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Epidemiological studies have demonstrated a strong association between cigarette smoking (CS) and chronic pancreatitis (CP); however, the exact mechanisms of this phenomenon remains unknown. The authors have previously shown that increased Ras expression activates the NF-κB mediated pathway and promotes development of CP. However, it is unclear whether a similar phenomenon occurs in CS-induced CP. Therefore, the aim of the study was to determine whether CS increases the expression of K-Ras, and promotes the development of CP in mice exposed to repeated episodes of acute pancreatitis (AP).C57BL6/cmdb mice were exposed to CS or a sham treatment for 12 weeks. After one week of exposure, half of the animals from both groups were additionally subjected to repeated cerulein treatment (once a week, for 10 consecutive weeks) to mimic recurrent episodes of AP. Extension of pancreatic damage was determined histologically by HE and Trichrome staining. The expression of K-Ras protein and downstream components (NF-κB, Cox-2, TGF-β) was evaluated by immunohistochemistry.C57BL6/cmdb mice exposed to CS or cerulein alone did not develop any chronic pancreatic damage. However, concomitant treatment with both of these agents caused focal acinar atrophy, with slight intralobular and perivascular areas of fibrosis, and inflammatory cells infiltration resembling mild CP. Moreover, immunohistochemistry examinations revealed increased pancreatic expression of K-Ras and NF-κB only in mice treated both with CS and cerulein.CS promotes development of CP in mice exposed to repeated episodes of AP. This process may be, at least partially, related to increased expression of K-Ras and NF-κB protein.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with organ failures and very high short-term mortality.To assess the incidence and factors predisposing to ACLF in patients with liver cirrhosis hospitalized due to acute gastrointestinal bleeding (GIB).We collected and retrospectively analyzed the data of 89 consecutive patients (59 males (66.2%), median age 53 years (range: 44-62 years), mean Model for End-Stage Liver Disease (MELD) score 14.42 ±6.5, median Child-Turcotte-Pugh score 10 (range: 8-11), and acute GIB (72 variceal bleeding and 17 non-variceal bleeding cases). Acute-on-chronic liver failure was diagnosed based on European Association for the Study of the Liver - Chronic Liver Failure Consortium definition.Twenty-seven (30.33%) patients met the criteria of ACLF during hospitalization: 8 (30%) had ACLF grade 1, 13 (48%) had ACLF grade 2 and 6 (22%) had ACLF grade 3. The most frequent organ failures were respiratory (22 (25%)), kidney (18 (20.23%)) and brain (17 (19.1%)) failure. The MELD score value, creatinine level and presence of hepatic encephalopathy (HE) on admission were significant predictors of ACLF in the multivariate logistic regression model with optimal cutoff point for MELD score of 18.313 and optimal cutoff point for creatinine level of 1.35 mg/dL.In-hospital risk of ACLF in cirrhotic patients hospitalized for acute gastrointestinal hemorrhage is high despite successful arrest of bleeding. Elevated creatinine level, MELD score and the presence of HE on admission are the best predictors of ACLF during hospitalization in such patients.

Purpose: Due to the lack of systematic data on antibiotic sensitivity, the treatment of the highly prevalent and pathogenic Helicobacter pylori (H. pylori) infection still poses a significant problem. Therefore, the aim of our study was to compare the efficacy of the three most commonly used anti-H. pylori therapies in northeastern Poland. Patients and Methods: This was a retrospective, single-center study performed on 289 outpatients with an H. pylori infection. Patients received one of the following three treatment regimens: (1) bismuth quadruple therapy (BQT) for 10 days, (2) metronidazole-based triple therapy (M-TT) for 10 or 14 days, and (3) levofloxacin-based triple therapy (L-TT) for 10 or 14 days. Results: BQT, M-TT, and L-TT accounted for 93.2% of prescribed anti-H. pylori therapies. The overall success rate for all treatment regimens was 84.1% (243/289). The effectiveness of first- and second-line therapy was similar and reached 83.8% and 86.2%, respectively. The efficacy of the individual treatment regimens was as follows: (1) BQT—89.4% (84/94), (2) M-TT—80.6% (112/139) and 78.8% (26/33) for 10 and 14 days, respectively, and (3) L-TT—84.6% (11/13) and 100% (10/10) for 10 and 14 days, respectively. The overall duration of treatment and type and dose of proton pump inhibitor (PPI) had no effect on the treatment efficacy. Conclusions: In the northeastern part of Poland, 10-day BQT and 10- or 14-day L-TT are effective treatment regimens for H. pylori eradication and have appear to be superior to M-TT. Practitioners in our clinic followed mostly local anti-H. pylori therapy guidelines.

Purpose Minimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis. Patients and methods Fifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score. Results MHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC ​= ​0.753, CI95% ​= ​0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE. Conclusions MHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC.

Introduction Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no relation with the severity of the symptoms. Aim To establish the efficacy of pantoprazole treatment in patients with erosive reflux disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing symptom relief and quality of life. Treatment duration and adverse events associated with pantoprazole treatment were analysed. Material and methods This meta-analysis was based on three multicentre, prospective, open-label, phase IV trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252 patients with GERD were included and treated with pantoprazole 40 mg once daily for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria. Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life on a rating scale from 1 to 10. Results Forty-five percent of patients fulfilled the healing criteria after 4 weeks of treatment, and 70% of patients after 8 weeks of treatment. Patients who failed to reach the healing criteria reported significant reduction of symptoms severity. The response to 8-week treatment was significantly higher in patients with ERD (76%) when compared to patients with NERD (64%). Discontinuation of treatment after 4 weeks was not associated with worsening of symptoms and did not affect quality of life. Pantoprazole treatment was associated with improvement of symptoms and the quality of life of GERD patients over 8 weeks of treatment and showed that GERD patients with persisting symptoms benefit from prolonging treatment to 8 weeks. Treatment with pantoprazole 40 mg was very well tolerated - more than 90% of patients were without adverse events throughout the whole study and only 4 patients discontinued the treatment due to adverse events related to pantoprazole treatment. Conclusions Pantoprazole 40 mg was associated with complete relief of GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore, the severity of symptoms was significantly reduced in patients without complete relief of symptoms. Pantoprazole also continuously improved the quality of life of GERD patients over 8 weeks of treatment and was very well tolerated throughout the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg once daily is an effective and well-tolerated choice for providing symptom relief of patients with GERD.

Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.

Background Cigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis. Methods C57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue). Results Mice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4+ cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8+ cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4+/CD8+ ratio both in the blood and colon and significantly increased B cell presence in the colon. Conclusions Our study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis. Electronic supplementary material The online version of this article (doi:10.1007/s00384-017-2882-9) contains supplementary material, which is available to authorized users.

Background Endoscopic techniques have become the first-line therapy in bariatric surgery-related complications such as leaks and fistulas. We performed a systematic review and meta-analysis on the effectiveness of self-expandable stents, clipping, and tissue sealants in closing of post-bariatric surgery leak/fistula. Methods A systematic literature search of the Medline/Scopus databases was performed to identify full-text articles published up to February 2019 on the use of self-expandable stents, clipping, or tissue sealants as primary endoscopic strategies used for leak/fistula closure. Meta-analysis of studies reporting stents was performed with the PRISMA guidelines. Results Data concerning the efficacy of self-expanding stents in the treatment of leaks/fistulas after bariatric surgery were extracted from 40 studies (493 patients). The overall proportion of successful leak/fistula closure was 92% (95% CI, 90–95%). The overall proportion of stent migration was 23% (95% CI, 19–28%). Seventeen papers (98 patients) reported the use of clipping: the over-the-scope clips (OTSC) system was used in 85 patients with a successful closure rate of 67.1% and a few complications (migration, stenosis, tear). The successful fistula/leak closure using other than OTSC types was achieved in 69.2% of patients. In 10 case series (63 patients), fibrin glue alone was used with a 92.8–100% success rate of fistula closure that usually required repeated sessions at scheduled intervals. The complications of fibrin glue applications were reported in only one study and included pain and fever in 12.5% of patients. Conclusions Endoscopic techniques are effective for management of post-bariatric leaks and fistulas in properly selected patients.

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis.Methods: The results of ...

Background and Aims Therapeutic endoscopy plays a critical role in the management of upper GI (UGI) postsurgical leaks. Data are scarce regarding clinical success and safety. Our aim was to evaluate the effectiveness of endoscopic therapy for UGI postsurgical leaks and associated adverse events (AEs) and to identify factors associated with successful endoscopic therapy and AE occurrence. Methods This was a retrospective, multicenter, international study of all patients who underwent endoscopic therapy for UGI postsurgical leaks between 2014 and 2019. Results Two hundred six patients were included. Index surgery most often performed was sleeve gastrectomy (39.3%), followed by gastrectomy (23.8%) and esophagectomy (22.8%). The median time between index surgery and commencement of endoscopic therapy was 16 days. Endoscopic closure was achieved in 80.1% of patients after a median follow-up of 52 days (interquartile range, 33-81.3). Seven hundred seventy-five therapeutic endoscopies were performed. Multimodal therapy was needed in 40.8% of patients. The cumulative success of leak resolution reached a plateau between the third and fourth techniques (approximately 70%-80%); this was achieved after 125 days of endoscopic therapy. Smaller leak initial diameters, hospitalization in a general ward, hemodynamic stability, absence of respiratory failure, previous gastrectomy, fewer numbers of therapeutic endoscopies performed, shorter length of stay, and shorter times to leak closure were associated with better outcomes. Overall, 102 endoscopic therapy–related AEs occurred in 81 patients (39.3%), with most managed conservatively or endoscopically. Leak-related mortality rate was 12.4%. Conclusions Multimodal therapeutic endoscopy, despite being time-consuming and requiring multiple procedures, allows leak closure in a significant proportion of patients with a low rate of severe AEs.

Objective We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype. Methods The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined. Results Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH > 4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH >6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH. Conclusions In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

Aim We aimed to assess the relationship between procoagulant imbalance and the occurrence of variceal bleeding in patients with liver cirrhosis. Methods We compared the results of chromogenic assay for the functional evaluation of the Protein C anticoagulant pathway (ThromboPath®), thromboelastometry and the levels of factor VII, VIII, and antithrombin in two groups of cirrhotic patients: Group 1 (n = 25) — patients with moderate or large esophageal or gastric varices, who had never experienced acute gastrointestinal bleeding and Group 2 (n = 24) — patients with a history of variceal bleeding. Results Despite the differences in MELD score and the results of basic laboratory tests indicating more severe cirrhosis and suggesting a greater risk of bleeding in Group 2, the results of thromboelastometry did not differ significantly between groups. The ThromboPath® test results [ThP B: 67.8 ± 13.4 versus 59.09 ± 12.4%, p = 0.023] and factor VII level [69.04 ± 24.16 vs 53.54 ± 25.06, p = 0.032] confirmed greater plasma procoagulant activity in Group 1 compared to Group 2. However, there were no statistically significant differences in thrombin generation after activation of the protein C. Plasma of patients in Group 2 was more resistant to anticoagulation with protein C compared to Group 1 (PICI%: 65.58 ± 7.24 versus 55.64 ± 13.07%, p = 0.001). Conclusion The results of our study confirm the lack of influence of coagulation disorders on the occurrence of variceal bleeding. Moreover, the results of ThromboPath® assay indicate hypercoagulability in patients with a history of variceal bleeding and more severe liver cirrhosis, compared to patients who have never bled.

The authors used cluster analysis of data from cardiovascular domains associated with exercise intolerance to help define prognostic phenotypes of patients with heart failure with preserved ejection fraction (HFpEF).Resting and postexercise echocardiography was performed in 177 patients with HFpEF and 51 asymptomatic control subjects sharing a common clinical profile. Patterns of features that determine exercise capacity were sought from automated hierarchical clustering of left ventricular (LV) diastolic and systolic function, left atrial function, right ventricular function, ventricular-arterial coupling, chronotropic reserve and myocardial fibrosis.Automated clustering separated a distinct subgroup characterized by a relatively isolated impairment of LV systolic reserve. The clinical factors identified by this process were used to define two phenotypes of patients with symptomatic HFpEF: those with reduced chronotropic and/or diastolic reserve (abnormal CR/DR; n = 137) and those with preserved heart rate reserve and exertional E/e' ratio 14 (normal CR/DR; n = 40). Change in global LV strain rate from rest to exercise was similar in patients with abnormal CR/DR (0.16 ± 0.18 secDiminished LV systolic reserve may represent the major identifiable cardiac functional abnormality associated with exercise intolerance in some patients with HFpEF. Despite significant functional limitation, these patients are characterized by a better prognosis than subjects with HFpEF with more physiologic abnormalities.

Introduction The presence of esophageal varices in liver cirrhosis indicates clinically significant portal hypertension (PH), that results from structural and dynamic changes in the liver and systemic circulation including the activation of several fibrotic and inflammatory pathways. We assessed if interleukin-18 (IL-18) and transforming growth factor-β1 (TGF-β1) serum levels can be used as PH markers and reflect its severity. Material and methods IL-18 and TGF-β1 peripheral blood levels were analyzed in 83 cirrhotic patients with esophageal varices compared to healthy individuals, in relation to MELD and Child-Pugh scores, laboratory and Doppler ultrasound parameters, and non-selective beta-blocker therapy (NSBB). Results IL-18 concentration was significantly higher in cirrhotic patients, while TGF-β1 concentration was lower than in controls. MELD score correlated positively with IL-18 levels and negatively with TGF-β1 levels. IL-18 levels correlated positively with bilirubin, INR, ALT and AST levels, and negatively with albumin levels and erythrocyte count. TGF-β1 levels correlated positively with platelet count, leukocyte, and erythrocyte count, and negatively with bilirubin levels and prothrombin time. Moreover, significant correlations were found: between IL and 18 levels and portal, mesenteric superior, and splenic vein velocity, and between TGF-β1 levels and splenic vein diameter and spleen size. In a subgroup of patients, IL-18 levels significantly decreased after NSBB. Conclusion The observed imbalance of peripheral IL-18 and TGF-β1 levels indicates clinically significant PH associated with the presence of esophageal varices in cirrhosis. The correlation of IL-18 levels with liver failure indicators and decrease with NSBB suggest an important role of IL-18 in disease progression and its potential use as noninvasive test for PH assessment.

Background Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy. Methods Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls. Results Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non-obese. At 50–54 weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50–54 weeks after therapy. Conclusion Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies.

In this paper, we present a new brain diagnostic method based on a computer aided multispectral ultrasound diagnostics method (CAMUD). We explored the standard values of the relative time of flight (RIT), as well as the attenuation, ATN, of multispectral longitudinal ultrasound waves propagated non-invasively through the brains of a standard Caucasian volunteer population across different ages and genders. For the interpretation of the volunteers health questionnaire and ultrasound data we explored various clustering and classification algorithms, such as PCA and ANOVA. We showed that the RIT and ATN values provide very good estimators of possible physiological changes in the brain tissue and can differentiate the possible high-risk groups obtained by other groups and methods (Russo et al. [1] ; Lloyd-Jones et al. [2] ; Medscape [3] ). Special attention should be given to the subgroup which included almost 39% of the volunteers. Respondents in this group have a significantly increased minimum ATN value (see Classification Trees). These values are strongly correlated with the identified risk of stroke factors being: age, increased alcohol consumption, cases of heart disease and stroke in the family as already shown by Rusco and as incorporated into Lloyd-Jones et al., “Heart Disease and Stroke Statistics – 2009 Update”, by the American Heart Association (AHA) and American Stroke Association (ASA), as updated recently in the 2015 “Stroke Prevention Guidelines”.

Objective The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. Materials and methods We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-β1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4–6 months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. Results (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-β1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-β2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-β1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. Conclusions Peripheral endothelin-1 and transforming growth factor-β1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is associated with an increased risk of esophageal cancer. Mitogen-activated protein kinases may play an important role in the pathogenesis of this process. We aimed to evaluate mitogen-activated protein kinases activity in esophageal mucosa of patients with BE and find possible relationship between reflux type and BE. Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease symptoms and endoscopically suspected esophageal metaplasia (ESEM) were prospectively enrolled for testing by a multichannel intraluminal impedance monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from methylene blue-positive pit patterns (sites suggesting specialized intestinal metaplasia [SIM]), from 2 cm above the Z-line and from cardial parts of the stomach. The biopsies were analyzed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen ESEMs had histologically proven metaplasia: eight patients had SIM and nine had gastric-type epithelia (GE). Biliary reflux was more evident in SIM (P = 0.019) but not in GE (P = 0.019); non-biliary reflux was typical for GE (P = 0.005) but not for SIM (P = 0.04). Strong activations of ERK and p38 were found predominantly in SIM, but not in normal esophageal mucosa (NE) (P = 0.01 and P < 0.001 respectively). Strong signals for active JNK and p38 were detected in GE, but not in NE (P = 0.006 and P = 0.02 respectively). ERK activity was significantly higher than p38 activity in ESEM patients only with GE (P = 0.02). The strong activation of ERK, but not JNK is indicative of SIM. The presence of bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in esophageal mucosa.

The exact time of initiation of total enteral nutrition (TEN) in severe acute pancreatitis (SAP) and its influence on the disease outcome are not well known.An analysis of 197 cases with predicted SAP allocated to: group A (n = 97), early TEN (started within the first 48 hours after admission to hospital); and group B (n = 100), delayed TEN (started after 48 hours).Infection of necrosis/fluid collections occurred in 4 patients in group A and 18 patients in group B (P0.05). Respiratory failure and transfer to intensive care unit occurred more frequently in group B than in group A (15 vs 5 and 15 vs 3 patients; P0.05). Multiple-organ failure was observed in 9 patients in group A and 16 patients in group B (P0.05). Seven patients in group A and 11 patients in group B underwent surgery (P0.05). All 9 reported deaths occurred in group B (P0.05). The time to start TEN was a predictor of infected necrosis/fluid collection (odds ratio, 4.09; P = 0.028).Delayed compared to early TEN is associated with higher mortality, increased frequency of infected necrosis/fluid collections, respiratory failure, and a need for intensive care unit hospitalization. Enteral nutrition in SAP should be started within 48 hours after admission to hospital.

Recent studies report an increased risk of enteric infections in patients treated with proton pump inhibitors (PPIs). Polymorphonuclear neutrophils (PMNs) play a key role in host response to bacterial infection. We evaluated the effect of omeprazole and pantoprazole treatment on the PMN function. Fifteen patients were treated with omeprazole 20 mg daily and 15 patients with pantoprazole 40 mg daily for 7 days. Treatment with omeprazole or pantoprazole had no effect on spontaneous nitroblue tetrazolium (NBT) test results. Significant increase in the percentage of phagocytes in the omeprazole group in stimulated NBT test (by 69%) was found. Treatment with omeprazole or pantoprazole had no effect on nitric oxide (NO) concentration in the PMN culture supernatant and serum, cyclic guanosine monophosphate concentration in the PMN culture supernatant and serum, as well as inducible nitric oxide synthase (iNOS) protein expression and p38 mitogen-activated protein kinase activity in PMNs. In conclusion, treatment with PPI has no effect on NO production and p38 mitogen-activated protein kinase activity in PMNs. Interestingly, short-term treatment with omeprazole but not with pantoprazole enhances PMN reactive oxygen species production.

Background and aim Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. Methods 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. Results We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4+ cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. Conclusion Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii.

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.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.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, P0.001). 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.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.

We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype.The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined.Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH.In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

OBJECTIVES The aim of this study was to assess the functional state of platelets in patients with mild acute pancreatitis and severe acute pancreatitis (S-AP). METHODS The number of platelets and their morphological parameters were measured with Advia 2120. β-Thromboglobulin and platelet factor 4 concentrations were determined by enzyme-linked immunosorbent assay method. To evaluate the expression of platelet glycoproteins, flow cytometry method was used. RESULTS At the time of admission, a multiparameter evaluation of the platelets' function in AP patients showed enhanced platelet activation, which was reflected by an increase in the number of large platelets, concentration of degranulation markers (platelet factor 4 and β-thromboglobulin), expression of glycoprotein (Gp) IIb/IIIa, and decreased mean platelet component. Only in S-AP patients at day 1 a decreased number of platelets and high expression of P-selectin and GpIa were observed, which may suggest their prognostic value. At day 30, the procoagulation state was still present in S-AP patients, because of increased platelets and number of large platelets as well as high GpIIb/IIIa expression. CONCLUSIONS These results may indicate an important role of platelet activation in the pathogenesis of acute pancreatitis and the development of complications in S-AP.

Purpose Determination of the type and frequency of complications developing after diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) as well as the risk factors predisposing to them. Material/Methods The retrospective study, including 734 ERCP performed in 550 patients, with 404 (55%) ES (endoscopic sphincterotomy) during a 4-year period. Results Among 734 ERCP procedures, 76.4% (561) had both diagnostic and therapeutic purpose, 15.2% (112) were only diagnostic. Complications developed after 26 procedures (3.5%): acute pancreatitis (AP) in 8 patients (1.09%), cholangitis in 7 (0.95%) and delayed bleeding in 11 (1.5%) patients. After 49 (6.7%) ES immediate bleeding was observed. The risk factors for AP were: unintentional pancreatic duct contrasting, mechanical lithotripsy, the use of the “pre-cut” technique and bile duct dilatation. Cholangitis was more common in cases with difficult cannulation at older age and with lower baseline bilirubin level. The risk factors for delayed bleeding were: location of the ampulla of Vater in the diverticulum and the use of the “pre-cut” technique. Immediate bleeding was more frequent after revision of bile ducts with Dormia's basket or with balloon, after introduction of contrast medium to the pancreatic duct or in ductal cholelithiasis. Conclusions ERCP performed in the endoscopy unit of a specialist hospital department is a relatively safe procedure, with a low burden of complications as compared to the benefits it provides to appropriately qualified patients.

Background Specialized intestinal metaplasia (SIM) in Barrett’s esophagus is a risk factor of esophageal adenocarcinoma. It often occurs focally and cannot be distinguished from surrounding columnar epithelium with conventional endoscopy. Aims The purpose of this study was evaluation of methylene blue (MB) staining and magnification endoscopy with comparison of pit-pattern classifications according to Endo and Guelrud, in detection of SIM in Barrett’s esophagus. Methods Twenty-five patients, aged 33–77 years (average 57 years), with displacement of Z line were prospectively enrolled and underwent gastroscopy with the use of magnification up to 115 times (Olympus GIF Q160Z). Biopsy for histopathologic examination was taken from sites stained with MB and/or places with particular pit patterns. A control group consisted of ten patients with normal gastro-esophageal junction. Results SIM was proved in nine patients, and significantly more frequently in patients with hiatal hernia and Barrett’s segment longer than 3 cm. Round or thin linear pit patterns according to Guelrud’s and small round and straight pit patterns according to Endo’s classification were coupled with columnar epithelium. SIM was associated with deep linear and foveolar pit patterns in Guelrud’s classification. Other pit patterns were less characteristic. Both classifications had high sensitivity (Endo’s 85.7%, Guelrud’s 92.8%) but poor specificity (respectively, 21.15 and 28.4%) in detection of SIM. Sensitivity and specificity of MB staining were, respectively, 71.4 and 40.6%. Conclusions Despite existing association between mucosal surface structure and histology, we find no convincing data indicating that pit-pattern evaluation may replace multiple biopsies taken according to recommendations from Seattle for detection of SIM in Barrett’s esophagus.

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.

Ghrelin and leptin are hormones regulating appetite and metabolic processes. Adiponectin plays an important role in the modulation of glucose and lipid metabolism.The objective of the study was to evaluate the levels of plasma ghrelin, leptin, and adiponectin in obese subjects treated with bioenterics intragastric balloon (BIB), low-calorie diet (1500 kcal), and physical exercise.BIB was placed for 6 months in 21 subjects with body mass index 47.3 +/- 5.7. The control group consisted of 15 morbidly obese subjects treated with a low-calorie diet and physical effort. Plasma hormone levels were determined by RIA.In the BIB group, the insertion of the balloon caused a considerable reduction in body mass over a 6-month period (17.1 +/- 8.0 kg) as compared with the control group (3.2 +/- 6.4 kg). After 1 month, the levels of ghrelin increased from 621.9 +/- 182.4 to 903.9 +/- 237 pg/ml and thereafter gradually decreased, reaching the starting level 3 months after the removal of the balloon. In the same group, the levels of leptin decreased from 61.3 +/- 36.7 to 39.9 +/- 17.5 ng/ml. In the control group, the corresponding levels of ghrelin and leptin remained relatively stable. During the observation period, in the BIB group, the levels of adiponectin remained unchanged as opposed to a transient increase noted in the control group.In patients with morbid obesity, weight loss induced by BIB is associated with a decrease in plasma leptin and a transient elevation of plasma ghrelin. It is likely that the changes in hormones regulating the energy balance caused by BIB can prevent an increase in adiponectin level.

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.