pandemic.
Testicular germ cell tumors are the most common malignancy among men aged 40 and less. Since the introduction of cisplatin-based combination chemotherapy, germ cell tumors are among the most curable ...solid tumors with cure rates of 95% in all patients and > 80% in metastatic disease.
Current standards and future developments in GCT treatment, including adjuvant chemotherapy, first line treatment for metastatic disease, and salvage regimens in case of relapse and refractory disease.
Maintaining therapeutic success while further reducing treatment-related toxicity is paramount. Cancer-specific survival in localized disease approximates 100%. Therefore, orchidectomy followed by active surveillance is the preferred approach for all seminomas and non-seminomas lacking lymphovascular invasion. Non-seminomas with lymphovascular invasion should be offered adjuvant treatment with one cycle of bleomycin, etoposide and cisplatin (BEP). The BEP regimen remains standard of care for metastatic disease, while the role of primary high-dose chemotherapy in case of inadequate tumor-marker decline or presence of high-risk features (i.e. mediastinal origin, non-pulmonary visceral metastases) remains to be elucidated. Several curative salvage chemotherapy combinations are available, i.e. TIP, VeIP, GIP or high-dose carboplatin and etoposide. GOP is the current option of choice in cisplatin-refractory patients. Novel targeted agents failed to improve treatment outcome so far.
Brain metastases occur in approximately 10% of patients with advanced metastatic germ cell tumors. Patients with nonseminomatous histology, lung metastases, and high β-human chorionic gonadotropin ...levels are at higher risk for synchronous brain metastases at first diagnosis and for relapsing with brain metastases after successful cisplatin-based chemotherapy. Patients with brain metastases should undergo multimodal treatment strategies, including cisplatin-based combination chemotherapy plus radiotherapy or surgery. However, the optimal combination and sequence of these strategies remain unclear and may differ between subgroups. But in all cases, chemotherapy must be part of treatment, even in patients with isolated cerebral relapse without systemic disease.
Introduction. The aim of our study was to investigate challenges faced by emergency physicians (EPs) who provide prehospital emergency care to patients with advanced incurable diseases and family ...caregivers in their familiar home environment. Methods. Qualitative study using semistructured interviews with open-ended questions to collect data from 24 EPs. Data were analyzed using qualitative content analysis. Results. We identified nine categories of challenges: structural conditions of prehospital emergency care, medical documentation and orders, finding optimal patient-centered therapy, uncertainty about legal consequences, challenges at the individual (EP) level, challenges at the emergency team level, family caregiver’s emotions, coping and understanding of patient’s illness, patient’s wishes, coping and understanding of patient’s illness, and social, cultural, and religious background of patients and families. EPs strengthened that the integrations of specialized prehospital palliative care services improved emergency care by providing resources to patients and family caregivers, enhancing the quality and availability of medical documentation and accessibility of aftercare in emergencies. Areas of improvement that were identified were to promote emergency physicians’ knowledge and skills in palliative care, communication, and family caregiver support by education and training. Furthermore, structures for better care on-site, thorough medical documentation, and specialized palliative care emergency facilities in hospital and prehospital care were requested. Conclusion. Prehospital emergency care in patients with advanced incurable diseases in their familiar home environment may be improved by training EPs in palliative care, communication, and caregiver support competences. Results underline the importance of collaborative specialized palliative care and prehospital emergency care.
Early integration of palliative care concurrently to standard cancer care is associated with several benefits for patients and their caregivers. However, communication barriers on part of the caring ...physicians often impede a timely referral to palliative care. This study describes the protocol of the evaluation of a communication skills training aiming to strengthen the ability of physicians to address palliative care related topics adequately and early during disease trajectory.
We will implement a communication skills training and evaluate it within a prospective, multi-centered, two-armed randomized controlled trial (RCT), which will be conducted at four sites in Germany. Eligible subjects are all physicians treating patients with advanced cancer in their daily routine. An intervention group (IG) receiving a group training will be compared to a wait-list control group (CG) receiving the training after completion of data collection. At pre- and post-measurement points, participants will conduct videotaped conversations with standardized simulated patients (SP). Primary outcome will be the external rating of communication skills and consulting competencies addressing palliative care related topics. Secondary outcomes on core concepts of palliative care, basic knowledge, attitudes, confidence and self-efficacy will be assessed by standardized questionnaires and self-developed items. A further external assessment of the quality of physician-patient-interaction will be conducted by the SP. Longitudinal quantitative data will be analyzed using covariate-adjusted linear mixed-models.
If the communication skills training proves to be effective, it will provide a feasible intervention to promote an earlier communication of palliative care related topics in the care of advanced cancer patients. This would help to further establish early integration of palliative care as it is recommended by national and international guidelines.
German Clinical Trials Register DRKS00017025 (date of registration: 4 June 2019).
Abstract Background Chemotherapy (CTX) with gemcitabine, oxaliplatin, and paclitaxel (GOP) has demonstrated efficacy with an overall response rate (ORR) of approximately 50% in patients with multiply ...relapsed or cisplatin-refractory germ cell cancer (GCC) or both within a phase II study. We analyzed the efficacy and safety of GOP in routine clinical practice within a registry of the German Testicular Cancer Study Group. Methods Overall, 63 patients with refractory GCC, who received GOP because of progression under cisplatin-based treatment or relapse after high-dose CTX, were included in this database. Patient characteristics, response rate, toxicity, progression-free and overall survival (OS) were analyzed. For further risk stratification, univariate and multivariate analyses were performed. Results GOP was applied as second to eighth treatment line (median fourth) after cisplatin-based CTX. The ORR was 44% with complete remissions achieved in 8 patients (4 patients with CTX plus additional residual tumor resections and 4 patients with CTX alone) and partial remissions achieved in 19 of all for best response evaluable patients. The median progression-free survival and OS were 4.0 months (95% CI: 3.08–4.94) and 13.3 months (95% CI: 9.50–17.06), respectively. Long-term OS of>2 years was achieved in 13 (21%), and grade III and IV toxicities, mainly thrombocytopenia and leukopenia, occurred in 29 patients. Conclusion Our results were similar compared with the previous results from the phase II study with a distinct activity with an ORR of 44%, and a long-term OS in 21% of the patients. Our data support the recommendation to use GOP ± secondary surgery in patients with multiply refractory metastatic GCC.
Abstract Background Patients with germ cell tumors (GCTs) receiving cisplatin-based chemotherapy are at increased risk of thrombosis, but the underlying cellular and molecular mechanisms remain ...obscure. Objective To study baseline tissue factor (TF) expression by GCT cell lines and its modulation by cisplatin treatment. Methods TF expression was assessed by single-stage clotting and thrombin generation assay, flow cytometry, ELISA, and Western blot analysis. Cell cycle analysis and detection of phosphatidylserine (PS) membrane exposure were carried out by flow cytometry. TF mRNA was analyzed by quantitative RT-PCR. Results Significant expression of TF-specific procoagulant activity (PCA) was detected on three non-seminoma (NT2, 2102Ep, NCCIT) and one seminoma cell line (TCam-2). Treatment with 0.4 μM cisplatin (corresponding to the IC50 ) for 48 hrs increased TF PCA on NT2 cells 3-fold, an effect that was largely independent of PS exposure and that could not be explained by translocation of active TF from intracellular storage pools. Cisplatin-induced TF PCA expression in NT2 cells did not occur before 12 hrs, but was steady thereafter and accompanied by a 2-fold increase in total and surface-located TF antigen. Importantly, increased TF gene transcription or production and release of an intermediate factor were not involved in this process. Cell cycle analysis suggested that cisplatin-induced G2/M arrest resulted in an accumulation of procoagulant TF on the membrane surface of NT2 cells. Conclusions In addition to induction of apoptosis/necrosis with PS-mediated activation of preformed TF, cisplatin may alter the procoagulant phenotype of GCT cells through an increase in total cellular TF antigen.
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