Klotho protein as a mediator of antioxidant defense in young people with gastroesophageal reflux disease and autoimmune thyroiditis

Aim: to establish the content and role of Klotho protein in the pathogenesis of gastroesophageal reflux disease, which occurs against the background of autoimmune inflammation in young people. Materials and methods. Three groups of patients were involved in the study: with the gastroesophageal reflux disease (GERD ) and autoimmune thyroiditis (AIT ) (120 persons), isolated GERD (45) and AIT (42) aged 18 to 25 years, of the same sex and duration of the disease. The content of Klotho protein was determined in the serum by ELISA, Elabscience reagents (ELISA, USA). Results. Significant increase in Klotho protein was detected in patients with GERD and especially in its combination with AIT relative to the control. Content of Klotho protein did not correlate with the morphological form of the disease and its duration. In patients with isolated AIT , Klotho protein level did not have a significant difference with control group. Conclusion. The GERD and its combination with AIT in young people are accompanied by an increase in Klotho protein content, as a result of the presence of an active inflammatory process in the esophagus mucosa and its stimulating effect on antioxidant defense processes.

News of European Pancreatology (based on the materials of the 52nd meeting of the European Pancreatic Club)

The 52nd meeting of the European Pancreatic Club was organized and conducted online in Paris on July 2–3, 2020. It is the first time the Congress took place online, with about a thousand of pancreatologists having participated in it. The high scientific, organizational and technical level of the congress should be noted. This review presents the most interesting research results in the following sections: anatomy of the pancreas, acute early chronic, autoimmune pancreatitis, cancer and other malignant pancreatic diseases, functional pancreatic insufficiency, enzyme replacement therapy, pancreatic steatosis, microbiota in pancreatic pathology. Dugic et al. (Sweden) conducted a systematic review “The effect of anatomical variants of the Wirsung’s duct on exocrine function and risk of pancreatic pathology”. Studies of the MEDLINE database from 1960 to 2019 were analyzed; data of 3234 patients were included. A classification of anatomical variants of the pancreatic duct system was compiled. A lecture by T. B. Gardner (Great Britain) on pancreatic steatosis drew great attention. The problem of pancreatic steatosis is surrounded by a number of unresolved issues; the terminology of pancreatic steatosis itself is unclear. Under conditions of oxidative stress, cytokines released from adipocytes trigger the local inflammation and dysfunction of the affected pancreatic cells. The pathogenesis of pancreatic steatosis requires further studies. The symposium on exocrine pancreatic insufficiency in pancreatic cancer played the central role in the congress. Professor E. Dominguez-Munoz (Spain) gave a lecture within the framework of the symposium. 80% of patients with pancreatic cancer have sarcopenia and/or cachexia. Sarcopenia and cachexia in pancreatic adenocarcinoma are the most obviousamong all tumor localizations. The pathogenesis of cachexia and sarcopenia in pancreatic cancer was analyzed in detail; the necessity of enzyme replacement therapy with Creon was substantiated. Particular attention was paid to the pathogenesis of pancreatic insufficiency after surgical treatment (pancreatic resections, pancreatectomy); the features of replacement therapy were highlighted. The meeting of the European Pancreatic Club, as usual, was informative and interesting

Chronic pancreatitis: what should be considered in diagnosis, treatment, and prognosis

The aim of the literature review is to draw attention of doctors to the need of considering not only well-known etiological factors, but also pathogenetic ones that have an impact on the progression, chronicity of the process, treatment, prevention, and prognosis. The role of alcohol, mechanism of obstruction of the pancreatic ducts in the occurrence of abdominal pain in chronic pancreatitis, and the development and progression of exocrine pancreatic insufficiency are discussed in detail.The issues of the onset of chronic pancreatitis in elder age, comorbidity with other diseases of the internal organs, with a lack of certain vitamins are considered. It is necessary to remember that exocrine insufficiency can be associated with the progression of glandular fibrosis, metabolic disorders, food intolerance, allergic syndrome, which provoke acute attacks.The author draws attention to the fact that the syndrome of inflammatory, enzymatic intoxication and the syndrome of disseminated intravascular coagulation should not be missed out in the acute nature of the process. Above-listed recommendations will help to correctly evaluate the clinical picture and prescribe the proper treatment, as well as to prevent the development of complicationsin time.

Bile acids, non-alcoholic fatty liver and pancreatic disease: chained by ursodeoxycholic acid?

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreatic disease (NAFPD) develop against the background of metabolic syndrome, systemic insulin resistance, oxidative stress, changes in lipid and carbohydrate metabolism. There are a number of similarities between NAFLD and NAFPD: the natural course of diseases proceeds from steatosis through inflammation to fibrosis and cancer, one of the etiopathogenetic factors is the disbalance of bile acids synthesis and low expression of farnesoid receptor X (FXR). One of the possible methods of treatment NAFLD and NAFPD is a correction of the biosynthesis of bile acids and increase FXR expression with FXR agonists. Ursodeoxycholic acid (UDCA) is a selective FXR agonist. It has a multipled spectrum of actions: anticholestatic, anti-apoptic, antioxidant, cytoprotective, antifibrotic, hypocholesterolemic, immunomodulatory, hepatoprotective. The ability of UDCA correct lipid and carbohydrate metabolism in combination with anti-inflammatory and antiapoptic effects may be of great importance for the treatment of NAFLD and NAFPD. The article reviews the results of clinical and experimental studies describing the efficacy of UDCA in NAFLD and some pancreatic diseases. It has been suggested that the therapy of UDCA can reduce the severity of NAFLD and NAFPDand improve the functional activity of hepatocytes and β cells. The need for randomized clinical trials was emphasized in order to make an informed decision on the expediency of including UDCA in the treatment of NAFLD and NAFPD.

Duodenum-preserving pancreatic head resections for surgical treatment of paraduodenal pancreatitis

Introduction. Up to date, no consensus exists on the surgical treatment of paraduodenal pancreatitis (PDP). Most authors prefer to perform pancreaticoduodenectomy when surgical treatment is indicated. However, such an aggressive approach may not always be justified for the treatment of benign disease. The aim of our study was to investigate the results of duodenum-preserving pancreatic head resections (DPPHR) for the treatment of PDP. Materials and methods. We performed a retrospective analysis of a database consisting of 112 patients with PDP treated in Shalimov National Institute of Surgery and Transplantology from 2014 to 2019. A total of 45 patients after DPPHR were included to the study. Such modifications of DPPHR as Frey’s, Beger’s and Berne’s procedures were used. The primary study endpoint was pain control assessed according to the Izbicki pain score before surgery and at follow-up visits. Secondary endpoints were defined as complication rate (Clavien — Dindo >2), hospital length of stay and 90-day mortality. All patients were followed-up for the assessment of pain cessation with a median of 33 months (range 8–54 months). Results. There were 42 males (93.3%) and 3 females (6.7%) in the study group. Preoperative Izbicki pain score result was 52.6 points. Follow-up pain score results were significantly lower at 11.7 points. Postoperative complication rate (Clavien — Dindo >2) was measured at 8.9%. Median hospital length of stay was 17.4 days. No mortality was recorded in the study group. All results were statistically significant (p<0.05). Conclusion. Application of DPPHR for the surgical treatment of PDP allows to achieve excellent results in terms of pain control (52.6 and 11.7 points on the Izbicki pain score before surgical intervention and at follow-up), while maintaining low complication (8.9%) and mortality (0%) rates.

Pancreatic steatosis: a giant step forward or recognition of ignorance

This review analyzes the terminology of pancreatic steatosis, the data about the prevalence of non-alcoholic fatty pancreas disease (NAFPD) were given. The etiological factors of NAFPD are usually subdivided into hereditary, metabolic, and toxic ones. The main etiopathogenetic factor of pancreatic fatty infiltration is obesity: it causes pancreatic infiltration by adipocytes, leading to the development of NAFPD. The pathogenesis of the disease is associated with adipocytic tissue dysfunction, which induces local and systemic inflammatory response with corresponding clinical consequences. Insulin resistance and oxidative stress play major role in the pathogenesis of NAFPD. From a histological point of view, NAFPD is a heterogeneous process, characterized by excessive intracellular accumulation of lipids and fatty infiltration followed by fatty replacement of the pancreas. NAFPD clinical picture is asymptomatic and nonspecific. Diagnosis of NAFPD is based primarily on the results of imaging methods (ultrasound, CT, MRI). A consequence of NAFPD is exocrine pancreatic insufficiency requiring enzyme replacement therapy. One of the NAFPD complications is the development of pancreatic adenocarcinoma. Currently, standards for the diagnosis, treatment and management of patients with NAFPD have not been developed yet, but on used the guidelines for the treatment of non-alcoholic fatty liver disease (rational diet, exercises, weight loss). The “gold standard” of enzyme replacement therapy, such as Creon®, is used for correction of exocrine pancreatic insufficiency. The detailed analysis of the clinical case of total pancreatic steatosis with severe exocrine pancreatic insufficiency was done in this article.

Bacterial overgrowth syndrome of upper parts of gastrointestinal tract in acute necrotizing pancreatitis

Aim: to study the changes in the microflora of the upper part of digestive tract during acute necrotizing pancreatitis. Material and methods. Acute necrotizing pancreatitis was induced in 42 white rats; changes in the mucous microflora of the upper part of digestive tract were studied. Bacteriological examination of the contents of the proximal small intestine was performed in 42 patients with acute necrotic pancreatitis during gastrofibroscopy. Results and discussion. Induction of acute necrotic pancreatitis was accompanied by impaired colonization resistance of the intestinal mucosa due to the elimination of bifidobacteria and lactobacilli: the frequency of their growth from the mucosa decreased threefold (p<0.01), and the population level, respectively, by 25% (p<0.05) and by 36% (p<0.02). The mucosa was actively colonized by gram-negative pathogenic and conditionally pathogenic enterobacteria at high population level (3.07‒5.39 lg CFU/g), which allowed this microflora to overcome the damaged intestinal barrier and translocate. Pathogenic Escherichia spp. and Proteus spp. were cultivated from the mesenteric lymph nodes in 24 hours; Enterobacteria spp. and Staphylococci spp. were isolated from portal blood, pancreatic tissue, and peritoneal cavity 48 hours after induction of acute pancreatitis. Eight strains of gram-negative microorganisms were identified in small intestine in 69% of patients before surgery. Similar microflora was cultivated from pathological foci in 57.4% of patients after surgery. Conclusion. Severe deficiency of autochthonous anaerobic microflora occurred in the upper parts of the digestive tract in acute necrotizing pancreatitis, causing excessive colonization by pathogenic and conditionally pathogenic microorganisms and promoting bacterial translocation.

Efficacy of antiinflammatory and metabolic bioregulation in complex therapy of chronic pancreatitis with the inflammatory changes of gastroduodenal zone organs

Background. The clinical course of chronic pancreatitis (CP) is characterized by symptomatic polymorphism, which is often associated with comorbidity of CP with other lesions of the gastrointestinal tract. Destructive-inflammatory processes of the upper gastrointestinal tract are very common. Such comorbidity is especially typical for young patients with CP (up to 45 years). The aim is to study the effectiveness of bioregulatory anti-inflammatory and metabolic therapy based on the dynamics of clinical indices and parameters of exocrine pancreatic function and the condition of the mucous membrane of the gastroduodenal zone of patients with CP. Materials and methods. We examined 50 patients with CP with exocrine insufficiency in the phase of unstable remission in combination with inflammatory diseases of the mucous membranes of the gastroduodenal zone. Group 1 (28 patients, age 40.25±1.34 years) received conventional treatment (CT) — pure pancreatin enzymes, proton pump inhibitors, antispasmodics or prokinetics (if necessary), enhanced by a step-by-step course of bioregulatory therapy, including parenteral course of anti-inflammatory drug Traumel C 2.2 ml intramuscularly twice a week (e.g., Monday and Thursday) and metabolic Ubiquinone Compositum 2.2 ml intramuscularly twice a week (e.g., Tuesday and Friday) № 5 each drug with the transition for oral administration of Traumel C per 1 tablet 1 hour after meals three times a day for 30 days. 22 patients with CP and concomitant exacerbation in gastroduodenal zone group 2 (age 41.34±1.21 years) received only complex CT. Results and discussion. A comparative analysis of the dynamics of treatment outcomes in the two study groups showed that almost all clinical signs of the disease, endoscopy and exocrine pancreatic function after treatment in the group using anti-inflammatory and metabolic bioregulatory therapy results were significantly better than in CT group. The mean time to normalization of mucous membranes of gastroduodenal zone in the group with an additional course of bioregulation was 14.4±0.86 days, while in the group of CT — 18.1±0.46 days. Conclusion. It was proved that the additional inclusion of step-by-step bioregulatory antiinflammatory (Traumel C) and metabolic (Ubiquinone Compositum) therapy according to the proposed scheme to the CT significantly more effectively (p˂0.05–0.001) improved the clinical course of the disease, contributed to the normalization of exocrine pancreatic function, as well as more quickly normalized the condition of the mucous membrane of the gastroduodenal zone — during 14.4±0.86 days, while in the group of CT — during 18.1±0.46 days.

Increased awareness enhances physician recognition of the role of smoking in chronic pancreatitis

Background: We have previously reported that physicians under-recognize smoking as a chronic pancreatitis (CP) risk factor. We hypothesized that availability of empiric data will influence physician recognition of this relationship. Methods: We analyzed data from 508 CP patients prospectively enrolled in the North American Pancreatitis Study-2 Continuation and Validation (NAPS2-CV) or NAPS2-Ancillary (AS) studies (2008–2014) from 26 US centers who self-reported ever-smoking. Information on smoking status, physician-defined etiology and identification of smoking as a CP risk factor was obtained from structured patient and physician questionnaires. We compared how often physician identified smoking as a CP risk factor in NAPS2-CV/NAPS2-AS studies with NAPS2-original study (2000–2006). Results: Enrolling physician identified smoking as a risk factor in significantly (all p< 0.001) greater proportion of patients in NAPS2-CV/AS studies when compared with NAPS2-original study among ever (80.7 vs. 45.3%), current (91.3 vs. 53%), past (60.3 vs. 30.2%) smokers, in those who smoked ≤1 pack/day (79.3 vs. 39.5%) or ≥1 packs/day (83 vs. 49.8%). In multivariable analyses, the enrolling physician was 3.32–8.49 times more likely to cite smoking as a CP risk factor in the NAPS2-CV/NAPS2-AS studies based on smoking status and amount after controlling for age, sex, race and alcohol etiology. The effect was independent of enrolling site in a sub-analysis limited to sites participating in both phases of enrollment. Conclusions: Availability of empiric data likely enhanced physician recognition of the association between smoking and CP. Wide-spread dissemination of this information could potentially curtail smoking rates in subjects with and those at risk of CP.

Gallbladder polyps: the more cases we observe, the more questions we ask

Background. Gallbladder polyps have recently become more common in practice of general practitioners and gastroenterologists due to the improvement of instrumental imaging of the abdominal cavity. Aim of study: to analyze the dynamics of development of gallbladder polyps at an outpatient appointment of a general practitioner (gastroenterologist). Materials and methods. A prospective clinical five-year study of patients with gallbladder polyps was conducted. All patients underwent ultrasound examination of the abdominal organs (Voluson E10) once every six months during five years. Number and nature of the growth of polyps, size of the gallbladder, presence/absence of complaints, and burdened history of neoplastic diseases were evaluated in the dynamics of observation. Data obtained were subjected to standard statistical processing. Results. The study included 33 patients (14 men, 19 women aged 24–65 years, average age 45.19±1.73 yrs). In the initial ultrasound study, the number of visualized polyps varied from 1 to 5 (on average, 2.09±0.95), the size of the neoplasms ranged from 2 mm to 10 mm (on average, 5.75±1.10 mm). Burdened heredity in oncopathology was noted in 42.86% of men and 31.58% of women. Legless polyps were more often diagnosed in men (14.29%), while in women, polyps increased in size in the dynamics of observation >10 mm and a higher frequency of surgical interventions (cholecystectomy) were more often recorded. Conclusion. Gallbladder polyps tend to grow slowly. We outlined the questions facing the clinician in the management of patients with gallbladder polyps in terms of choosing the optimal tactic and surgical treatment due to the possible malignancy of these formations.