[Pancreatic cancer risk: alcoholic and non-alcoholic beverages].

This article provides an overview of the metaanalyzes (PubMed, 19952019) of alcohol and non-alcoholic (coffee, tea, dairy products) beverage consumption in relation to risk of pancreatic cancer PC (PubMed, 19952019). Increased the PC risk was associated with high alcohol intake. The increased risk for heavy drinking did not explained by residual confounding by history of pancreatitis or tobacco smoking or diabetes. Light-moderate alcohol intake may reduced the PC risk, probably due to the fasting insulin levels decrement, which leads to the diminished the РС risk. The association between alcohol and the PC was stronger in men than in women. Some metaanalyzes demonstrated that a small amount of coffee may reduce PC risk, and a large amount to increase PC risk. Another meta-analyzes have not confirmed any association between the PC risk and coffee or tea consumption. One meta-analysis revealed a direct association of the PC risk with the dairy products consumption, but most research showed no such connection. Nutrition is considered to be associated with the PC risk, but the degree of risk due to structure of beverages consumption (dose, duration, alcohol, coffee, tea, dairy products pattern) is still not clear.

[Risk factors for pancreatitis and pancreatic cancer].

AIM: To identify and compare the frequency of alcohol consumption, tobacco smoking, levels of main macronutrients, vitamins and mineral elements consumption in patients with acute (AP) and chronic pancreatitis (CP) and pancreatic cancer (PC). MATERIALS AND METHODS: At the observational clinical cross-sectional uncontrolled case-study 65 patients with AP or CP (group 1) and 45 patients with PC (group 2) were examined. A survey of patients was carried out: questionnaire on tobacco smoking, a frequency questionnaire on alcohol consumption, a questionnaire for assessing the frequency of food consumption. RESULTS: The frequency of smoking (33.8, 20.0%; p0.05), alcohol consumption 1 times/week during the last year (21.5, 15.6%; p0.05) did not differ significantly between the two groups. The highest consumption rates of total, vegetable, animal protein, total carbohydrates, refined sugar, animal fat, cholesterol, MUFA, dietary fiber, vitamins (-carotene, vitamin B1, B2, C, PP), mineral elements (iron, potassium, calcium, magnesium, sodium, phosphorus) and the daily energy content of the diet were determined in PC than in the AP and CP group. Among patients of group 1, deficient intake of fat-soluble vitamin A (93.3, 54.8%; p=0.009) and vitamin E (80.0, 48.4%; p=0.041) was more common in the subgroup of patients with excretory pancreatic insufficiency than without it, and the chance of having hypercholesterolemia was associated with a deficient intake of vitamin E [Ex(B)=3.3, 95% CI 1.59.3; p=0.027]. CONCLUSION: There were no differences in the frequency of smoking and alcohol consumption between patients with AP and CP and PC. The highest indices of the main macronutrients, daily energy content of the diet, micronutrients (except for vitamins A, E) were found in PC than in the group of patients with AP and CP. Among patients with AP and CP with excretory pancreatic insufficiency, a lower intake of fat-soluble vitamins was noted and associations of hypercholesterolemia with deficient intake of vitamin E were obtained.

[Genetic aspects of pancreatic cancer].

The purpose of the review--to analyze the basic data on modifiable and genetic risk factors of pancreatic cancer (PC). PC is the most fatal disease that kills about 95% of patients. Among the known risk factors for PC only for smoking, obesity, and family history a positive association with the PC risk in meta-analyzes confirmed. The PC etiology remains unclear, more than 90% of patients acquire it sporadically. Currently, the most significant genes for PC include KRAS2, p16/CDKN2, TP53, SMAD4/DPC4. Mutations in the KRAS noted in 90% of cases of pancreatic ducts adenocarcinoma. p16/CDKN2A mutation is accompanied by a 38-fold increased risk of PC compared with the general population. TP53 mutations are associated not only with carcinogenesis but also PC metastasis, as well as SMAD4/DPC4 mutations. Study of the role of genetic aspects in the PC development is necessary both to identify individuals with high PC risk, as well as for the development of gene-specific treatments, such as inhibitors of proteins, histone deacetylase, and histone acetyltransferase (vorinostat, belinostat, entinostat, panobinostat, curcumin) are in clinical trials.

[Pancreatitis, pancreatic cancer and obesity: hypothesis and facts].

THE PURPOSE OF THE REVIEW: Analyze the basic data on the role of obesity in the pathogenesis of pancreatic cancer (PC) and the modern mechanisms of this association. RECENT LITERATURE DATA: In the European Union and in Russia incidence of pancreatic diseases increases, such pancreatic cancer (PC) ranks 10th among cancer diseases. Obesity is a risk factor for not only of severe acute pancreatitis, but also PC at that independently of diabetes. In a meta-analysis the PC risk in obese increased by 47%, while the person with a central obesity have a higher PC risk compared to those with a peripheral type of obesity (odds ratio = 1,45, 95% CI: 1,02-2,07), but association between BMI and PC risk in this Japanese population may be different from that in Western populations, sometimes inversely. The link between obesity and PC is explained by insulin resistance and hyperinsulinemia: was proved a direct correlation between the level of circulating C-peptide and PC, low levels of serum adiponektin and leptin increase the PC risk. There are also genetic risk factors for PC: a statistically significant interaction between IVS1-27777C> and IVS1-23525A>T genotypes of the FTO gene with obesity and the PC risk: AA genotype in patients with BMI < 25 kg/m2 reduced PC risk by 22%-28% (p < 0,0001), and with BMI ≥ 25 kg/m2 was associated with 54%-60% increased PC risk (p < 0,0015). Lifestyle factors (smoking, consumption of saturated fats, etc.) increase the PC risk.

[The association of indicators of serum lipids and bile in individuals with the family history, burdened by a bile stone disease].

PURPOSE: To evaluate serum and bile lipids levels in persons with and without positive family history of gallstone disease (PFH GSD). MATERIALS AND METHODS: 165 people were surveyed: 71 people with PFH GSD and 94 persons without PFH GSD. was evaluated: in serum--total cholesterol--TCh, triglycerides--TG, HDL, in the gallbladder bile--cholesterol (BCh), total bile acids (TBA), TBA/BCh coefficient (TBC), sialic (SA) and cholic acid (CA). RESULTS: TCh (5.3 +/- 0.13 mmol/L), TG (2.1 +/- 0.13 mmol/L) blood serum levels and BCh (3.6 +/- 0.2 g/l) were higher in persons with PFH GSD than in those without PFH GSD (4.8 +/- 0.1; 1.2 +/- 0.09 and 2.8 +/- 0.2, respectively), and HDL (1.0 +/- 0.04 mmol/L) and TBC levels (6.9 +/- 0.5 Units) in persons with PFH GSD were lower than in those without PFH GSD (1.5 +/- 0.03 and 9.3 +/- 0.8, respectively), p < 0.05 in all cases. TBA, SA and CA levels did not differ between two groups. CONCLUSION: PFH GSD was associated with blood serum lipid profile (total cholesterol, triglycerides, HDL) and the composition of bile (bile cholesterol, TBA/BCh coefficient).

[Mutual influence of gastrointestinal pathology and hospital-acquired infection].

Review of the literature devoted to one of the most important problems of modern medicine--nosocomial infections (NI). In the article there are examined relevant, epidemiology, pathogenesis, and criteria for NO determining. Special attention is paid to the mutual influence of gastrointestinal tract pathology and nosocomial infections.

[The role of feeding behaviour hormones in the development of cholelithiasis].

THE PURPOSE. To analyze the possible association between gallstone disease (GSD), and some adipokine: leptin, adiponectin, ghrelin, resistin, kaheksin (TNFalpha), visfatin. RECENT EVIDENCE IN THE LITERATURE. The prevalence of GSD increases by a factor not so much with age (in women - 6.0%, 7.9%, 8.5% and 18.6%, respectively, four age decade from 25 to 64 years - according to the epidemiological study in the frame of the WHO "Monica" in Novosibirsk in 1994-1995 years), but with metabolic disorders: GSD diagnosed in 17.6% in diabetes mellitus, in obesity III-IV degree - up to 100%. Leptin regulates the expression of genes responsible for the pathogenesis of cholesterol GSD -cholecystokinin receptor gene A, acetylcholine receptor beta2, Ca-calmodulin-dependent protein kinase, mucin3, carboxylesterazy, HMG-CoA reductase. Was found negative correlation of GSD with adiponectin levels and positive - with visfatin levels. Elevated ghrelin levels performs protective role to GSD (OR = 0,27, p = 0,02). In the analysis of GSD-associated regions on chromosome 1 p, genes TNFR2 receptor and TNFRSF1B included in a number of positional candidate genes.

[Opisthorchiasis: tradition and innovation].

THE PURPOSE OF THE REVIEW: Present new data on the causative agent, pathogenesis, diagnosis and treatment of opisthorchiasis. RECENT LITERATURE DATA: When samples of parasites were genotyped by novel nuclear marker Pm-int9, it was shown various properties of Opisthorchis viverrini, O. felineus and C. sinensis. It has been proven the oxidant damage to DNA of biliary epithelium cells infected with opisthorchiasis, and overexpressed of cellular protooncogene c-Ski, as well as platelet-derived growth factor alpha (Pdgfa) gene, which in some cases leads to the development of cholangiocarcinoma. Describes the innovations in the diagnosis of opisthorchiasis: primers OP1 and OP2 are used to amplify the ITS2 region rDNK eggs and metacercariae of Opisthorchis in feces. Opisthorchiasis treatment remains traditional - praziquantel, at least - with albendazole. Treatment of opisthorchiasis patients with praziquantel was shown to reduce inflammation-mediated tissue damage and carcinogenesis.

[Basic risk factors and quality of a life at gallstone disease patients].

THE AIM: to investigate possible associations between quality of a life (QoL) and basic risk factors of the Gallstone disease--GSD--sex, age, adiposity, diabetes mellitus, an arterial hypertension. MATERIALS AND METHODS: QoL at 142 GSD patients by means of questionnaire MOS SF-36 and a specific questionnaire to GSD patients "Gallstone Impact Checklist" (GIC) has been estimated. RESULTS AND CONCLUSIONS: among GSD patients a male (on a pain scale of GIS), age (on scales PF, RP, RE of SF-36), obesity (on all scales of questionnaire GIC, except a dyspepsia scale, and on scale PF of SF-36) and a diabetes mellitus (on scales of emotions, a food and eating an overall account of GIC) associated with considerable decrease in the QoL indices, but the presence of arterial hypertension does not influence.

[Frequency combination of a gallstone disease and diabetes].

THE PURPOSE: Analyze national characteristics of prevalence and association between gallstone disease (GSD) and diabetes mellitus (DM), both in the world and in Western Siberia, and some possible mechanisms of this association. RECENT LITERATURE DATA: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of DM and GSD worldwide, many risk factors are common to these diseases (overweight, age, arterial hypertension, dyslipidemia, etc.). In some studies it was shown a higher prevalence of gallstones among patients with DM compared with persons without DM, in others - there were no association between GSD and DM. In epidemiological study in frame of the WHO "MONICA" in the unorganized population of Novosibirsk in Western Siberia (1994-1995 years) it was shown, that in the male population aged 35-54 years found no relationship between GSD and DM, in the female population aged 25-64 the prevalence of GSD was 10,5% and among women with DM the frequency of GSD showed 37.5% (univariate analysis: OR = 5.0 (CI 2.04-12.2, p = 0.001). The association between GSD and DM in women remained in multivariate logistic regression analysis, which includes age, BMI, arterial hypertension: OR = 3.9 (95% CI 1.47-10.5, p = 0.006). In the female population aged 25-64 years the prevalence of diabetes was 6.7%, among women with gallstone disease--20.0%, p < 0.05. Possible mechanisms for the relationship between GSD and DM--gallbladder hypomotility, decrease of cholecystokinin-A receptor (CCK-A) gene expression and decreased sensitivity to CCK, insulin resistance, decreased activity of PPAR-receptors (peroxisome proliferator-activated receptor) in patients with DM.

[UDCA in the treatment of nonalcoholic fatty liver disease].

As a signaling molecule with system endocrine function, UDCA improves insulin sensitivity by activating the nuclear farnezoid X-receptor; as a ligand for the TGR5/Gpbar-1 receptor, UDCA is able to stimulate the secretion of GLP-1. UDCA ameliorate of the anti-oxidative defenses in NAFLD, normalizes NAD+/NADH ratio, beta-oxidation. UDCA improves the liver biochemical and histological picture in NASH, also reduces hepatocytes apoptosis and restores adiponectin levels; in other studies, these data are not confirmed. In the experiment, UDCA prevents the development of steatosis in the liver. UDCA may increase efficiency in combination with statins, thiazolidinediones, vitamin E. Further controlled prospective trials are needed for research of the UDCA effect in NAFLD.

[UDCA in the treatment of nonalcoholic fatty liver disease].

As a signaling molecule with system endocrine function, UDCA improves insulin sensitivity by activating the nuclear farnezoid X-receptor; as a ligand for the TGR5/Gpbar-1 receptor, UDCA is able to stimulate the secretion of GLP-1. UDCA ameliorate of the anti-oxidative defenses in NAFLD, normalizes NAD+/NADH ratio, beta-oxidation. UDCA improves the liver biochemical and histological picture in NASH, also reduces hepatocytes apoptosis and restores adiponectin levels; in other studies, these data are not confirmed. In the experiment, UDCA prevents the development of steatosis in the liver. UDCA may increase efficiency in combination with statins, thiazolidinediones, vitamin E. Further controlled prospective trials are needed for research of the UDCA effect in NAFLD.

[Lipid peroxidation in patients with acute and chronic pancreatitis].

OBJECTIVE: To assess the initial levels of lipid peroxidation (LPO) products in LDL and to study changes in oxidative resistance (OR) of precipitated LDL in acute and chronic pancreatitis patients (OP and CP). METHODS: were examined 39 CP patients and 37 OP patients, and the control group - 7 persons without pancreatic diseases and diabetes mellitus (DM). All CP patients were examined in the acute stage, OP patients - in the first 5 days after admission to hospital. Determination of LPO products in LDL and OR of LDL to Cu2+ - induced oxidation were carried out its own method (Ragino, 1998). RESULTS: In CP patients the initial level of LPO products in LDL was higher (8.9 +/- 1.5 nmol MDA/mg LDL protein) than in those in control group (5.3 +/- 0.8) and in OP patients (5.0 +/- 0.5, p<0.05), and the OR of LDL is significantly lower than those in the control group. In AP and CP patients with permanent pain syndrome in the left hypochondrium initial level of LPO products in LDL is much higher (7.0 +/- 0.6, and 5.0 +/- 0.6, p = 0,016), and OR of LDL after 0, 5, 1 and 2 h incubation with Cu2+ (2 h: 31.7 +/- 1.8 and 23.2 +/- 1.9, p = 0.002) - much lower compared with AP and CP patients without pain. Only CP patients combined with DM type 2 were defined reducing the OR of LDL after 0.5, 1 and 2 h incubation with Cu2+. CONCLUSION: The activity of LPO in the blood and LDL were affected in AP and CP patients.

[Quality of life in chronic pancreatitis patients with metabolic syndrome (M-Annheim classification)].

Among 81 patients with chronic pancreatitis (CP) metabolic syndrome (MS) diagnosed in 51.8% of persons; the frequency of MS in possible, probable and definite forms of CP, and well as in various of index of CP severity (A, B, C, D) did not differ. Average of QOL in all the examined patients with CP, assessed by SF-36 questionnaire, were: the scale of FF--47.2 +/- 3.6; RF--8.3 +/- 3.3; BP--37.4 +/- 2.3; GH--33.7 +/- 2.1; V--46.5 +/- 1.7; SF--65.0 +/- 2.7; REF--10.0 +/- 3.7; MH--59.9 +/- 1.9. Mean QoL in CP patients, assessed by questionnaire GIQLI, were: on a scale of symptoms (C)--41.8 +/- 2.0; emotions (E)--8.3 +/- 0.6; physical functioning (PF) - 10.0 +/- 1.0; treatment (T)--3.8 +/- 0.1; social functioning (SF)--10.6 +/- 0.4; the total score (TS)--74.4 +/- 3.3. QoL in patients with biliary, alcoholic or idiopathic etiology of CP did not differ neither by SF-36, nor by GIQLI. In CP patients with MS QoL in the scales RFF, GH and REF by SF-36 questionnaire and in the scales of E, TS by questionnaire GIQLI were significantly better than in CP patients without MS.

[Role of hyperlipidemia in cholelithiasis].

THE PURPOSE OF THE REVIEW: Was analyzed basic data on the contribution of blood serum lipids in the development of gallstone disease (GSD) in the world as well as in northern Russia, as well as the association of cholelithiasis and coronary heart disease (CHD). RECENT LITERATURE DATA: Worldwide, there is suffer from cholelithiasis 10 to 15% of the population. In Russia, about 60% of adults have a lipid metabolism. According to some epidemiological and clinical studies, serum lipid profile did not differ in patients with and without gallstone disease, in others with cholelithiasis observed hyperlipidemia. In an epidemiological study in the unorganized population of Novosibirsk cholelithiasis occurs more frequently among men and women with lipid disorders. Indigenous peoples of the North Asian Russia this disease is less common than among the aliens, which was accompanied by a more moderate hyperlipidemia. There was a positive association between gallstone disease and coronary heart disease. Despite the fact that hypertriglyceridemia and hypo by a majority of authors are recognized risk factors for gallstone disease, a consensus on the contribution of blood serum lipids in the pathogenesis of gallstone no. Since gallstone mostly composed of cholesterol, probably need to examine the level of serum lipids in a moment of gallstones after this time can be obscured link hyperlipidemia and holelitgenesis.

[Genetic aspects of digestive diseases. Part 1].

The paper presents the data available in the literature on mutations in known genes in pancreatitis, such as cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI/SPINK1), cystic fibrosis (CFTR), and apolipoprotein E (APOE) genes, as well as the new candidate gene--chymotrypsinogen (CTRC). It also gives the results of the authors studies estimating the spread of the mutations in the PRSS1 (2.5%), PSTI/SPINK1 (3.3%), and CFTR (0.8%) genes, as well as APOE polymorphism in patients with pancreatitis. It is shown that the E4 allele of the APOE gene was more frequently identified in patients with acute pancreatitis than in those with chronic pancreatitis (0.143 +/- 0.05 and 0.026 +/- 0.02, respectively; p < 0.05). An overview is given of 7 major classes of candidate genes implicated in the pathogenesis of cholesterol cholelithiasis (CL): hepatic enzymes regulating blood lipid composition; receptors of lipoproteins, hepatic and intestinal membrane and intracellular transport proteins; factors regulating the transcription of lipids and bile salts, cholecystokinin and its receptors, and mucin. In the authors' epidemiological study, the spread of APOE alleles and genotypes did not differ in women with and without CL; low molecular-weight apolipoprotein(a) isoforms (B, S2) were significantly found in patients with CL than in those without CL; the spread of the CG genotype in the TRPM8 gene was significantly lower in women with cholesterol CL than that in the Novosibirsk population. These polymorphisms have been proved to be associated with bile cholesterol concentrations in women with cholesterol CL. The opposite effect of the APOE4 allele on gallbladder stone formation processes is demonstrated, by using the APOE polymorphism as an example, which shows it necessary to examine each specific population to elicit a possible association between the polymorphism of different genes and gastrointestinal tract diseases.

[Quality of life of patients with cholecystolithiasis in the remote period after cholecystectomy].

UNLABELLED: The aim of the study was to evaluate the quality of life in patients with gallstone disease (GSD) in the remote period after cholecystectomy for various forms of surgical intervention and the disease (latent or symptomatic). Also we compared them with the indicators of quality of life of patients with cholecystolithiasis. MATERIALS AND METHODS: In an open clinical study were surveyed 170 patients with gallstone disease, of which 60 people were operated for gallstone disease, 110 patients had cholecystolithiasis. At 1/3 of patients with gallstone disease was asymptomatic, in 2/3--with clinical manifestations. To assess the quality of life using were validated specific questionnaire for patients with gallstone disease--Gallstone Impact Checklist. RESULTS: Among all patients with cholelithiasis who underwent cholecystectomy that asked for gastroenterologists help patients the quality of life was significantly worse on the scale of power (26.0 +/- 2.8 points) and the joint account (89.0 +/- 9.6 points) than in patients with stones in the gallbladder (16.5 +/- 2.2 and 61.0 the mini-access (total score 83.6 +/- 13.7 points), did not differed from those after laparoscopic cholecystectomy (85.0 +/- 10.9 points, p > 0.05). For those patients with cholelithiasis in which the disease before surgery were no symptoms quality of life (general account) decreased more significantly (to 29.8%) compared to patients with cholelithiasis who have this disease before the operation proceeded with clinical manifestations (4.1%), when compared with the total score of all examined patients with CL. CONCLUSIONS: Quality of life in patients with gallstone disease in the postoperative period after cholecystectomy was significantly worse than the individual scales of the questionnaire GIC compared to patients with stones in the gallbladder, regardless of the type of operation (from the mini-access or laparoscopic). In this patient with a latent course of gallstone disease before the operation quality of life significantly worse on all scales than patients with clinical symptoms before surgery.

[Lithogenicity of bile and serum lipoproteins (A) in cholelitiasis in women].

Blood serum Lp (a) level's increasing accompanied significant rising of gallbladder bile lithogenicity in the women with gallstone disease (GSD) with verified cholesterol gallstones. Apolipoprotein (a) (Apo (a)) isoforms B, S1 (most atherogenic) frequency in the women with GSD was significantly higher, and isoforms Apo (a) 0, S4 - significantly lower than in the women in control group without GSD. Gallbladder bile was significantly more lithogenic in the women with GSD who had Apo (a) B and S1 isoforms than in women with GSD with isoforms Apo (a) 0 and S4.

[Lipoprotein(a)--a new independent cholelithiasis risk factor?].

AIM: To study the level of lipoprotein(a)--Lp(a) in the blood serum and incidence of isoforms of apolipoprotein(a)--apo(a) in males and females with cholelithiasis and free of it in population of Novosibirsk; to assess possible correlations between Lp(a) level in the blood, apo(a) isoforms and bile lithogenicity in females with cholesterol cholelithiasis. MATERIAL AND METHODS: Examination of the representative samples of 870 females aged 25-64 years and 405 males aged 35-54 years has detected cholelithiasis in 91 females and 19 males. RESULTS: Serum levels of Lp(a) are associated with cholelithiasis. Risk of the latter in males (Lp(a) > 28 mg/dl) and females (Lp(a) > 24 mg/dl) is estimated. It is confirmed that isoforms of apo(a) B, S1 and S2 in females and isoforms of apo(a) B, S2 in males with cholelithiasis occur much more frequently than in individuals free of cholelithiasis while isoform apo(a) S4 is rare. Females with cholesterol cholelithiasis have positive correlation between blood Lp(a) levels, the presence of isoforms apo(a) B, S1 and bile lithogenicity. CONCLUSION: Males and females with cholelithiasis have more frequent high concentrations of Lp(a) (> 30 mg.dl) while low levels (0-5 mg/dl) are rare. There is a correlation between blood levels of Lp(a), apo(a) isoforms, bile lithogenicity in females with cholesterol cholelithiasis.

[APOE gene polimorphism and lithogenicity of the bile in the women with cholelithiasis].

AIM: to study the frequency of alleles and genotypes of APOE gene in women with gallstone disease (GSD), and also to research the association of the APOE gene polymorphism and bile lithogenicity indices. MATERIALS AND THE METHODS: were investigated 104 women after cholecystectomy about verified cholesterol gallstones, and 176 women from the female Novosibirsk population, they were control group for the comparison of the frequency of APOE alleles and genotypes. Gallbladder bile (bile cholesterol, common bile acids) was investigated in women with GSD. Blood serum lipids and APOEgene polymorphism were studied in all women. RESULTS: APOE gene polymorphism in the women with GSD did not differ from those registered in control group from women population. At the presence of APOE4 allele at the women with GSD the significant increase of gallbladder biliary cholesterol level was marked. In the women with GSD with various APOE genotypes average levels of blood serum lipids, common bile acids and bile cholesterol indices were similar.