Introduction Up to one-fifth of breast cancer survivors will develop chronic breast cancer-related lymphoedema (BCRL). To date, complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage. This international randomised trial aims to evaluate advantages of microsurgical interventions plus CDT versus CDT alone for BCRL treatment. Methods and analysis The effectiveness of LVA and/or VLNT in combination with CDT, which may be combined with liposuction, versus CDT alone will be evaluated in routine practice across the globe. Patients with BCRL will be randomly allocated to either surgical or conservative therapy. The primary end point of this trial is the patient-reported quality of life (QoL) outcome ‘lymphoedema-specific QoL’, which will be assessed 15 months after randomisation. Secondary end points are further patient-reported outcomes (PROs), arm volume measurements, economic evaluations and imaging at different time points. A long-term follow-up will be conducted up to 10 years after randomisation. A total of 280 patients will be recruited in over 20 sites worldwide. Ethics and dissemination This study will be conducted in compliance with the Declaration of Helsinki and the International Council for Harmonisation-Good Clinical Practice (ICH-GCP) E6 guideline. Ethical approval has been obtained by the lead ethics committee ‘Ethikkommission Nordwest- und Zentralschweiz’ (2023-00733, 22 May 2023). Ethical approval from local authorities will be sought for all participating sites. Regardless of outcomes, the findings will be published in a peer-reviewed medical journal. Metadata detailing the dataset’s type, size and content will be made available, along with the full study protocol and case report forms, in public repositories in compliance with the Findability, Accessibility, Interoperability and Reuse principles. Trial registration number NCT05890677 .
Artificial carbon dioxide leakage into a shallow aquifer was monitored using stable carbon isotope measurements at a field site near the town of Wittstock, Brandenburg, Germany. Approximately 400 000 L of CO2 were injected into a shallow aquifer at 18 m depth over 10 days. The 13C/ 12C ratios of the CO2 were measured in both groundwater and soil gas samples to monitor the distribution of the injected CO2 plume and to evaluate the feasibility and reliability of this approach to detect potential CO2 leakage, for example from carbon capture and storage (CCS) sites. The isotopic composition of the injected CO2 (δ13C −30.5 ‰) was differentiable from the background CO2 (δ13C −21.9 ‰) and the artificial CO2 plume was monitored over a period spanning more than 204 days. The results demonstrate that this stable isotope monitoring approach can be used to identify CO2 sources and detect potential CO2 migration from CCS sites into overlying shallow aquifers or even into the upper subsurface. A significant difference between the isotope ratios of the natural background and the injected CO2 is required for this monitoring approach to be effective.
The long-term aesthetic appearance of scars is of great importance to patients. Biobrane (Smith and Nephew, Fort Worth, Texas), a biosynthetic skin dressing, is a successfully established dressing for the treatment of superficial wounds. A new silk barrier dressing (Dressilk; Prevor, Moulin de Verville, France) has also shown good results in wound healing. This study evaluated the long-term scar quality of superficial wounds treated with these dressings.From February 2012 to May 2013, 11 patients with burns in need of skin grafting received donor site treatment. Study authors dressed 2 adjacent, standardized, partial-thickness skin graft donor sites on each participant with Biobrane or Dressilk. Scar formation on both treated areas was compared 24 months after initial application using subjective and objective assessment methods.Independent of treatment, the majority of the patients described scar quality similar to normal skin using subjective and objective evaluation tools. However, for scar perfusion, significantly lower oxygen saturation was shown in both treated areas compared with untreated skin.Comparatively, the 2 wound dressings showed similar results, making silk dressings an interesting alternative to biosynthetic ones.
Conversion of tumor subtype frequently occurs in the course of metastatic breast cancer but is a poorly understood phenomenon. This study aims to compare molecular subtypes with subsequent lung or pleural metastasis.In a cohort of 57 patients with breast cancer and lung or pleural metastasis (BCLPM), we investigated paired primary and metastatic tissues for differential gene expression of 269 breast cancer genes. The PAM50 classifier was applied to identify intrinsic subtypes, and differential gene expression and cluster analysis were used to further characterize subtypes and tumors with subtype conversion.In primary breast cancer, the most frequent molecular subtype was luminal A (lumA; 49.1%); it was luminal B (lumB) in BCLPM (38.6%). Subtype conversion occurred predominantly in lumA breast cancers compared with other molecular subtypes (57.1% v 27.6%). In lumA cancers, 62 genes were identified with differential expression in metastatic versus primary disease, compared with only 10 differentially expressed genes in lumB, human epidermal growth factor receptor 2 (HER2)-enriched, and basal subtypes combined. Gene expression changes in lumA cancers affected not only the repression of the estrogen receptor pathway and cell cycle-related genes but also the WNT pathway, proteinases (MME, MMP11), and motility-associated cytoskeletal proteins (CK5, CK14, CK17). Subtype-switched lumA cancers were further characterized by cell proliferation and cell cycle checkpoint gene upregulation and dysregulation of the p53 pathway. This involved 83 notable gene expression changes.Our results indicate that gene expression changes and subsequent subtype conversion occur on a large scale in metastatic luminal A-type breast cancer compared with other molecular subtypes. This underlines the significance of molecular changes in metastatic disease, especially in tumors of initially low aggressive potential.
