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Introduction Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract with relapsing-remitting episodes that are very burdensome for the patient. Understanding the sociodemographic factors that affect a patient’s quality of life helps us to better understand the behavior and life circumstances of the patient as well as the patient’s ability to cope with the stresses caused by IBD. Aim The aim of the study was to identify factors that affect the quality of life of patients with IBD. Material and methods The study involved 100 patients with confirmed IBD (50 subjects with Crohn’s disease and 50 subjects with ulcerative colitis). Women constituted 45% (n=45) of the study group, while the remaining 55% (n=55) of the group were men. The mean age of the respondents participating in the study was 37.27±13.38. The youngest patient was 20 years old and the oldest was 76. The respondents were treated at the Department of General and Colorectal Surgery and at the Department of Digestive Tract Diseases (both at Medical University in Łódź, Poland). Data were collected using the SF-36 general questionnaire, the IBDQ specific questionnaire, and the original author’s questionnaire. Participation in the study was anonymous and voluntary. A significance level of 0.05 was adopted in the statistical analysis. Results The study showed that the quality of life of IBD patients is reduced. The psychosocial factors influencing the quality of life of IBD patients include education, place of residence, professional activity, having a spouse, and lack of surgical intervention. However, no significant relationship was found between the respondents’ gender and age and their quality of life in any of the domains of the SF-36 and IBDQ questionnaire. Conclusions The occurrence of IBD, a chronic and incurable disease, reduces the quality of life of those patients. However, a higher level of education, living in a larger community, and increased physical activity all have a positive impact on the quality of life of patients with IBD.

BACKGROUND AND AIM The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, with poor prognosis resulting mostly from late diagnosis. Surgery remains the most effective treatment and early detection significantly increases the overall survival. Biomarkers used for diagnosis and to monitor the response to treatment, such as carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), are not adequate as early detection markers of PDAC, partly due to low sensitivity/specificity. Therefore, new biomarkers for PDAC are critically needed. This review aims at recent advancements in the identification and characterization of new biomarkers, microRNAs, which might prove useful in the early detection of PDAC.

Background: Although duodenal diverticula are associated with less frequent pathology than the colonic diverticula in the large intestine, their periampullary position may have significant clinical implications. The aim of the study was to identify any possible correlation between the type of localisation of the major duodenal papilla, duodenal diverticula, and some particular clinical issues. Materials and methods: In total, 628 patients (408 females and 220 males; aged 21–91 years), who underwent endoscopic retrograde cholangiopancreatography were included in this study. The patients were divided into two groups: a study group comprising 66 (10.5%) patients with periampullary position of diverticula (group A), and a control group comprising 562 (89.5%) patients without diverticula (group B). Results: A duodenal diverticulum was diagnosed in the periampullary position in 66/628 (10.5%) patients: 41 women (aged 52–91 years) and 25 men (aged 54–83 years). Conclusions: Three types of localisation were observed for the major duodenal papilla with regard to the diverticula, with the most common type being next to each other (type III). In patients with diverticula, similar frequencies of gallstone occurrence are observed in men and women. Patients with papilla in the diverticulum who underwent cholecystectomy are more prone to develop lithiasis.

Leukocytapheresis, a blood purification therapy, exerts anti-inflammatory effects by removing activated leukocytes from the peripheral blood through extracorporeal circulation. It is a potential option of treatment for patients with inflammatory bowel diseases (IBD), especially those with ulcerative colitis (UC), who do not respond to conventional therapy. Given that it has a favourable safety profile and seems to have steroid sparing effects, its position in the treatment of UC is likely to expand. However, there is inadequate evidence to draw any conclusions about the efficacy of leukocytapheresis in patients with Crohn's disease, and it should only be used in accordance with special arrangements for consent. Considering the current level of knowledge, it is essential to conduct large, well-designed, randomized clinical trials to evaluate the effects of leukocytapheresis in the management of IBD patients.

Contains fulltext : 229360.pdf (Publisher’s version ) (Closed access) BACKGROUND: The G-protein-coupled receptor Class C Group 6 Member A (GPRC6A) is activated by multiple ligands and is important for the regulation of calcium homeostasis. Extracellular calcium is capable to increase NLRP3 inflammasome activity of the innate immune system and deletion of this proinflammatory pathway mitigated pancreatitis severity in vivo. As such this pathway and the GPRC6A receptor is a reasonable candidate gene for pancreatitis. Here we investigated the prevalence of sequence variants in the GPRC6A locus in different pancreatitis aetiologies. METHODS: We selected 6 tagging SNPs with the SNPinfo LD TAG SNP Selection tool and the functional relevant SNP rs6907580 for genotyping. Cohorts from Germany, further European countries and China with up to 1,124 patients and 1,999 controls were screened for single SNPs with melting curve analysis. RESULTS: We identified an association of rs1606365(G) with alcoholic chronic pancreatitis in a German (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.89, p = 8 × 10(-5)) and a Chinese cohort (OR 0.78, 95% CI 0.64-0.96, p = 0.02). However, this association was not replicated in a combined cohort of European patients (OR 1.18, 95% CI 0.99-1.41, p = 0.07). Finally, no association was found with acute and non-alcoholic chronic pancreatitis. CONCLUSIONS: Our results support a potential role of calcium sensing receptors and inflammasome activation in alcoholic chronic pancreatitis development. As the functional consequence of the associated variant is unclear, further investigations might elucidate the relevant mechanisms.

Introduction Insulin-like growth factor 1 (IGF-1) has been connected with development of pancreatic ductal adenocarcinoma (PDAC). Aim To evaluate the serum concentration levels of IGF-1 and insulin-like growth factor binding protein 2 (IGFBP-2) in patients with chronic pancreatitis (CP) and PDAC. Their values in diabetes mellitus (DM) were also assessed. Material and methods The study included 83 patients with CP, 92 patients with PDAC, and 20 subjects as a control group. The concentrations of IGF-1 and IGFBP-2 were estimated with ELISA (Corgenix UK Ltd, R&D Systems). Results The IGF-1 was higher in CP compared with PDAC (81.11 ±57.18 ng/ml vs. 53.18 ±36.05 ng/ml, p < 0.001), and both CP and PDAC were different from controls (81.11 ±57.18 ng/ml vs. 70.66 ±16.57 ng/ml, p < 0.001 and 53.18 ±36.05 ng/ml vs. 70.66 ±16.57 ng/ml, p < 0.001). CP without cysts have lower IGF-1 compared to those with CP and cysts (60.35 ±34.68 ng/ml vs. 93.55 ±64.78 ng/ml, p < 0.05). IGF-1 in CP without DM was higher compared to IGF-1 in PDAC without DM (91.13 ±65.48 ng/ml vs. 54.75 ±40.41 ng/ml, p < 0.001). In CP and DM the IGF-1 was elevated in comparison to PDAC and DM (62.20 ±32.38 ng/ml vs. 48.45 ±24.88 ng/ml, p < 0.05). IGFBP-2 was higher in CP compared to PDAC (512.42 ±299.77 ng/ml vs 301.59 ±190.36 ng/ml, p < 0.001). In CP and PDAC the IGFBP-2 level was elevated compared to the control group (512.42 ±299.77 ng/ml vs. 51.92 ±29.40 ng/ml, p < 0.001 and 301.59 ±190.36 ng/ml vs. 51.92 ±29.40 ng/ml, p < 0.001). IGFBP-2 in CP without DM was higher compared to PDAC without DM (559.39 ±281.43 vs. 296.53 ±196.93, p < 0.001). Conclusions IGF-1 and IGFBP-2 may be biomarkers of CP and PDAC. IGF-1 may be an indicator that signals whether pancreatic diabetes is from CP or PDAC.

Pareneteral manifestations of Crohn’s disease (ChLC), apart from the most common skin and joint symptoms include also complications from the respiratory system. In addition chronic pharmacotherapy of ChLC, especially 5-aminosalicylic acid or anti-TNF- α drugs, is associated with possible pulmonologic side effects, sometimes difficult to differentiate. In this study, we describe a patient with ChLC, with a history of pneumocystic pneumonia, who was diagnosed with exfoliative institial pneumonitis as a result of chronic use of mesalazine. This disease is characterized by accumulation of alveolar macrophages in the lumen of the alveoli and intrabepticular septum. The most common etiologic factor is exposure to tobacco smoke. Our patient, non-smoker, was finally diagnosed after lung biopsy and histopathological evaluation. The gradual clinical improvement after mesalazine was an additional factor confirming the etiology of the disease. This side effect of mesalazine is not common but it should be considered in all patient treated with 5-aminosalicylic acid.

Background/objectivesAcute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP.Methods and analysisThe REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort.Ethics and disseminationThe study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals.Trial registration numberNCT04647097

Aim: Fibrosis is observed both in pancreatic cancer (PDAC) and chronic pancreatitis (CP). The main cells involved in fibrosis are pancreatic stellate cells (PSCs), which activate alpha smooth muscle actin (αSMA), which is considered to be the best-known fibrosis marker. The aim of the study was to evaluate the expression of the αSMA in patients with PDAC and CP as the possible differentiation marker. Methods: We enrolled 114 patients undergoing pancreatic resection: 83 with PDAC and 31 with CP. Normal fragments of resected specimen from 21 patients represented the control tissue. The immunoexpressions of αSMA were detected in tissue specimens with immunohistochemistry (Abcam antibodies, GB). Results: Mean cytoplasmatic expression of αSMA protein in PDAC stromal cells was significantly higher compared to CP: 2.42 ± 0.37 vs 1.95 ± 0.45 (p < 0.01) and control group 0.61 ± 0.45 (p < 0.01). Strong immunoexpression of the αSMA protein was found in the vast majority (80.7%) of patients with PDAC, in about half (58%) of patients with CP, and not at all in healthy tissue. The expression of αSMA of different intensity was found in all patients with PDAC and CP, while in healthy tissue was minimal or absent. In PDAC patients, αSMA expression was significantly higher in tumors of diameter higher than 3 cm compared to smaller ones (p = 0.017). Conclusions: Presented findings confirm the significant role of fibrosis in both PDAC and CP; however, they do not confirm the role of αSMA as a marker of differentiation.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene

Background The role of the incretin hormone, glucagon-like peptide (GLP-1), in Crohn’s disease (CD), is still poorly understood. The aim of this study was to investigate whether colitis is associated with changes in blood glucose levels and the possible involvement of the incretin system as an underlaying factor. Methods We used a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Macroscopic and microscopic score and expression of inflammatory cytokines were measured. The effect of colitis on glucose level was studied by measurement of fasting glucose and GLP-1, dipeptidyl peptidase IV (DPP IV) levels, prohormone convertase 1/3 (PC 1/3) and GLP-1 receptor (GLP-1R) expression in mice. We also measured the level of GLP-1, DPP IV and expression of glucagon (GCG) and PC 1/3 mRNA in serum and colon samples from healthy controls and CD patients. Results Fasting glucose levels were increased in animals with colitis compared to controls. GLP-1 was decreased in both serum and colon of mice with colitis in comparison to the control group. DPP IV levels were significantly increased in serum, but not in the colon of mice with colitis as compared to healthy animals. Furthermore, PC 1/3 and GLP-1R expression levels were increased in mice with colitis as compared to controls. In humans, no differences were observed in fasting glucose level between healthy subjects and CD patients. GLP-1 levels were significantly decreased in the serum. Interestingly, GLP-1 level was significantly increased in colon samples of CD patients compared to healthy subjects. No significant differences in DPP IV levels in serum and colon samples were observed between groups. Conclusions Changes in the incretin system during colitis seem to contribute to the impaired glucose levels. Differences in incretin levels seem to be modulated by degrading enzyme DPP-IV and PC 1/3. Obtained results suggest that the incretin system may become a novel therapeutic approach in the treatment of CD.

Estrogens exert immunomodulatory action in many autoimmune diseases. Accumulating evidence highlights the meaningful impact of estrogen receptors in physiology and pathophysiology of the colon. However, the significance of G protein-coupled estrogen receptor (GPER) on Crohn’s disease (CD), one of the inflammatory bowel disease (IBD) types, is still elusive. Our study revealed GPER overexpression at the mRNA and protein levels in patients with CD. To evaluate the effects of GPER activation/inhibition on colitis development, a murine 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced model of CD was used. We showed that activation of GPER reduces mortality, improves macroscopic and microscopic scores and lowers C-reactive protein (CRP) level. The impact of estrogen signaling on the suppression of the intestinal inflammation was proved by immunohistochemistry. It was demonstrated that GPER activation is accompanied by modulation of extracellular-signal regulated kinase (ERK) signaling pathway and expression level of genes involved in signal transmission and immune response as well as the expression of some microRNAs (miR-145, miR-148-5p and miR-592). Our study revealed that the membrane-bound estrogen receptor GPER mediates anti-inflammatory action and seems to be a potent therapeutic target in maintaining remission in CD.

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.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.

Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities, glutathione (GSH) level, and IL-1β, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1β expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P < 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 = 3.1 × 10−5). Conclusions: Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk. Impact: This large case–control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10-9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.

Background: The negative impact of a high-fat diet on the course of gastroesophageal reflux disease (GERD) has been previously reported. Free fatty acid receptors (FFARs) may be mediators of this phenomenon. The aim of this study was to characterize the role of FFARs in the course of nonerosive (NERD) and erosive (ERD) reflux disease. Methods: Collectively, 73 patients (62 with GERD and 11 healthy controls (HCs)) were recruited to the study. Esophageal biopsies were drawn from the lower third of the esophagus and kept for further experiments. Quantitative, real-time polymerase chain reaction was used to assess the expression of FFAR1, FFAR2, FFAR3, and FFAR4 in biopsies. Histological evaluation of dilated intracellular spaces (DISs) was also performed. Results: FFAR3 exhibited the highest expression, and FFAR4 exhibited the lowest expression in all esophageal samples. Higher relative expression of FFAR1 and FFAR2 and significantly higher expression of FFAR3 (p = 0.04) was noted in patients with GERD compared to respective HCs. Patients with nonerosive GERD (NERD) presented higher expression of all FFARs compared to patients with erosive GERD (ERD) and respective HCs. Interestingly, in patients with ERD, the expression of FFAR3 was lower than in HCs. Significant, weak, positive correlation was found for FFAR3 and FFAR4 expression and DIS scores (r = 0.36, p &lt, 0.05 for FFAR 3, and r = 0.39, p &lt, 0.05 for FFAR4). Conclusions: In this study, we show that FFARs may play a role in GERD pathogenesis, particularly in the NERD type. It may be assumed that FFARs, in particular FFAR3 and FFAR4, may have diagnostic and therapeutic potential in GERD.

The causes of disordered sleep, frequently reported by patients with inflammatory bowel diseases (IBD), are poorly understood. The study aimed to evaluate sleep quality in IBD patients and to identify factors affecting their sleep. IBD patients (n = 133) and healthy controls (HC, n = 57) were included in the study and completed sleep questionnaires (Pittsburgh Sleep Quality Index (PSQI), Athens insomnia scale (AIS), and Epworth sleepiness scale (ESS)), Beck Depression Inventory (BDI), and pain scales (Visual Analogue Scale and Laitinen Pain Scale). IBD patients attained higher scores in all sleep questionnaires compared to HC: PSQI, AIS, and ESS (all p &lt, 0.001). They also had prolonged sleep latency (p &lt, 0.001) with reduced sleep efficiency (p &lt, 0.001). Patients in exacerbation of IBD had higher scores in PSQI (p = 0.008), ESS (p = 0.009), but not in AIS, compared to those in remission. Participants with comorbid chronic diseases had higher scores in PSQI and AIS, but not in ESS, compared to others. Multiple regression revealed that the sleep questionnaire results were significantly affected by mood level (BDI), but not by the aforementioned pain scales. Sleep impairment in IBD patients is a common problem that deserves attention in everyday clinical practice and mood level seems to be the main factor affecting the quality of sleep in IBD patients.

Acute pancreatitis (AP) is one of the most frequent gastrointestinal causes of hospital admission [1, 2]. There are a lot of risk factors of AP, but 70–75% of all cases of AP result from alcohol abuse or cholelithiasis [3]. Severe abdominal pain, vomiting, and nausea are the main symptoms of AP [2, 4]. However, manifestation from other organs may occur in the course of this disease.

BACKGROUND GPR18 is a recently deorphanized receptor which was reported to act with several endogenous cannabinoid ligands. Here, we aimed to describe the role of GPR18 in intestinal inflammation and inflammatory pain. METHODS The anti-inflammatory activity of selective GPR18 agonist, PSB-KK-1415, and antagonist, PSB-CB5, was characterized in semi-chronic and chronic mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The extent of inflammation was evaluated based on the macroscopic and microscopic scores, quantification of myeloperoxidase (MPO) activity, and Western blot analyses of tumor necrosis factor-α (TNF-α) and interleukin-6 in colonic tissue. The expression of GPR18 in colonic samples from patients with Crohn's disease (CD) was quantified using real-time PCR. The anti-nociceptive potential of the agonist in intestinal inflammation was evaluated in the mouse model of inflammatory pain. KEY RESULTS In semi-chronic colitis, PSB-KK-1415 reduced macroscopic score (1.79 ± 0.22 vs. 2.61 ± 0.48), expression of TNF-α (1.89 ± 0.36 vs. 2.83 ± 0.64), and microscopic score (5.00 ± 0.33 vs. 6.45 ± 0.40), all compared to mice with colitis. In chronic colitis, PSB-KK-1415 decreased macroscopic score (3.33 ± 1.26 vs. 4.00 ± 1.32) and MPO activity (32.23 ± 8.51 vs. 41.33 ± 11.64) compared to inflamed mice. In the mouse model of inflammatory pain, PSB-KK-1415 decreased the number of pain-induced behaviors in both, controls (32.60 ± 2.54 vs. 58.00 ± 6.24) and inflamed mice (60.83 ± 2.85 vs. 85.00 ± 5.77) compared to animals without treatment with PSB-KK-1415 (P

BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1x10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset≤50, and 4142 controls from the PANDoRA consortium while in the in silico data we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15x10-4 ). In conclusion we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature. This article is protected by copyright. All rights reserved.

Background: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. Methods: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. Results: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. Conclusions: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP. (C) 2020 IAP and EPC. Published by Elsevier B.V.

In memory of Professor Witold Bartnik These guidelines constitute an update of the previous „Recommendations on the management of irritable bowel syndrome” issued in 2008. They have been developed by a Task Force organized by the Governing Board of the Polish Society of Gastroenterology. They discuss, with particular emphasis on new scientific data covering papers published since 2008: the etiology, epidemiology, clinical presentation, diagnostic principles and criteria for the diagnosis, and recommendations for the treatment of irritable bowel syndrome (IBS). The English-language acronym for the syndrome (IBS) has become popular in medical and popular scientific language, it is also widely recognized by patients who identify with this diagnosis. Therefore, in the discussed guidelines, this is what we will use.

BACKGROUND Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 2 (IGFBP-2) are proteins that belong to the IGF axis, which is involved in glucose and lipid metabolism and may as well promote carcinogenesis. GOALS The aim of this study was to evaluate the serum concentration levels of IGF-1 and IGFBP-2 in patients with newly diagnosed pancreatic adenocarcinoma (PDAC) to verify their possible role in the diagnosis of the disease. STUDY The study included 69 patients with PDAC and 20 healthy controls. The concentrations of IGF-1 and IGFBP-2 were estimated by means of ELISA. The study protocol was approved by the Bioethics Committee at the Medical University of Lodz in Poland. RESULTS PDAC patients compared with controls have a significantly lower mean serum IGF-1 level (45.83±30.03 vs. 70.66±60.57 ng/mL; P

Introduction While irritable bowel syndrome (IBS) is not life-threatening for most, it has enormous influence on quality of life (QOL) and mental health. Aim To evaluate the association between QOL and depressive symptoms in IBS patients. Material and methods A total of 87 patients and 56 healthy subjects were enrolled consecutively. All participants were asked to complete self-administered questionnaires: an IBS-specific quality of life (IBS-QOL) questionnaire and the Beck Depression Inventory questionnaire (BDI). Results Mean BDI score was higher in IBS group than in controls. IBS-QOL score was significantly lower in IBS patients compared to the control group, in all IBS-QOL domains: dysphoria (DY), interference with activity (IN), body image (BI), health worry (HW), food avoidance (FA), social relation (SR), and sexual (SX) and relationship (RL) issues. QOL DY, IN, and BI scores and overall score were significantly lower in women with IBS compared to men. We found that BDI score was significantly negatively correlated with IBS-QOL score in the domain of DY, IN, HW, FA, SR, and RL scores and overall QOL score. We also found a negative correlation between older age and health worry. RL and IN QOL scores represented the highest correlation with BDI score. Conclusions Irritable bowel syndrome is connected with impaired patient quality of life and high prevalence of depression with high correlation rate of both parameter scores. Assessment of depression and QOL should be provided during patient visits in outpatients clinics.

INTRODUCTION. Clostridium difficile associated colitis became over last years a worldwide medical issue. It involves patients of the Polish hospitals too. The aim of the study was the analysis of CDAD incidence and the course of infection in Gastroenterology Ward of Regional Specialist Hospital of Zgierz, 2012-2015. MATERIAL AND METHODS. Retrospective analysis of the medical documentation of 79 patients with CDAD was performed. Demographic and epidemiological data and the clinical course of infection were analyzed. RESULTS. The study group comprised of women in 59,5% and men in 40,5%. The patients’ average age was 70,5 years. The average hospitalization period was 10,3 days. CDAD infection seasonality was proved, with statistically significant peak in springtime. 73% of patients were previously hospitalized and 85% - had co-morbidities. 76% of patients underwent antibiotherapy, whilst 29% - used PPI prior to CDAD diagnosis. 50,6% of patients had severe CDAD diagnosed. The recurrence reached 14%. In 19% of patients CDAD resulted in death. DISCUSSION. The results of the study confirm increase of the incidence of the patients with CDAD in Gastroenterology Ward over 4-years’ observation. The prevalence was higher among 65+ patients, after prior hospitalization and antibiotherapy. The co-morbidities was a significant risk factor, especially common in severe cases. CONCLUSION. The results we obtained confirm substantial importance of Clostridium difficile infection leading to antibiotherapy- associated diarrhea among adults, causing prolonged hospitalization, increased prevalence and mortality of patients. Getting to know and minimizing the risk factors will prevent the future outbreak of the disease.

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).