Radiofrequency Ablation in Patients with Barrett's Esophagus- related Neoplasia - Long-Term Outcomes in the Czech National Database.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) with/without endoscopic resection (ER) is the standard endoscopic treatment modality for Barrett's esophagus (BE) related neoplasia (BORN). The main aim of this study was to assess the long-term outcomes of RFA in patients with BORN. METHODS: We retrospectively analyzed the prospectively collected data from the Czech national database. Main outcomes were: complete remission of neoplasia (CR-N), complete remission of intestinal metaplasia (CR-IM), recurrence of both neoplasia and IM, and safety. RESULTS: From a total of 170 patients with BORN treated with RFA, 136 patients were analyzed. They were followed up for a median of 27.5 months. Fifty-six patients (41%) had low-grade intraepithelial neoplasia (LGIN), 46 (34%) had high-grade intraepithelial neoplasia (HGIN) and 34 (25%) had early adenocarcinoma (EAC). RFA was combined with previous ER in 65 patients (48%). CR-IM and CR-N were achieved in 77.9% (95% CI 70.0-84.6%) and 98.5% (95% CI 94.8-99.8%). Among 30 patients without CR-IM, 22 (73%) did not have macroscopic signs of BE. Recurrent neoplasia was detected in 4.5% of patients (6/134) and 15% (16/106) experienced a recurrence of IM at the level of the neo-Z-line. Diagnosis of cancer was an independent risk factor for recurrent IM after RFA (OR 7.0, 95% CI 1.6-30.9, p<0.0005). CONCLUSION: RFA is highly effective in achieving remission in patients with BORN. A significant proportion of patients did not achieve CR-IM or had a recurrence of IM despite macroscopically absent BE. Recurrence of neoplasia was infrequent but not negligible, thus, patients after successful RFA still require endoscopic surveillance.

Is functional dyspepsia really that frequent?

The literature shows, that the prevalence of functional dyspepsia is between 11 and 29.2 % in general population. The first goal of this study was to present a narrative review of the current findings of functional dyspepsia. The second goal was to find out the prevalence of functional dyspepsia in the II. Internal Clinic of Gastroenterology and Geriatry in Teaching Hospital of Olomouc (Czech Republic). According to the clinical experience, the prevalence of patients with functional dyspepsia seems to be not as high as literature shows. Normal gastroscopy findings are mandatory for the diagnosis of functional dyspepsia. That is why we examined 302 patients with indications for gastroscopy. According to the Rome IV criteria and normal gastroscopy findings, the diagnosis of functional dyspepsia was made only in 10 (3.31 %) patients. 108 patients have received repeated gastroscopy after 4 to 6 months period. But, none of them came with the diagnosis functional dyspepsia. Our results suggest, that the prevalence of functional dyspepsia after careful gastroscopic examination is lower than in the previous literature. This observation could change our view of functional dyspepsia and its diagnostics. Keywords: functional dyspepsia - gastroscopy - prevalence - Rome IV criteria.

[Epicardial fat and osteoprotegerin - does a mutual relation exist? Pilot study]. / Epikardiální tuk a osteoprotegerin - existují vzájemné souvislosti? Pilotní studie.

INTRODUCTION: Epicardial fat (EPI) plays important role in development of metabolic and cardiovascular diseases. According to population studies EPI represents independent risk factor of cardiovascular diseases (CVD) and also for neoplasms. Osteoprotegerin (OPG) is a glycoprotein which have role in regulation of immune and cardiovascular systems. High serum levels of OPG are connected with high cardiovascular risk. The aim of our study was to evaluate possible correlation between EPI and OPG level in asymptomatic relatives of patients with CVD. MATERIAL AND METHODS: 53 asymptomatic relatives (37 male) (median age 53 years) of patients with CVD (ischemic heart disease, cerebrovascular disease) were included. Physical examination and biochemistry analysis were performed. GE Vivid 7 (GE Medical) was used for echocardiography. EPI was measured according to guidelines using parasternal long axis in diastole as a space in front of right ventricle. RESULTS: EPI was present in 46 subjects (86.8 %) with mean value of 2.91 mm. In 10 subjects was the amount of EPI > 5 mm. Spearmann correlation analysis found statistically significant correlation between EPI and OPG (r = 0.271; p = 0.05) and age (r = 0.500; p < 0.0001). We have not found correlation between EPI, glycaemia and level of insulin, glycated Hb, total, LDL, HDL cholesterol and triglycerides. CONCLUSION: We have found positive correlation between EPI and OPG. More studies are needed to confirm applicability of this correlation in risk stratification.Key words: cardiovascular risk - epicardial fat - osteoprotegerin.

[Treatment of liver cirrhosis - actually possibility of ambulant internist]. / Aktuální moznosti lécby jaterní cirhózy v ambulanci internisty.

UNLABELLED: There are 40 000-60 000 patients with cirrhosis in the Czech Republic. 2 000 die of this disease yearly. This group of patients needs a complex treatment and it is mostly an internist cooperating with other specialists. The most important for an ambulant internist is to diagnose the disease as soon as possible and start with treatment of chronic liver disease that could lead to a cirrhosis. It means especially chronic viral hepatitis, alcoholic or non-alcoholic steatosis/steatohepatitis, auto-immune liver damage and metabolic disease. The next step is to diagnose the cirrhosis in time when it is in no manifest stage. The third step is to diagnose and treat the liver decompensation. It means consequences of the portal hypertension, it is ascit, esophageal or gastric varices, hepatorenal syndrome. Next there are consequences of the metabolic insufficiency, it is icterus, coagulopathy and hepatic encephalopathy. It is necessary to diagnose and cure cholestasis from the very first extrahepatic causes. For a successful treatment of the hepatocellular carcinoma originated almost exclusively in the grounds of the cirrhosis must be early diagnosed. The ambulant internist respective hepatologist must diagnose the stage of the cirrhosis and decide when a hospitalization is necessary. Also a close cooperation with other specialists is urgent if it is about a liver transplantation. The treatment of successive stages of the cirrhosis is a topic of the showed educational article. KEY WORDS: compensated/decompensated liver cirrhosis - diet/nutrition in liver cirrhosis - etiology and diagnose of liver cirrhosis - treatment of liver insufficiency/failure - treatment of portal hypertension and its complications.

Acute pancreatitis as the first manifestation of duodenal MALT lymphoma.

BACKGROUND: Possibly any tumor that can cause mechanical obstruction of the distal bile duct can induce acute pancreatitis. However, acute pancreatitis as the first clinical manifestation of duodenal lymphoma is extremely rare. OBJECTIVE: To report the case of a patient with acute pancreatitis as an extremely rare first manifestation of duodenal MALT lymphoma and possible association with erythema nodosum. METHODS: Case report of a 66-year-old woman who was diagnosed with acute pancreatitis caused by infiltration with duodenal lymphoma. RESULTS: Acute pancreatitis was confirmed by CT imaging. Detailed investigation revealed a duodenal mass causing pancreatic injury. Histological analysis established the diagnosis of MALT lymphoma. The patient's medical history also included erythema nodosum. Complete remission of the malignancy was achieved with chemotherapy. CONCLUSION: This is the first published case report of acute pancreatitis caused by the growth of duodenal MALT lymphoma. An association with erythema nodosum is possible.

Treatment of recent-onset type 1 diabetic patients with DiaPep277: results of a double-blind, placebo-controlled, randomized phase 3 trial.

OBJECTIVE: To evaluate safety and efficacy of DiaPep277 in preserving ß-cell function in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: DIA-AID 1 is a multinational, phase 3, balanced-randomized, double-blind, placebo-controlled, parallel-group clinical study. Newly diagnosed patients (N = 457, aged 16-45 years) were randomized to subcutaneous injections of DiaPep277 or placebo quarterly for 2 years. The primary efficacy end point was the change from baseline in the area under the glucagon-stimulated C-peptide curve. Secondary end points were the change from baseline in mixed-meal stimulated C-peptide secretion and in fasting C-peptide and achieving target HbA1c ≤7% (≤53 mmol/mol). Partial remission (target HbA1c on insulin ≤0.5 units/kg/day) and hypoglycemic event rate were exploratory end points. RESULTS: DiaPep277 was safe and well tolerated. Significant preservation of C-peptide secretion was observed in the DiaPep277-treated group compared with the placebo (relative treatment effects of 23.4%, P = 0.037, and 29.2%, P = 0.011, in the modified intent-to-treat [mITT] and per-protocol [PP] populations, respectively). The mixed-meal stimulation failed to distinguish between the groups. There was a trend toward efficacy in fasting C-peptide levels, though not statistically significant. Significantly more DiaPep277-treated than placebo-treated patients maintained target HbA1c (mITT 56% versus 44%, P = 0.03; PP 60% versus 45%, P = 0.0082) and entered partial remission (mITT 38% versus 29%, P = 0.08; PP 42% versus 30%, P = 0.035). DiaPep277 treatment reduced the relative hypoglycemic event risk (mITT by 20%; PP by 28%). CONCLUSIONS: DiaPep277 safely contributes to preservation of ß-cell function and to improved glycemic control in patients with type 1 diabetes.

Mitochondrial changes in adenocarcinoma of the pancreas.

The aim of our study was to analyse the mitochondrial ultrastructure in primary ductal adenocarcinomas of the pancreas and to compare it with normal pancreatic cells. 52 samples of adenocarcinoma of the pancreas obtained by surgical resection or by endosonographic biopsy were examined. Compared to normal mitochondrial ultrastructure in non-tumorous cells, the mitochondria in cancer cells had a dense matrix and condensed configuration or with lucent-swelling matrix associated with disarrangement and distortion of cristae and partial or total cristolysis. Functionally, these structural alterations presume the presence of hypoxia-tolerant and hypoxia-sensitive cancer cells.

Acute upper gastrointestinal bleeding in liver cirrhosis patients.

OBJECTIVES: This study focuses on the etiology of acute upper gastrointestinal (GIT) bleeding in liver cirrhosis patients. METHODS: A prospective examination of 137 liver cirrhosis patients with acute upper GIT bleeding. All patients underwent endoscopic examination and in the case of multiple findings, definition of the source of bleeding was based on the endoscopic report. RESULTS: The most frequent causes of acute bleeding were: oesophageal varices (57.7%), peptic gastric and duodenal ulcers (18.2%), portal hypertension gastropathy (9.5%), gastric varices (5.1%), reflux oesophagitis (2.9%), Mallory-Weiss syndrome (2.9%) and erosive gastropathy (1.5%). A negative diagnosis was made in not more than 2.2% of patients. The majority of cases showed multiple findings in the upper digestive tract, each of which was a potential cause of bleeding. The mortality in all bleeding cirrhotic patients was 14.6%, 18.6% of which occurred in the varicose type of bleeding and 7.8% in the non-varicose type. CONCLUSIONS: Portal hypertension led to bleeding caused by varices and portal hypertension gastropathy in 72.3% of patients, 62.8% of patients suffered from purely varicose bleeding and 37.2% from non-varicose bleeding. Early, detailed endoscopic examination leading to appropriate diagnosis and treatment is of paramount importance.

Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals.

BACKGROUND: Barrett's esophagus (BE) is a disease with a rising prevalence in western countries probably due to the unhealthy lifestyle. In significant number of cases it develops to esophageal adenocarcinoma. Two decades ago, important gene regulators (microRNAs) were discovered and their attendance in the process of malignant transformation was demonstrated (e.g. miR-192, 196a, 203). Our aim was to select the patients with the increased risk of malignant transformation before the cancer develops. METHODS: 71 patients with BE disease were selected, slides from FFPE blocks were prepared, the lesions were microdissected and a qPCR relative expression analysis for selected microRNAs (generally known to be connected with malignant transformation process) was carried out. RESULTS: We demonstrated unequivocal statistically significant upregulation of two microRNAs (miR-192, 196a) and downregulation of miR-203 and positive miR-196a correlation with progression from intestinal metaplasia to adenocarcinoma compared to normal individuals. CONCLUSIONS: We hypothesize that there do exist changes of selected microRNAs which can undoubtedly distinguish the patients with BE from normal healthy individuals.

Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding.

Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices.

Endosonography versus endoscopic retrograde cholangiopancreatography in diagnosing extrahepatic biliary obstruction.

OBJECTIVE: Endosonography (EUS) performed prior to endoscopic retrograde cholangiopancreatography (ERCP) or surgery in patients with a low to moderate probability of choledocholithiasis can reduce morbidity, mortality and costs. AIMS: This study aimed at evaluating the sensitivity and specificity of EUS and transabdominal ultrasonography (TUS) compared to ERCP in a cohort of 100 patients diagnosed with extrahepatic biliary obstruction. METHODS: There were four working groups. The first group processed the initial data including history, physical examination and assessment of laboratory markers of cholestasis. The second group examined TUS. The third group examined the pancreas and biliary tree using EUS, always prior to ERCP. The fourth working group carried out ERCP. RESULTS: The sensitivity and accuracy of EUS in the diagnosis of common bile duct dilatation were 84% and 83%, respectively, i.e. significantly higher (p=0.0001) than TUS (46% and 66%, respectively). The specificities of methods (82%, 91%) were not significantly different (p=0.218). The sensitivity and accuracy of EUS in the diagnosis of pathological content of the common bile duct were 88% and 92%, respectively, i.e. significantly higher (p<0.0001) than TUS (33% and 64%). The specificities of the methods (96%, 94%) were not significantly different (p=0.641). The incidence of choledocholithiasis in the high-risk group was significantly higher than in the moderate-risk group (p=0.012). CONCLUSION: Radial EUS is a method with high sensitivity, specificity, positive and negative predictive values. It should therefore be preferred to ERCP in patients with low or moderate risk of choledocholithiasis.

Incidence, severity, and etiology of drug-induced acute pancreatitis.

INTRODUCTION: Drug-induced acute pancreatitis is considered to be a rare diagnosis. The incidence of drug-induced acute pancreatitis is usually estimated from case reports. AIM: The aim of this study was to determine the incidence, etiology, and severity of drug-induced pancreatitis during a 2-year period in a tertiary hospital. METHODS: The study was conducted as a retrospective analysis of all cases of pancreatitis in the University Hospital in Olomouc (1,432 beds) in 2006-2007. All cases of acute pancreatitis were re-evaluated and divided according to the causative factor. In drug-induced cases, the WHO Probability Scale for the evaluation of causality relationship was used. RESULTS: The inclusion criteria were met by 170 medical files. There were 91 (53%) cases in men and 79 (47%) in women, and mean age was 57 years old (5-91 years old). The etiology was in 53% biliary, 31% alcohol-induced, 12% other determined, and in 4% the cause could not be established. The proportion of drug-induced acute pancreatitis was 5.3% and it was the third most frequent cause of the AP. Azathioprine was the most frequent causative factor (three cases in two patients); all the other causative drugs were documented only in single cases: mesalazine, dexamethasone, ramipril, mycophenolate mofetil, cytarabine, and valproate. CONCLUSIONS: The diagnosis of drug-induced acute pancreatitis seems to be underestimated because of the difficulties in determining the causative agent and the need for a retrospective re-evaluation of the suspected causative factors. The disease is more probable in younger persons, women, and patients suffering from Crohn's disease.

Double-blind randomized multicenter study comparing the efficacy and safety of 10-day to 5-day terlipressin treatment of bleeding esophageal varices.

BACKGROUND/AIMS: The aim of the study was to compare the efficacy and safety of 5-day terlipressin treatment of bleeding esophageal varices to 10-day treatment period. METHODOLOGY: Of 25 patients with variceal bleeding, 15 were randomized to receive terlipressin for day 1-5 and placebo for day 6-10 (Group A), and 10 to receive terlipressin for day 1-10 (Group B). RESULTS: The bleeding was stopped in 24 patients (96%). Rebleeding till day 42 was observed in 9 (36%) patients (5 in group A, 4 in group B, ns). 2 patients died in group B (due to rebleeding till day 5) and one in group A (rebleeding between day 5-10). Transfusion needs were lower in group B (2.7 +/- 2.6TU compared to 4.13 +/- 5.8 TU in group A, ns). Serious AE leading to treatment discontinuation were observed in 1 patient in group A (peripheral ischemia) and none in B, non-significant AE in 3 patients in group A (hypertension), and in 3 in group B (hypertension, hyponatremia, epiparoxysm). CONCLUSIONS: Prolonged treatment with terlipressin did not prove significant decrease of mortality or bleeding recurrence; lower rebleeding rate after day 5 and tendency towards lower transfusion requirements were observed. Prolonged treatment had no influence on AE rate.

Endoscopic treatment of multiple pancreatic abscesses case report and review of the literature.

AIMS: Pancreatic abscesses are treated surgically and the role of endotherapy is still to be established. We describe the case of successful endoscopic management of two pancreatic abscesses in a critically ill patient. METHODS: A patient was admitted to the hospital for severe acute pancreatitis. One month later the patient developed pancreatic sepsis. CT scan showed two large abscesses. The first was bulging to the posterior wall of the stomach and another at the tail of the pancreas. Parenteral antibiotic therapy was administered. The clinical status of the patient rapidly deteriorated and the patient was unfit for surgical intervention. The endoscopic retrograde cholangiopancreatography was performed. The pancreatic duct communicated with the abscess at the tail of the pancreas. The drainage of this abscess was done transpapillarily. Endoscopic cystogastrostomy was performed to treat the pancreatic abscess that bulged to the posterior gastric wall. A double nasocystic tube was placed for continuous lavage of the abscess. Pseudomonas aeruginosa was cultured and antibiotics were administered according to sensitivity tests. The clinical status returned gradually to normal. A follow-up CT scan 4 months later showed complete resolution of abscesses. RESULT: The drainage of the abscesses was done by the means of endoscopic cystogastrostomy and transpapillary stent insertion. This was a minimally invasive intervention, by which we avoided surgical intervention that bears significant mortality and morbidity. CONCLUSION: Endoscopic drainge of pancreatic abscesses may be the therapy of choice in such patients mainly because it does not prevent the chance of subsequent surgical intervention if needed.

Terlipressin-induced ventricular arrhythmia.

During intravenous treatment with terlipressin for recurrent gastrointestinal (GI) bleeding, a 50-year-old male with no history of heart disease developed a newly prolonged QT interval and torsade de pointes. Risk factors present for acquired long QT syndrome were mineral dysbalance and a history of alcohol abuse with hepatic impairment. The patient was brought back to a normal sinus rhythm after a single 300-J counter-shock. Terlipressin was discontinued, and the patient's QTc interval subsequently returned to baseline. During 6 weeks of monitoring, arrhythmia did not recur.