Integration of different criteria for borderline resectable pancreatic cancer using classification tree analysis: the use of radiological tumour-vascular interface in correlation with surgical and pathological outcomes.

AIM: To integrate various criteria for borderline resectable pancreatic cancer (BRPC) based on radiological parameters using classification tree analysis. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the requirement for informed consent. Two hundred and thirty-five tumour-vein interfaces and 67 tumour-artery interfaces in 245 patients with surgically confirmed pancreatic ductal adenocarcinoma who underwent both preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were assessed by two independent readers. Radiological parameters for evaluation of the tumour-vascular interface were boundary, length of interface, degree of circumferential interface, and contour deformity of affected vessels. Classification tree analysis was performed to determine parameters associated with vascular invasion using pathological and surgical results as the reference standard. RESULTS: In the classification tree analysis for the tumour-vein interface, contour deformity and degree of circumferential interface were the first and second determining factors, respectively, for both surgical and pathological vascular invasion. For the tumour-artery interface, boundary and degree of circumferential interface were the first and second determining factors for surgical invasion, while contour deformity and length of interface were the first and second determining factors for pathological invasion. The BRPC group of modified criteria arbitrarily formed based on the results had similar surgical (74.1-81.6%) and pathological (54.3-63.3%) venous invasion compared to that of the National Comprehensive Cancer Network (NCCN) criteria, and the lowest surgical (33.3%) and pathological (6.7%) arterial invasion compared with those in previously established criteria for BRPC (43.3-55.6% and 22.2-26.1%, respectively). CONCLUSION: Various criteria for BRPCs were integrated using classification tree analysis, and a modified criterion for BRPC, which provides satisfactory results, was established.

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling.

The objective of this study was to describe the population pharmacokinetics (PK) of mosapride under fasting and fed conditions. A single 5-mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs. Plasma concentrations of mosapride were subsequently measured by liquid chromatography-tandem mass spectrometry. Data were analyzed using modeling approaches with the NONMEM 7.2 software. A one-compartment open PK model utilizing model event time (MTIME) with first-order absorption and first-order elimination was found to be more appropriate than all other PK models tested. The absorption rate constants of mosapride were significantly decreased under fed conditions, compared to fasting conditions. The observed bootstrap medians of PK parameters were generally consistent with the corresponding population mean estimates. Furthermore, with the exception of some mosapride concentrations, most of observed data fell into the range of the 5th and 95th percentiles of the simulated values. Overall, the final model was able to describe the observed mosapride concentrations reasonably well. These findings suggest that food intake affects both the rate and extent of absorption of mosapride and that the pharmacological effect of mosapride can differ significantly depending on food intake.

A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy.

We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) influencing overall survival (OS) of small-cell lung cancer (SCLC) patients. We prospectively collected blood samples from 139 SCLC patients who participated in phase II studies of irinotecan and cisplatin (IP) chemotherapy as first-line therapy. Among 334 127 SNPs, which passed quality control, seven showed significant association with OS. The rs16950650CT, rs7186128AG or GG, rs17574269AG, rs8020368CC, rs4655567CC, rs2166219TT or rs2018683TT showed shorter OS compared with control alleles. Among the seven SNPs, rs4655567, rs8020368 and rs2018683 were significantly associated with a resistant relapse (RR). In the multivariate analysis, rs8020368CC was significantly associated with higher risk of RR (odds ratio=16.7, P=0.007). In vitro and in silico analysis showed that SNPs in C14orf49 might be associated with epithelial-to-mesenchymal transition. This exploratory GWAS identified candidate SNPs that may be predictive of the clinical outcome of SCLC patients receiving IP.

Effects of Citrus junos by-products fermented with multistrain probiotics on growth performance, immunity, caecal microbiology and meat oxidative stability in broilers.

1. The present study was conducted to develop Citrus junos probiotics (CJP), using by-products of Citrus junos fermented with multispecies probiotic bacteria including Saccharomyces cerevisiae, Enterococcus faecium, Lactobacillus acidophilus and Bacillus subtilis. The effects of dietary CJP on the growth performance, immune status, caecal microbiology and meat oxidative stability of broiler were investigated. 2. A total of 240 one-day-old Ross broiler chicks were used in a 35-d experiment in which the chicks were randomly allotted to one of the 4 dietary treatments (0, 5, 10 and 20 g CJP/kg diet) in a completely randomised design. 3. Dietary supplementation of 5 g/kg CJP significantly increased body weight, average daily gain and average daily feed intake of broiler during the overall experimental period. 4. Serum immunoglobulin (Ig)M concentration was significantly increased by 10 and 20 g/kg CJP, whereas the IgG and IgA concentration remained unaffected. In addition, 20 g/kg CJP significantly inhibited proliferation of Escherichia coli without affecting the concentration of Lactobacillus or Bacillus spp. 5. A significant reduction in the thiobarbituric acid reactive substances values of breast and thigh meat was observed in response to increasing concentration of dietary CJP. 6. Thus, the results suggest that CJP up to a concentration of 20 g/kg can be used in the diet of broilers to improve immunity and to reduce caecal E. coli and TBARS values of breast and thigh meat without any adverse effects on growth performance.

Comparison of single and blend acidifiers as alternative to antibiotics on growth performance, fecal microflora, and humoral immunity in weaned piglets.

The banning of the use of antibiotics as feed additive has accelerated investigations of alternative feed additives in animal production. This experiment investigated the effect of pure citric acid or acidifier blend supplementation as substitute for antibiotic growth promoters on growth performance, fecal microbial count, and humoral immunity in weaned piglets challenged with Salmonella enterica serover Typhimurium and Escherichia coli KCTC 2571. A total of 60 newly weaned piglets (crossbred, 28-d-old; average 8 kg initial weight) were randomly assigned to four dietary treatments in a completely randomized design. Dietary treatments included NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.5% pure citric acid), and T2 (basal diet+0.4% acidifier blend). All piglets were orally challenged with 5 mL of culture fluid containing 2.3×10(8) cfu/mL of E. coli KCTC 2571 and 5.9×10(8) cfu/mL of S. typhimurium at the beginning of the experiment. The PC group showed the highest ADG and ADFI, whereas gain:feed was improved in the PC and T1 group (p<0.05). All dietary treatments showed significant reduction in fecal counts of Salmonella and E. coli, compared to NC (p<0.05), with PC being better than T1 and T2. Significant elevation in fecal Lactobacillus spp. counts was shown by treatments with T1, T2, and PC, whereas Bacillus spp. counts were increased by treatment with T1 and T2 compared to NC and PC diet (p<0.05). Serum IgG concentration was increased by T1 diet (p<0.05), whereas IgM and IgA were not significantly affected by any of the dietary treatments (p>0.05). From these above results, it can be concluded that, as alternatives to antibiotics dietary acidification with pure citric acid or acidifiers blend did not fully ameliorate the negative effects of microbial challenges in respect of growth performance and microbial environment, however improved immunity suggested further research with different dose levels.

Seamustard (Undaria pinnatifida) Improves Growth, Immunity, Fatty Acid Profile and Reduces Cholesterol in Hanwoo Steers.

The study was designed to evaluate the effect of 2% seamustard (Undaria pinnatifida) by-product (SW) on growth performance, immunity, carcass characteristics, cholesterol content and fatty acid profile in Hanwoo steers. A total of 20 Hanwoo steers (ave. 22 months old; 619 kg body weight) were randomly assigned to control (basal diet) and 2% SW supplemented diet. Dietary SW supplementation significantly (p<0.05) improved average daily gain and gain:feed ratio as well as serum immunoglobulin G concentration. Chemical composition and quality grade of meat and carcass yield grades evaluated at the end of the trial were found to be unaffected by SW supplementation. Dietary SW significantly reduced meat cholesterol concentration (p<0.05). Dietary SW supplementation significantly reduced the myristic acid (C14:0) and palmitoleic acid (C16:ln-7) concentration, while SW increased the concentration of stearic acid (C18:0) and linolenic acid (C18:3n-3) compared to control (p<0.05). Dietary SW supplementation had no effect on saturated fatty acids (SFA), unsaturated fatty acids, poly unsaturated fatty acid (PUFA) or mono unsaturated fatty acid content in muscles. A reduced ratio of PUFA/SFA and n-6/n-3 were found in SW supplemented group (p<0.05). In conclusion, 2% SW supplementation was found to improve growth, immunity and fatty acid profile with significantly reduced cholesterol of beef.

A genome-wide association study for irinotecan-related severe toxicities in patients with advanced non-small-cell lung cancer.

The identification of patients who are at high risk for irinotecan-related severe diarrhea and neutropenia is clinically important. We conducted the first genome-wide association study (GWAS) to search for novel susceptibility genes for irinotecan-related severe toxicities, such as diarrhea and neutropenia, in non-small-cell lung cancer (NSCLC) patients treated with irinotecan chemotherapy. The GWAS putatively identified 49 single-nucleotide polymorphisms (SNPs) associated with grade 3 diarrhea (G3D) and 32 SNPs associated with grade 4 neutropenia (G4N). In the replication series, the SNPs rs1517114 (C8orf34), rs1661167 (FLJ41856) and rs2745761 (PLCB1) were confirmed as being associated with G3D, whereas rs11128347 (PDZRN3) and rs11979430 and rs7779029 (SEMAC3) were confirmed as being associated with G4N. The final imputation analysis of our GWAS and replication study showed significant overlaps of association signals within these novel variants. This GWAS screen, along with subsequent validation and imputation analysis, identified novel SNPs associated with irinotecan-related severe toxicities.

Effects of resveratrol and essential oils on growth performance, immunity, digestibility and fecal microbial shedding in challenged piglets.

A study was conducted to evaluate the effects of resveratrol and essential oils from medicinal plants on the growth performance, immunity, digestibility, and fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg initial weight, 28-d-old) were randomly allotted to four dietary treatments with 3 replications of 4 piglets each. The dietary treatments were NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.2% resveratrol), and T2 (basal diet+0.0125% essential oil blend). All piglets were orally challenged with 5 ml culture fluid containing 2.3×10(8) cfu/ml of Escherichia coli KCTC 2571 and 5.9×10(8) cfu/ml Salmonella enterica serover Typhimurium. The PC group (p<0.05) showed the highest average daily gain (ADG) and average daily feed intake (ADFI) throughout the experimental period, although feed conversion ratio (FCR) was improved in the T1 group (p>0.05). Serum IgG level was increased in the T1 group, whereas TNF-α levels was reduced in the supplemented groups compared to control (p<0.05). The PC diet improved the dry matter (DM) digestibility, whereas PC and T2 diets improved nitrogen (N) digestibility compared to NC and T1 diets (p<0.05). Fecal Salmonella and E. coli counts were reduced in all treatment groups compared to control (p<0.05). Fecal Lactobacillus spp. count was increased in the T2 group compared to others (p<0.05). Dietary treatments had no significant effect on fecal Bacillus spp. count throughout the entire experimental period. Based on these results, resveratrol showed strong potential as antibiotic alternatives for reversing the adverse effects of weaning stress on growth performance, immunity and microbial environment in E. coli and Salmonella-challenged piglets.

Does hepatorenal syndrome affect the result of liver transplantation? Clinical observations.

Hepatorenal syndrome (HRS) is a reversible, functional renal failure that occurs in patients with advanced hepatic failure. However, the reported rates of complete recovery of renal function and patient survivals after orthotopic liver transplantation (OLT) are variable. The aim of this study was to compare the outcomes after OLT between patients with HRS and those without HRS (no-HRS). We established exclusion criteria to select study patients who underwent OLT in a single center between January 2005 and October 2008. The exclusion criteria included the following: (1) malignancy, (2) <18 years of age, (3) other than primary OLT, (4) ABO mismatch or hemophilia, (5) no liver cirrhosis, and (6) survival >1 month after OLT. We selected 71 subjects, including 8 HRS and 63 no-HRS patients. No significant differences were observed in the estimated glomerular filtration rate (eGFR) between the 2 groups except for a lower eGFR on the day of and 1 month after OLT in the HRS group: 108.3 ± 40.5 versus 31.4 ± 14.1 mL/min and 85.4 ± 15.0 versus 57.3 ± 12.1 mL/min (P = .000 and P = .014, respectively). The renal function of 6/7 HRS patients who survived >1 year improved. The 1-year patient survival rate after OLT in HRS patients was similar to that without HRS: 95% versus 86% (P = .37). We concluded that HRS had minimal effects on patient survival and return of acceptable renal function.