Pathophysiology and risk factors for cholelithiasis in patients with Crohn's disease.

Cholelithiasis is more common in patients with Crohn's disease (CD) than in the healthy population. The aim here was to examine risk factors for cholelithiasis in a cohort of CD patients and to compare the prevalence of cholelithiasis in a cohort of CD patients with that in a control group. This was a single-center retrospective case-control study. The cohort comprised all consecutive CD patients who underwent abdominal ultrasound from January 2007 to January 2018. The control group comprised age- and gender-matched non-CD patients referred for upper gastrointestinal tract dyspepsia. The study included 238 CD patients and 238 controls. The prevalence of cholelithiasis in the CD and control groups was 12.6 % and 9.2 %, respectively (risk ratio (RR), 1.36; p=0.24). Univariate analysis revealed that cholelithiasis was associated with multiple risk factors. Multivariate analysis identified age (OR, 1.077; 95 % CI, 1.043-1.112; p<0.001) and receipt of parenteral nutrition (OR, 1.812; 95 % CI, 1.131-2.903; p=0.013) as independent risk factors for cholelithiasis in CD patients. The prevalence of cholelithiasis in CD patients was higher than that in the control group; however, the difference was not statistically significant. Age and receipt of parenteral nutrition were independent risk factors for cholelithiasis in CD patients.

Impact of smoking cigarette on the mRNA expression of cytokines in mucosa of inflammatory bowel disease.

It is well known that smoking is the risk factor in the development and clinical course of Crohn s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ruzinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn s disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF ? (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1 (p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF ?, which could be associated with a worsening of the disease and response to therapy.

Influence of vitamin D on the expression of mRNA of cytokines in the mucosa of inflammatory bowel disease patients.

The aim of this study was to analyze the influence of 25(OH)VD serum concentration on the expression of mRNA cytokines (IL-6, IL-8, IL-12, IL-17, IL-23, TNFα, CCR1, CCR2, CCR5, CCR9, CCL5, TLR2, TLR4, TLR5, CD207 ,CD206, FoxP3) in mucosa of IBD patients. The cohort consisted of 86 IBD patients (48 CD and 38 UC) followed at the IBD center of University Hospital Bratislava-Ruzinov. We performed colonoscopy in each patient and took biopsies from mucosa of sigma and terminal ileum. Serum concentration of 25(OH)VD was assessed at the time of colonoscopy. mRNA was extracted from mucosal biopsy samples for each cytokine. Then we analyzed the correlation between VD and the expression of mRNA of cytokines from biopsies samples.  In CD we observed a significant positive correlation of serum concentration 25(OH)VD and the expression mRNA level of IL-6. There was also trend towards significant positive correlation of the expression mRNA of TNFα, IL-10, IL-23, TLR 2 in inflamed mucosa of terminal ileum as well as the expression mRNA of CCR5 and CCR1 in non-inflamed mucosa from terminal ileum. We also found a trend towards positive correlation between 25(OH)VD and the expression mRNA of IL-23, TLR4, CD 207, CCR1, CCR5 and CD 206 in non-inflamed mucosa of sigma in UC.VD significantly correlated with the levels of expression of several inflammatory cytokines including TNFα in colonic mucosa of patients with IBD (Tab. 4, Fig. 3, Ref. 31).

Dosing interval and diagnosis predict infliximab levels in patients with inflammatory bowel disease on maintenance treatment.

OBJECTIVE: The aim of the study was to identify factors influencing infliximab (IFX) trough levels (TL) in patients with inflammatory bowel disease (IBD). METHODS: This was a multicentre cross-sectional study performed at 5 large IBD centres in Slovakia. The cohort consisted of IBD patients, treated either with original IFX or CT-P13 biosimilar, who were examined for the IFX TL and antidrug antibodies (ADA) in a central laboratory. RESULTS: The patient cohort consisted of 116 consecutive IBD patients, 68 with Crohn's disease (CD) and 48 with ulcerative colitis (UC). CD patients had significantly lower IFX TL compared to UC, 2.41 (0.998-5.56) mg/L vs. 4.49 (1.76-8.41) mg/L, p = 0.017. During maintenance treatment, significantly higher mean IFX TL were observed in patients with a 4 week dosing interval than in patients with a 6 or 8 (7.44±3.6 µg/mL vs. 4.19±4.2 vs. 3.30±3.1 µg/mL, p = 0.011 and p< 0.0001, respectively). There was no difference in median TL IFX between original IFX and biosimilar CT-P13 (3.25 (1.24-6.52) mg/L vs. 3.03 (1.30-7.10)). IFX TL correlated with ADA (p=0.005). Multiple regression analysis revealed two independent factors for IFX TL: dosing interval (p<0.0001) and diagnosis (p=0.02). CONCLUSION: In the present study we observed that IBD patients assigned to an intensified dosing interval during maintenance therapy have significantly higher IFX TL than patients receiving conventional 8 week interval. Patients with UC had significantly higher IFX TL.

Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy.

BACKGROUND AND AIMS: Relapse rates after discontinuing anti-tumor necrosis factor-α (TNFα) therapy of inflammatory bowel disease (IBD) patients in deep remission are poorly understood. This prospective single-center open-label study evaluated the relapse rates of IBD patients after stopping anti-TNFα therapy. METHODS: All IBD patients who were in clinical remission and stopped anti-TNFα therapy in 2011-2013 and were followed up for at least 12 months were enrolled. The "Ultradeep" patients were in calprotectin-negative (<50 ng/g) deep remission for at least six months and ceased anti-TNFα therapy on physician recommendations. The "clinical" patients were in clinical but not deep remission and ceased anti-TNFα therapy for other reasons. Relapse rates were assessed and relapse risk factors identified. RESULTS: One year after stopping, 27 % and 27 % of the Ultradeep (n = 11) and Clinical (n = 11) patients relapsed, respectively. Two years after stopping, 57 % and 62 % relapsed, respectively (p = 0.89). All relapsed patients who underwent retreatment with anti-TNFα therapy re-entered remission. Male sex was a significant risk factor for relapse (p = 0.03). CONCLUSION: Our study showed that even highly selected IBD patients who lack clinical, endoscopic or laboratory signs of disease activity have a relatively high relapse rate in the follow-up period after ceasing anti-TNFα therapy (Tab. 2, Fig. 3, Ref. 24).

The prevalence and risk factors for osteoporosis in patients with inflammatory bowel disease.

AIM: Osteoporosis is a known chronic complication of inflammatory bowel diseases (IBD). The aim of our study was to describe the prevalence of reduced bone mineral density (BMD) in IBD patients and to identify crucial risk factors for osteoporosis. METHODS: The cohort consisted of 76 IBD patients, 40 with Crohn's disease (CD) and 36 with ulcerative colitis (UC). Clinical characteristics of every patient were recorded, i.e. age, sex, duration of the disease, clinical behavior, location of disease according to Montreal classification, surgeries, steroid medication, sIBDQ, and smoking habits. We examined the serum 25-hydroxyl vitamin D3 (25-OHD3) in each patient. The BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck. RESULTS: Osteoporosis was documented in 10 IBD patients (13.2 %), while osteopenia in 35 of them (46.1 %). Patients with CD have significantly lower femoral Z score than patients with UC. Femoral Z score was strongly associated with disease duration, and in CD patients suffering from stricturing form, with ileic or ileocolic location and history of proctocolectomy or total colectomy. Patients with osteoporosis had a significantly lower level of 25-OHD3 than patients with normal BMD. CONCLUSION: Patients with long disease duration and those suffering from stricturing form of CD with ileic/ileocolic location and history of proctocolectomy/total colectomy are at higher risk of developing osteoporosis than other IBD patients. The high proportion of osteopenia/osteoporosis in our study underlines the importance of BMD measurement in all IBD patients as a base for initiating the appropriate treatment (Tab. 1, Fig. 3, Ref. 63).

Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD patients.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. It has been suggested that TPMT genetic polymorphisms lead to dose-related hematopoietic toxicity. Since there are major ethnic differences in the prevalence of particular TPMT variants, it is important for each country to study their own prevalence in order to estimate the role of TPMT variants-related thiopurines toxicity in population suffering from particular inflammatory bowel disease (IBD). AIMS: The aim of this study was to determine the frequency of the four most common allelic variants of TPMT gene in the population of Slovak IBD patients. METHODS: TPMT genetic polymorphisms (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C) were amplified using PCR and consequently genotyped with genetic analyzer. The allele frequencies of particular allelic variants were calculated and compared with other Caucasian populations reported so far. RESULTS: Three hundred and thirty IBD patients were included; 196/132/2 cases of Crohn´s disease/ulcerative colitis/unclassified colitis; 180 (55 %) males. Ninety-three percent of patients were homozygous for wild-type TPMT variant. Heterozygous genotype of any of the studied polymorphisms was present in 6 % of patients while only one patient was homozygous for TPMT*3A allele (0.3 %). The most prevalent mutant allele was that of TPMT*3A (3.2 %). The distribution of most common allelic variants of TPMT gene among Slovak IBD patients was in accordance with previously reported prevalence in Caucasian populations. CONCLUSION: This study shows the prevalence of TPMT genetic polymorphisms in population of Slovak IBD patients. As in other Caucasian populations, the most common mutant allelic variant is that of TPMT*3A while the prevalence of homozygosity is relatively low (Tab. 3, Ref. 22).

The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

BACKGROUND AND AIMS: The thiopurine drugs, azathioprine (AZA) and 6-mercaptopurine, are established in the treatment of inflammatory bowel diseases (IBD). Polymorphisms in thiopurine S-methyltransferase (TPMT) gene have been associated with adverse drug reactions (ADRs) to AZA. METHODS: The aim of this study was to evaluate TPMT polymorphisms and AZA-related toxicity in a Slovak cohort of 220 IBD patients treated with AZA. In every patient, the dose and duration of AZA therapy, concomitant 5-aminosalicylate (5-ASA) medication, frequency, type, time to onset, dose of ADR and concomitant 5-ASA at the onset of ADR were recorded. Each patient was also genotyped for the presence of variant TPMT alleles (*2,*3A,*3B,*3C). Frequency, type and circumstances of ADRs were compared according to TPMT status. RESULTS: Of the 220 patients, 205 (93.2 %) were wild-type (TPMT*1/*1), one (0.5%) carried a TPMT*1/*3C allele, 13 (5.9 %) carried TPMT *1/*3A allele and one was homozygous for TMPT *3A allele. No TPMT *2 mutation was found. The incidence of adverse drug reactions was 62/205 (30.2 %) in the wild-type group as compared to 13/15 (86.7 %) in the TPMT mutation group, p=2.10-5. Leukopenia (WBC< 3.0*10^9/L) occurred in 21/205 (10.2 %) patients with wild type TPMT versus 11/15 (73.3 %) patients with TPMT mutations, p=0.000001. There was no significant difference between TMPT groups in gastrointestinal or other ADRs. No impact of 5-ASA on the incidence and severity of AZA adverse drug reactions was observed. CONCLUSION: The incidence of leukopenia in TPMT mutant patients was significantly higher and more severe as compared to TPMT wild type patients. We observed no impact of concomitant 5-ASA therapy on AZA induced toxicity (Tab. 4, Fig. 2, Ref. 37).

Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD patients.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. It has been suggested that TPMT genetic polymorphisms lead to dose-related hematopoetic toxicity. Since there are major ethnic differences in the prevalence of particular TPMT variants, it is important for each country to study their own prevalence in order to estimate the role of TPMT variants-related thiopurines toxicity in the particular inflammatory bowel disease (IBD) population. AIMS: The aim of this study was to determine the frequency of the four most common allelic variants of TPMT gene in the population of Slovak IBD patients. METHODS: TPMT genetic polymorphisms (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C) were amplified using PCR and consequently genotyped on genetic analyzer. The allele frequencies of particular allelic variants were calculated and compared with other Caucasian populations reported so far. RESULTS: Three hundred and thirty IBD patients were included; 196/132/2 Crohn´s disease/ulcerative colitis/unclassified colitis, 180 (55 %) males. Ninety-three percent of patients were homozygous for wild type TPMT variant. Heterozygous genotype of any of the studied polymorphisms was present in 6 % of patients, only one patient was homozygous for TPMT*3A allele (0.3 %). The most prevalent mutant allele was TPMT*3A (3.2 %). The distribution of the most common allelic variants of TPMT gene among Slovak IBD patients were in accordance with previously reported prevalence in Caucasian populations. CONCLUSION: This study shows the prevalence of TPMT genetic polymorphisms in the Slovak IBD patient`s population. As in other Caucasian populations, the most common mutant allelic variant is TPMT*3A, and the prevalence of homozygosity is relatively low (Tab. 3, Ref. 16).

[Prevalence of liver disease markers among patients with metabolic risk factors]. / Prevalencia markerov polkodenia pecene u pacientov s metabolickými rizikovými faktormi.

INTRODUCTION: Non-alcoholic fatty liver disease is one of the most common liver diseases. It's prevalence among patients with metabolic risk factors (obesity, type 2 diabetes, hypertension, lipid disorders) without previously recognized liver disease is not completely known. Aims of our study were to determine the prevalence of liver lesions (elevated alanin aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) above normal range and ultrasound signs of liver steatosis) among the study group of patients with at least one metabolic risk factor, to compare it with the control group with no risk factor, to investigate it's association with the number of metabolic risk factors and to identify it's closest independent predictors. METHODS: Patients with other known liver diseases were excluded. Among 482 patients 429 were in the study group and 53 in the control group. RESULTS: In the study group the prevalence ofALT, GGT elevation and signs ofsteatosis was 12.1, 29.9, 38.3%, comparing to 5.7, 11.9 and 5.7% in the control group respectively. The differences were statistically significant. With the increasing number of risk factors we found growing prevalence of GGT elevation and signs of steatosis, but ALT elevation was equally prevalent. In multiple logistic regression the only independent predictor of ALT elevation was obesity, predictors of GGT elevation were type 2. diabetes and signs of steatosis, signs of steatosis were independently associated with overweight, obesity, type 2 diabetes and hypertriglyceridemia. CONCLUSIONS: Markers of liver disease do have a clinical and prognostic impact on the liver and cardiometabolic risk and therefore we suggest they should be actively screened in this group of patients.

[Impact of basal prolactin levels on the prevalence of complications and the prognosis of patients with liver cirrhosis]. / Vplyv bazálnej koncentrácie prolaktínu na výskyt komplikácií a na prognózu pacientov s cirhózou pecene.

INTRODUCTION: Prolactin concentration was proved to be associated with complications of cirrhosis. METHODS: This relationship was investigated on the group of 90 patients predominantly males with alcoholic cirrhosis. Basic clinical and laboratory data were collected at entry as well as complications of cirrhosis already present. Patients were followed for the mean of 434 days and events such as variceal bleeding, hepatorenal syndrome and death were recorded. RESULTS: We found that 16.7% of patients had elevated serum prolactin levels, and had significantly higher Child-Pugh and MELD scores as well as higher ascites and encephalopathy stage. By comparing prolactin concentration quartiles we found complications of cirrhosis such as ascites, higher INR, jaundice and higher Child-Pugh and MELD scores more often with increasing prolactin concentrations. The most prominent was the relationship to hepatic encephalopathy (0 vs 31% between the 1st and 4th quartile, p < 0.05) to which the prolactin levels above 10.5 microg/l had a sensitivity of 92.9% and negative predictive value of 97%. Kaplan-Meier survival curve showed that patients in the 1st comparing to the 4th quartile had significantly higher survival rates (85.2 vs 50%, p = 0.046, hazard ratio = 0.2881). Prolactin levels > 11.91 microg/l had 80.8% sensitivity and 87.8% negative predictive value to predict death during the follow up period. CONCLUSION: Basal prolactin concentration could therefore be used as an alternative marker of hepatic encephalopathy and death in a selected subset of patients with cirrhosis.

Positive family history promotes participation in colorectal cancer screening.

BACKGROUND: Participation rates in colorectal cancer (CRC) screening are rather low. We evaluated the interest of first degree relatives (FDR) of CRC patients to participate in a colonoscopy screening and compared the findings to controls with a negative family history. METHODOLOGY: There were 235 CRC patients diagnosed in our centre in 1984-2001. These were mailed an invitation letter for a preventive examination for their FDR older than 40 years and a questionnaire about occurrence of malignancies in their family. Colonoscopy was performed in 52 FDR and sex/age matched controls. RESULTS: The questionnaire was delivered to 196 patients. Thirty four (17.3%) patients responded. Positive family history for CRC was reported in 12/34 (35.3%) patients, compared to expected 3.4 patients (p = 0.04; OR 4.2; 95% CI = 1.05-17.89). Fifty two of 94 (55.3%) FDR participated in a screening and CRC was diagnosed in 2 and CRA in 18 patients compared to 1 CRC and 9 CRA in control group (p = 0.04; Kaplan-Meier p = 0.04). CONCLUSIONS: Positive family history seems to be a motivation factor for a participation in a CRC screening program. Consistent with previous studies the prevalence of CRA and CRC was significantly higher in the group of FDR compared to controls (Tab. 3, Fig. 1, Ref. 20).

[Bone changes in patients after partial gastric resection]. / Kostné zmeny u pacientov po parciálnej resekcii zalúdka.

Metabolic diseases of the bones may be a serious complication of gastrectomy. The pathogenesis of osseous changes is multifactorial. The most important causes include a reduced intake of dairy products, their fastened passage through the stomach and reduced calcium and vitamin D absorption. The objective of the work was to assess bone changes in patients after partial gastrectomy. From a total number of 261 patients with a minimal 10-year history of gastrectomy, in the investigation 31 patients were included (18 men and 13 women) who met the required criteria. The results were compared with a control group of 18 men and 13 women of equal age. The authors compared also groups of patients with the condition after surgery type Billroth I (8 patients) and Billroth II (23 patients). In all investigated subjects the authors examined the bone density in the area of the lumbar spine and neck of the femur and parameters of osteoresorption and osteoformation. The authors found a significant reduction of bone density in the area of the spine and neck of the femur (p < 0.001) and a significantly higher level of total alkaline phosphatase and intact parathormone in serum and N-terminal telopeptide collagen type I in urine (p < 0.001), as compared with the control group. The other parameters did not differ in the investigated groups. The authors did not find a statistically significant difference in the investigated parameters between patients after resection Billroth I and Billroth II. The results confirm the need of early diagnosis and treatment of bone changes in patients after partial gastrectomy.

[Pharmacoeconomics in the therapy of peptic ulcer]. / Farmakoekonomika v terapii peptických vredov.

The great prevalence and chronic nature of peptic ulcers traditionally represent a great economic load for the system of health care. The exponentially growing therapeutic and diagnostic possibilities of the treatment of peptic diseases are under a strong economic pressure from health-insurance companies. The use of an economic model for the management of peptic diseases aims to maximize health benefit from limited sources of the health services. It can be said already now that the detection of the Helicobacter pylori infection ranks among the most important discoveries of the 20th century. Elimination of the Helicobacter pylori infection can produce a dramatic reduction in relapses of peptic ulcers, which is reflected not only in the improved quality of life but also in a subsequent economic contribution. The present authors paid attention to the financial costs of the combined therapy for eradication of the Helicobacter pylori infection in the course of the years 1998-2001.

Plasma gastrin levels in alcoholic and idiopathic chronic pancreatitis patients free from Helicobacter pylori infection.

BACKGROUND: Previous studies on gastrin levels in chronic pancreatitis (CP) patients have given conflicting results. These studies did not take into consideration the influence of Helicobacter pylori (H. pylori) infection on gastrin release. Also, there is no previous study that compared alcoholic CP patients to patients with idiopathic pancreatitis. Our aim was to measure basal and postprandial plasma gastrin levels in all CP patients, including subgroups of alcoholic, idiopathic, severe and mild CP patients, and compare them with healthy subjects after the eradication of H. pylori infection. PATIENTS AND METHODS: Basal and postprandial gastrin levels were measured in 30 patients with CP (10 patients with alcoholic and 20 patients with idiopathic CP) and in 25 healthy subjects. RESULTS: A significant increase in basal gastrin levels was found only in a subgroup of alcoholic CP (P<0.05) in comparison to healthy subjects. A significant increase in postprandial plasma gastrin levels (P<0.01) was found in all chronic pancreatitis compared to healthy subjects. CONCLUSION: In the absence of H. pylori infection, plasma gastrin levels were significantly higher in chronic pancreatitis patients than in healthy subjects. Chronic alcoholism, however, does not appear to be the only factor responsible for the increased plasma gastrin levels in these patients.

Plasma cholecystokinin and somatostatin levels in chronic pancreatitis patients.

BACKGROUND/AIMS: The existence of a negative-feedback mechanism between pancreatic enzyme secretion and intraduodenal proteases and the role of cholecystokinin in its mediation in humans is debatable. The presence of such a feedback mechanism in chronic pancreatitis patients with exocrine enzyme deficiency possibly leads to an increase in cholecystokinin plasma levels. Somatostatin has been used in many studies in the therapy of pain in chronic pancreatitis and plays a role in the regulation of cholecystokinin levels, however data on its plasma levels are still lacking. METHODOLOGY: Basal and the postprandial cholecystokinin and somatostatin levels in 30 patients with chronic pancreatitis (11 with severe chronic pancreatitis and 19 with mild chronic pancreatitis) were measured 14 days after discontinuation of enzymatic substitution therapy and then were compared with the levels taken from 25 healthy subjects. RESULTS: The cholecystokinin postprandial plasma levels were significantly higher in patients with chronic pancreatitis when compared with those of healthy individuals (P < 0.01). Basal, somatostatin, cholecystokinin and postprandial somatostatin levels were not significantly higher than those in healthy subjects. There was no correlation between basal and postprandial levels of cholecystokinin and somatostatin in our study. CONCLUSIONS: The cholecystokinin postprandial plasma levels were significantly higher in all patients with chronic pancreatitis when compared with healthy individuals, which suggests the role of cholecystokinin in the feedback control of pancreatic secretion.

[Effect of pancreatic substitutes on fecal and serum elastase and on pain in patients with chronic pancreatitis]. / Vplyu pankreatickej substitúcie na fekálnu a sérovú elastázu a na bolest' u pacientov s chronickou pankreatitídou.

Views on the existence of a negative feedback between pancreatic secretion and intraduodenal of proteases in humans are controversial. The objective of the study was to find out whether enzyme substitution will have an impact on pancreatic enzyme secretion and pain in chronic pancreatitis. The preparation Panzytrate 2500 (2 x 3 capsules/day containing 1250 units of proteases per capsule) was administered for a 4-week period. In 18 patients with chronic pancreatitis (7 with the severe and 11 with the medium severe and mild form of pancreatitis) the faecal and serum pancreatic elastase was assessed one day before and one day after enzyme substitution therapy. A significant reduction of the faecal elastase concentration (p = 0.03) and serum elastase (p = 0.00375) was recorded in patients with mild and medium severe CP. The values of faecal and serum pancreatic elastase 1 were insignificantly reduced also in patients with severe chronic pancreatitis. Pain relief was statistically significant already after two weeks' administration of enzyme substitution therapy (p = 0.0233) and after four weeks' treatment (p = 0.00766). The results support the importance of the negative feedback on regulation of pancreatic secretion and the positive effect of substitution therapy on pain in chronic pancreatitis.

[Therapy of acute pancreatitis]. / Terapia akútnej pankreatitídy.

The mortality rate in acute pancreatitis (AP) is significantly lower in patients hospitalized directly at the intensive care unit than in patients admitted to hospital in 2 weeks after the assessment of diagnosis, prophylactic administration of low-molecular protease inhibitor reduces the occurrence of post ERCP pancreatitis a well a coincident complications. Despite rational considerations concerning the significance of pryphylactic administration of antibodies (ATB) in severe AP, there still not enough convincing data which could be recommended a standard therapy. One of the concepts of causal therapy of AP. Suggest that inhibition of exocrine pancreatic enzymatic secretion reduces autodigestion of the gland (setting the gland at rest). The reports on success of secretin-inhibiting substances a glucagon, calcitonin, atropine and somatostatin require confirmation in randomized or accurately defined comparable groups. The initial studies on the therapeutic significance of lexipanphate-antagonist of platelet activating factor (PAF) in acute pancreatitis is promising. A long-term lavage had reduced the mortality.

[Etiology and pathogenesis of acute pancreatitis]. / Etiológia a patogenéza akútnej pankreatitídy.

The theory of pancreatic gland autodigestion by pancreatic enzymes assumed by Chiari 1886 as the crucial moment in the pathogenesis of acute pancreatitis (AP) remains accepted so far. The appearance of mutations of cationic trypsinogen gene on the 7th chromosome in several families with hereditary AP, supports the significance of trypsin in the initiation of AP. The generally recognized etiologic factors of AP include the biliary tract disease and alcohol. Opie in his "Common Channel theory" assumed that the impacted gallstone in the ampulla of Vater could cause a permanent obstruction and subsequently AP. Later clinical studies have confirmed that a short-term block of the common pancreatic duct caused by migrating gallstones is associated with onset of AP. Chronic consumption of alcohol evokes subclinical pancreatic disturbances already prior to the onset of AP. PAP (pancreatic associated protein) being the marker of pancreatic inflammation was significantly increased in chronic alcoholism without signs of AP. Many pathophysiological concepts and effective therapeutic procedures which were successful in the animal studies have not turned out to be appropriate in man. The destruction of both cellular structure and cellular connections is an early event in the development of experimental AP. There is much evidence that free oxygen radicals and the disturbances of microcirculation determine the severeness of AP. The roles of NO (nitric oxide) and kinins remain to be clarified cytokins a interleukin 2 (IL2) and interleukin 10 (IL10) had a protective effect in experimental AP. In humans the antagonist of PAF (platelet activating factor) had reduced the occurrence of organ failure. There is hope, that this knowledge, will lead to new therapeutic possibilities.

[One day surgery--personal experience]. / One day surgery--vlastné skúsenosti.

The authors present their own experience with surgery carried out in the out-patient department in 1985-1996. It is a modern, effective, reliable and above all economical therapeutic method, because it maintains the standard of surgery while saving the costs of hospitalisation. It is a very attractive method for patients who want to return to work as soon as possible. As many as 87% patients were satisfied with surgical treatment of the anus and rectum.