Infliximab Biosimilar (Remsima™) in Therapy of Inflammatory Bowel Diseases Patients: Experience from One Tertiary Inflammatory Bowel Diseases Centre.

BACKGROUND: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. METHODS: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. RESULTS: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. CONCLUSION: Switching of IBD patients from original to biosimilar IFX is effective and safe.

Switching From Originator Adalimumab to the Biosimilar SB5 in Patients With Inflammatory Bowel Disease: Short-term Experience From a Single Tertiary Clinical Centre.

BACKGROUND AND AIMS: Patients' perspectives after switching from originator to biosimilar adalimumab have yet to be assessed. We evaluated the efficacy of switching from the originator adalimumab to a biosimilar compound [SB5] in patients with inflammatory bowel disease [IBD]. METHODS: Data on IBD patients who were switched from the originator to biosimilar adalimumab [SB5] at IBD Center ISCARE were analysed. Disease activity was assessed using standard clinical indices (Harvey-Bradshaw index [HBI] for Crohn's disease [CD] and partial Mayo score for ulcerative colitis [UC]), and laboratory parameters (C-reactive protein [CRP] and faecal calprotectin [FC]). Trough levels and anti-drug antibodies were measured. Patients were evaluated 10 weeks [W10] after the switch, and results were compared with the control group of patients on originator compound. RESULTS: A total of 93 patients switched to biosimilar adalimumab were included [CD 86%] and were matched to 93 controls for age, gender, diagnosis, and disease activity. There was no difference in the disease activity in either SWITCH or ORIGINATOR cohorts between Weeks 0 and 10. Similarly, no difference was found between cohorts at both prespecified time points. Moreover, no significant differences in CRP or FC concentrations were seen between W0 and W10 either in the SWITCH, or in the ORIGINATOR cohort [p >0.05]. Adalimumab serum trough levels remained stable after the switch. No new safety signals were detected. CONCLUSIONS: Our study confirmed that switching IBD patients from the originator adalimumab to a biosimilar compound [SB5] does not affect treatment efficacy.

DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic.

Colorectal cancer represents a complex disease where susceptibility may be influenced by genetic polymorphisms in the DNA repair system. In the present study we investigated the role of nine single nucleotide polymorphisms in eight DNA repair genes on the risk of colorectal cancer in a hospital-based case-control population (532 cases and 532 sex- and age-matched controls). Data analysis showed that the variant allele homozygotes for the Asn148Glu polymorphism in the APE1 gene were at a statistically non-significant increased risk of colorectal cancer. The risk was more pronounced for colon cancer (odds ratio, OR: 1.50; 95% confidence interval, CI: 1.01-2.22; p=0.05). The data stratification showed increased risk of colorectal cancer in the age group 64-86 years in both individuals heterozygous (OR: 1.79; 95% CI: 1.04-3.07; p=0.04) and homozygous (OR: 2.57; 95% CI: 1.30-5.06; p=0.007) for the variant allele of the APE1 Asn148Glu polymorphism. Smokers homozygous for the variant allele of the hOGG1 Ser326Cys polymorphism showed increased risk of colorectal cancer (OR: 4.17; 95% CI: 1.17-15.54; p=0.03). The analysis of binary genotype combinations showed increased colorectal cancer risk in individuals simultaneously homozygous for the variant alleles of APE1 Asn148Glu and hOGG1 Ser326Cys (OR: 6.37; 95% CI: 1.40-29.02; p=0.02). Considering the subtle effect of the DNA repair polymorphisms on the risk of colorectal cancer, exploration of gene-gene and gene-environmental interactions with a large sample size with sufficient statistical power are recommended.

[Calprotectin levels in patients with idiopathic inflammatory bowel disease comparison of two commercial tests]. / Stanovení koncentrace kalprotektinu ve stolici u nemocných s idiopatickými strevními zánety-srovnání dvou komercních testu.

BACKGROUND: Fecal calprotectin test is a simple, non-invasive, rapid and inexpensive diagnostic tool allowing differentiation between GIT functional disorders and inflammatory conditions and relapse prediction in non-specific inflammatory bowel disease. In the last year, commercially available ELISA diagnostic kits, using either monoclonal or polyclonal antibodies against a heterodimeric complex, calprotectin, for the detection of fecal calprotectin, started to be marketed. OBJECTIVE: To compare two ELISA kits for the detection of fecal calprotectin differing from each other in the used type of antibody (monoclonal versus polyclonal). MATERIAL AND METHODS: Two ELISA kits were assessed: Calprotectin ELISA (Bühlmann, Basel, Switzerland) using a monoclonal antibody against calprotectin and PhiCal Calprotectin ELISA (R-Biopharm, Darmstadt, Germany) using a polyclonal antibody against calprotectin. We analyzed fecal eluates from patients with Crohn's disease (CD, n=36) and ulcerous colitis (UC, n=29) and from healthy controls (n=98). Data were analyzed using software Statistica CZ 8.0 (Statsoft, Tulsa, U.S.A.) and measurement variability parameters (linearity, repeatability, stability) and test sensitivity and specificity were established and the methods were compared. RESULTS: The two kits showed adequate accuracy (intra- and inter-assay variation < 10%). The dilution linearity test indicated superiority of the Calprotectin ELISA Bühlmann kit, in particular for high calprotectin levels. The results of the two methods showed good correlation: Pearson's correlation coefficient r = 0.83, limit difference according to Bland-Altman plot ranged from 17% to 30%. Diagnostic sensivity rates were 79% for the Calprotectin ELISA Bühlmann kit and 74% for the Calprotectin ELISA R-Biopharm kit, the test specificity rates were 87% and 84%, respectively. CONCLUSIONS: Both of the tested kits have comparably good measurement parameters, the Bühlmann kit using monoclonal antibody against calprotectin showed higher sensitivity and specificity. In view of their availability, sensitivity and performance, the fecal calprotectin ELISA kits are helpful diagnostic tools for clinical practice.

Mutation analysis of the MYH gene in unrelated Czech APC mutation-negative polyposis patients.

Some of the APC negative FAP and AFAP cases have recently been found to be attributable to MYH associated polyposis (MAP). MAP is an autosomal recessive syndrome associated with 5-100 colorectal adenomas and caused by mutation in the MYH gene. Here, we screened for germline MYH mutations in 82 APC-mutation-negative probands with classical and attenuated familial adenomatous polyposis using the denaturing high performance liquid chromatography (DHPLC) method in combination with sequencing. Altogether 12 previously reported changes and four novel genetic alterations, mostly in intronic sequences, were identified. The results revealed the presence of biallelic germline MYH mutations in two patients. These patients were compound heterozygotes for two of the most common germline mutations c.494 A>G (p.Y165C); c.1,145 G>A (p.G382D). These variants are established to be associated with adenomatous polyposis and colorectal cancer. No novel pathogenic mutation has been identified in our study.

[Risk of drug interactions and their possible solutions in the population of patients with inflammatory bowel disease]. / Riziko lékových interakcí a jejich mozná resení v populaci pacientu s idiopatickým strevním zánetem.

Concurrent use of several medicinal preparations is connected with an increased risk of the occurrence of drug interactions. This study analyzes the complete pharmacotherapy of 573 patients diagnosed with inflammatory bowell disease. An analysis of the medication of the cohort of patients tested identified potential drug interactions of all degrees of gravity. All drug interactions in the study were considered to be only potential, and therefore they are not known to cause any complications for the patient. An important factor in the process of revealing drug interaction may be the pharmacist during dispensation in a pharmacy. Pharmacist's expertise of the problems of drug interactions is a component of his/her professional competence and should be continuously intensively increased in postgraduate education. This study is not limited to simply stating the occurrence of potential drug interactions. It is also focused on the management of drug interactions from the party of the physician and the pharmacist and attempts to outline the way of encountering this problem.

Treatment Steps, Surgery, and Hospitalization Rates During the First Year of Follow-up in Patients with Inflammatory Bowel Diseases from the 2011 ECCO-Epicom Inception Cohort.

BACKGROUND AND AIMS: The ECCO-EpiCom study investigates the differences in the incidence and therapeutic management of inflammatory bowel diseases [IBD] between Eastern and Western Europe. The aim of this study was to analyse the differences in the disease phenotype, medical therapy, surgery, and hospitalization rates in the ECCO-EpiCom 2011 inception cohort during the first year after diagnosis. METHODS: Nine Western, five Eastern European centres and one Australian centre with 258 Crohn's disease [CD], 380 ulcerative colitis [UC] and 71 IBD unclassified [IBDU] patients [female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years] participated. Patients' data were registered and entered in the web-based ECCO-EpiCom database [www.epicom-ecco.eu]. RESULTS: In CD, 36 [19%] Western Europe/Australian and 6 [9%] Eastern European patients received biological therapy [p = 0.04], but the immunosuppressive [IS] use was equal and high in these regions [Eastern Europe vs Western Europe/Australia: 53% vs 45%; p = 0.27]. Surgery was performed in 17 [24%] CD patients in Eastern Europe and 13 [7%] in Western Europe/Australia [p < 0.001, pLogRank = 0.001]. Of CD patients from Eastern Europe, 24 [34%] were hospitalized, and 39 [21%] from Western Europe/Australia, [p = 0.02, pLogRank = 0.01]. In UC, exposure to biologicals and colectomy rates were low and hospitalization rates did not differ between these regions during the 1-year follow-up period [16% vs 16%; p = 0.93]. CONCLUSIONS: During the first year after diagnosis, surgery and hospitalization rates were significantly higher in CD patients in Eastern Europe compared with Western Europe/Australia, whereas significantly more CD patients were treated with biologicals in the Western Europe/Australian centres.

[Toxic megacolon]. / Toxické megakolon.

Toxic megacolon belongs to the severe acute complications of inflammatory bowel diseases. The frequency is 1.6-21.4% among patients with ulcerative colitis and 0.3-2% in those with Crohn's disease. The main characteristics of toxic megacolon are toxemia, sepsis and distension of the colon due to the diminished muscular tone, loss of motor activity and increased amount of colonic gas. Sepsis and/or perforation of the large bowel can complicate this situation. The most important diagnostic procedure is the abdominal X-ray. Should the diameter of colonic distension exceed 60 mm, the diagnosis of toxic megacolon has been confirmed. Conservative treatment of toxic megacolon consists of water and electrolyte replacement, total parenteral nutrition, administration of corticosteroids and broad-spectrum antibiotics and repeat patient's prone positioning. If medical therapy is not successful during the first 72 hours, surgical intervention is indicated. The most common procedure is subtotal colonic resection with creation of an ileostomy. Patients with toxic megacolon should be managed at specialised centers, where cooperation of experienced gastroenterologists, surgeons and intensive care experts is possible.

[Nonvariceal acute upper digestive tract hemorrhage--therapeutic approach]. / Nevarikózní akutní krvácení do horní cásti zazívacího traktu--terapeutický prístup.

Nonvariceal acute upper gastrointestinal hemorrhage continues to be a frequent cause for hospital admission, consumes considerable financial resources and belongs to diagnoses associated with significant morbidity and mortality. Despite the progress in endoscopic and intensive care therapies the mortality remained unchanged. It results from the increasing number of high risk patients, namely the older ones with significant comorbidity. The cornerstone of therapeutical success is considered to be the adequate hemodynamic and ventilatory stability, initiation of pharmacotherapy with proton pump inhibitors and eventually somatostatin, and in particular, the early endoscopy using modern methods of hemostasis. In case of two unsuccessful endoscopic sessions the surgical approach is justified.

[Fixation of a non-adjustable gastric band using an anterior gastric wall cuff (randomized study)]. / Fixace neadjustabilní gastrické bandáze manzetou z prední steny zaludku (randomizovaná studie).

We have been concerned with bariatric surgery at the First Surgical Clinic of th General Faculty Hospital, First Medical Faculty, Charles University Prague since 1983. In 1983-1986 vertical gastroplasties were made, between 1986 and 1993 non-adjustable gastric bands were provided by the laparotomic approach. Since 1993 when we were the first to implement a gastric band operation (GB) by the laparoscopic route, this method is used as the standard method. In 1993-1998 we made at the First Surgical Clinic 517 laparoscopic GB operation on account of morbid obesity in patients with a body mass index of 34-49 kg/m2. The group comprised 449 women and 59 men. The most frequent late complication in our group of morbidly obese patients who had a laparoscopically administered GB was in 5.1% enlargement of the proximal pouch above the GB by dilatation of its wall or slippage of the anterior wall proximally under the GB with a subsequent disorder of gastric evacuation and vomiting. We tried to reduce the incidence of this complication by fixing the GB by a cuff made from the anterior gastric wall. To test the effectiveness of the suggested fixation of the non-adjustable GB by a cuff we implemented in 1998-1999 a prospective randomized study in a group of 80 morbidly obese patients divided into experimental group n1-GB + C with the cuff and a control group n2-GB - C without a cuff. We investigated the incidence of the mentioned complication and the changed volume of the pouch above the GB after one year. Endoscopic assessment of the size of the pouch above the GB after surgery and after one year revealed that in group n1-GB + C the mean increase of the pouch volume was 14.6 ml, i.e. 124% of the original size, while in group n2-GB - C the mean increase of the volume was 33.6 ml, i.e. 154.1% of the original size (p < 0.001). Based on the assembled results and aware of the fact that small groups were involved, we should like to express the assumption that the suggested modification, i.e. fixation of a non-adjustable GB by a cuff made from the anterior gastric wall can reduce the incidence of the complication of slippage of the anterior gastric wall proximally above the bandage.

[6 years' personal experience with duodenum-sparing procedures in chronic pancreatitis]. / Nase sestileté zkusenosti s duodenum setrícími výkony pro chronickou pankreatitidu.

The First Surgical Clinic of the First Medical Faculty Charles University and General Faculty Hospital Prague made operations of the pancreas ever since 1971. In the work sooner or later all approaches to surgical treatment of pancreatitis were reflected. The authors present a brief review of results and their own experience since 1994 when duodenum sparing operations were introduced. Indications for surgical treatment were based on the diagnosis by US, CT and ERCP, in exceptional cases MR, after evaluation by a pancreatologist, roentgenologist and surgeon. The group of patients with chronic pancreatitis was extended by 15 patients from a group operated because of preoperative suspicion of a malignant pancreatic tumour not confirmed during and after surgery. In those Whipple's operation was performed. The same operation was performed in three patients with chronic pancreatitis with serious changes in the area of the head of the pancreas. In 111 patients a drainage and duodenum sparing operation was performed. Of these in 46x according to Neger, 9x according to Frey, 10x modification of these operations, 37x Partington-Rochelle's procedure. The authors did not record postoperative complications after the classical Beger operation and the hospital stay was on average by five days shorter as compared with the classical method of Whipple. When evaluating postoperative complaints and problems (pain, malnutrition, physical constitution and social position) the authors recorded equally favourable results as after non-complicated duodenopancreatectomy. They varied, depending on the patient s co-operation round 87% while after longitudinal drainage of the duct a satisfactory result was recorded in 78% of the operated patients. The authors consider Beger's operation logical because of the removal of the main tissue mass of the head of the pancreas, responsible for pain, complications caused by fibrosis in the area round the bile duct and duodenum, responsible for the deterioration of the compartment syndrome in the left half of the gland. Its result is destruction of the remainder of exocrine and endocrine tissue. Of 170 operated patients one patient with decompensated diabetes died. Based on their own experience the authors do not consider repeated re-operations an absolute contraindication of Beger's operation when conditions permit. A problem is, in their opinion, fibrosis in the vicinity of the pancreas and portal overpressure.

Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia: results of the 2011 ECCO-EpiCom inception cohort.

BACKGROUND AND AIMS: The aim of the present study was to validate the IBD (inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom (European Crohn's and Colitis Organization-Epidemiological Committee) inception cohort by including a second independent inception cohort from participating centers in 2011 and an Australian center to investigate whether there is a difference in the incidence of IBD between Eastern and Western European countries and Australia. METHODS: Fourteen centers from 5 Eastern and 9 Western European countries and one center from Australia participated in the ECCO-EpiCom 2011 inception cohort. Patients' data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu. RESULTS: A total of 711 adult patients were diagnosed during the inclusion year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72 (10%) from Australia; 259 (37%) patients were diagnosed with Crohn's disease, 380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000 in Western Europe and 30.3/100,000 in Australia. Significantly more patients were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (43% vs. 27%, p=0.02). CONCLUSION: Incidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different from that reported in the 2010 cohort.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Fatal myelotoxicity after azathioprine treatment.

Azathioprine and 6-mercaptopurine have been used for many years in the treatment of inflammatory bowel disease. Approximately 0.3% of the population are homozygous for variant alleles associated with extremely low thiopurine S-methyltransferase enzyme activity. We describe the case of a young patient with ulcerative colitis, homozygous for TPMT*3A alleles, who suffered fatal azathioprine-induced myelotoxicity after standard dosing with azathioprine. Screening for decreased activity of TPMT in patients prior to azathioprine treatment is advised to minimize the risk of drug-induced toxicity.

Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs.

Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR = 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR = 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR = 2.9, 95% CI 1.5-5.7) and p.R702W (OR = 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.-308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.

[Adverse effects of nonsteroidal antirheumatic agents on the digestive tract]. / Nezádoucí úcinky nesteroidních antirevmatik na trávicí trakt.

In this review the authors focus on the adverse GIT events during long-term treatment with non-steroid anti-inflammatory drugs, and explain pathogenesis of the NSA induced gastropathy and enteropathy. The risk groups of patients and prophylactic and therapeutic modalities are discussed. There are indices that most of the NSA gastric ulcers don't induce clinical symptoms, and massive bleeding may be the first clinical manifestation. This is why the clinical symptoms cannot be used as predictors of NSA gastropathy. It seems, on the author's clinical experience, that more than half cases of massive non-variceal bleeding from upper GIT is induced by non-steroid anti-inflammatory drugs and acetylsalicylic acid. NSA-gastropathy often presents with multifocal ulcers and erosions in the antrum of the stomach. The course of massive bleeding induced by NSA is associated with high rate of lethality.

[Choice of surgical procedure in operations for chronic pancreatitis--personal experience]. / Který chirurgický výkon volit v operacní lécbe chronického zánetu slinivky brisní--nase zkusenosti.

The First Surgical Clinic of the First Medical Faculty of Charles University and General Faculty Hospital in Prague made operations of the pancreas ever since 1971. In the work sooner or later all approaches to surgical treatment pancreatitis were reflected. The authors present a brief review of results and their own experience since 1994 when duodenum-sparing operations were introduced. Indications for surgical treatment were based on the diagnosis by US, CT and ERCP, in exceptional case MR, after evaluation by a pancreatologist, roentgenologist and surgeon. The group of patients with chronic pancreatitis was extended by 21 patients from a group operated because of preoperative suspicion of a malignant pancreatic tumour not confirmed during and after surgery. In those Whipple's operation was preformed. The same operation was performed in three patients with chronic pancreatitis with serious changes in the area of the head of the pancreas. In 123 patients a drainage and duodenum sparing operation was preformed, of these in 57 according to Beger, 19 according to Frey, 37 Partington-Rochelle's procedure. The authors record two sepsis postoperative complications after the classical Beger operation and the hospital stay was on average by five days shorter as compared with the classical method of Whipple. When evaluating postoperative complaints and problems (pain, malnutrition, physical constitution and social position) the authors recorded equally favourable results as after non-complicated duodenopancreatectomy. They varied, depending on the patients co-operation round 84-87% while authors consider Beger's operation logical because of the removal of the main tissue mass of the head of the pancreas, responsible for pain, complications caused by fibrosis in the area round the bile duct and duodenum, responsible for the deteriation of the compartment syndrome in the left half of the gland. Its result is destruction of the remainder of exocrine and endocrine tissue. Of 187 operated patients one patient with decompensated diabetes died postoperatively. Based on their own experience the authors do not consider repeated re-operations an absolute contraindication of Beger's operation when conditions permit. A problem is, in their opinion, fibrosis in the vicinity of the pancreas and portal overpressure.