Up-To-Date View on the Clinical Manifestations and Complications of Chronic Pancreatitis

Chronic pancreatitis is an inflammatory disease that causes irreversible anatomical changes including infiltration of inflammatory cells, fibrosis and pancreatic calcification with destruction of the structure of the gland, leading to abdominal pain, endocrine and exocrine dysfunction. Pancreatic exocrine insufficiency (PEI) prevalence in chronic pancreatitis varies between 40 and 94%. PEI is diagnosed by direct and indirect tests. Nutritional status is assessed by anthropometric indicators; laboratory tests—hemoglobin, plasma proteins (albumin, prealbumin, retinol-binding protein, transferrin), fat-soluble vitamins A, D, E, K; micronutrients. Pancreatic enzyme replacement therapy (PERT) is a fundamental part of PEI treatment. An optimal PERT could prevent serious PEI complications such as metabolic bone disease, adverse cardiovascular events, cachexia, poor quality of life and mortality. A periodic screening for PEI complications with a respect to their primary and secondary prophylaxis is mandatory. Diabetes mellitus secondary to pancreatic disease is defined as pancreatogenic diabetes or type 3c diabetes mellitus. Patients with chronic pancreatitis are at increased risk for pancreatic cancer influenced by smoking, alcohol abuse, chronic inflammation and pancreatic stellate cells over-proliferation. However, chronic pancreatitis could be further complicated with splenic vein thrombosis, pseudocysts, duodenal or biliary obstruction, pseudoaneurysm and pancreatic duct stones which might require endoscopic or surgical treatment

<em>Helicobacter pylori</em> Infection

Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium commonly found in the stomach. Major part of the world’s population is infected with H. pylori and is at increased risk of severe gastritis, peptic ulcer disease, and gastric cancer. Most studied virulence factors of the bacterium are the cytotoxin-associated gene (CagA) and the vacuolating cytotoxin A (VacA). The H. pylori infection is diagnosed by invasive (histological examination, culture, and rapid urease test, which require endoscopy and biopsy) and noninvasive methods (serology, urea breath test, and stool antigen test). H. pylori eradication is preferred for a long-term prevention of complications. Current treatments consist of antibiotics and adequate PPI dose and can be divided into two strands—with or without bismuth. Achieving an eradication rate of >90% is an indicator for effective treatment. Due to the increasing levels of antibiotic resistance, the standard triple therapy is largely replaced with a quadruple therapy, especially in countries with high resistance rates. Antimicrobial susceptibility testing should be performed after the second-line treatment failure, leading to an individualized patient treatment. Clear explanations and patients’ compliance are of great importance for a better outcome

Current View on Autoimmune Gastritis

Autoimmune gastritis (AIG) is a chronic inflammatory disease of the gastric corpus and fundus. Although still unclear, genetic and environmental factors, antigenic mimicry or cross-reactivity are proposed pathogenic mechanisms. Parietal cells destruction results in loss of intrinsic factor and increased gastric pH due to hypochlorhydria and G-cell proliferation. Furthermore, atrophy, intestinal, pancreatic and spasmolytic polypeptide-expressing metaplasia are observed. AIG is underdiagnosed, however, proper diagnostic approach, including endoscopic, serological and histopathological assessment, is required. Gastroscopy with corpus and fundus biopsies is a gold standard. A serological combination of anti-parietal cell antibodies, intrinsic factor antibody, anti-Helicobacter pylori IgG, gastrin, pepsinogen I and pepsinogen I/II ratio improves the diagnostic sensitivity and specificity and allows atrophy level prediction. AIG might manifest with multifactorial iron deficiency anemia, vitamin B12 deficiency (pernicious anemia), neurological and neuropsychiatric conditions, small intestinal bacterial overgrowth and gastrointestinal infections. AIG association with other autoimmune diseases is well-established. Gastric cancer and gastric carcinoid are neoplastic transformations of a continuous chronic inflammation. Patients with AIG should be carefully monitored as no specific AIG therapy is available and disease complication could be fatal

Gastric Microbiota: Between Health and Disease

The etiologic link between H. pylori infection and gastric chronic inflammation and related complications has been well established, but pathogenic pathways are still widely discussed and not sufficiently clear. The introduction of culture-independent molecular techniques has allowed better understanding of the gastric microbiota and has revealed that, when present, H. pylori represents the main colonizer but is part of a far more complex and dynamic microbiota than previously thought. This conceptual shift has made way for new pathogenic theories, focused on the interrelations between H. pylori and other gastric microbiota. Main factors that affect the gastric microbiota are gastric acidity, inflammation, and environmental factors, such as diet and drugs. Previous studies have made progress in explaining the complex interactions between gastric microorganisms in healthy individuals and their role in the development of related gastroduodenal (peptic ulcers and gastric cancer (GC)) and extraintestinal diseases, but more scientific proof is needed. This review presents current knowledge on gastric microbiota and its role in health and in the development of gastroduodenal diseases

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study

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

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations

Background & objectives: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis. Methods Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals. Results The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31–82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy. Conclusions The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care