Perioperative risk of pancreatic head resection-nomogram-based prediction of severe postoperative complications as a decisional aid for clinical practice.

PURPOSE: To develop nomograms for pre- and early-postoperative risk assessment of patients undergoing pancreatic head resection. METHODS: Clinical data from 956 patients were collected in a prospectively maintained database. A test (n = 772) and a validation cohort (n = 184) were randomly generated. Uni- and multi-variate analysis and nomogram construction were performed to predict severe postoperative complications (Clavien-Dindo Grades III-V) in the test cohort. External validation was performed with the validation cohort. RESULTS: We identified ASA score, indication for surgery, body mass index (BMI), preoperative white blood cell (WBC) count, and preoperative alkaline phosphatase as preoperative factors associated with an increased perioperative risk for complications. Additionally to ASA score, BMI, indication for surgery, and the preoperative alkaline phosphatase, the following postoperative parameters were identified as risk factors in the early postoperative setting: the need for intraoperative blood transfusion, operation time, maximum WBC on postoperative day (POD) 1-3, and maximum serum amylase on POD 1-3. Two nomograms were developed on the basis of these risk factors and showed accurate risk estimation for severe postoperative complications (ROC-AUC-values for Grades III-V-preoperative nomogram: 0.673 (95%, CI: 0.626-0.721); postoperative nomogram: 0.734 (95%, CI: 0.691-0.778); each p ≤ 0.001). Validation yielded ROC-AUC-values for Grades III-V-preoperative nomogram of 0.676 (95%, CI: 0.586-0.766) and postoperative nomogram of 0.677 (95%, CI: 0.591-0.762); each p = 0.001. CONCLUSION: Easy-to-use nomograms for risk estimation in the pre- and early-postoperative setting were developed. Accurate risk estimation can support the decisional process, especially for IPMN-patients with an increased perioperative risk.

Fatty acids in breast milk and development of atopic eczema and allergic sensitisation in infancy.

BACKGROUND: One of the explanations for the increasing prevalence of atopic diseases is a relative low perinatal supply of n-3 fatty acids. However, this does not explain the protective effects of whole-fat dairy products or high levels of transfatty acids in breast milk, observed in some studies. We evaluated the role of perinatal supply of fatty acids in the early development of atopic eczema and allergic sensitisation. METHODS: Fatty acids, including n-3 long-chain polyunsaturated fatty acids (LCPs) as well as ruminant fatty acids (rumenic acid, cis-9,trans-11-C18:2 conjugated linoleic acid; and vaccenic acid, trans-11-C18:1), were determined in breast milk sampled at 1 month postpartum from 310 mother-infant pairs in the KOALA Birth Cohort Study, the Netherlands. Children were followed for atopic outcomes until 2 years of age. RESULTS: Higher concentrations of n-3 LCPs as well as ruminant fatty acids were associated with lower risk of (1) parent-reported eczema, (2) atopic dermatitis (UK Working Party criteria), and (3) sensitisation at age 1 year (as revealed by specific serum IgE levels to cow's milk, hen's egg and/or peanut). In multivariable logistic regression analysis, the inverse associations between ruminant fatty acid concentrations in breast milk and atopic outcomes were found to be independent from n-3 LCPs. CONCLUSIONS: The results confirm a protective role of preformed n-3 LCPs in the development of atopic disease. Moreover, this is the first study in humans confirming results from animal studies of protective effects of ruminant fatty acids against the development of atopic manifestations.

Trans fatty acids in human milk are an indicator of different maternal dietary sources containing trans fatty acids.

The trans fatty acid (TFA) patterns in the fats of ruminant meat and dairy products differ from those found in other (processed) fats. We have evaluated different TFA isomers in human breast milk as an indicator of dietary intake of ruminant and dairy fats of different origins. Breast milk samples were collected 1 month postpartum from 310 mothers participating in the KOALA Birth Cohort Study (The Netherlands). The study participants had different lifestyles and consumed different amounts of dairy products. Fatty acid methyl esters were determined by GC-FID and the data were evaluated by principal component analysis (PCA), ANOVA/Post Hoc test and linear regression analysis. The two major principal components were (1) 18:1 trans-isomers and (2) markers of dairy fat including 15:0, 17:0, 11(trans)18:1 and 9(cis),11(trans)18:2 (CLA). Despite similar total TFA values, the 9(trans)18:1/11(trans)18:1-ratio and the 10(trans)18:1/11(trans)18:1-ratio were significantly lower in milk from mothers with high dairy fat intake (40-76 g/day: 0.91 +/- 0.48, P < 0.05) compared to low dairy fat intake (0-10 g/day: 1.59 +/- 0.48), and lower with strict organic meat and dairy use (>90% organic: 0.92 +/- 0.46, P < 0.05) compared to conventional origin of meat and dairy (1.40 +/- 0.61). Similar results were obtained for the 10(trans)18:1/11(trans)18:1-ratio. We conclude that both ratios are indicators of different intake of TFA from ruminant and dairy origin relative to other (including industrial) sources.

Prolonged cytotoxic effect of aqueous extracts from dried viscum album on bladder cancer cells.

Aqueous extracts from whole dried mistletoe (Viscum album L., Iscucin) are often used in anti-cancer treatment. We studied the effect of extracts obtained from mistletoe bushes that grew on different host trees on bladder cancer cells by means of MTT-colorimetric cell proliferation/survival assays. The extracts possessed concentration-dependent cytotoxic properties whose extent varied with the host tree, but did not always correlate with the corresponding mistletoe lectin content. A 2-hours treatment of bladder cancer cells triggered a later, strong cytotoxic effect. This prolonged effect suggests that instillation with Iscucin has therapeutic potential for bladder cancer patients.

Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations.

BACKGROUND: Medulloblastoma constitute more than 20% of all paediatric brain tumours and are the most common malignant brain tumours in children. Adjuvant chemotherapy has seen a strong increase in the use of complementary medicine for cancer treatment. Evidence for cytotoxic and apoptotic effects of Viscum album (Mistletoe) in vitro is available, however, no data concerning paediatric tumours, especially paediatric brain tumours, has been provided so far. MATERIALS AND METHODS: In order to compare the receptiveness of medulloblastoma cells to different Viscum album preparations, in vitro cytotoxic effects of eight Viscum album extracts on four different paediatric medulloblastoma cell lines were analysed by MTT-Tests. Lectin contents of the extracts were determined to correlate them with the mitochondrial activity of mistletoe-treated cells. Flowcytometric analyses with Annexin V-FITC staining were carried out to quantify the amount of apoptotic cells compared to necrotic and viable cells. RESULTS: Data obtained with the medulloblastoma cell lines, Daoy, D342, D425 and UW-288-2, treated with Viscum album preparations from eight dissimilar host trees (Iscucin Abietis, Pini, Populi, Mali, Salicis, Crataegi, Quercus and Tiliae), indicated a significant growth-inhibition of all cell lines, yet the cell susceptibility was dissimilar against the different extracts. The decrease in mitochondrial activity and increase in apoptosis correlated with the lectin content of the used preparation in a dose-dependent manner. CONCLUSION: These in vitro results show that paediatric medulloblastoma cells respond to Viscum album preparations, by undergoing cell death through apoptosis and that this growth-inhibition correlates with the lectin content of the used preparation.

Human cancer cells exhibit in vitro individual receptiveness towards different mistletoe extracts.

In vitro cytotoxic effects of three aqueous mistletoe extracts on cell physiology against different human tumor cell lines and primary cancer cells were investigated in order to compare the receptiveness of different cancer cells against different mistletoe products. Therefore cell proliferation (BrdU-incorporation assay), mitochondrial activity (MTT-testing) and necrotic cell toxicity (LDH assay) were assayed over serial dilutions of the test products. Data obtained with HELA-S3, MOLT-4, MFM-223, COR-L51, KPL-1 and VM-CUB1 tumor cell lines and Iscador M (20 mg/ml), Iscador Q (20 mg/ml) and Abnobaviscum Fraxini -2 (20 mg/ml) indicated significant growth-inhibition of all cell lines, but also different cell susceptibilities against the different extracts. These variations were not only monitored on established cell lines but also on primary mamma carcinoma cells from surgical resectates. Concerning cell proliferation and mitochondrial activity Abnobaviscum Fraxini exhibits stronger inhibitory effects compared to products from the Iscador series. In case the evaluation was standardized on the active contents of VAA-I within the different products, the Iscador extracts possess higher cytotoxic activity. Pure viscotoxins and mistletoe lectins exhibited less effects than the extracts. The simultaneous presence of pure mistletoe lectins and mistletoe polysaccharides diminished the VAA-mediated cytotoxic effects. The presence of fetal calf serum (FCS) in cultivation media during in vitro testing diminished the cytotoxic effects of mistletoe extracts. It was shown that in vivo application of mistletoe preparations led to the formation of antibodies against unknown compounds of the extracts, diminishing the cytotoxic effect.