Miroslav Vujasinovic

Low prevalence of exocrine pancreatic insufficiency in patients with diabetes mellitus

INTRODUCTION Exocrine pancreatic insufficiency (EPI) can occur in patients with diabetes mellitus (DM). Incidence of EPI and its clinical significance remain poorly defined. The aim of our study was to determine whether exocrine pancreatic function is impaired in patients with DM. PATIENTS AND METHODS One hundred and fifty consecutive patients, mean age 59.0 (± 12.0 years), with DM lasting at least 5 years were included in the study. We included 50 patients with type 1 DM (DM1), 50 insulin-treated patients DM type 2 (DM2-insulin) and 50 non-insulin treated patients with DM type 2 (DM2 no-insulin). Diagnosis of DM was established from health records, lasting 15.0 ± 9.9 years on average. EPI was diagnosed with a fecal elastase-1 concentration (FE1) of less than 200 μg/g (ELISA). RESULTS FE1 was reduced in 8 (5.4%) patients: mildly reduced (100-200 μg/g) in 4 patients (2.7%) and markedly reduced (<100 μg/g) in 4 patients (2.7%). Frequency of EPI was 3 in DM1, 5 in DM2(insulin) and none in DM2 (no-insulin) groups. CONCLUSIONS EPI in DM occurred less frequently than in previous studies, probably due to our strict exclusion criteria (age, alcohol intake).

Randomized clinical trial comparing 10-day sequential, 7-day concomitant and 7-day standard triple therapies for Helicobacter pylori eradication.

Objectives To compare triple therapy with sequential and concomitant therapies directly in a head-to-head comparison in Helicobacter pylori-infected patients. Design Patients were allocated randomly as follows: a triple therapy with esomeprazole (20 mg), amoxicillin (1000 mg) and clarithromycin (500 mg) twice daily for 7 days; a sequential therapy with 5 days of esomeprazole (20 mg) and amoxicillin (1000 mg) twice daily, followed by 5 days of esomeprazole (20 mg), clarithromycin (500 mg) and metronidazole (400 mg) twice daily; or a concomitant therapy consisting of esomeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg) twice daily for 7 days. Results A total of 356 consecutive patients were included. The eradication rates for the triple, sequential and concomitant therapies were 83.6% [95% confidence interval (CI) 76.9–90.4%], 94.2% (95% CI 90.0–98.4%) and 91.7% (95% CI 86.7–96.6%), respectively, in the intention-to-treat population. The differences were significant only between triple and sequential therapies (P=0.01). The primary resistance rates to amoxicillin, clarithromycin and metronidazole were 0.6, 10.5 and 25.9%, respectively. Concomitant therapy was significantly better than triple therapy in cases with clarithromycin resistance (P=0.01). Conclusion Ten-day sequential therapy was significantly better than 7-day triple therapy in a clinical setting with low rates of clarithromycin and dual resistance. Concomitant therapy was significantly better than standard triple therapy in the subgroup of patients with clarithromycin-resistant strains.

Pancreatic Exocrine Insufficiency in Pancreatic Cancer

Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis.

AIM To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. RESULTS One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. CONCLUSION As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful.

Exocrine pancreatic insufficiency, MRI of the pancreas and serum nutritional markers in patients with coeliac disease

Objectives To determine whether exocrine pancreatic function is impaired in patients with coeliac disease (CD) in our population and to evaluate its clinical importance. Methods Pancreatic exocrine function was determined by measuring faecal elastase-1 (FE) concentration. CD was diagnosed by serological testing using IgA anti-tissue transglutaminase antibody (IgAtTg) and small bowel biopsy using the Marsh classification. MRI of the pancreas was performed to evaluate any morphological changes. The study took place from January 2012 to December 2013. Results 90 patients (73 women and 17 men) of mean age 43.8±17.7 years (range 20–80) were included in the study. Mean time from CD confirmation was 5.8±0.7 years (range 1–25). Exocrine pancreatic insufficiency (EPI) was diagnosed in four (4.4%) patients (one with mild EPI and three with severe EPI). MRI showed no morphological changes in any of the four patients. In all patients with EPI at least one serological nutritional marker was below the lower limit of normal. Conclusions EPI is present in a small number of patients with CD. EPI should be excluded in all patients with CD in the presence of overt malnutrition or in cases of persistent gastrointestinal symptoms despite a gluten-free diet. Measurement of a serum nutritional panel, regardless of the presence of clinical symptoms of EPI, can be of clinical importance. MRI should be performed to exclude any morphological change in the pancreas.

The Scandinavian baltic pancreatic club (SBPC) database: design, rationale and characterisation of the study cohort

Abstract Objectives: Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. Methods: Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. Results: The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48–67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. Conclusion: The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent.

Helicobacter pylori treatment results in Slovenia in the period 2013-2015 as a part of European Registry on Helicobacter pylori Management

Abstract Background Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in the world affecting over 50% of the world’s population. H. pylori is a grade I carcinogen, responsible for the development of 89 % of noncardia gastric cancers. In the present study we analyzed the data for H. pylori eradication treatments in Slovenia. Patients and methods Slovenia is a part of the European Registry on Helicobacter pylori Management from the beginning. In seven medical institutions data for H. pylori eradication treatments was collected for 1774 patients from April 16th 2013 to May 15th 2016. For further modified intention to treat (mITT) analysis 1519 patients were eligible and for per protocol (PP) analysis 1346 patients. Results Patients’ dropout was 11.4%. Eradication rate for 7 day triple therapy with proton pump inhibitor (PPI) + Clarithromycin (C) + Amoxicillin (A) was 88.7% PP and 72.0% mITT; for PPI + C + Metronidazole (M) 85.2% PP and 84.4% mITT. Second line 14 day therapy PPI + A + Levofloxacin had 92.3% eradication rate PP and 87.1% mITT. Ten to fourteen day Bismuth quadruple therapy was the therapy in difficult to treat patients. At the end all patients that adhered to prescribed regimens were cured of their H. pylori infection. Conclusions High dropout rate deserves further analysis. Slovenia is still a country with < 15% H. pylori resistance to clarithromycin, triple therapy with PPI plus two antibiotics reaches PP eradication rate > 85%, but mITT eradication rates are suboptimal.

Premalignant gastric lesions in patients included in National colorectal cancer screening

Abstract Background Gastric cancer is the fifth most common malignancy in the world with almost one million new cases annually. Helicobacter pylori infection causes 89% of all gastric cancers. Premalignant lesions (atrophy and intestinal metaplasia) develop after several decades of inflammation. Secondary prevention with gastroscopy is possible, but it is costly and has a low compliance rate. Alternative procedures like serology testing for pepsinogen I and II and pepsinogen I/II ratio are available to select patients for surveillance gastroscopies. Patients and methods In seven outpatient endoscopic units, 288 patients (154 men; 53.5%), average age 60.68 years, tested positive in National colorectal cancer screening programme SVIT, were included in the study. Gastropanel (BioHit, Finland) was used as a serologic biopsy method. Results We found 24 patients (12 men, mean age 63.7 years) with pepsinogen (pepsinogen I/II < 3 and/or pepsinogen I < 30 μg/L). Premalignant changes were found on gastric biopsies in 21 patients (7.3% incidence). Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) ≥ 1 was found in 20 patients; Operative Link for Gastritis Assessment (OLGA) ≥ 1 was found in 19 patients. Combined accuracy for preneoplastic lesions in Gastropanel positive patients was 87.5%. H. pylori seropositivity was found in 219 patients (76%). Only 24% of our population had normal results. Conclusions Gastropanel test has proven to be a reliable non-invasive test for advanced gastric preneoplastic lesions that can select patients for further gastroscopy. We found high H. pylori seropositivity in older age groups in Slovenia.

Pancreatic Exocrine Insufficiency after Bariatric Surgery

Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult. Steatorrhea, weight loss, maldigestion and malabsorption are pathognomonic for both clinical conditions. Altered anatomy after bypass surgery can make the diagnostic process even more difficult. Fecal elastase-1 (FE1) is a useful diagnostic test. PEI should be considered in all patients after bariatric surgery with prolonged gastrointestinal complaints that are suggestive of maldigestion and/or malabsorption. Appropriate pancreatic enzyme replacement therapy should be part of the treatment algorithm in patients with confirmed PEI or symptoms suggestive of this complication.

Tricuspid valve endocarditis caused by Eikenella corrodens.

Abstract Background. Infectious endocarditis of the tricuspid valve is rare in non-intravenous drug users and patients without central venous devices. The most frequent causative agents are staphylococci, rarely other bacteria. Methods. We describe a case of a 57-year-old patient without history of drug abuse that was admitted to our hospital because of fever with chills, dry cough, loss of appetite and wasting lasting for a few months. He had a venous ulcer on the right foot and interdigital inflammation on both feet. Eikenella corrodens was isolated from blood cultures. Transthoracic echocardiography showed a large vegetation on the anterior leaflet of tricuspid valve. CT scan oh the thorax showed probable septic emboli. The patient was treated conservatively with prolonged double antibiotic regimen. During the treatment there were no further complications. Conclusions. In our patients a rare form of tricuspid valve endocarditis was confirmed, caused by Eikenella corrodens . The possibility of infectious endocarditis should always be considered in patients with prolonged fever, especially when a possible causative agent is isolated from blood cultures.