Bilaterales Mammakarzinom und Lokalrezidiv: Prävalenz von BRCA-1- und BRCA-2-Genmutationen an einem unselektionierten Kollektiv

BACKGROUND: Mutations of the BRCA 1/BRCA 2 genes strongly predispose towards the development of contralateral breast cancer. We therefore investigated a hospital-based series of patients with bilateral breast cancer and a comparison group of patients with unilateral breast cancer, pairwise matched by age and family history, for mutations of the BRCA 1/BRCA 2 genes. PATIENTS AND METHODS: Between 1995 and 2000 genomic DNA from blood samples of 75 patients with bilateral breast cancer, who received postoperative radiotherapy, was analyzed for mutations of all coding regions and flanking intron sequences of the BRCA 1/BRCA 2 genes by single strand conformation polymorphism analysis (SSCP) and sequencing of aberrant findings. The results were compared to 75 unilateral breast cancer patients who were screened for common mutations in the BRCA 1 and BRCA 2 genes. Treatment results of patients with bilateral disease were analyzed with regard to a possible carriership of a BRCA 1/BRCA 2 gene mutation. RESULTS: Five distinct frameshift deletions (one in BRCA 1, four in BRCA 2) were identified in six patients with bilateral breast cancer. Three of six carriers developed local relapse, whereas this was the case in only nine of 69 non-carriers. After radiotherapy local relapse occurred in five patients (five of 126 irradiated breasts or chest walls). Three of these patients (60%) were carriers of a pathogenic BRCA 1/BRCA 2 mutation. In the comparison group of patients with unilateral breast cancer three pathogenic BRCA 1 mutations were identified. CONCLUSIONS: We failed to confirm an increased prevalence of BRCA 1/BRCA 2 mutations in our hospital-based series of patients with bilateral breast cancer. However, local relapse, especially when occurring after radiotherapy, may be predictive for an underlying pathogenic BRCA 1 and BRCA 2 gene mutation in patients with bilateral breast cancer.     

Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk

A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82–1.18, p values: 6.96 × 10⁻⁴–3.28 × 10⁻⁸), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.     

Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction

Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC). Currently, neither prevention (vaccines) nor treatments (antivirals) are available for combating this disease. CVA24v attaches to cells by binding Neu5Ac-containing glycans on the surface of cells which facilitates entry. Previously, we have demonstrated that pentavalent Neu5Ac conjugates attenuate CVA24v infection of human corneal epithelial (HCE) cells. In this study, we report on the structure-based design of three classes of divalent Neu5Ac conjugates, with varying spacer lengths, and their effect on CVA24v transduction in HCE cells. In relative terms, the most efficient class of divalent Neu5Ac conjugates are more efficient than the pentavalent Neu5Ac conjugates previously reported.

Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC).     

Designing the European registry on minimally invasive pancreatic surgery: a pan-European survey

BackgroundThe recent Miami international evidence-based guidelines on minimally invasive pancreatic surgery (MIPS) advise all centers that perform MIPS to participate in multicenter registries to safeguard optimal outcomes and patient safety. During the design phase of a pan-European registry on MIPS, the European consortium of Minimally Invasive Pancreatic Surgery (E-MIPS) sought input from European HPB surgeons.MethodsAn anonymous online questionnaire with 23 questions on MIPS practice was sent to all member centers of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and E-MIPS.ResultsCompleted questionnaires were obtained from 98 centers in 23 countries, of which 75 (76.5%) were academic centers. Centers had a median annual pancreatoduodenectomy volume of 45. The most-performed MIPS procedure was laparoscopic distal pancreatectomy (93.9% of centers). Minimally invasive pancreatoduodenectomy was performed in 49% of all centers. Some 25 centers already participated in an ongoing national registry, and were willing to share their data with the European registry on MIPS. The most mentioned (45.4%) maximum time for processing one patient's data into the registry was 10–15 min.ConclusionThis European survey showed considerable support for the European registry on MIPS.     

Quantifiable Contrast-Enhanced Ultrasound Explores the Role of Protection,Rest, Ice (Cryotherapy), Compression and Elevation (PRICE) Therapy on Microvascular Blood Flow

The aim of this randomized controlled laboratory study was to evaluate the role of standardized protection, rest, ice (cryotherapy), compression and elevation (PRICE) therapy on microvascular blood flow in human skeletal muscle. Quantifiable contrast-enhanced ultrasound was used to analyze intramuscular tissue perfusion (ITP) of the rectus femoris (RF) and vastus intermedius (VI) muscles in 20 healthy athletes who were randomly assigned to PRICE or control groups. Baseline perfusion measurements (resting conditions, T₀) were compared with cycling exercise (T₁), intervention (PRICE or control, T₂) and follow-up at 60 min post-intervention (T₃). The 20 min PRICE intervention included rest, cryotherapy (3°C), compression (35 mm Hg) and elevation. After intervention, PRICE demonstrated a decrease of ITP in VI (–47%, p = 0.01) and RF (–50%, p = 0.037) muscles. At T_3, an ongoing decreased ITP for the RF (p = 0.003) and no significant changes for the VI were observed. In contrast, the control group showed an increased ITP at T₂ and no significant differences at T₃. PRICE applied after exercise led to a down-regulation of ITP, and the termination of PRICE does not appear to be associated with a reactive hyperemia for at least 60 min after treatment.     

Critical appraisal of the International Study Group of Pancreatic Surgery (ISGPS) consensus definition of postoperative hemorrhage after pancreatoduodenectomy

Purpose  

Postpancreatectomy hemorrhage (PPH) is one of the most serious complications after pancreatoduodenectomy (PD). This study analyzed and validated the International Study Group of Pancreatic Surgery (ISGPS) definition of PPH and aimed to identify risk factors for early (<24 h) and late PPH.     

The need for extended intensive care after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

Purpose  

Pancreaticoduodenectomy (PD) is standard for patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head, neck, and uncinate process, but it is associated with a relatively high morbidity. This study aimed to identify risk factors for extended postoperative intensive care unit (ICU) admission and assess the impact of ICU treatment on patient survival.