Adhesion molecules in peritoneal dissemination: function,prognostic relevance and therapeutic options

Peritoneal dissemination is diagnosed in 10–25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2β1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLe^x and Le^x, chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLe^a and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete.     

Mother–child emotion dialogues: the disrupting effect of maternal history of communal sleeping

The study examined associations between mothers’ upbringing background (kibbutz vs. home) and maternal-sensitive guidance of emotional conversations with their preschool children; children’s cooperation and exploration; and the coherence of their conversations. Using a quasi-experimental design, 112 children and their mothers (72 kibbutz raised, 40 home) completed the Autobiographical Emotional Event Dialogue. We hypothesized that maternal kibbutz upbringing would be associated to lower levels of mothers’ sensitive guidance of the conversations, children’s lower cooperation and exploration, and lower overall coherence. Results showed no upbringing-related differences for the mothers, but significant differences were found for the children, with children of kibbutz-raised mothers showing less cooperation and exploration, and lower levels of coherence for these dyads. The role of maternal background in shaping the interaction with their child is discussed.     

An Integrative Model of Subcortical Auditory Plasticity

In direct conflict with the concept of auditory brainstem nuclei as passive relay stations for behaviorally-relevant signals, recent studies have demonstrated plasticity of the auditory signal in the brainstem. In this paper we provide an overview of the forms of plasticity evidenced in subcortical auditory regions. We posit an integrative model of auditory plasticity, which argues for a continuous, online modulation of bottom-up signals via corticofugal pathways, based on an algorithm that anticipates and updates incoming stimulus regularities. We discuss the negative implications of plasticity in clinical dysfunction and propose novel methods of eliciting brainstem responses that could specify the biological nature of auditory processing deficits.     

Identification of Inflamed Atherosclerotic Lesions In Vivo Using PET-CT

Inflammation plays a major pathogenetic role in the development of atherosclerotic plaques and related thromboembolic events. The identification of vulnerable plaques is of the utmost importance, as this may allow the implementation of more effective preventive and therapeutic interventions. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for tracing inflammation within plaques. However, its relationship to immunohistochemical findings in different territories of the peripheral circulation was not completely elucidated. We aimed to determine whether plaque inflammation could be measured by PET in combination with computer tomography (CT) using FDG and what is the relationship between FDG uptake and immunohistochemical findings in the removed atherosclerotic lesions of the femoral and carotid arteries. The study included 31 patients, 21 patients with high-grade stenosis of the internal carotid artery (ICA) and 10 patients with occlusion of the common femoral artery (CFA), all of whom underwent endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was performed. FDG uptake was measured as the maximum blood—normalized standardized uptake value, known as the target to background ratio (TBR max). TBR max amounted to 1.72?±?0.8, and in patients with ICA, stenosis was not significantly different from patients with CFA occlusion. Immunohistochemical and morphometric analyses of the plaques obtained at endarterectomy showed that the density of T lymphocytes and macrophages (number of cells per square millimeter) was significantly higher in subjects with stenosis of the ICA than in subjects with occlusion of the femoral arteries: lymphocytes, 1.26?±?0.21 vs. 0.77?±?0.29; p?=?0.02 and macrophages, 1.01?±?0.18 vs. 0.69?±?0.23; p?=?0.003. In the whole group of patients, the density of inflammatory cells significantly correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r?=?0.60; p?<?0.01 and macrophages, r?=?0.65; p?<?0.01. The results of our study show that FDG uptake is related to the accumulation of inflammatory cells in atherosclerotic lesions. This finding suggests that FDG uptake reflects the severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it could be an indicator of their vulnerability. However, data from large outcome studies is needed to estimate the usefulness of this technique in identifying the most dangerous atherosclerotic lesions and vulnerable patients.     

Body mass index-adapted prospective coronary computed tomography angiography. Determining the lowest limit for diagnostic purposes

Purpose

To investigate the value of 4 different protocols for prospectively triggered 256-slice coronary computed tomography angiography (coronary CTA).

Methods

Two hundred and ten patients underwent prospectively triggered coronary CTA for suspected or known coronary artery disease (CAD). Patients with heart rate >75 bps before the scan despite ß-blocker administration and with arrhythmia were excluded. From January to September 2010, 60 patients underwent coronary CTA using a non-tailored protocol (120 kV; 200 mAs) and served as our ‘control’ group. From September 2010 to April 2012, based on the body mass index (BMI) of the examined patients (BMI subgroups of < 25; 25–28; 28–30, and ≥ 30 kg/m²) current tube voltage and tube current were: (1) slightly, (2) moderately or (3) strongly reduced, resulting into the 3 following BMI-adapted acquisition groups: (1) a ‘standard’ (100/120 kV; 100–200 mAs; n = 50), 2) a ‘low dose’ (100/120 kV; 75–150 mAs; n = 50), and 3) an ‘ultra-low dose’ (100/120 kV; 50–100 mAs; n = 50) protocol.

Results

Patients examined using the non-tailored protocol exhibited the highest radiation exposure (3.2 ± 0.4 mSv), followed by the standard (1.6 ± 0.7 mSv), low-dose (1.2 ± 0.6 mSv) and ultra-low dose protocol (0.7 ± 0.3 mSv) (radiation savings of 50%, 63% and 78% respectively). Overall image quality was similar with standard dose (1.9 ± 0.6) and low-dose (2.0 ± 0.5) compared to the non-tailored group (1.9 ± 0.5) (p = NS for all). In the ultra-low dose group however, image quality was significant reduced (2.7 ± 0.6), p < 0.05 versus all other groups).

Conclusion

Using BMI-adapted low dose acquisitions image quality can be maintained with simultaneous radiation savings of ∼65% (dose of ∼1 mSv). This appears to be the lower limit for diagnostic coronary CTA, whereas ultra-low dose acquisitions result in significant image degradation.