ObjectiveAlcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.Design1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used.ResultsWe replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk.ConclusionAn inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.

These findings indicate a potential clinical significance of serum TIMP-1 and MMP-9 measurements in the diagnosis and prognosis of patients with PC, respectively.

Hematopoietic cytokines (HCs) can affect the growth and spread of cancer. Therefore, in the present study, we investigated in pancreatic cancer patients the serum levels of selected HCs, such as stem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) in relation to a control group and to a group of patients with chronic pancreatitis. Classical tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum level of cytokines with the tumor stage. The diagnostic sensitivity, specificity, positive and negative predictive values and receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers were defined. The cytokines were measured in 48 patients with pancreatic cancer, in 23 patients with chronic pancreatitis and in 40 healthy subjects. HCs were determined using ELISA. CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, IL-3, GM-CSF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group. The serum levels of M-CSF and tumor markers were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of SCF, M-CSF and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels in the pancreatitis group correlated positively with the tumor markers tested--CEA and CA 19-9. The diagnostic sensitivity of SCF and specificity of M-CSF and tumor markers were the highest. The SCF and M-CSF areas under the ROC curve were greater than the areas for other cytokines. These results suggest the potential usefulness of HCs in pancreatic cancer detection; however, further investigations of early-stage pancreatic cancer patients and confirmation by a prospective study are necessary.

Background and ObjectiveIrritable Bowel Syndrome (IBS) has a substantial impact on health-related quality of life (HR-QoL) but high-quality data pre- and post-treatment using the IBS–Quality of Life (IBS-QOL) measure are limited. The objective of this study was to evaluate the changes from baseline of the IBS-QOL scores, symptom scores and health economic data in IBS patients, after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide.MethodsThis was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China).ResultsA total of 607 patients were enrolled. At baseline, the IBS-QOL total scores were 52.0 in Poland, 48.9 in Egypt, 51.9 in Mexico, 76.4 in China and 56.4 overall. Increases in IBS-QOL total score were statistically significant at Weeks 4 and 8 overall and in each country (overall: 11.8 at Week 4, 24.3 at Week 8; p < 0.001). Improvements were shown in all IBS-QOL subscales and scores. Symptoms and health economic outcomes were improved. Furthermore, the favourable safety profile of these treatments was confirmed in this study.ConclusionsThis study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.

Stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) have assumed an increasing importance in cancer biology. In the present study we investigated the serum levels of these cytokines in pancreatic cancer patients in relation to controls and to patients with benign lesions of the pancreas (chronic pancreatitis group). The classical tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum levels of cytokines with tumor stage. We also defined the receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers. The cytokines were measured in 47 patients with pancreatic cancer, in 27 patients with chronic pancreatitis and in 35 healthy subjects. SCF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group, but only the serum levels of M-CSF, CEA and CA 19-9 were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of cytokines and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels correlated positively with the tested tumor markers. The M-CSF area under the ROC curve was higher than the SCF area. These results suggest that M-CSF is a better candidate for a pancreatic cancer tumor marker than SCF.