16S rRNA gene primer choice impacts off-target amplification in human gastrointestinal tract biopsies and microbiome profiling.

16S rRNA amplicon sequencing or, more recently, metatranscriptomic analysis are currently the only preferred methods for microbial profiling of samples containing a predominant ratio of human to bacterial DNA. However, due to the off-target amplification of human DNA, current protocols are inadequate for bioptic samples. Here we present an efficient, reliable, and affordable method for the bacteriome analysis of clinical samples human DNA content predominates. We determined the microbiota profile in a total of 40 human biopsies of the esophagus, stomach, and duodenum using 16S rRNA amplicon sequencing with the widely used 515F-806R (V4) primers targeting the V4 region, 68F-338R primers and a modified set of 68F-338R (V1-V2M) primers targeting the V1-V2 region. With the V4 primers, on average 70% of amplicon sequence variants (ASV) mapped to the human genome. On the other hand, this off-target amplification was absent when using the V1-V2M primers. Moreover, the V1-V2M primers provided significantly higher taxonomic richness and reproducibility of analysis compared to the V4 primers. We conclude that the V1-V2M 16S rRNA sequencing method is reliable, cost-effective, and applicable for low-bacterial abundant human samples in medical research.

The association between duration of and indications for proton pump inhibitor use and risk of gastric polyps.

OBJECTIVES: The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. METHODS: A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. RESULTS: Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. CONCLUSION: Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.

Malignant complications of celiac disease: a case series and review of the literature.

BACKGROUND: Celiac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis is based on evaluating specific autoantibodies and histopathologic findings of duodenal biopsy specimens. The only therapy for celiac disease is a gluten-free diet. Celiac disease can be complicated by malnutrition, other autoimmune diseases, refractoriness to treatment, and gastrointestinal tumors. This article presents seven cases of malignancies in patients with celiac disease. Its objective is to raise awareness of the malignant complications of celiac disease, leading to earlier diagnosis and improved outcomes. CASE PRESENTATION: Seven cases of malignant complications of celiac disease occurred among 190 patients followed at the Department of Internal Medicine and Gastroenterology, University Hospital Brno from 2014 to 2021. We describe these cases and the presentation, diagnostic process, course, management, and outcomes for each, along with proposed potential risk factors of malignant complications. There was one Caucasian man who was 70 years old and six Caucasian women who were 36, 46, 48, 55, 73, and 82 years old in our cohort. Of the seven cases of malignancies in our cohort, four patients were diagnosed with small bowel adenocarcinoma, one with diffuse large B-cell lymphoma, one with carcinoma of the tongue, and one with colorectal carcinoma. CONCLUSIONS: Malignancies occurred in 3.7% of patients followed up for celiac disease. Awareness of the malignant complications of celiac disease, risk factors, presentation, and disease course could lead to earlier diagnosis and improved outcomes.

Lack of Association between Epidermal Growth Factor or Its Receptor and Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma: A Case-Control Study.

The epidermal growth factor (EGF) and its receptor (EGFR) gene-gene interactions were shown to increase the susceptibility to esophageal cancer. However, the role of the EGF/EGFR pathway in the development of gastroesophageal reflux disease (GERD) and its complications (reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC)) remains unclear. This association study is aimed at investigating functional EGF and EGFR gene polymorphisms, their mRNA expression in esophageal tissues, and EGF plasma levels in relation to RE, BE, and EAC development in the Central European population. 301 patients with RE/BE/EAC (cases) as well as 98 patients with nonerosive reflux disease (NERD) and 8 healthy individuals (controls) were genotyped for +61 A>G EGF (rs4444903) and +142285 G>A EGFR (rs2227983) polymorphisms using the TaqMan quantitative polymerase chain reaction (qPCR). In random subgroups, the EGF and EGFR mRNA expressions were analyzed by reverse transcription qPCR in esophageal tissue with and without endoscopically visible pathological changes; and the EGF plasma levels were determined by enzyme-linked immunosorbent assay. None of the genotyped SNPs nor EGF-EGFR genotype interactions were associated with RE, BE, or EAC development (p > 0.05). Moreover, mRNA expression of neither EGF nor EGFR differed between samples of the esophageal tissue with and without endoscopically visible pathology (p > 0.05) nor between samples from patients with different diagnoses, i.e., RE, BE, or EAC (p > 0.05). Nevertheless, the lower EGF mRNA expression in carriers of combined genotypes AA +61 EGF (rs4444903) and GG +142285 EGFR (rs2227983; p < 0.05) suggests a possible direct/indirect effect of EGF-EGFR gene interactions on EGF gene expression. In conclusion, EGF and EGFR gene variants and their mRNA/protein expression were not associated with RE, BE or EAC development in the Central European population.

The Use of Confocal Laser Endomicroscopy in Diagnosing Barrett's Esophagus and Esophageal Adenocarcinoma.

Confocal laser endomicroscopy (CLE) is a diagnostic technique that enables real-time microscopic imaging during microscopic examination and evaluation of epithelial structures with 1000-fold magnification. CLE can be used in the diagnosis of various pathologies, in pneumology, and in urology, and it is very widely utilized in gastroenterology, most importantly in the diagnosis of Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), biliary strictures, and cystic pancreatic lesions. A literature search was made in MEDLINE/PubMed and Google Scholar databases while focusing on diagnostics using CLE of BE and EAC. We then examined randomized and observational studies, systematic reviews, and meta-analyses relating to the utilization of CLE in BE and EAC diagnostics. Here, we discuss whether CLE can be a suitable diagnostic method for surveillance of BE. Even though many studies have proven that CLE increases diagnostic accuracy in detecting neoplastic transformation of BE, CLE is still not used as a standard diagnostic tool in BE surveillance due to a deficiency of scientific evidence. More studies and data are needed if CLE is to find a place as a new technique in BE surveillance.

CYP2C19 Gene Profiling as a Tool for Personalized Stress Ulcer Prophylaxis With Proton Pump Inhibitors in Critically Ill Patients - Recommendations Proposal.

To this date, there are no recommendations for personalized stress ulcer prophylaxis (SUP) in critical care that would take the patient's individual genetic predispositions into account. Of drugs used for this purpose, proton pump inhibitors (PPIs) are the first-choice drugs in intensive care unit patients. The degradation of proton pump inhibitors is mediated by cytochrome P450 (CYP) enzymes; in particular, CYP2C19 and, to a lesser extent, CYP3A4 are involved. Expression and metabolic activity of, namely in, CYP2C19 is significantly affected by single nucleotide polymorphisms, the drug metabolization rate varies greatly from ultrarapid to poor and likely influences the optimal dosage. As these CYP2C19 predictive phenotypes via CYP2C19 haplogenotypes (rs12248560/rs4244285) can be relatively easily determined using the current standard equipment of hospital laboratories, we prepared a set of recommendations for personalized PPI-based stress ulcer prophylaxis taking into account the patient's CYP2C19 predictive phenotype determined in this way. These recommendations are valid, in particular, for European, American and African populations, because these populations have the high representations of the CYP2C19*17 allele associated with the overexpression of the CYP2C19 gene and ultrarapid degradation of PPIs. We propose the CYP2C19 gene profiling as a tool for personalized SUP with PPI in critically ill patients.

Achalasia and acromegaly: Co-incidence of these diseases or a new syndrome?

BACKGROUND: Acromegaly is a disorder associated with hypersecretion of growth hormone, most usually caused by a pituitary adenoma. Dysmotility of the gastrointestinal tract has been reported in acromegalic patients. Achalasia is a disorder characterized by aperistalsis of the oesophagus with incomplete lower oesophageal sphincter relaxation and whose aetiology remains unknown. Mutations in some genes have previously been associated with the development of acromegaly or achalasia. The study aims were to analyse mutations in selected genes in a woman having both of these diseases, to identify their aetiological factors, and to suggest explanations for the co-incidence of acromegaly and achalasia. METHODS AND RESULTS: A female patient with acromegaly, achalasia, and a multinodular thyroid gland with hyperplastic colloid nodules underwent successful treatment of achalasia via laparoscopic Heller myotomy, a thyroidectomy was performed, and the pituitary macroadenoma was surgically excised via transnasal endoscopic extirpation. Germline DNA from the leukocytes was analysed by sequencing methods for a panel of genes. No pathogenic mutation in AAAS, AIP, MEN1, CDKN1B, PRKAR1A, SDHB, GPR101, and GNAS genes was found in germline DNA. The somatic mutation c.601C>T/p.R201C in the GNAS gene was identified in DNA extracted from a tissue sample of the pituitary macroadenoma. CONCLUSIONS: We here describe the first case report to our knowledge of a patient with both acromegaly and achalasia. Association of acromegaly and soft muscle tissue hypertrophy may contribute to achalasia's development. If one of these diagnoses is determined, the other also should be considered along with increased risk of oesophageal and colorectal malignancy.

Overexpression of CD44v8-10 in Colon Polyps-A Possible Key to Early Diagnosis.

Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon. Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses. Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner. Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique. Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.

Liver cirrhosis and pregnancy: a case report and review of literature.

Liver cirrhosis is a chronic liver disease in which the liver tissue and the vascular beds are remodeled leading to impaired hepatic function. Portal hypertension and subsequent esophageal varices are a frequent complication of liver cirrhosis and are a cause of mortality in patients with liver cirrhosis. Pregnancy in women with liver cirrhosis is uncommon, the incidence being about 1 in 5 950 pregnancies. Hepatocellular damage and the associated alteration in the metabolism of the sex hormones is thought to be responsible and leads to anovulation. In spite of all these factors, women with cirrhosis can and do become pregnant. Pregnancy is successful in most of the patients with chronic liver disease, but maternal and fetal complication rates are still high for decompensated liver cirrhosis. Portal hypertension associated with pregnancy is a high-risk situation as both pregnancy and portal hypertension share some of the hemodynamic changes. Risks of variceal bleeding and hepatic decompensation increases many fold during pregnancy. Despite the possible complications mentioned above, the maternal-fetal morbidity and mortality rates have been decreased by the current developments in hepatology, prevention of bleeding from varices with drugs and/or endoscopic variceal ligation, improvement in liver transplantation, and an increased experience in these issues. We present a case of a 31-year-old female patient with liver cirrhosis who successfully managed pregnancy and birth without complications after the insertion of transjugular intrahepatic portosystemic shunt (TIPS). Unfortunately, 2 years after delivery, the patient developed lymphoblastic lymphoma and, despite intensive therapy for this disease, the patient died at the age of 40. We did not find any link between liver cirrhosis and lymphoblastic lymphoma.

Unusual Biliary Complication following Christmas Eve Dinner.

We present a case of a fish bone impacted in the papilla of Vater resulting in dyspepsia and mild elevation in liver function tests, which was subsequently treated endoscopically. Fish bones are one of the most commonly encountered swallowed foreign bodies. However, involvement of the biliary tract, such as the one described by us, represents an extremely rare complication of fish bone ingestion. The diagnosis of a foreign body in the biliary tract can be difficult, and early endoscopic or surgical extraction may be required to avoid complications such as biliary stone formation, obstructive jaundice, cholangitis or cholecystitis, and/or biliary sepsis. Prompt endoscopic treatment can avoid severe biliary complications or surgical therapy.

Biomarkers for non-endoscopic examination of esophageal mucosa.

Gastroesophageal reflux disease (GERD) is a multifactorial disease; an individual´s genetic predisposition may contribute to the development of this disorder. Endoscopic methods and histological examination are commonly used to diagnose GERD and its complications such as Barretts esophagus (BE) and esophageal adenocarcinoma (EAC). For BE screening in high-risk individuals as well as monitoring the development of BE dysplasia, esophageal mucosa samples could be taken using modern non-endoscopic procedures to minimize invasiveness of the procedure and improve patient adherence and compliance with a treatment. Esophageal mucosa samples taken by non-endoscopic or endoscopic biopsy can be analyzed both by immunohistochemistry and molecular biology analysis for specific biomarkers. Markers such as caudal type homeobox 2 (CDX2) and protein p53 have found their use in GERD diagnosis, and therefore research in recent years has focused on identifying other biomarkers that could reliably predict the development and progression of BE or EAC. This review article summarizes information on modern non-endoscopic methods of sampling from the esophagus mucosa and biomarkers, which have been studied in connection with the prediction and diagnosis of BE and EAC and have a potential for the use in clinical practice.

Small bowel adenocarcinoma diagnosed by video capsule endoscopy in a patient with celiac disease: a case report and review of literature.

Celiac disease is an immune mediated entheropathy triggered by gluten in genetically predisposed individuals. Patients with celiac disease are at a higher risk of gastrointestinal malignancies. Diagnosis at an advance stage is one of the factors of an unfavorable prognosis of these complications. Our patient is a woman who was diagnosed with celiac disease at 53 years of age. After two years on a gluten-free diet she developed sideropenic anemia. No source of bleeding was found on the esophagogastroduodenoscopy or colonoscopy. Video capsule endoscopy revealed exulcerated bleeding stenosis in the jejunum, in front of which the capsule lodged. There were no signs of infiltration on simultaneous CT enterography. The patient was operated on and the infiltration of the jejunum was resected. The specimen was evaluated by a histopathologist as a moderately differentiated adenocarcinoma. Due to the risk factors, the patient received adjuvant chemotherapy. The knowledge of the malignant complications of celiac disease, their risk factors and the possibilities of modern enteroscopic methods could help in the early diagnosis and improvement of the prognosis of these diseases. Due to a lack of data and an absence of guidelines, treatment of a small bowel adenocarcinoma is based on an expert agreement and guidelines for colon cancer. Surgical treatment is the only potentially curative option. For stage II with risk factors and stage III adjuvant chemotherapy should be considered.

Incidence trends of esophageal cancer in the Czech Republic by histological subtype and stage and prescription rate of acid suppressing drugs.

BACKGROUND: Incidence of esophageal adenocarcinoma (EAC) associated with gastroesophageal reflux disease has increased substantially in developed countries during the past decades. We aimed to analyze trends in incidence of esophageal cancer (EC) by histological subtypes and trends in acid suppressing drugs prescription in the Czech Republic. METHODS: The incidence of EC by histological subtypes, sex, and stage from 1984-2017 was examined using data from the Czech National Cancer Registry. Defined daily doses of acid inhibiting drugs were analyzed from annual reports by the State Institute for Drug Control. RESULTS: Age standardized incidence of EAC in men increased annually by 4.88 % with 95 % confidence interval (CI) (4.32, 5.45) from 1984 to 2017, and by 5.11 % (95 % CI, 4.02, 6.20) in women. Squamous cell carcinoma increased annually by 5.52 % (95 % CI, 2.49, 8.64) from 1984 to 1994 with subsequent slower increase by 0.87 % (95 % CI, 0.25, 1.50) from 1994 to 2017. It still represents 50 % of all EC in 2017. The comparable early stages of EAC showed similar annual percentage change of 5.77 %. From 2001 to 2018 the use of proton pump inhibitors increased dramatically from 6.8 to 72.9 defined daily doses per 1000 inhabitants. CONCLUSION: The incidence of EAC is still increasing in the Czech Republic, however it represents less than half of ECs. The incidence of squamous cell carcinoma is relatively stable. Broad use of acid suppressing drugs did not seem to impact the incidence of EAC even in early stages.

Confocal laser endomicroscopy in the diagnostics of esophageal diseases: a pilot study.

BACKGROUND: Probebased confocal laser endomicroscopy (pCLE) is a novel diagnostic technique for endoscopy which enables a microscopic view at a cellular resolution in realtime. Endoscopic detection of early neoplasia in the distal esophagus is difficult and often these lesions can be missed. The aim of the pilot study was to obtain characteristic pCLE figures in esophageal diseases for following studies, and to evaluate the possible future role of pCLE in the diagnostics of dysplastic Barretts esophagus (BE) or early esophageal adenocarcinoma (EAC). METHODS: A review of the current literature was performed and previously published pCLE images and classifications of esophageal diseases were searched and studied first. In phase two of the pilot study patients with esophageal diseases such as reflux esophagitis, BE and EAC were enrolled and scheduled for upper endoscopy with pCLE. A healthy cohort was also included. RESULTS: From January 2019 to July 2019, a total of 14 patients were enrolled in this prospective pilot study: 3 patients with reflux esophagitis, 4 with BE, 3 with EAC and 4 persons were included in the healthy cohort. The endoscopy with pCLE was performed and characteristic pCLE figures were obtained. The correct diagnoses based on realtime pCLE were evaluated by an endoscopist in 11 of the 14 cases (78.6 %). CONCLUSION: It was possible to obtain typical pCLE images of esophageal diseases during a standard capassisted endoscopic procedure. pCLE seems to be a feasible new technique in BE surveillance and early neoplastic lesion detection. However, more studies and data on larger number of patients are needed.

Non-invasive prediction of persistent villous atrophy in celiac disease.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy that is primarily treated with a gluten-free diet (GFD). Mucosal healing is the main target of the therapy. Currently, duodenal biopsy is the only way to evaluate mucosal healing, and non-invasive markers are challenging. Persistent elevation of anti-tissue transglutaminase antibodies (aTTG) is not an ideal predictor of persistent villous atrophy (VA). Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies (aDGP) and abdominal ultrasonography are lacking. AIM: To evaluate the ability of aTTG, aDGP, small bowel ultrasonography, and clinical and laboratory parameters in predicting persistent VA determined using histology. METHODS: Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy, levels of aTTG and aDGP, and underwent small bowel ultrasonography were included in this retrospective cohort study. We evaluated the sensitivity, specificity, and positive and negative predictive values of aTTG, aDGP, small bowel ultrasonography, laboratory and clinical parameters to predict persistent VA. A receiver operating characteristic (ROC) curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction. RESULTS: Complete data were available for 82 patients who were followed up over a period of four years (2014-2018). Among patients included in the analysis, women (67, 81.7%) were predominant and the mean age at diagnosis was 33.8 years. Follow-up biopsy revealed persistent VA in 19 patients (23.2%). The sensitivity and specificity of aTTG using the manufacturer's diagnostic cutoff value to predict atrophy was 50% and 85.7%, respectively, while the sensitivity and specificity of aDGP (using the diagnostic cutoff value) was 77.8% and 75%, respectively. Calculation of an optimal cutoff value using ROC analysis (13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA) increased the accuracy and reached 72.2% [95% confidence interval (CI): 46.5-90.3] sensitivity and 90% (95%CI: 79.5-96.2) specificity for aDGP IgA and 66.7% (95%CI: 41.0-86.7) sensitivity and 93.7% (95%CI: 84.5-98.2) specificity for aTTG IgA. The sensitivity and specificity of small bowel ultrasonography was 64.7% and 73.5%, respectively. A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9% and 98% for aTTG IgA and to 90.0% and 97.8% for aDGP IgA. Laboratory and clinical parameters had poor predictive values. CONCLUSION: The sensitivity, specificity, and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values. The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Acute portal vein thrombosis in noncirrhotic patients - different prognoses based on presence of inflammatory markers: a long-term multicenter retrospective analysis.

Background: Portal vein thrombosis (PVT) is a partial or complete thrombotic occlusion of the portal vein and is rare in noncirrhotic patients.Patients and methods: 78 adult patients with noncirrhotic acute PVT without known malignity were evaluated. Patients with initial CRP level 61-149 mg/l were excluded.Results: Patients were divided into two groups - the first one (33 patients) was characterized with signs of inflammation and CRP over 149 mg/l. The second group (45 patients) was without signs of inflammation and CRP level less than 61 mg/l. The frequency of prothrombotic hematologic factors was statistically significantly different in levels of factor VIII and MTHFR 677 C mutation. All patients from both groups underwent the same oncologic and hemato-oncologic screening which was positive in 23 patients (51.1%) in the group without signs of inflammation. In the group of patients with clinical and laboratory signs of inflammation oncologic and hemato-oncologic screening was positive only in 1 patient (3.0%). Complete portal vein recanalization was achieved in 19.2%, partial recanalization in 26.9%.Conclusions: Patients with clinical signs of inflammation and acute PVT have a low risk of malignancy in contrast to patients without signs of inflammation and acute PVT, which have a high risk of oncologic or hemato-oncologic disease. Patients with negative hemato-oncologic screening should be carefully observed over time because we expect they are at higher risk for the development of hemato-oncologic disease, independent from the presence and number of procoagulation risk factors.

GAPPS - Gastric Adenocarcinoma and Proximal Polyposis of the Stomach Syndrome in 8 Families Tested at Masaryk Memorial Cancer Institute - Prevention and Prophylactic Gastrectomies.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare variant of familial adenomatous polyposis. It is an autosomal-dominant cancer-predisposition syndrome with massive polyposis of the stomach and a significant risk of gastric adenocarcinoma. Li et al., 2016, described point mutations in the Ying Yang 1 binding site of the APC gene 1B promoter associated with GAPPS syndrome. The first GAPPS syndrome in a Czech family was described in 2016. At Masaryk Memorial Cancer Institute, GAPPS syndrome was diagnosed in eight families using Sanger sequencing. In all families, one mutation in promoter 1B of APC gene NM_001127511: c.-191T>C was detected. This mutation was not found in any patient with multiple colon polyposis without a detected classic mutation in the APC gene. In total, 24 carriers of this mutation in promoter 1B of the APC gene were detected. Out of those 24 carriers, 20 had massive gastric polyposis with more than 100 fundic glandular polyps diagnosed between the age of 22 and 65, 5 had already died of adenocarcinoma of the stomach (at the ages of 29, 40, 59, 60 and 64, respectively) and another woman was treated at the age of 29. Two female carriers do not yet have polyposis of the stomach at the ages of 31 and 65, respectively; one female carrier has incipient polyposis at the age of 58. A male carrier does not have any clinical symptoms, gastroscopy was not indicated because of his age. Prophylactic total gastrectomy with D2 lymphadenectomy has already been performed 6 times at Masaryk Memorial Cancer Institute, in 5 cases without adenocarcinoma at the ages of 27, 34, 44, 51 and 66, respectively; in one female carrier adenocarcinoma of the stomach was detected in a histology specimen. Two prophylactic gastrectomies with D1 lymphadenectomy were performed at University Hospital Brno at the ages of 42 and 50, respectively. In the Czech Republic point mutation c.-191T>C (rs879253783) in the 1B promoter of the APC gene is a frequent cause of gastric polyposis with a high risk of gastric adenocarcinoma, even at a young age. Positively tested individuals are recommended to high-risk oncology clinic. A necessary part of the discussion with the patient is information about a preventive gastrectomy.

Viewpoints of the target population regarding barriers and facilitators of colorectal cancer screening in the Czech Republic.

BACKGROUND: Public awareness of colorectal cancer (CRC) and uptake of CRC screening remain challenges. The viewpoints of the target population (asymptomatic individuals older than 50) regarding CRC screening information sources and the reasons for and against participation in CRC screening are not well known in the Czech Republic. This study aimed to acquire independent opinions from the target population independently on the health system. AIM: To investigate the viewpoints of the target population regarding the source of information for and barriers and facilitators of CRC screening. METHODS: A survey among relatives (aged 50 and older) of university students was conducted. Participants answered a questionnaire about sources of awareness regarding CRC screening, reasons for and against participation, and suggestions for improvements in CRC screening. The effect of certain variables on participation in CRC screening was analyzed. RESULTS: Of 498 participants, 478 (96%) respondents had some information about CRC screening and 375 (75.3%) had participated in a CRC screening test. General practitioners (GPs) (n = 319, 64.1%) and traditional media (n = 166, 33.3%) were the most common information sources regarding CRC screening. A lack of interest or time and a fear of colonoscopy or positive results were reported as reasons for non-participation. Individuals aged > 60 years [adjusted odds ratio (aOR) = 2.30, 95% confidence interval (CI) (1.42-3.71), P = 0.001], females (aOR = 1.95, 95%CI (1.26-3.01) P = 0.003), and relatives of CRC patients (aOR = 4.17, 95%CI (1.82-9.58) P = 0.001) were more likely to participate in screening. Information regarding screening provided by physicians - GPs: (aOR = 8.11, 95%CI (4.90-13.41), P < 0.001) and other specialists (aOR = 4.19, 95%CI (1.87-9.38), P = 0.001) increased participation in screening. Respondents suggested that providing better explanations regarding screening procedures and equipment for stool capturing could improve CRC screening uptake. CONCLUSION: GPs and other specialists play crucial roles in the successful uptake of CRC screening. Reduction of the fear of colonoscopy and simple equipment for stool sampling might assist in improving the uptake of CRC screening.

Current trends in the diagnosis and treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease and its typical symptoms heartburn and regurgitation is one of the most common gastrointestinal disorders. Besides esophageal symptoms awareness of extraesophageal symptoms is increasing. The diagnosis is usually based on history of symptoms and on endoscopically visible esophageal injury in some patients. Normal endoscopic finding and refractory symptoms on standard treatment should evoke further examination. Proton pump inhibitors have been the mainstay of medical therapy. Long term maintenance treatment may raise awareness of side effects and therapeutic alternatives. This review is focused of current available diagnostic and therapeutic strategies for gastroesophageal reflux disease. Key words: Barrett´s esophagus - esophageal impedance - esophageal stricture - fundoplication - gastroeso-phageal reflux - gastroesophageal reflux disease - proton pump inhibitors.

The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies with increasing incidence. The poor prognosis is due to the aggressive nature of the tumor, late detection, and the resistance to chemotherapy and radiotherapy. A radical surgery procedure is the only treatment that has been shown to improve the 5-year survival rate to 20-25%. However, the majority of patients (80-85%) are diagnosed with locally advanced or metastatic disease and just 15-20% patients are diagnosed in an early stage allowing them to undergo the potentially curative surgical resection. The early detection of PDAC without the use of invasive methods is challenging and discovery of a cost-effective biomarker with high specificity and sensitivity could significantly improve the treatment and survival in these patients. In this review, we summarize current and newly examined biomarkers in early PDAC detection.