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Metastatic colorectal cancer (mCRC) is a devastating disease causing 700.000 deaths annually worldwide. Metastases most frequently develop in the liver. Partial hepatectomy has dramatically improved clinical outcome and is the only curative treatment option for eligible patients with mCRC. Pre-clinical studies have shown that surgical procedures can have tumor-promoting local 'side-effects' such as hypoxia and inflammation, thereby altering the behaviour of residual tumor cells. In addition, systemically released factors following (colon or liver) surgery can act as a wakeup-call for dormant tumor cells in distant organs and/or help establish a pre-metastatic niche. Tumor handling during resection may also increase the number of circulating tumor cells. Despite the overwhelming amount of pre-clinical data demonstrating the pro-tumorigenic side effects of surgery, clinical evidence is scarce. Indications for hepatic surgery are rapidly increasing due to a rise in the incidence of mCRC and a trend towards more aggressive surgical treatment. Therefore, it is increasingly important to understand the principles of surgery-induced tumor growth, in order to devise perioperative or adjuvant strategies to further enhance long-term tumor control. In the current study we review the evidence for surgery-stimulated tumor growth and suggest strategies to assess the clinical relevance of such findings. [ABSTRACT FROM AUTHOR]

Background & Aims Colon tumors contain a fraction of undifferentiated stem cell−like cancer cells with high tumorigenic potential. Little is known about the signals that maintain these stem-like cells. We investigated whether differentiated tumor cells provide support. Methods We established undifferentiated colonosphere cultures from human colon tumors and used them to generate stably differentiated cell lines. Antibody arrays were used to identify secreted factors. Expression of genes involved in stemness, differentiation, and the epithelial to mesenchymal transition was measured using reverse transcription quantitative polymerase chain reaction. Expression of KIT in human tumors was analyzed with gene expression arrays and by immunohistochemistry. Colonospheres were injected into the livers of CBy.Cg-Foxn1nu/J mice. After liver tumors had formed, hypoxia was induced by vascular clamping. Results Differentiated cells from various tumors, or medium conditioned by them, increased the clonogenic capacity of colonospheres. Stem cell factor (SCF) was secreted by differentiated tumor cells and supported the clonogenic capacity of KIT + colonosphere cells. Differentiated tumor cells induced the epithelial to mesenchymal transition in colonosperes; this was prevented by inhibition of KIT or SCF. SCF prevented loss of clonogenic potential under differentiation-inducing conditions. Suppression of SCF or KIT signaling greatly reduced the expression of genes that regulate stemness and the epithelial to mesenchymal transition and inhibited clonogenicity and tumor initiation. Bioinformatic and immunohistochemical analyses revealed a correlation between expression of KIT- and hypoxia-related genes in colon tumors, which was highest in relapse-prone mesenchymal-type tumors. Hypoxia induced expression of KIT in cultured cells and in human colon tumor xenografts and this contributed to the clonogenic capacity of the tumor cells. Conclusions Paracrine signaling from SCF to KIT, between differentiated tumor cells and undifferentiated stem-like tumor cells, helps maintain the stem-like features of tumor cells, predominantly under conditions of hypoxia. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a process to produce hydrogen-rich gas at temperatures between 650 and 700 °C, by steam reforming of char produced in a pyrolysis reactor. To achieve this, the experimental work was divided into three sections all of which primarily focus on the production of hydrogen by steam reforming. The first section investigated the impact of different chars, produced from different biomasses, and the second and third considered the effects of temperature and residence time on gas composition and yield. Feedstocks selected for this study included apple pomace, birch sawdust, coffee husk, corn cobs, dried distilled grains, hemp seeds, sugar cane and tobacco stalks. It was found that hydrogen yield, calculated as a mass percentage of biomass processed, was highest for chars produced from hemp seeds, tobacco stalk, corn cobs and coffee husk and lowest for apple pomace and sugar cane. A relationship has been derived between char yield and production of hydrogen, especially in the case of hemp seeds. Consequently, a trend was discovered (R 2 = 0.90) when comparing the ash free char yield with the carbon content of the feedstock, which is useful to estimate char yields on an ash free basis if the carbon content is known. An inverse relationship was observed, for tobacco stalk, between the quantity of hydrogen produced and its purity, represented as a mole percentage of hydrogen in the gas stream, for the three different steam reforming temperatures (650, 675 & 700 °C). The residence time investigation showed that decreasing the vapour residence time, reduced both hydrogen production and purity, possibly as a result of the water gas shift reaction. [ABSTRACT FROM AUTHOR]

Abstract: Stenosis strongly alters the flow field inside a blood vessel not only through geometric changes but also due to changing the mechanical properties of the vessel. Since the flow field has via, e.g., the oscillating wall-shear stress (WSS), a significant effect on the pathogenesis of atherosclerosis a better understanding of the unsteady velocity field and the fluid-structure interaction is necessary. Time-resolved particle-image velocimetry (TRPIV) is combined with simultaneous measurements of the static pressure inside an elastic, axisymmetric stenosed, transparent vessel at pulsatile flow in a range of Reynolds numbers and Womersley numbers . The location of the elastic wall and the near-wall velocity distribution is highly resolved to determine the unsteady WSS. The effect of the vessel elasticity on the flow is analyzed by the velocity distribution, the vessel dilatation, and the static pressure. At dilatations of the vessel model up to 5% the measurement quantities exhibit phase lags and deviations from the temporal bulk flow distribution which depend on the exciting frequency. Below the eigenfrequency local dilatation and static pressure are in phase. Above the eigenfrequency a higher mode oscillation superimposed onto the bulk flow in the throat region of the stenosis exits which is caused by a phase shift in the dilatation on both sides of the stenosis. The TRPIV measurements show the stenosis to induce a jet through the throat together with complex flow structures like ring vortices. The unsteady footprints of these structures are evidenced by oscillating WSS distributions which also aggravate stenosis. [Copyright &y& Elsevier]

Abstract: Background: Congenital diaphragmatic hernia (CDH) can be repaired on or off extracorporeal membrane oxygenation (ECMO). In many centers, operating off ECMO is advocated to prevent bleeding complications. We aimed to compare surgery-related bleeding complications between repair on or off ECMO. Methods: All patients with CDH repair and ECMO treatment between January 1, 1995, and May 31, 2008, were retrospectively reviewed. Tranexamic acid was routinely given to all patients repaired on ECMO for 24 hours perioperatively after 2003. Extra-fluid expansion, transfusion, or relaparotomy caused by postoperative bleeding were scored as surgery-related bleeding complications and were related to the Extracorporeal Life Support Organization (ELSO) registry. We used χ 2 test and t test for statistics. Results: Demographic data and surgery-related bleeding complications in the on-ECMO group were not significantly different compared with the off-ECMO group (P = .331) in our institute. In contrast, more surgery-related bleeding complications were reported by ELSO in their on-ECMO group (P < .0001). Conclusion: In contrast to the data from the ELSO registry, we did not observe significantly more surgery-related bleeding complications after CDH repair on ECMO. Using a specific perioperative hemostatic treatment enabled us to perform CDH repair on ECMO with a low frequency of bleeding complications, thereby taking advantage of having the physiologic benefits of ECMO available perioperatively. [Copyright &y& Elsevier]

Background & Aims: Stem cells of normal tissues have resistance mechanisms that allow them to survive genotoxic insults. The stem cell–like cells of tumors are defined by their tumor-initiating capacity and may have retained these resistance mechanisms, making them resistant to chemotherapy. We studied the relationship between resistance to the topoisomerase I inhibitor irinotecan and tumor-initiating potential in human colonosphere cultures and in mice with colorectal xenograft tumors. Methods: Colonosphere cultures were established from human colorectal tumor specimens obtained from patients who underwent colon or liver resection for primary or metastatic adenocarcinoma. Stem cell and differentiation markers were analyzed by immunoblotting and fluorescence-activated cell sorting. Clone- and tumor-initiating capacities were assessed by single-cell cloning and in immune-deficient mice. Sensitivity to irinotecan was assessed in vitro and in tumor-bearing mice. The relationship between drug resistance and tumor-initiating capacity was tested by fluorescence-activated cell sorting of colonosphere cells, based on expression of ABCB1 and aldehyde dehydrogenase (ALDH) activity. Results: Colonosphere cultures had a high capacity to initiate tumors in mice and were resistant to irinotecan. Inhibition of the drug-efflux pump ABCB1 by PSC-833 allowed irinotecan to eradicate tumor-initiating cells. However, ABCB1 was expressed only by a subpopulation of differentiated tumor cells that did not form clones or tumors. Conversely, tumor-initiating cells were ABCB1-negative and were identified by high ALDH activity. Tumorigenic ALDHhigh/ABCB1negative cells generated nontumorigenic ALDHlow/ABCB1positive daughter cells in vitro and in tumor xenografts. PSC-833 increased the antitumor efficacy of irinotecan in mice. Conclusions: The resistance of colorectal tumors to irinotecan requires the cooperative action of tumor-initiating ALDHhigh/ABCB1negative cells and their differentiated, drug-expelling, ALDHlow/ABCB1positive daughter cells. [Copyright &y& Elsevier]

Abstract: The effects of air temperature and flowrate on the drying of cylindrical carrot samples, which were blanched, peeled, or unaltered, were investigated in a tunnel dryer. The drying was carried out at 21, 42 and 56°C, and at air superficial velocities of 0.5, 0.625, 0.75 and 0.95m/s. The Henderson and Pabis model was used to compare results to previous works, but was deemed inadequate since it did not allow for biomass shrinkage or external mass transfer limitations to be taken into account. A simpler approximation was implemented using Crank’s surface evaporation equations to develop a model able to predict the diffusivity and mass transfer coefficient for the thin-sliced carrot samples, modelled as a slab, while accounting for shrinkage and both internal and external mass transfer limitations. Using this new model, an Arrhenius relation with activation energy of 31.76kJ/mol successfully described the effect of temperature on the diffusivity. [Copyright &y& Elsevier]

Background & Aims: Hartnup amino acid transporter B0AT1 (SLC6A19) is the major luminal sodium-dependent neutral amino acid transporter of small intestine and kidney proximal tubule. The expression of B0AT1 in kidney was recently shown to depend on its association with collectrin (Tmem27), a protein homologous to the membrane-anchoring domain of angiotensin-converting enzyme (ACE) 2. Methods: Because collectrin is almost absent from small intestine, we tested the hypothesis that it is ACE2 that interacts with B0AT1 in enterocytes. Furthermore, because B0AT1 expression depends on an associated protein, we tested the hypothesis that Hartnup-causing B0AT1 mutations differentially impact on B0AT1 interaction with intestinal and kidney accessory proteins. Results: Immunofluorescence, coimmunoprecipitation, and functional experiments using wild-type and ace2-null mice showed that expression of B0AT1 in small intestine critically depends on ACE2. Coexpressing new and previously identified Hartnup disorder–causing missense mutations of B0AT1 with either collectrin or ACE2 in Xenopus laevis oocytes showed that the high-frequency D173N and the newly identified P265L mutant B0AT1 transporters can still be activated by ACE2 but not collectrin coexpression. In contrast, the human A69T and R240Q B0AT1 mutants cannot be activated by either of the associated proteins, although they function as wild-type B0AT1 when expressed alone. Conclusions: We thus show that ACE2 is necessary for the expression of the Hartnup transporter in intestine and suggest that the differential functional association of mutant B0AT1 transporters with ACE2 and collectrin in intestine and kidney, respectively, participates in the phenotypic heterogeneity of human Hartnup disorder. [Copyright &y& Elsevier]

Abstract: Background: Superoxide anions released by activated macrophages during surgery are considered to be responsible for local cellular damage. Application of CO2 pneumoperitoneum during laparoscopy affects superoxide anion release, but the underlying mechanism remains unclear and the data reported are conflicting. We investigated the direct and pH-mediated impact of CO2 and air on macrophage superoxide anion production. Methods: Cells of the NR 8383 rat macrophage cell line were incubated for 2 hours in 5% CO2, 100% CO2, and room air or pH 7.4, pH 6.5, and pH 5.5. The extracellular pH was monitored during incubation. At 0, 2, and 6 hours after incubation, the release of superoxide anions was determined fluorometrically. The mitochondrial activity was determined via the conversion of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] during and after incubation. Results: Extracellular pH decreased to 6.4 during incubation in a CO2 atmosphere. The release of superoxide anions was significantly reduced immediately after CO2 incubation. It was restored at all other time-points. Decreasing the extracellular pH to 6.5 had no effect on superoxide anion release, whereas acidification of the extracellular milieu to pH 5.5 significantly suppressed subsequent superoxide release. Mitochondrial activity was significantly decreased by CO2 up to 2 hours and by acidic milieu up to 6 hours. Incubation in room air had no effect. Conclusions: Incubation in CO2 can directly suppress macrophage superoxide anion production. This effect is of short duration, fully reversible, and not correlated to changes in extracellular pH or mitochondrial activity. Air contamination does not affect macrophage superoxide anion release. We speculate that CO2 pneumoperitoneum could attenuate the intraoperative free radical production by directly inhibiting superoxide anion release of macrophages without long-lasting suppression of macrophages and their capacity to release superoxide anions postoperatively. [Copyright &y& Elsevier]

In the common implementation of external preference mapping consumer preferences are fitted as polynomial functions of the first two principal components (PCs) of the sensory data. A major weakness of the method is the relatively small number of consumers that can be significantly fitted. Several researchers have proposed to improve the consumer fit by including higher-numbered PCs in the analysis. We have explored the possibility of including higher-numbered PCs while restricting the model choice to the simplest polynomial function, i.e. the (linear) vector model. In addition, we have developed a heuristic decision rule for determining the number of PCs to keep in the fit. A practical example is discussed where the consumer fit improved from 51% (two PCs, polynomial) to 80% (five PCs, vector). [Copyright &y& Elsevier]