Threshold-based prediction of the coagulation zone in sequential temperature mapping in MR-guided radiofrequency ablation of liver tumours

Objective

To evaluate different cut-off temperature levels for a threshold-based prediction of the coagulation zone in magnetic resonance (MR)-guided radiofrequency (RF) ablation of liver tumours.

Methods

Temperature-sensitive measurements were acquired during RF ablation of 24 patients with primary (6) and secondary liver lesions (18) using a wide-bore 1.5?T MR sytem and compared with the post-interventional coagulation zone. Temperature measurements using the proton resonance frequency shift method were performed directly subsequent to energy application. The temperature maps were registered on the contrast-enhanced follow-up MR images acquired 4?weeks after treatment. Areas with temperatures above 50°, 55° and 60°C were segmented and compared with the coagulation zones. Sensitivity and positive predictive value were calculated.

Results

No major complications occurred and all tumours were completely treated. No tumour recurrence was observed at the follow-up examination after 4?weeks. Two patients with secondary liver lesions showed local tumour recurrence after 4 and 7?months. The 60°C threshold level achieved the highest positive predictive value (87.7?±?9.9) and the best prediction of the coagulation zone.

Conclusions

For a threshold-based prediction of the coagulation zone, the 60°C cut-off level achieved the best prediction of the coagulation zone among the tested levels.

Key Points

? Temperature monitoring can be used to survey MR-guided radiofrequency ablation ? The developing ablation zone can be estimated based on post-interventional temperature measurements ? A 60°C threshold level can be used to predict the ablation zone ? The 50°C and 55°C temperature zones tend to overestimate the ablation zone     

Arzneimitteltherapiesicherheit bei Kindern

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Bei Kindern und Jugendlichen treten Medikationsfehler häufiger auf als bei Erwachsenen, da die Evidenz oft fehlt und die...     

Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases

Smoking-related interstitial lung diseases are characterized by the accumulation of macrophages and Langerhans cells, and fibrotic remodeling, which are linked to osteopontin (OPN) expression. Therefore, OPN levels were investigated in bronchoalveolar lavage (BAL) cells in 11 patients with pulmonary Langerhans cell histiocytosis (PLCH), 15 patients with desquamative interstitial pneumonitis (DIP), 10 patients with idiopathic pulmonary fibrosis, 5 patients with sarcoidosis, 13 otherwise healthy smokers, and 19 non-smoking controls. Furthermore, OPN overexpression was examined in rat lungs using adenoviral gene transfer. We found that BAL cells from patients with either PLCH or DIP spontaneously produced abundant amounts of OPN. BAL cells from healthy smokers produced 15-fold less OPN, and those cells from non-smoking healthy volunteers produced no OPN. BAL cells from patients with either idiopathic pulmonary fibrosis or sarcoidosis produced significantly less OPN, as compared with patients with PLCH. These data were confirmed by immunochemistry. Nicotine stimulation increased production of both OPN and granulocyte-macrophage colony stimulating factor by alveolar macrophages from smokers. Nicotinic acetylcholine receptor expression resembled the pattern of spontaneous OPN production and was dramatically increased in both PLCH and DIP. OPN overexpression in rat lungs induced lesions similar to PLCH with marked alveolar and interstitial accumulation of Langerhans cells. Our findings suggest a pathogenetic role of increased OPN production in both PLCH and DIP by promoting the accumulation of macrophages and Langerhans cells.Cigarette smoke is linked to a variety of lung diseases including chronic obstructive pulmonary disease, lung cancer, and interstitial lung diseases. Respiratory bronchiolar interstitial lung disease, desquamative interstitial pneumonitis (DIP), and pulmonary Langerhans cell histiocytosis (PLCH) belong to the group of smoking-related interstitial lung diseases.^1,2,3 Cigarette smoke is a complex mixture of more than 4000 compounds and is known to cause systemic and pulmonary effects.⁴ However, the underlying mechanisms as to how cigarette smoking leads to the changes observed in smoking-related interstitial lung diseases are largely unknown.^1,2,3Cigarette smoke induces inflammation, oxidative stress, and tissue injury, and has an important effect on the number, distribution, and activation state of macrophages and Langerhans cells.^5,6 There is a strong epidemiological link between PLCH and smoking. PLCH is characterized by the accumulation of activated Langerhans cells originating from the distal bronchiole walls.^1,2,3,7 The accumulations of Langerhans cells are poorly demarcated and extend to the adjacent alveoli, which often contain an abundance of pigmented macrophages. These areas show morphological changes similar to DIP.^7,8 In DIP, the predominant feature is the accumulation of alveolar macrophages, densely filling the alveolar lumen, combined with moderate fibrotic interstitial remodeling.^1,2As measured by bronchoalveolar lavage (BAL) in healthy individuals, cigarette smoking induces a 5- to 10-fold increase in alveolar macrophages in a dose-response curve.^9,10,11 It was shown that concentrations of granulocyte-macrophage colony stimulating factor (GMCSF) in patients with PLCH are increased,¹² but the mechanisms that lead to the expansion of the pulmonary macrophage pool and fibrosis in smokers are poorly understood.^1,2,3 Based on the findings of a microarray study, Woodruff et al¹³ have recently proposed that alveolar macrophages from smokers exhibit a distinctive macrophage activation state that is accompanied by increased OPN expression. Osteopontin is a glycoprotein found in the extracellular matrix of bone.¹⁴ However, multiple studies have reported cytokine properties of OPN in cell-mediated immunity.¹⁴ Further, OPN exhibits a strong chemotactic activity for macrophages, monocytes, Langerhans cells, and dendritic cells.^15,16,17In the context of these findings we speculated that OPN might be involved in the pathogenesis of smoking-related lung interstitial diseases. We found abundant OPN production by alveolar macrophages from patients with PLCH and DIP. Alveolar macrophages from both healthy smokers and patients with DIP and PLCH show up-regulated nicotine receptor expression as a sign of chronic nicotine stimulation. Further, nicotine directly induced OPN and GMCSF in alveolar macrophages. Our data provides evidence for a role of osteopontin in the pathogenesis of smoking- related interstitial lung diseases.     

Volume therapy with colloid solutions preserves intestinal microvascular perfusion in endotoxaemia

Colloid solutions have been suggested to improve microvascular perfusion due to their anti-inflammatory properties. Whether this also applies for the gut, an important immunological organ vulnerable to hypoperfusion is unknown. This study investigated intestinal microcirculation of endotoxaemic rats after volume therapy with colloid solutions such as hydroxyethyl starch (HES) and gelatin or isotonic saline (NaCl). In addition intestinal oxygenation and morphology as well as mesenteric leukocyte-endothelium interaction were quantified. Rats were anaesthetised with urethane and ketamine, mechanically ventilated, and monitored haemodynamically. Normotensive endotoxaemia was induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (LPS, 1.5 mg kg(-1) h(-1)). After 1 h of LPS infusion either 6% HES (16 ml kg(-1)), 4% gelatin (16 ml kg(-1)) or 0.9% NaCl (64 ml kg(-1)) were infused for 1 h. Using intravital microscopy, functional capillary density (FCD) and red blood cell velocity (RBCV) were measured in the mucosa of the terminal ileum at baseline and 3 h after volume therapy. In another set of animals, mesenteric leukocyte-endothelium interaction was determined 3 h after volume therapy. In all animals intestinal lactate/pyruvate ratio and intestinal morphology were assessed. Three hours after volume therapy, FCD decreased in NaCl (808 [749/843] cm(-1); median [quartiles] P<0.05 versus baseline) but not in HES (995 [945/1036] cm(-1)) and gelatin (988 [867/1193] cm(-1)) groups. RBCV, lactate/pyruvate ratio and intestinal morphology did not differ among groups. Also mesenteric leukocyte-endothelium interaction was not significantly influenced by either treatment. In conclusion, early volume therapy with HES or gelatin, but not with NaCl, preserved gut microvascular perfusion during endotoxaemia but did not have a significant effect on tissue oxygenation nor morphological appearance in this experimental model. An anti-inflammatory effect of colloid solutions was not seen and fails to explain the changes in intestinal microcirculation.     

The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model

T cell Ig mucin 1 (TIM-1) plays an important role in regulating immune responses in autoimmune and asthma models, and it is expressed on both Th1 and Th2 cells. Using an antagonistic TIM-1-specific antibody, we studied the role of TIM-1 in alloimmunity. A short course of TIM-1-specific antibody monotherapy prolonged survival of fully MHC-mismatched vascularized mouse cardiac allografts. This prolongation was associated with inhibition of alloreactive Th1 responses and preservation of Th2 responses. TIM-1-specific antibody treatment was more effective in Th1-type cytokine-deficient Stat4(-/-) recipients as compared with Th2-type cytokine-deficient Stat6(-/-) recipients. Subtherapeutic doses of rapamycin plus TIM-1-specific antibody resulted in allograft acceptance and prevented the development of chronic allograft vasculopathy. Allograft survival via this treatment was accompanied by a Th1- to Th2-type cytokine switch. Depletion of natural Tregs abrogated the graft-protecting effect of the TIM-1-specific antibody. Importantly, CD4(+)CD25(+) Tregs obtained from long-term survivors had enhanced regulatory activity as compared with naive CD4(+)CD25(+) Tregs. Consistent with this, TIM-1-specific antibody treatment both preserved Tregs and prevented the expansion of alloreactive effector Th1 cells in an alloreactive TCR transgenic adoptive transfer model. These studies define previously unknown functions of TIM-1 in regulating alloimmune responses in vivo and may provide a novel approach to promoting transplantation tolerance.     

The impact of miscarriage and stillbirth on maternal–fetal relationships: an integrative review

Objective: To synthesise and summarise existing literature investigating whether and how psychological distress as a consequence of perinatal loss and associated coping impact upon maternal–fetal relationships subsequent to miscarriage and stillbirth.

Background: Although now widely accepted that the relationship between mother and child develops in utero, little is known about how a previous miscarriage or stillbirth impacts upon these processes in a subsequent pregnancy.

Methods: An integrative review methodology was chosen for the review.

Results: Fifteen empirical and theoretical articles were reviewed and summated into two topic areas: psychological distress following perinatal loss and the subsequent maternal–fetal relationship, and coping following perinatal loss and the subsequent maternal–fetal relationship.

Conclusions: Studies show that perinatal loss can cause psychological distress in subsequent pregnancy. It is not clear whether and how such distress impacts on maternal–fetal relationships because studies have yielded mixed findings. Mothers employ a complex self-protective mechanism to cope with this distress, and use strategies to reassure themselves and to maintain hope that the pregnancy will result in a live birth. It is not clear whether the use of this mechanism impacts upon the development of the mother–fetus relationship in subsequent pregnancy. Further research is now required to determine how these strategies are employed, the impact of these strategies on pregnancy-specific anxiety, maternal–fetal relationships and the postnatal attachment relationship. Health professionals working with parents in these circumstances should acknowledge that anxiety and associated coping behaviours are common, and support be provided when parents show signs of considerable psychological distress.     

Microsatellite instability in pediatric and adult high-grade gliomas

About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (approximately 25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.     

B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: implications for the lesion pathogenesis of multiple sclerosis

The co-inhibitory B7-homologue 1 (B7-H1/PD-L1) influences adaptive immune responses and has been proposed to contribute to the mechanisms maintaining peripheral tolerance and limiting inflammatory damage in parenchymal organs. To understand the B7-H1/PD1 pathway in CNS inflammation, we analyzed adaptive immune responses in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced EAE and assessed the expression of B7-H1 in human CNS tissue. B7-H1(-/-) mice exhibited an accelerated disease onset and significantly exacerbated EAE severity, although absence of B7-H1 had no influence on MOG antibody production. Peripheral MOG-specific IFN-gamma/IL-17 T cell responses occurred earlier and enhanced in B7-H1(-/-) mice, but ceased more rapidly. In the CNS, however, significantly higher numbers of activated neuroantigen-specific T cells persisted during all stages of EAE. Experiments showing a direct inhibitory role of APC-derived B7-H1 on the activation of MOG-specific effector cells support the assumption that parenchymal B7-H1 is pivotal for delineating T cell fate in the target organ. Compatible with this concept, our data investigating human brain tissue specimens show a strong up-regulation of B7-H1 in lesions of multiple sclerosis. Our findings demonstrate the critical importance of B7-H1 as an immune-inhibitory molecule capable of down-regulating T cell responses thus contributing to the confinement of immunopathological damage.