Antibiotic-Resistant Strains of Helicobacter pylori in 50 Antibiotic Treatment-Naive Children in Northeast Poland Diagnosed by Gastric or Duodenal Biopsy Between February 2019 and May 2022.

BACKGROUND In recent years, an increasing prevalence of Helicobacter pylori resistance to antibiotics has been observed. The aim of this study was to assess antibiotic resistance of Helicobacter pylori in previously untreated children from northeast Poland. MATERIAL AND METHODS Inclusion criteria comprised suspicion of Helicobacter pylori infection based on the presence of Helicobacter pylori antigen in the stool and/or characteristic macroscopic lesions seen on esophagogastroduodenoscopy. Samples of the gastric and/or duodenal mucosa were collected from 82 children with a median age of 13 years (range 3-17) during esophagogastroduodenoscopy between February 2019 and May 2022. The material was cultured, and positive Helicobacter pylori strains were tested for drug resistance to amoxicillin, metronidazole, and clarithromycin using the quantitative antibiotic concentration gradient stripe method E-test. RESULTS Based on biopsy culture, Helicobacter pylori infection was confirmed in 50 (61%) children. Helicobacter pylori resistance was most common to clarithromycin (n=19; 38%), followed by metronidazole (n=15; 30%), and the least frequent to amoxicillin (n=13; 26%). The resistance to 1 antibiotic was found in 14 children (28%). Double-drug resistance was noted in 3 children (6%) and triple drug resistance in 9 children (18%). In the whole group, 24 children (48%) were susceptible to all 3 antibiotics. CONCLUSIONS In this study, conducted for the first time in treatment-naïve children in northeast Poland, we found a high proportion of Helicobacter pylori strains resistant to at least 1 antibiotic. Our results may help in the appropriate choice of antibiotics for treatment of Helicobacter pylori in our region.

Questionnaire-Based Study of 81 Patients in Poland to Evaluate the Course of Inflammatory Bowel Disease and the Effects of the COVID-19 Pandemic on Quality of Life and Mental State from February to June 2021.

BACKGROUND The COVID-19 pandemic affected many people worldwide, including those with chronic diseases. Our objective was to analyze its influence on medical care and the course of inflammatory bowel disease (IBD) in Poland. MATERIAL AND METHODS In 2021, 81 patients in Poland with IBD completed an original anonymous questionnaire about the impact of the COVID-19 pandemic on the course of their disease and mental status. The printed questionnaire was distributed to IBD patients treated at the Gastroenterology Outpatient Clinic of the University Clinical Hospital in Bialystok, and an online questionnaire was sent to patients via social media. Statistical analysis was performed using the chi-squared test, with a significance level of P<0.05. RESULTS The study group consisted of 46 women and 35 men with a mean age of 32.42 years. Fifty-nine patients had ulcerative colitis and 22 had Crohn disease. Patients reported significant deterioration in medication availability (50.62%) and restricted access to gastroenterology outpatient clinics (51.90%) (P<0.05). Of patients who contracted COVID-19, 89.47% did not require hospitalization, 32.10% (26/81) were asymptomatic, mild, or moderate, despite immunosuppressive biological treatment (27.16%, 22/81), or steroids (18.52%, 15/81). Over 50% of respondents stated the pandemic negatively affected their mental state and 30% of them associated that with worsening IBD. CONCLUSIONS During the pandemic, respondents were mainly concerned with difficulties in accessing the gastroenterology clinic and limited drug availability. The pandemic negatively affected patients' mental state. In cases of COVID-19 disease, patients with IBD were mostly asymptomatic and did not require hospitalization, despite therapy affecting the immune system.

The course of acute pancreatitis in children and potential simple laboratory markers of severity - A single Centre retrospective study.

AIM: To evaluate the usefulness of routinely measured biochemical and complete blood count parameters as potential markers of the severity of paediatric acute pancreatitis (AP). METHODS: The retrospective study included children with AP hospitalised over a 3 years period. Demographic, clinical and laboratory data were collected. RESULTS: In total, 55 patients were enrolled in the study. Mild AP was diagnosed in 45 children (82%), moderately severe in 7 (13%), and severe in 3 patients (5%). Together 10 children (18%) were categorised into a single severe group. Children with severe AP had higher white blood cell and platelet counts on admission as well as a C-reactive protein (CRP) concentration after 48 h. The CRP concentration after 48 h (cut-off: 127.2 mg/L) and the white blood cell count on admission (cut-off: 13.5x103 /µl) were found to be statistically significant markers in predicting the severity of the disease. The CRP concentration after 48 h was demonstrated as an independent predictor. CONCLUSION: Severe AP is observed in a quite significant percentage of children. The white blood cell count on admission and the CRP concentration after 48 h (as an independent predictor) may be potential simple laboratory markers of the severity of the disease.

The Etiology of Cholelithiasis in Children and Adolescents-A Literature Review.

The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment.

Nanomechanical Hallmarks of Helicobacter pylori Infection in Pediatric Patients.

BACKGROUND: the molecular mechanism of gastric cancer development related to Helicobacter pylori (H. pylori) infection has not been fully understood, and further studies are still needed. Information regarding nanomechanical aspects of pathophysiological events that occur during H. pylori infection can be crucial in the development of new prevention, treatment, and diagnostic measures against clinical consequences associated with H. pylori infection, including gastric ulcer, duodenal ulcer, and gastric cancer. METHODS: in this study, we assessed mechanical properties of children's healthy and H. pylori positive stomach tissues and the mechanical response of human gastric cells exposed to heat-treated H. pylori cells using atomic force microscopy (AFM NanoWizard 4 BioScience JPK Instruments Bruker). Elastic modulus (i.e., the Young's modulus) was derived from the Hertz-Sneddon model applied to force-indentation curves. Human tissue samples were evaluated using rapid urease tests to identify H. pylori positive samples, and the presence of H. pylori cells in those samples was confirmed using immunohistopathological staining. RESULTS AND CONCLUSION: collected data suggest that nanomechanical properties of infected tissue might be considered as markers indicated H. pylori presence since infected tissues are softer than uninfected ones. At the cellular level, this mechanical response is at least partially mediated by cell cytoskeleton remodeling indicating that gastric cells are able to tune their mechanical properties when subjected to the presence of H. pylori products. Persistent fluctuations of tissue mechanical properties in response to H. pylori infection might, in the long-term, promote induction of cancer development.

Pancreatic Disorders in Children with Inflammatory Bowel Disease.

Background and Objectives: Inflammatory bowel disease (IBD) is a chronic condition and mainly affects the intestines, however, the involvement of the other organs of the gastrointestinal tract (upper part, pancreas, and liver) have been observed. The coexistence of IBD with pancreatic pathology is rare, however, it has been diagnosed more frequently during recent years in the pediatric population. This article reviews the current literature on the most common pancreatic diseases associated with IBD in the pediatric population and their relationship with IBD activity and treatment. Materials and Methods: We performed a systematic review of data from published studies on pancreatic disorders, also reported as extraintestinal manifestations (EIMs), among children with IBD. We searched PubMed and Web of Science to identify eligible studies published prior to 25 April 2020. Results: Forty-four papers were chosen for analysis after a detailed inspection, which aimed to keep only the research studies (case control studies and cohort studies) or case reports on children and only those which were written in English. The manifestations of IBD-associated pancreatic disorders range from asymptomatic increase in pancreatic enzymes activity to severe disease such as acute pancreatitis. Acute pancreatitis (AP) induced by drugs, mainly thiopurine, seems to be the most- often-reported pancreatic disease associated with IBD in children. AP associated with other than drug etiologies, and chronic pancreatitis (CP), are rarely observed in the course of pediatric IBD. The pancreatic involvement can be strictly related to the activity of IBD and can also precede the diagnosis of IBD in some pediatric patients. The course of AP is mild in most cases and may occasionally lead to the development of CP, mainly in cases with a genetic predisposition. Conclusions: The involvement of the pancreas in the course of IBD may be considered as an EIM or a separate co-morbid disease, but it can also be a side effect of IBD therapy, therefore a differential diagnosis should always be performed. As the number of IBD incidences with concomitant pancreatic diseases is constantly increasing in the pediatric population, it is important to include pancreatic enzymes level measurement in the workup of IBD.

Diagnosis of autoimmune neutropenia in a 10-month-old boy - a case report.

Neutropenia, congenital or acquired, is related to impaired granulocyte production in the bone marrow or increased destruction by antibodies. Autoimmune neutropenia of infancy (AIN) is associated with the occurrence of antineutrophil antibodies. AIN is the most common cause of neutropenia in infants and young children. However, its incidence is low. Detection of anti-neutrophil antibodies is an important step in confirming the diagnosis of AIN, although their detection is difficult due to low titer and poor avidity. In differential diagnosis, another cause of neutropenia should be considered, such as a drug-induced mechanism, viral infection, autoimmune and metabolic disease, hematological conditions or immune deficiency syndromes. Despite the benign course of AIN, serious infectious complications can occur. Spontaneous remission of neutropenia was observed in 95% of patients during 24 months of follow-up. We present a case of a 10-month-old boy with deafness, heart defect and Morgagni-Larrey hernia diagnosed in our department because of formation of a skin abscess due to autoimmune neutropenia.

Immunohistochemical markers for eosinophilic esophagitis.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated esophageal disease with eosinophil-dominated inflammation. The incidence of the disease is rapidly increasing in both children and adults. The pathogenesis of the disease is still not well understood. We present a review of the literature devoted to the EoE immunopathology, in particular the markers of inflammation and epithelial integrity, and their usefulness in disease monitoring and therapy. METHODS: We performed a systematic search of the MEDLINE/PubMed databases for studies to examine the use of immunohistochemistry as a diagnostic tool for EoE. RESULTS: The gold standard of EoE diagnosis requires multiple endoscopies with biopsies for histological assessment. The minimum number of eosinophils evaluated in hematoxylin-eosin staining to diagnose EoE is 15 per high-power field in at least one esophageal mucosa biopsy. However, in some cases, the count of eosinophils is not specific and insufficient as the only indicator. Recent works confirm the usefulness of assessment of some biomarkers in establishing the diagnosis and monitoring the treatment effects. CONCLUSIONS: Immunohistochemistry seems to be a promising option not only in clinical recognition, but also in the selection and monitoring of treatment effects. However, these methods have not yet recommended for routine clinical use.

Usefulness of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in clinical characterisation of children with newly diagnosed Crohn's disease.

AIM: The aim of this study was to determine the relation of non-invasive markers representing gut mucosal damage (metalloproteinase-9 (MMP-9)) and remodelling (tissue inhibitor of metalloproteinase-1 (TIMP-1)) with Crohn's disease (CD) phenotype, disease activity scores (clinical and endoscopic) and radiological evaluation of the ileum in newly diagnosed children. METHODS: Serum and faecal MMP-9 and TIMP-1 concentrations were determined with the sandwich enzyme-linked immunoassay technique. The performance of each marker with reference to the Paris classification, disease activity scores and magnetic resonance enterography results was assessed using non-parametric tests. RESULTS: A total of 32 children with CD demonstrated higher levels of serum and faecal MMP-9 and TIMP-1 compared with a control group including children without gastrointestinal inflammatory disease (all P < 0.05). Only the serum MMP-9 concentration was significantly higher in children with L3 (ileocolonic) compared with children with L1 (distal ileum). The serum TIMP-1 level was significantly higher in patients with an magnetic resonance enterography-detected ileum involvement longer than 51 mm and in children with severe disease activity compared with other patients. The serum MMP-9 level was lower in patients with stenosis combined with prestenotic dilation compared with children without stenosis. CONCLUSION: Increased serum and faecal MMP-9 and TIMP-1 concentrations are some reliable markers of inflammation in newly diagnosed children with CD, but without facilitating clear phenotyping of the disease.

Protective effect of cigarette smoke on the course of dextran sulfate sodium-induced colitis is accompanied by lymphocyte subpopulation changes in the blood and colon.

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.

The effect of penicillin administration in early life on murine gut microbiota and blood lymphocyte subsets.

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.

Longitudinal observation of children with enhanced total serum IgE.

BACKGROUND: Long-term studies on the evolution of elevated total IgE (tIgE) concentration are in demand. OBJECTIVE: To investigate the prevalence of allergic diseases and influential factors in children with high tIgE levels during a 5-year period. METHODS: Children with high tIgE levels (>100 IU/mL) were study subjects. After the 5-year follow-up, an interview with the parents, clinical examination, and evaluation of tIgE and specific IgE (sIgE) to selected food and inhalant allergens were performed. RESULTS: The mean tIgE decreased significantly after 5 years in girls and boys regardless of the place of residence. Monosymptomatic patients accounted for most cases throughout the study, with the highest tIgE level at the beginning. After follow-up, the percentage of polysymptomatic patients increased. Their mean tIgE level was significantly higher than in the other groups. After follow-up, 11.7% of participants remained asymptomatic, and another 11.7% reported relief from symptoms. Allergy symptoms persisted in most children with normal tIgE levels. The 2-allergen sensitization was the most common through the study. Only patients sensitized to 4 allergens had unchanged levels of mean tIgE after follow-up and those with the highest mean tIgE level had a newly diagnosed sensitization to at least 1 allergen. A significant decrease of sIgE level was observed for food allergens. The values of sIgE to inhalant allergens even increased after the 5-year follow-up, despite decreased tIgE levels. CONCLUSION: In children with allergy and an elevated concentration of tIgE, the increasing or stable value of tIgE could be a useful parameter for the prediction of the development of polysymptomatic allergy.

PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo.

Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its dominant-negative form PML-retinoic acid receptor α (PMLRARα). We found PMLRARα interaction with Fas in acute promyelocytic leukemia (APL)-derived cells and APL primary cells, and PML-Fas complexes in normal tissues. Binding of PMLRARα to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. PMLRARα blockage of Fas apoptosis was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signaling complex. PMLRARα expression in mice protected the mice against a lethal dose of agonistic anti-Fas antibody (P < .001) and the protected tissues contained Fas-PMLRARα-cFLIP complexes. Taken together, PMLRARα binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. The presence of PML-Fas complexes across different tissues implicates that PML functions in apoptosis regulation and tumor suppression are mediated by direct interaction with Fas.

Pancreatic Involvement in the Course of Inflammatory Bowel Disease in Children-A Multi-Center Study.

The coexistence of inflammatory bowel disease (IBD) with pancreatic pathology is rare in children. A retrospective analysis of data from 1538 children diagnosed with IBD in 2014-2021 was conducted to determine the frequency and causes of pancreatitis and asymptomatic hyperlipasemia (HL) or hyperamylasemia (HA) in this group of patients. Among the 176 children (11.4%) with pancreatic involvement (PI), acute pancreatitis (AP) was diagnosed in 77 children (43.8%), and HA or HL was observed in 88 children (50.0%). Only a few patients were diagnosed with autoimmune or chronic pancreatitis (6.2%). PI was observed at the time of the IBD diagnosis in 26.1% of the cases. A total of 54.5% of the patients had moderate to severe IBD, and 96% had colonic involvement at the time of diagnosis of PI. Idiopathic PI was the most common (57%), followed by drug-induced PI (37%) and azathioprine (AZA). In patients with AZA-induced AP, the successful introduction of 6-mercaptopurine (6-MP) to therapy was noted in 62.5% of the children. Our results suggest that routine monitoring of pancreatic enzymes in patients with IBD should be performed, especially after the initiation of the AZA treatment. The presence of transient HA/HL in IBD does not necessarily indicate pancreatic pathology.

Successful Treatment with Corticosteroids in an 11-Year-Old Patient with Crohn's Disease and Myopericarditis-Case Report.

Extraintestinal manifestations (EIMs) are observed in 15-20% of patients with inflammatory bowel disease (IBD). One of the rare EIMs is myocarditis, the incidence of which is estimated at around 1%. The main cause of myocarditis is a viral infection. Other causes include autoimmune diseases and drug complications (sulfasalazine, mesalazine). We present the case of an 11-year-old girl with Crohn's disease (CD) with EIMs, manifested as hip joint inflammation and erythema nodosum. At the same time, the symptoms of myopericarditis appeared with changes in electrocardiogram (ECG), echocardiography and high troponin I concentration. Therapy with corticosteroids resulted in the resolution of skin lesions and cardiological symptoms. Systemic connective tissue diseases, viral and bacterial infections were excluded in the differential diagnosis. The suspicion of mesalazine-induced EIMs was also ruled out as the symptoms resolved despite continued therapy with mesalazine. No further recurrences of myopericarditis were observed.

Are Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Useful as Markers in Diagnostic Management of Children with Newly Diagnosed Ulcerative Colitis?

Matrix Metaloproteinase-9 (MMP-9) and Tissue Inhibitor of Metaloproteinase-1 (TIMP-1), enzymes involved in tissue remodelling, have been previously reported to be overexpressed in the colonic mucosa of patients with Ulcerative colitis (UC). The aim of this study was to determine the relation of MMP-9 and TIMP-1 with UC phenotypes, the disease activity index and routinely tested inflammatory markers in newly diagnosed paediatric patients. The study group comprised 35 children diagnosed with UC and 20 control groups. Serum and faecal concentrations of MMP-9 and TIMP-1 were estimated using enzyme-like immunosorbent assay kits and correlated to the disease activity index (Paediatric Ulcerative Colitis Activity Index, PUCAI), UC phenotype (Paris Classification), inflammatory markers and endoscopic score (Mayo score). Children with UC presented with significantly higher serum and faecal concentrations of studied markers compared to the control group. Both serums, MMP-9 and TIMP-1, were higher in children with more extended and severe lesions in the colon. Furthermore, serum MMP-9 correlated with the Mayo score, Paris classification and C-reactive protein (CRP) levels. Serum TIMP-1 showed correlation with PUCAI, Paris Classification, CRP levels and the erythrocyte sedimentation rate. Serum and faecal levels of MMP-9 and TIMP-1 are useful in discriminating UC patients and non-invasive assessments of disease phenotypes. It seemed that simultaneous measurement of these proteins in combination with other common markers of inflammation could be applied in clinical practice.

Analysis of Sphingolipids in Pediatric Patients with Cholelithiasis-A Preliminary Study.

(1) Background: Disturbances in the sphingolipid profile are observed in many diseases. There are currently no data available on the evaluation of sphingolipids and ceramides in cholelithiasis in children. The aim of this study was to evaluate the concentrations of sphingolipids in the sera of pediatric patients with gallstones. We determined their relationship with anthropometric and biochemical parameters. (2) Methods: The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, ultra-high-performance liquid chromatography-tandem mass spectrometry. (3) Results: The prospective study included 48 children and adolescents diagnosed with gallstones and 38 controls. Serum concentrations of total cholesterol (TC); sphinganine (SPA); ceramides-C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer and C24:1-Cer; and lactosylceramides-C16:0-LacCer, C18:0-LacCer, C18:1-LacCer, C24:0-LacCer and C24:1-LacCer differed significantly between patients with cholelithiasis and without cholelithiasis. After adjusting for age, gender, obesity and TC and TG levels, we found the best differentiating sphingolipids for cholelithiasis in the form of decreased SPA, C14:0-Cer, C16:0-Cer, C24:1-LacCer and C24:0-LacCer concentration and increased C20:0-Cer, C24:1-Cer, C16:0-LacCer and C18:1-LacCer. The highest area under the curve (AUC), specificity and sensitivity were determined for C16:0-Cer with cholelithiasis diagnosis. (4) Conclusions: Our results suggest that serum sphingolipids may be potential biomarkers in pediatric patients with cholelithiasis.

The development of cigarette smoke induced chronic pancreatitis in mice is associated with increased expression of K-Ras and NF-κB.

INTRODUCTION AND OBJECTIVE: 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). MATERIAL AND METHODS: 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 H&E and Trichrome staining. The expression of K-Ras protein and downstream components (NF-κB, Cox-2, TGF-ß) was evaluated by immunohistochemistry. RESULTS: 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. CONCLUSIONS: 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.

Microbiome-Friend or Foe of Pancreatic Cancer?

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.

Liver Pathology in Children with Diagnosed Inflammatory Bowel Disease-A Single Center Experience.

BACKGROUND: Inflammatory bowel disease (IBD) in children is frequently associated with liver pathology manifested as transient elevation of liver enzymes or specified liver diseases. The aim of the study was to evaluate the prevalence and the type of liver pathology in children with IBD within 2 years' follow-up after the IBD diagnosis. METHODS: We retrospectively reviewed records of children with IBD. Liver pathology was defined as elevated activity of liver enzymes (alanine transaminase (ALT) and/or gamma-glutamyl transpeptidase (GGT)) and bilirubin concentration in serum and/or as pathological changes of the organ on imaging tests (abdominal ultrasound and/or magnetic resonance cholangiopancreatography) or on liver histology performed when indicated. RESULTS: Liver pathology was detected in 21 from 119 children (18%), including 7 (17%) with Crohn's disease (CD) and 14 (18%) with ulcerative colitis (UC). Specified diagnosis for liver abnormality was found in 14 of 21 children (67%), including primary sclerosing cholangitis (PSC, 19%), non-alcoholic fatty liver disease (NAFLD, 19%), autoimmune sclerosing cholangitis (ASC, 5%), autoimmune hepatitis (AIH, 5%), cholelithiasis (5%), drug-induced liver disease (9%) and viral infection (herpes simplex virus, 5%). Most patients manifested mild IBD or were in clinical remission at the time of liver pathology diagnosis. 14% of patients with liver disease (including only cases with PSC) were diagnosed before IBD, 33% at the same time, and 52% in the later period. Patients with the specified diagnosis of liver pathology were younger, had higher ALT activity and more often demonstrated liver abnormalities on imaging tests. UC patients with idiopathic elevation of liver enzymes had higher pediatric ulcerative colitis activity index scores compared to children with specified liver disease. CONCLUSIONS: Liver pathology was observed in a significant percentage of children with IBD in our study. The majority of cases of hepatobiliary abnormalities were detected after diagnosis of IBD; therefore, children with IBD should undergo routine monitoring of liver enzymes.