Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.

OBJECTIVE: Alcohol-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. DESIGN: 1959 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. RESULTS: We 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. CONCLUSION: An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.

Diet for women with irritable bowel syndrome - a preliminary study

Background: Irritable Bowel Syndrome (IBS) is one of the most frequent digestive system diseases, of various medical signs. It is assumed that proper life style, including appropriate, rational diet is a factor helpful for treating such a disorder. Objective: The purpose of this paper was to assess the selected dietary habits, and to evaluate the nutritional value of daily food rations for patients with a mixed type of Irritable Bowel Syndrome. Material and Methods: The questionnaire survey involved a group of 32 women suffering from a mixed type of Irritable Bowel Syndrome (The Rome III Diagnostic Criteria were used to diagnose the disease). The control group was comprised of 32 healthy women. The methods used to assess the diet were divided into quantitative and qualitative ones. Results: The most frequent dietary mistakes among patients with IBS were associated with snacking sweets (83.0% of the subjects) and fruit (17.0% of the subjects) between the meals. A higher intake of sucrose was found amongst women with IBS, than in the case of the control group (p=0.0169). The analysis of the results demonstrated a significantly higher intake of water (derived from drinks and foods) amongst patients with IBS, than in the case of women of the control group (p=0.0267). An insufficient intake of plant proteins and polyunsaturated fatty acids was recorded in both groups. The supply of protein in general, animal protein, fat in general, saturated fatty acids and sodium, exceeded the recommended norm, both amongst women with IBS and women of the control group. Conclusions: The obtained examination results showed that there are significant dietary improprieties in the diet of women suffering from IBS. In order to eliminate these mistakes in the future, it seems justified to extend the knowledge on rational nutrition amongst patients with IBS.

The Impact of an Individual Educational Program on the Quality of Life and Severity of Symptoms of Patients with Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional diseases of the gastrointestinal tract. A typical symptom is changed bowel patterns: diarrhea, constipation, or alternation of the two. Abdominal pains vary in intensity and location, with periods of exacerbation and remission, causing disorganization in everyday life and work. Educational intervention could be one strategy to improve the well-being of IBS patients. Only a few trials have examined this hypothesis. The aim of this study was to examine the effect of an educational program combined with elements of behavioral therapy, individualized for each patient, on quality of life (QOL) and severity of pain of patients with IBS. METHODS: In total, 150 IBS patients and 100 healthy persons in the control group were included. QOL (36-Item Short Form Health Survey, SF-36) and pain severity (Visual Analogue Scale) were measured at baseline and six months after education of IBS patients. RESULTS: At baseline, patients with IBS showed highly significantly worse QOL. In the IBS group, significantly higher physical component summary (PCS) and mental component summary (MCS) scores were noted for 35- to 50-year-old patients compared to other patients. Six months after education and behavioral therapy, significant improvement in QOL and a significant decrease in the subjective perception of pain severity were noted compared to values before therapeutic education. CONCLUSION: An educational program combined with elements of behavioral therapy, individualized for patients with IBS, is an important part of therapy for these patients.

Diagnostic and therapeutic recommendations in pancreatic ductal adenocarcinoma. Recommendations of the Working Group of the Polish Pancreatic Club.

These recommendations refer to the current management in pancreatic ductal adenocarcinoma (PDAC), a neoplasia characterised by an aggressive course and extremely poor prognosis. The recommendations regard diagnosis, surgical, adjuvant and palliative treatment, with consideration given to endoscopic and surgical methods. A vast majority of the statements are based on data obtained in clinical studies and experts' recommendations on PDAC management, including the following guidelines: International Association of Pancreatology/European Pancreatic Club (IAP/EPC), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN) and Polish Society of Gastroenterology (PSG) and The National Institute for Health and Care Excellence (NICE). All recommendations were voted on by members of the Working Group of the Polish Pancreatic Club. Results of the voting and brief comments are provided with each recommendation.

Diagnostic and therapeutic recommendations for chronic pancreatitis. Recommendations of the Working Group of the Polish Society of Gastroenterology and the Polish Pancreas Club.

This article describes the latest diagnostic and therapeutic recommendations in chronic pancreatitis, developed by the Working Group of the Polish Society of Gastroenterology and the Polish Pancreas Club. The recommendations refer to the diagnosis of chronic pancreatitis, autoimmune pancreatitis, conservative management, treatment of pain, and exocrine and endocrine pancreatic insufficiency, treatment of chronic pancreatitis by endoscopic and surgical methods, and oncological surveillance of chronic pancreatitis. This paper refers to the Polish recommendations published in 2011, which have been updated and supplemented. All recommendations were voted by experts of the Polish Society of Gastroenterology and the Polish Pancreas Club, who evaluated them each time on a five-degree scale, where I meant full acceptance, II - acceptance with some reservation, III - acceptance with serious reservation, IV - rejection with some reservation and V - full rejection. The results of the voting, together with a brief commentary, have been included with each recommendation put to the vote. In addition, the expert group assessed the value of clinical studies on which the statements are based, on a scale where A means high (based on meta-analyses and randomised clinical trials), B means medium (based on clinical trials and observational studies), and C means low (based mainly on expert opinion).

The effect of omeprazole treatment on the gut microflora and neutrophil function.

BACKGROUND AND AIM: Proton pump inhibitors (PPIs) may increase the risk of Clostridium difficile infections. There are interactions between gut microbiota and innate immune cells including neutrophils. We evaluated the effect of treatment with omeprazole on the gut microflora and neutrophil function. METHODS: In 50 patients, we evaluated the effect of 4-week omeprazole treatment (n=25 with 20mg per day and n=25 with 20mg twice daily) on intragastric pH, results of stool culture and lactulose hydrogen breath test (LHBT) and neutrophil function. RESULTS: The treatment caused significant increase of the mean intragastric pH, especially in the group with 20mg omeprazole twice daily (from 2.05±0.59 to 5.06±1.6, P<0.001). In LHBT, the increase of hydrogen concentration was observed in higher percentage of patients with 20mg of omeprazole twice daily, compared to patients with the lower dose (42.1% vs 29.4%; ns). Four weeks of omeprazole treatment have caused considerable changes in stool culture results. Patients treated with higher dose of omeprazole have had some tendency to decrease diversity of colonic microflora in comparison with patients treated with the lower dose of omeprazole. Treatment with omeprazole did not result in C. difficile positive stool culture and had no significant effect on neutrophil function. CONCLUSIONS: Omeprazole treatment have caused considerable changes in stool culture results. Patients treated with the higher dose had some tendency to decreased diversity of colonic microflora and towards changes in fermenting bacteria of the gut. The potential effect of omeprazole on gut microflora does not depend on neutrophil function deterioration.

The influence of nitric oxide synthesis modulation on the pancreatic acinar cells in caerulein-induced acute pancreatitis. An ultrastructural and morphometric study.

The goal of our study was to evaluate the influence of NO synthesis modulation on the ultrastructural changes in the pancreatic acinar cells in connection with morphometric assessment of the volume and numerical densities of mitochondria (Vvm, Nvm) and zymogen granules (Vvz, Nvz) in caerulein-induced acute pancreatitis (AP). During AP induction rats were treated with L-arginine--substrate for NO synthesis, N(G)-nitro-L-arginine (L-NNA)--NO synthase inhibitor, gliceryl trinitrate (NTG)--NO donor, L-arginine+L-NNA or saline. This study demonstrated that administration of L-NNA leads to the formation of numerous, large autophagosomes and mitochondria oedema in pancreatic acinar cells. Treatment with L-arginine or NTG during AP induction resulted in a diminution of the ultrastructural changes with a concomitant increase of Vvz. Vvm and Nvm were significantly lower in the L-arginine treated group compared to the untreated AP. The results indicate that: L-NNA enhances damage to acinar cells which may be indicative of a protective role for endogenous NO in oedematous AP. The application of L-arginine or NTG decreases the damage to acinar cells evaluated ultrastructurally, suggesting the morphological changes accompanying the onset of AP in rats after the administration of either substrate for endogenous NO synthesis or exogenous NO donor follow a favourable course.

A Rare Spontaneous Gastrobiliary Fistula.

We report the case of a 69-year-old man with a spontaneous gastrobiliary fistula. Internal biliary fistulas are usually the result of longstanding, untreated choledocholithiasis, cholecystolithiasis, peptic ulcers or rarely neoplasia. This patient's unspecific clinical picture led to a late diagnosis, which was made during surgery. How to cite this article: Chwiesko A, Jurkowska G, Kedra B, Okulczyk B, Kamocki Z, Dabrowski A. A Rare Spontaneous Gastrobiliary Fistula. Euroasian J Hepato-Gastroenterol 2014;4(2):101-103.

The impact of Helicobacter pylori on EGF, EGF receptor, and the c-erb-B2 expression.

PURPOSE: Increased expression of epidermal growth factor (EGF), its receptor (EGFR), and c-erb-B2 protein, which is homological with the EGF receptor, in gastric mucosa, may play a role in gastric carcinogenesis. We assessed if the infection and eradication of Helicobacter pylori (H. pylori) affects the gastric expression of growth factors and serum gastrin concentrations. PATIENTS/METHODS: We examined immunohistochemically gastric EGF and both receptors' expression in: gastric cancer (GC; n=29), chronic gastritis with H. pylori infection (GHp+; n=40) before and after eradication and in patients without H. pylori infection (GHp-; n=42). RESULTS: Before the eradication therapy, gastric mucosal EGF and both receptor's expressions in GHp+ patients were increased compared to GHp- (p<0.05), but were similar to GC. After eradication, EGF and the receptor's expression significantly decreased in the gastric body. Both EGFR and c-erb-B2 expression in the antrum were still higher than in GHp- (p<0.05), and remained comparable to GC. CONCLUSIONS: In patients with H. pylori infection the gastric mucosal EGF, EGFR, and c-erb-B2 expressions are similar to those observed in gastric cancer. The persistence of the antral expression of receptors after eradication, at a level comparable to the gastric cancer group, suggests their eventual role in the progression of changes initiated by H. pylori toward carcinogenesis.

Quality of life in patients with Irritable Bowel Syndrome (IBS), assessed using the IBS-Quality of Life (IBS-QOL) measure after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide: results of an international prospective observational cohort study in Poland, Egypt, Mexico and China.

BACKGROUND AND OBJECTIVE: Irritable 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. METHODS: This was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China). RESULTS: A 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. CONCLUSIONS: This study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.

Clinical significance of the measurements of serum matrix metalloproteinase-9 and its inhibitor (tissue inhibitor of metalloproteinase-1) in patients with pancreatic cancer: metalloproteinase-9 as an independent prognostic factor.

OBJECTIVE: Pancreatic cancer (PC) is a malignant tumor with high mortality. Aggressive growth and metastases of PC are the result of basement membrane degradation that may be attributed to the action of matrix metalloproteinase-9 (MMP-9). The aim of the study was to determine the diagnostic and prognostic significance of the measurements of serum MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with PC. METHODS: The study involved 78 patients with PC, 45 with chronic pancreatitis, and 70 healthy subjects. We assayed the serum concentrations of MMP-9, TIMP-1, and classic tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen) and defined the prognostic value and the diagnostic criteria for all the proteins tested. RESULTS: In the patients with PC, the serum levels of MMP-9, TIMP-1, and the tumor markers were higher as compared with those in the patients with chronic pancreatitis and the healthy subjects. The diagnostic sensitivity and the area under the receiver operating characteristic curve for TIMP-1 were higher than for MMP-9 and the tumor markers. The elevated preoperative concentration of MMP-9 was a significant independent prognostic factor for the patients' survival. CONCLUSIONS: 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 in the sera of patients with pancreatic cancer.

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.

Stem cell factor and macrophage-colony stimulating factor in patients with pancreatic cancer.

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.