Pancreatitis in Pregnancy-Comprehensive Review.

Acute and chronic pancreatitis, until recently observed incidentally in pregnancy, has occurred much more frequently in the last 2-3 decades. Particularly severe complications for the mother and fetus may be a consequence of acute pancreatitis. Therefore, it is important to know more about the diagnostic and therapeutic possibilities of pancreatic diseases in the course of pregnancy. Epidemiology, causes, clinical characteristics, differential diagnosis, and complex management are presented in this review. Particular emphasis is on the prevention of acute pancreatitis (AP) through the proper diagnosis and treatment of cholelithiasis and hypertriglyceridemia, both before and during pregnancy. The most up-to-date reports and management strategies are presented. This publication contributes to a wide group of scientists and practitioners better understanding the discussed issues, and indicates the directions of research for the future.

Gullo's syndrome - what do we know?

Benign pancreatic hyperenzymemia (Gullo's syndrome) is characterized by a more than threefold increase of the serum pancreatic enzymes lipase and amylase activity in the absence of any pancreatic disease. Recently, there is an increase in describing cases of Gullo's syndrome in medical literature. Gullo's syndrome is a diagnosis of exclusion, and clinicians should be aware of various other conditions which can cause elevation of pancreatic enzymes. However, the diagnostic pathway should be done with the right accuracy to avoid unnecessary examinations.

The influence of erythropoietin on apoptosis and fibrosis in the early phase of chronic pancreatitis in rats.

INTRODUCTION: Chronic pancreatitis (CP) is a continuing, inflammatory process of the pancreas, characterised by irreversible morphological changes. The identification of pancreatic stellate cells resulted in the development of research on the pathogenesis of CP. Erythropoietin (Epo) regulates the interaction between apoptosis and inflammation of the brain, kidney, and heart muscle. Erythropoietin receptors were also found in the pancreas, in particular on the islet cells. Our objective was to evaluate the influence of Epo on fibrosis and apoptosis in experimental CP. MATERIAL AND METHODS: The experiments were performed on 48 male Wistar rats (250-350 g). The animals were divided into six equal groups (I - control, II - chronic cerulein - induced pancreatitis, III - 1 ml of Epo sc, IV - 0.5 ml of Epo sc, V - CP treated with 1 ml Epo, VI - CP treated with 0.5 ml Epo). The blood for gelatinases and pancreata for the morphological examinations and immunohistochemistry were collected. RESULTS: A slight reduction of interstitial oedema and less severe fibrosis were noticed in the groups treated with Epo. Reduced expression of caspase-3 and α-actin, and a lack of Bcl-2 expression were observed in areas with inflammation. There was no expression of caspase-9 observed in all groups. There were no statistically significant differences between the groups in the activity of gelatinases. CONCLUSIONS: Erythropoietin seems to have the effect of reducing fibrosis and apoptosis in an experimental model of CP.

Serum miR-210-3p can be used to differentiate between patients with pancreatic ductal adenocarcinoma and chronic pancreatitis.

Patients with chronic pancreatitis (CP) are at risk of developing pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, there are no suitable non-invasive biomarkers for differentiation between CP and PDAC; however, potential molecular candidates include circulating miRNAs due to ease of extraction, their stability and tissue specificity. Therefore, the aim of the present study was to identify potential serum marker(s) that may be used for differentiating between CP and PDAC. In total, 77 patients were enrolled in the present study; 34 patients with CP, 26 patients with PDAC and a control group of 17 healthy individuals. Expression of miR-10b-5p, miR-106b-5p, miR-210-3p and miR-216a-5p in serum was determined by reverse transcription-quantitative PCR. Serum miRNA expression levels in patients with CP, PDAC and in the control group were compared. Routine biochemical blood parameters were determined and correlation analysis of these parameters with miRNA expression was performed. Expression of miR-210-3p was increased in the sera of patients with PDAC compared with the CP patients (P=0.015) and with the control group (P<0.001). MiR-106b-5p (P=0.056) and miR-10b-5p (P=0.080) were not significantly upregulated in patients with PDAC compared with those with CP. Analysis of miRNA expression in relation to laboratory blood parameters showed positive correlations between miR-210-3p with alkaline phosphatase (r=0.605; P=0.022) and with γ-glutamyltranspeptidase (r=0.529; P=0.029) in PDAC. The novel finding of the present study was that miR-10b-5p was positively correlated with C-reactive protein (r=0.429; P=0.047) in patients with PDAC and with carbohydrate antigen 19-9 (r=0.483; P=0.005) in CP. Based on the preliminary data obtained in the present study, it was concluded that miR-210-3p may be used as a non-invasive biomarker that can be used to distinguish between patients with PDAC and CP.

Malnutrition in Chronic Pancreatitis: Causes, Assessment Methods, and Therapeutic Management.

Purpose: In recent years, more and more emphasis has been placed on early diagnosis and adequate treatment of malnutrition in the course of chronic diseases (CP). One of these diseases is chronic pancreatitis in which malnutrition may develop as a consequence of abdominal pain, vomiting, diarrhea, and alcohol abuse. The aim of this review paper is recognized if we can improve the nutritional status of patients with CP. Methods: This paper is based on systematic literature review according to the PubMed. Results: One of the most important problems is lack of "gold standard" in screening of nutritional status in patients with CP, especially in outpatient clinics. Another problem is preventing malnutrition in these patients and beginning treatment already at significant stages of disease. To prevent malnutrition you must first recognize the causes of malnutrition in CP, adequately assess its severity using one of available questionnaires and then apply the appropriate therapeutic management. At each visit, remember to assess the nutritional status of the patient, including laboratory markers and anthropometric measurements. Patients should be advised to stop smoking and drinking alcohol and to use adequate enzyme supplementation. Conclusion: Patients with CP should be led by a team of gastroenterologist, diabetologist, and psychologist and consulted by a dietitian, specialist of pain treatment, and surgeon.

Quality of life of patients with irritable bowel syndrome before and after education.

OBJECTIVES: The aim of the present study was to analyse the impact of education of patients with irritable bowel syndrome (IBS) on their quality of life. METHODS: The study was carried out at the Gastroenterology Outpatient Clinic of the Independent Public Clinical Hospital No. 4 in Lublin and Gastroenterology Outpatient Clinic of the Cardinal Stefan Wyszynski Regional Specialist Hospital in Lublin in the years 2010-2011. The quality of life was analysed using the Quality of Life Questionnaire (QOL-Q R. Schalock, K. Keith). The group of 83 patients with the diagnosis of irritable bowel syndrome, who gave their consent for inclusion in the study, was provided with information about the essence of the disease, disease-related diet and lifestyle, course of the disease, medications, and check-ups. RESULTS: Our patients educated by the physician, nurse and those provided with written information had substantially higher scores in multi-dimensional aspects of the quality of life after education. Six months after education patients with IBS showed a significantly higher quality of life in all aspects, i.e. Satisfaction, Competence/productivity, Empowerment/independence and Social inclusion/community integration. The understanding of the essence of their disease contributed to a decrease in anxiety associated with the neoplastic disease and worrying symptoms, which significantly reduced the incidence of complaints. CONCLUSIONS: 1. Quality of life of patients with irritable bowel syndrome is substantially reduced in all the examined spheres. 2. Education of patients with IBS resulted in enhanced quality of life and reduced disease-related complaints. 3. Education of patients with IBS plays a significant role in the entire therapeutic process.

The genetic predisposition and its impact on the diabetes mellitus development in patients with alcoholic chronic pancreatitis.

The most common cause of chronic pancreatitis (CP) is alcohol abuse. The aim of the present study was to identify patients with genetic predisposition to CP abusing alcohol. The question posed was whether CP manifests at a younger age and diabetes mellitus develops earlier in individuals with genetic predisposition. The study encompassed 79 patients with alcoholic chronic pancreatitis (ACP) and control group (100 persons). The following mutations were determined: R122H and N29I of PRSS1 and N34S of SPINK1 as well as E366K and E288V of SERPINA 1. No R122H and N291 mutations were observed in the group of ACP patients and in controls. Moreover, there was no E288V mutation. In 79 ACP patients, six SPINK 1 (N34S/wt) mutations were observed. In the control group, one heterozygous SPINK 1N34S gene mutation was found (P = 0.0238). Two PiZ mutations were identified in patients with ACP and one analogical mutation in controls. Amongst patients with ACP as well as SPINK1 and PiZ mutations, the onset of disease was observed earlier and developed earlier. The prevalence of SPINK1 mutation is higher in patients with ACP than in healthy populations. This mutation together with the effects of alcohol accelerates the development of ACP and of diabetes mellitus.

Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases.

BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES: We carried out a PubMed search of English-language articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS: The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION: The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases is observed, but the exact role of these enzymes demands further studies.

Neurofibroma of the stomach without Recklinghausen's disease: a case report.

Neurofibromas of the stomach can occur in the course of Recklinghausen's disease. Sporadic gastric neurofibroma appears rarely. This tumour may look like an ulcer and can be a cause of abdominal pain, nausea, and bleeding from the gastrointestinal tract. We reported a 61-year-old women complaining of stomachache for several months. Gastroscopy revealed a tumour with ulceration in the prepyloric part of the stomach. Helicobacter pylori infection was also present. Helicobacter pylori eradication and prolonged treatment of proton pump inhibitors did not decrease the ailments or the size of the tumour. It was not possible to determine the nature and origin of the tumour by carrying out examinations such as endoscopic ultrasound and computed tomography of the abdomen. Only after surgery and histopathological examination with immunohistochemistry was this tumour identified as a neurofibroma. In order to differentiate the tumour the following immunohistochemical examinations were carried out: CD34 (slightly +), CD117 (-), S-100 (+), desmin (-), NSE (+), GFAP (-), SMA (-), bc12 (-), CD99 (-), ALK1 (-), and MiB (1-1.5%). In such cases excision of the tumour is the preferred treatment.

Pancreatic and gastric heterotopy in the gastrointestinal tract.

Heterotopic or ectopic tissue is a congenital anomaly defined as the presence of the tissue outside its normal location. This tissue is usually discovered incidentally and may be asymptomatic or may present with non-specific gastrointestinal (GI) symptoms. Two types of heterotopic tissues, pancreatic and gastric, predominantly occur in the GI tract. The frequency of ectopic pancreas found in autopsy studies is approximately 0.5%-13.7%. Heterotopic pancreatic tissue can be located anywhere along the GI tract; the most common sites are the stomach (27.5%), duodenum (25.5%), colon (15.9%), esophagus, and Meckel`s diverticulum. It has been found in approximately one per 500 surgical procedures involving the upper GI tract. It can also occur in the gallbladder, biliary tract, spleen, liver, omentum, mesentery, lung and pelvis. Likewise, heterotopic gastric mucosa can occur anywhere along the GI tract yet its most common locations are different from those of heterotopic pancreatic tissue. In this paper we present heterotopy characteristics in particular locations. Gastric or pancreatic heterotopy, although rare, should be taken into consideration in differential diagnosis of unexplainable abdominal pain, bleeding from the GI tract or weight loss. Once heterotopy has been detected, appropriate treatment can be implemented which will reduce the risk of complications.

Angiogenesis-related biomarkers in patients with alcoholic liver disease: their association with liver disease complications and outcome.

Angiogenesis is believed to be implicated in the pathogenesis of alcoholic liver disease (ALD). We aimed to explore the usefulness and accuracy of plasma angiogenic biomarkers for noninvasive evaluation of the severity of liver failure and ALD outcome. One hundred and forty-seven patients with ALD were prospectively enrolled and assessed based on their (1) gender, (2) age, (3) severity of liver dysfunction according to the Child-Turcotte-Pugh and MELD scores, and (4) the presence of ALD complications. Plasma levels of vascular endothelial growth factor (VEGF-A) and angiopoietins 1 and 2 (Ang1 and Ang2) were investigated using ELISAs. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Significantly higher concentrations of Ang2 and VEGF-A in ALD patients as compared to controls were found. There was no difference in Ang1 levels in both groups. A positive correlation of Ang2 levels with INR (Rho 0.66; P < 0.0001) and its inverse correlation with plasma albumin levels (Rho -0.62; P < 0.0001) were found. High Ang2 concentrations turned out to be an independent predictor of severe liver dysfunction, as well as hepatic encephalopathy and renal impairment. Ang2 possessed the highest diagnostic and prognostic potential among three studied angiogenesis-related molecules.

The effects of the adenosine A3 receptor agonist IB-MECA on sodium taurocholate-induced experimental acute pancreatitis.

The role of adenosine A3 receptors and their distribution in the gastrointestinal tract have been widely investigated. Most of the reports discuss their role in intestinal inflammations. However, the role of adenosine A3 receptor agonist in pancreatitis has not been well established. The aim of this study is [corrected] to evaluate the effects of the adenosine A3 receptor agonist on the course of sodium taurocholate-induced experimental acute pancreatitis (EAP). The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C--control rats, I--EAP group, and II--EAP group treated with the adenosine A3 receptor agonist IB-MECA (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w. i.p. at 48, 24, 12 and 1 h before and 1 h after the injection of 5% sodium taurocholate solution into the biliary-pancreatic duct. Serum for α-amylase and lipase determinations and tissue samples for morphological examinations were collected at 2, 6, and 24 h of the experiment. In the IB-MECA group, α-amylase activity was decreased with statistically high significance compared to group I. The activity of lipase was not significantly different among the experimental groups but higher than in the control group. The administration of IB-MECA attenuated the histological parameters of inflammation as compared to untreated animals. The use of A3 receptor agonist IB-MECA attenuates EAP. Our findings suggest that stimulation of adenosine A3 receptors plays a positive role in the sodium taurocholate-induced EAP in rats.

The decrease of serum MMP-2 activity corresponds to alcoholic cirrhosis stage.

Because of numerous limitations for liver biopsy, a noninvasive marker of liver cirrhosis is sought. Promising indicators seem to be matrix metalloproteinases (MMPs) that are responsible for degradation of extracellular matrix. The aim of the study was to evaluate the gelatinase activities (MMP-2 and MMP-9) in patients with different stages of alcoholic cirrhosis. Sixty-seven outpatients who presented various stages of alcoholic cirrhosis according to Child-Turcotte-Pugh criteria and 26 healthy control subjects were enrolled. Blood samples were collected for MMP-2 and MMP-9 activities. A significant decrease of serum MMP-2 activity was noted in stages B and C of cirrhosis in comparison with control. Serum MMP-9 activity did not depend on the stage of cirrhosis. The MMP-2 levels, but not those of MMP-9, may be of value in understanding the pathogenesis and progression of alcoholic cirrhosis.

Activated and inactivated PPARs-γ modulate experimentally induced colitis in rats.

BACKGROUND: This study sought to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats. MATERIAL/METHODS: Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), was administrated intraperitoneally 120 mg/kg 4 times every other day. Rosiglitazone 8 mg/kg was administrated by gastric tube 4 times. Body weight was measured daily. After killing, the large intestinal tissue was weighed and collected for histopathologic and immunoenzymatic tests. Levels of IL-6, IL-10, and myeloperoxidase (MPO) were determined in serum and in intestinal homogenates. RESULTS: Rats receiving rosiglitazone had higher body weight, whereas large intestine weight/length ratio was lower; histology showed fewer inflammatory markers. Rats receiving TNBS and TNBS along with BADGE had more intensive inflammatory changes. Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10. Decreased levels of MPO indicate reduced neutrophil-dependent immune response. The antagonist of PPAR-γ increased IL-6 in serum and decreased IL-10 in intestinal homogenates. Bisphenol A diglycidyl ether administrated to healthy animals increases serum IL-6 levels. CONCLUSIONS: Rosiglitazone inhibits experimental inflammation; administration of its selective antagonist abolishes this protective influence. Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10. Agonists of PPARs-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.

Erythropoietin inhibits liver gelatinases during galactosamine-induced hepatic damage in rats.

Matrix metalloproteinase (MMP)-2 and -9 (gelatinases) participate in extracellular protein remodeling. Moreover, they are involved in the development of hepatic fibrosis. The goal of this study was to evaluate liver gelatinase activities after erythropoietin (Epo) treatment (1U/dose, sc) in experimentally damaged livers of rats treated with D-galactosamine (Gal, 800 mg/kg/dose, ip). Sixty rats were divided into six equal groups: I - received 5 doses of Epo and a single dose of Gal [the experiment duration (ED): 10 days]; II - received 5 doses of Epo and 3 doses of Gal (ED: 14 days); III - received only 5 doses of Epo (ED: 9 days); IV - received 3 doses of Gal (ED: 5 days);V - received a single dose of Gal (ED: 1 day); VI - control group (ED: 9 days). The animals were sacrificed and the livers were collected 48 h after the last drug administration. The activity of gelatinases was measured using gelatin zymography. No fluctuations in gelatinase activities were observed after the administration of a single dose of Gal in comparison to the control group. However, a significant increase in gelatinase activities was observed after treatment with three doses of Gal. Five doses of Epo administrated before Gal treatment prevented elevated gelatinase activities: MMP-9 activity was comparable to control, and MMP-2 activity was decreased (group II). The gelatinase activities was lower in group I and II in comparison to the control group. These results revealed that Epo decreases MMP-2 and MMP-9 activity, suggesting that it is a hepatoprotective agent against hepatic damage induced by galactosamine injection.

Rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma)-specific agonist, as a modulator in experimental acute pancreatitis.

BACKGROUND: The purpose of this experiment was to investigate the role of PPAR ligands in the course of inflammation and of rosiglitazone, a PPAR-gamma-specific agonist, on the course of experimental acute pancreatitis (EAP). MATERIAL/METHODS: EAP was induced by administration of 5% sodium taurocholate injected into the pancreatic duct. The inflammatory activity was evaluated by biochemical scores (alpha-amylase, lipase, aminotransferases, and bilirubin), morphological changes (determined by light microscopy, H+E stained), and immunohistochemical reactions (ICAM, nitrotyrosine). RESULTS: Rosilgitazone administered in the course of EAP at a dose 50 mg/kg p.o. decreased the intensity of morphological changes (edema, inflammatory infiltrates, necrosis, and erythrocyte extravasations). In the rosiglitazone-treated animals all the biochemical parameters of EAP were statistically significantly decreased. Immunohistochemical reactions against ICAM-1 and nitrotyrosine showed that rosiglitazone decreased the intensity of inflammatory reactions in the groups of treated animals. CONCLUSIONS: PPAR-gamma agonists modulate the course of the inflammatory reaction. The administration of rosiglitazone decreased the intensity of the inflammatory process in the course of sodium taurocholate-induced EAP.

The effects of environmental factors on the prevalence of Helicobacter pylori infection in inhabitants of Lublin Province.

The aim of the study was to analyse the prevalence of H. pylori infection in adult inhabitants of Lublin Province. The effects of living conditions and lifestyle on the infection frequency were evaluated. The study included 585 adults randomly chosen for the epidemiological analysis of H. pylori infection in the Lublin region within the project commissioned by the Ministry of Health (PCZ 08-09) and State Committee for Scientific Research (C007/P05/2000). The study was based on a personal questionnaire and determinations of anti/Hp antibodies in IgG class using the ELISA method. High titres of anti/Hp antibodies (> 24 IU/ml) were demonstrated in 78.5 % of the subjects. In Lublin Province the infected individuals constitute 72 % of inhabitants, in the big towns--74 % and in small towns--95 %. According to the place of birth: among those born in the country 87 % are infected, compared to 78.4 % in the small towns and 64 % in the big towns, respectively. Positive test results were observed in 79 % of farmers, 78 % of manual workers and 75 % of mental workers. The percentage of the affected neglecting basic hygienic rules exceeded 90 %. With increased frequency of hygienic measures the number of the H. pylori infected individuals decreased to 65 %. The prevalence of H. pylori infection among the inhabitants of the Lublin region is lower than that found in town inhabitants. Lublin Province shows the lowest level of H. pylori infection in Poland. The H. pylori infection is strongly affected by the lack of basic rules of personal hygiene and improper diet.

The role of pancreatic stellate cells and cytokines in the development of chronic pancreatitis.

Chronic pancreatitis is a disease whose pathomechanism has not yet been fully explained. Some progress has been made in recent years, however, mainly due to the identification and description of pancreatic stellate cells (PSCs). In 1998 Bachem observed that the vitamin A-storing cells present in the pancreas, when subjected to activation, transformed into myofibroblasts capable of producing collagens I and II and fibronectin, which contributes to fibrosis in chronic pancreatitis. The development of chronic pancreatitis also seems likely to be affected by the cytokines, among other things, as a result of repeated PSC activation. The current literature provides more and more data suggesting that cytokines play an important role in the regulation of inflammation and fibrosis in CP. A major role in the pathogenesis of chronic pancreatitis is attributed to interleukin 1, 6, 10, tumour necrosis factor a (TNF-a) and transforming growth factor b1 (TGF-b1). All these factors have pro- and anti-inflammatory effects, and act simultaneously. Their effects on PSCs can be synergistic, antagonistic or complementary. Further comprehensive studies are needed to determine precisely the role of the individual cytokines and PSCs, as well as their relationships. However, the present state of our knowledge suggests that repeated episodes of AP and thus exposure to increased cytokine secretion may contribute to persistent chronic activation of PSCs, resulting in pancreatic fibrosis and chronic pancreatitis.

Helicobacter pylori infection and the risk of adenocarcinoma of the esophagus.

In the recent years, the prevalence of adenocarcinomas of the esophagus has substantially increased. At present its prevalence in the USA is comparable to that of squamous carcinoma (5/100,000 a year). In 80-90% of cases esophageal adenocarcinoma is located in 1/3 of the lower esophagus and is mainly derived from Barrett's esophagus (BE). The role of Helicobacter pylori (Hp) infection in the pathogenesis of gastritis and gastric ulcer disease has been well known and documented. However, its role in the pathogenesis of esophageal reflux disease, its complications, particularly regarding the risk of Barrett's esophagus and adenocarcinoma is still being studied. The relation between Hp infection and BE has been discussed for many years. The importance of the problem is warranted by the wide prevalence of both Hp infection and reflux disease in the population. The above mentioned findings confirm the protective effects of Hp infection in BE. Despite numerous studies some doubts concerning the relations between Hp infection and BE are still to be explained.