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Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at an early stage. The standard surveillance regimen includes random 4-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding, and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents a real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1,000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patients. The main advantages would be real-time diagnosis and decision-making, greater diagnostic accuracy, and evaluation of larger area compared to random biopsies. Clinical pCLE studies in the esophagus show high diagnostic accuracy, and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key Messages: Despite promising results, its role in routine use in patients with BE remains questionable primarily due to lack of well-organized double-blind randomized trials.

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP >= 345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F >= F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (beta = 2.6, p < 0.001) as a positive predictor and lobular inflammation (beta = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis.

BACKGROUND: Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and third in terms of cancer deaths. In clinical practice, magnetic resonance imaging (MRI) is used as a second‐line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha‐fetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast‐enhanced imaging study (computed tomography (CT) or MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is considered valid to diagnose hepatocellular carcinoma. The detection of hepatocellular carcinoma amenable to surgical resection could improve the prognosis. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma may, therefore, be missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of MRI may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of MRI in people with chronic liver disease who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma. OBJECTIVES: Primary: to assess the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease. Secondary: to assess the diagnostic accuracy of MRI for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease, and to identify potential sources of heterogeneity in the results. SEARCH METHODS: We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Hepato‐Biliary Group Diagnostic Test of Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, and three other databases to 9 November 2021. We manually searched articles retrieved, contacted experts, handsearched abstract books from meetings held during the last 10 years, and searched for literature in OpenGrey (9 November 2021). Further information was requested by e‐mails, but no additional information was provided. No data was obtained through correspondence with investigators. We applied no language or document‐type restrictions. SELECTION CRITERIA: Studies assessing the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross‐sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six‐month follow‐up. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS‐2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and we tabulated the results. We used a hierarchical meta‐analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double‐checked all data extractions and analyses. MAIN RESULTS: We included 34 studies, with 4841 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time interval between the index test and the reference standard was rarely defined. Regarding applicability, we judged 15% (5/34) of studies to be at low concern and 85% (29/34) of studies to be at high concern mostly owing to characteristics of the participants, most of whom were on waiting lists for orthotopic liver transplantation, and due to pathology of the explanted liver being the only reference standard. MRI for hepatocellular carcinoma of any size and stage: sensitivity 84.4% (95% CI 80.1% to 87.9%) and specificity 93.8% (95% CI 90.1% to 96.1%) (34 studies, 4841 participants; low‐certainty evidence). MRI for resectable hepatocellular carcinoma: sensitivity 84.3% (95% CI 77.6% to 89.3%) and specificity 92.9% (95% CI 88.3% to 95.9%) (16 studies, 2150 participants; low‐certainty evidence). The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results. AUTHORS' CONCLUSIONS: We found that using MRI as a second‐line imaging modality to diagnose hepatocellular carcinoma of any size and stage, 16% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 16% of people with resectable hepatocellular carcinoma would improperly not be resected, while 7% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.

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Background: Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and fourth in terms of cancer deaths. In clinical practice, computed tomography (CT) is used as a second-line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha-foetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast-enhanced imaging study CT or magnetic resonance imaging (MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is valid to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma is, therefore, missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of CT may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CT in people with chronic liver disease, who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma. Objectives: Primary: to assess the diagnostic accuracy of multidetector, multiphasic contrast-enhanced CT for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, either in a surveillance programme or in a clinical setting. Secondary: to assess the diagnostic accuracy of CT for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease. Search methods: We searched the Cochrane Hepato-Biliary Trials Register, Cochrane Hepato-Biliary Diagnostic-Test-Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science until 4 May 2021. We applied no language or document-type restrictions. Selection criteria: Studies assessing the diagnostic accuracy of CT for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. Data collection and analysis: At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses. Main results: We included 21 studies, with a total of 3101 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time-interval between the index test and the reference standard was rarely defined. Regarding applicability in the patient selection domain, we judged 14% (3/21) of studies to be at low concern and 86% (18/21) of studies to be at high concern owing to characteristics of the participants who were on waiting lists for orthotopic liver transplantation. CT for hepatocellular carcinoma of any size and stage: sensitivity 77.5% (95% CI 70.9% to 82.9%) and specificity 91.3% (95% CI 86.5% to 94.5%) (21 studies, 3101 participants; low-certainty evidence). CT for resectable hepatocellular carcinoma: sensitivity 71.4% (95% CI 60.3% to 80.4%) and specificity 92.0% (95% CI 86.3% to 95.5%) (10 studies, 1854 participants; low-certainty evidence). In the three studies at low concern for applicability (861 participants), we found sensitivity 76.9% (95% CI 50.8% to 91.5%) and specificity 89.2% (95% CI 57.0% to 98.1%). The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results. Authors' conclusions: In the clinical pathway for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, CT has roles as a confirmatory test for hepatocellular carcinoma lesions, and for staging assessment. We found that using CT in detecting hepatocellular carcinoma of any size and stage, 22.5% of people with hepatocellular carcinoma would be missed, and 8.7% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 28.6% of people with resectable hepatocellular carcinoma would improperly not be resected, while 8% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results

BackgroundMetabolic risk factors, such as obesity, hypertension, andhyperlipidemiaare independent risk factors for the development of various complications in acute pancreatitis (AP).Hypertriglyceridemiadose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role ofhyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet.MethodsWe analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1)glycosylated hemoglobin(HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binarylogistic regressionaccounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables.ResultsBoth on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p7mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasingHbA1cwith increasing LOH (p

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To assess the diagnostic accuracy of magnetic resonance imaging for the diagnosis of hepatocellular carcinoma of any size and at any stage in people with chronic liver disease. SECONDARY OBJECTIVES: To assess the diagnostic accuracy of MRI for the diagnosis of resectable HCC in adults with chronic liver disease. To identify potential sources of heterogeneity, we plan to investigate the effects of the following variables: study date; inclusion of people without cirrhosis; study location (population differences); participant selection; different HCC stages; different reference standards; different liver cirrhosis aetiologies; differences in prior testing; predefinition of magnetic resonance (MR) positivity criteria; and type of contrast media (see Investigations of heterogeneity).

Introduction Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP. Methods The Hungarian Pancreatic Study Group prospectively collected multicentre clinical data on 1435 adult AP patients between 2012 and 2017. Pain was characterized by its intensity (mild or intense), duration prior to admission (hours), localization (nine regions of the abdomen) and type (sharp, dull or cramping). Results 97.3% of patients (n = 1394) had pain on admission. Of the initial population with acute abdominal pain, 727 patients answered questions about pain intensity, 1148 about pain type, 1134 about pain localization and 1202 about pain duration. Pain was mostly intense (70%, n = 511/727), characterized by cramping (61%, n = 705/1148), mostly starting less than 24 h prior to admission (56.7%, n = 682/1202). Interestingly, 50.9% of the patients (n = 577/1134) had atypical pain, which means pain other than epigastric or belt-like upper abdominal pain. We observed a higher proportion of peripancreatic fluid collection (19.5% vs. 11.0%; p = 0.009) and oedematous pancreas (8.4% vs. 3.1%; p = 0.016) with intense pain. Sharp pain was associated with AP severity (OR = 2.481 95% CI: 1.550-3.969) and increased mortality (OR = 2.263, 95% CI: 1.199-4.059) compared to other types. Longstanding pain (>72 h) on admission was not associated with outcomes. Pain characteristics showed little association with the patient's baseline characteristics. Conclusion A comprehensive patient interview should include questions about pain characteristics, including pain type. Patients with sharp and intense pain might need special monitoring and tailored pain management. Significance Acute abdominal pain is the leading presenting symptom in acute pancreatitis; however, we currently lack specific guidelines for pain assessment and management. In our cohort analysis, intense and sharp pain on admission was associated with higher odds for severe AP and several systemic and local complications. Therefore, a comprehensive patient interview should include questions about pain characteristics and patients with intense and sharp pain might need closer monitoring.

Background: We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in nonalcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared to patients with non-significant or no liver fibrosis. Methods: NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum. Results: Patients with nonalcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (p

Obesity is a serious global public health problem. It is a complex disease caused by a combination of several factors including overeating and a sedentary lifestyle, genetic susceptibility and environmental factors. Substantial scientific evidence indicates that increase in obesity prevalence correlates with increase in production and human exposure to environmental chemicals, suggesting that a long list of chemical compounds that can be found all around us may play a role in the etiology of obesity.Endocrine disrupting compounds (EDCs) are chemicals that can interfere with the function of endocrine system. A subclass of EDCs that can disrupt a great number of metabolic processes including normal development of adipose tissue and balance of lipid metabolism thus leading to obesity are called obesogens. They can be found in electronics, plastics, furniture, clothes, cosmetics and also in the air, water and food that people consume. Persistent organophosphate pesticides, flame retardants, nicotine and plastics have all been linked to obesity particularly if exposure occurs during early life (in utero, newborns). Early development is the most vulnerable period for obesogen exposure leading to epigenetic changes that persist throughout life.Current knowledge on obesogens is probably just „the tip of the iceberg“ and future research is needed as well as increasing public awareness of this problem and its implications to human health. It is important to establish control over obesogens and try to prevent or at least limit the exposure of people, especially children and pregnant women, to these dangerous and harmful chemical compounds.

We aimed to assess the level of obesity knowledge among first-year and final-year medical students in Croatia (future medical workforce) in order to identify the potential gaps and to lay a basis for tailoring and updating medical educational programme/curriculum, as well as additional national public health and stewardship activities.

Aim our aim was to explore the association between life habits and the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as the surrogate markers of liver steatosis and fibrosis in a large cohort of nonalcoholic fatty liver disease (NAFLD) patients. Methods In this prospective, cross‐sectional study we had analyzed 1998 patients with diagnosed NAFLD. Sleeping duration was categorized in three groups: short (S) (8h) sleep duration. Coffee drinking was categorized into no (0), moderate (1–2) and frequent (≥3) consumption (in cups/day). Smoking was categorized as yes vs. no. Results Frequent coffee consumers had the lowest prevalence of obesity, hypertension, dyslipidemia, and diabetes. Furthermore, coffee non‐consumers had highest values of hepatic enzymes, CAP and LSM. Moderate sleep duration was associated with lower values of CAP and LSM. Coffee consumption was associated with lower CAP in all the multivariate models (CAP unadjusted and model 1,2 and 3), with largest effect in most frequent coffee consumers (≥3, model 3). Also, most frequent coffee consumers were associated with lower LSM in unadjusted model, model 1 and 2, while this was not the case for model 3 and those who consumed 1‐2 cups of coffee per day. Reduced sleeping was confirmed as risk factor for elevated CAP in most of the models (unadjusted and model 1 and 2). Also, negative association of LSM was also confirmed in unadjusted model and model 2. Patients which slept 6‐8 hours per day were mostly associated with lower CAP and LSM. Smoking status wasn't associated with CAP or LSM values. Conclusion Coffee consumption has beneficial effect on CAP and LSM and this effect is dose dependent since and independent of a variety of relevant confounders. We have shown that moderate sleep duration has also beneficial effect on CAP and LSM.

Aim: To evaluate the effects of vitamin D on transient elastography (TE, FibroScan) indices of liver steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement [LSM]) in adults with non-alcoholic fatty liver disease (NAFLD). Patients and methods: In this randomized (2:1), double-blind, single- centre, 12-month trial, patients with NAFLD were treated with vitamin D (1000 IU/day) (n = 201) or a matching placebo (n = 110). Two co-primary outcomes were changes in CAP and LSM after 360 days of treatment versus baseline. Two main secondary outcomes were CAP/LSM changes after 180 days of treatment. Results: Both CAP and LSM gradually decreased in vitamin D-treated patients and slightly increased in the placebo arm. Vitamin D was superior to placebo for both primary outcomes (mean differences in CAP and LSM changes (-49.5 dB/m [95% CI -59.5 to -39.4] and -0.72 kPa [95% CI -1.43 to 0.00], respectively) and both secondary outcomes (-22.1 dB/m [-32.1 to -12.1] and -0.89 kPa [-1.61 to -0.17], respectively). Of a number of exploratory outcomes (change at 12 months vs. baseline), vitamin D reduced serum uric acid (-17.9 μmol/L [-30.6 to -5.2]), gamma- glutamyltransferase (-8.9 IU/L [-15.5 to -2.3)] and fasting serum insulin levels (-5.1 pmol/L [-9.3 to -0.8]) as well as the homeostatic model assessment of insulin resistance index (-1.6 [-3.1 to -0.2]) (false discovery rate [5%]-adjusted P- values between .0572 and .0952). Conclusion: Low- medium dose supplementation of vitamin D (1000 IU/day) over 12 months reduces TE indices of liver steatosis (CAP) and fibrosis (LSM) in NAFLD patients.

Aims To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD). Methods In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ± 11.7 months. Results During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23–2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients. Conclusion This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.

Although the incidence of the most frequent malignant gastric tumour, adenocarcinoma, has been decreasing, during the last decades the incidence of proximal localizations of gastric cancer as well as esophagogastric cancer has been increasing. Due to the late detection of initially advanced disease the outcomes of treatment for the patients are unsatisfactory. Diagnosis is set by tumour biopsy during endoscopy. The basis of treatment of locoregional disease is surgery in combination with perioperative chemotherapy. Alternatively, if no preoperative chemotherapy is administered, adjuvant chemoradiotherapy or chemotherapy should be performed. Metastatic disease is treated with palliative chemotherapy and best supportive care. Treatment decisions should be individualized according to patients’ characteristics and made after multidisciplinary team discussion. The following text presents the clinical guidelines in order to standardize the diagnostic procedures, treatment and monitoring of patients with gastric cancers in the Republic of Croatia.

Colorectal cancer (CRC) is one of the most common malignant tumors in Western countries. The treatment outcomes of this disease have improved significantly in recent years due to the improvement of diagnostic methods (pathohistology, radiology, nuclear medicine), screening and treatment improvements: surgical and oncological (chemotherapy, immunotherapy, radiotherapy). Additional progress has been made in the definition of prognostic and predictive factors of CRC. It is very important to emphasize the multidisciplinary approach to patients with CRC and to make a decision on optimal treatment based on evidence.

Introduction:Pain is the most common symptom in acute pancreatitis(AP) and is part of the diagnostic criteria. Its clinical characteristics in APhave not been detailed.Aims:Therefore, we aimed to characterize acute abdominal pain in AP.Materials and Methods:The Hungarian Pancreatic Study Group hasprospectively collected multicenter clinical data of 1435 adult AP patientsbetween 2012 and 2017. The pain was characterized by its intensity (mild, intense), duration prior to admission (hours), localization (9 regions of theabdomen), and type (sharp, dull, cramping). Associations between paincategory groups and outcome parameters were investigated.Results:97.3% of patients (n¼1394) had pain on admission. Pain wasmostly intense (70%, n¼511), cramping (61%, n¼705), and epigastric (48%, n¼687). More intense pain was associated with disease severity (p¼0.021), and we observed higher proportion of peripancreaticfluid collection(19.5% vs 11.0% ; p¼0.009) and edematous pancreas (8.4% vs 3.1% ; p¼0.016)on on-admission imaging with intense pain. Sharp pain was associatedAbstracts / Pancreatology 21 (2021) S18eS119S36 N. GedeS. KissA. VinczeJ. BajorI. SzaboZ. SzepesF.IzbekiJ. GervainJ. HamvasZ. VitalisE. FeherS.CraiV. SallinenE.Ramirez MoldandoA. MeczkerP.VarjúG. PoropatD. StimacN.FaluhegyiA. MisetaT. NagyA. VereczkeiZ.MartonP.J. HegyiP. HegyiA.ParniczkyA. Szentesi with AP severity (OR¼2.481 95% CI: 1.550-3.969) and increased mortality(OR¼2.263, 95% CI: 1.199e4.059) compared to other pain types. Long- standing pain (>72 h) on admission was not associated with outcomes ; however, it was associated with milder (p

The most common known underlying cause of gastroparesis is diabetes mellitus. General symptoms and signs include nausea, vomiting, bloating and early satiety. The diagnosis of diabetic gastroparesis (DGP) is closely made based on clinical history, exclusion of gastrointestinal obstruction by endoscopy and abdominal ultrasound, and confirmation of delay in gastric emptying by gastric emptying scintigraphy. First-line interventions for DGP are dietary modifications and prokinetic- antiemetic therapy. In cases resistant to maximal medical therapy, gastric electrical stimulation is indicated.The aim is to alleviate both the severity and frequency of symptoms, improve gastric emptying, ameliorate patient’s nutritional status and to optimize glycemic control.

To explore the effect of nonalcoholic fatty liver as a hepatic manifestation of metabolic syndrome on the severity of acute pancreatitis. We hypothesized that patients with nonalcoholic fatty liver would have a more severe form of acute pancreatitis.We retrospectively analyzed 822 patients hospitalized with acute pancreatitis. We diagnosed acute pancreatitis and determined its severity according the revised Atlanta classification criteria from 2012. We assessed nonalcoholic fatty liver with computed tomography.There were 198 (24.1%) patients out of 822 analyzed who had nonalcoholic fatty liver. Patients with nonalcoholic fatty liver had statistically higher incidence of moderately severe (35.4% vs. 14.6%; p=0.02) and severe acute pancreatitis (20.7% vs. 9.6%; p0.001) compared to patients without nonalcoholic fatty liver. At the admission patients with nonalcoholic fatty liver had higher values of C-reactive protein as well as at day three, higher APACHE II score at admission and significantly higher incidence of organ failure and local complications as well as higher values of computed tomography severity index compared to patients without nonalcoholic fatty liver. We found independent association between the occurrence of moderately severe and severe acute pancreatitis and nonalcoholic fatty liver (OR 2.13, 95%CI 1.236-3.689). Compared to patients without nonalcoholic fatty liver, patients with nonalcoholic fatty liver had a higher death rate, however not statistically significant (5.6% vs. 4.3%; p=NS).Presence of nonalcoholic fatty liver at admission can indicate a higher risk for developing more severe forms of acute pancreatitis and could be used as an additional prognostic tool.

Aim To investigate the prevalence and severity of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus type 2 (T2DM), based on increased controlled attenuation parameter (CAP) and liver stiffness measurements obtained by transient elastography. In addition, we aimed to identify parameters that correlate with increased elastographic parameters of steatosis and fibrosis to provide a better indication when a patient with T2DM should be screened for NAFLD. Methods We conducted prospective, cross-sectional study of 679 consecutive adult patients with diagnosed T2DM mean age 65.2±11.6. NAFLD was defined by transient elastography. In 105 patients a percutaneous liver biopsy (LB) was done. Results The prevalence of NAFLD based on transient elastography was 83.6%. Independent factors associated with increased CAP were higher body mass index, longer T2DM duration, higher serum triglyceride, lower levels of vitamin D, higher C-reactive protein, and higher HOMA-IR. The prevalence of moderate liver fibrosis was 26.9% and advanced liver fibrosis 12.6%. Independent factors associated with moderated fibrosis based on elastography were higher body mass index and higher levels of alanine aminotransferase (ALT), while independent factors associated with advanced fibrosis were female gender, higher body mass index, higher levels of ALT, gama-glutamil transferase and C-reactive protein. Sixty-four (60.9%) of 105 patients with LB had NAFLD activity score ≥5. Regarding the presence and stages of fibrosis based on LB, moderate fibrosis was found in 29.5% of patients, while 29.5% had advanced fibrosis and 6.7% cirrhosis. Conclusion This study supports more aggressive screening for NAFLD and fibrosis in patients with T2DM.

Due to the high virulence of the SARS-CoV-2 virus, the infection rate in the community has led to a state of pandemic, leading to the introduction of new emergency measures all over the world. With the aim of controlling and preventing the SARS-CoV-2 viral epidemic, the health institutions performing medically assisted reproduction (MAR) suspended any new MAR treatments in order to reduce the burden on the health care system and implement current social distancing recommendations. Considering the favorable epidemiological situation in Croatia, our perspective is that it is time to conceive, plan and bring forth guidelines for restarting work in MAR centres, taking into account the selection of patients and organization of good laboratory and clinical practices with emphasis on the safety of patients and health workers. In regard to epidemiological knowledge, it is important to establish the reorganization of work in MAR centres including epidemiological measures of reducing unnecessary stays in closed spaces, the usage of protective gear by patients and health workers and disinfection of the working spaces and equipment.

Objectives: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. Methods: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. Results: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P=0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94–2.99, P=0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P=0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49–2.13), P=0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20minutes, were risk factors. Conclusions: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

Background: Conventional approaches in the management of obesity offer only a limited potential for sustained weight loss. Moreover, bariatric surgery, although momentarily being the most effective weight-loss treatment, has some serious pitfalls, such as significant morbidity rate, high substantial costs and limited patient applicability. Hence, there is a substantial need for endoscopic approaches to obesity. Summary: The aim of this article is to provide a historical overview of bariatric endoscopy in the management of obesity; moreover to selectively review and evaluate the currently available endoscopic weight-loss techniques and devices, and third to identify new directions and future prospects in this rapidly advancing field. Key Messages: Bariatric endoscopy procedures efficiently replicate some of the anatomical features and the physiological effects of the traditional weight-loss surgical approaches, while at the same time being more applicable, entirely reversible, less-invasive, safer and more cost effective. Endoscopic modalities in the treatment of obesity can be categorized into the following: restrictive procedures, malabsorptive procedures, gastric function/emptying regulation, gastric aspiration, and so on. To conclude, it is of high importance to constantly evaluate the long-term efficacy and safety of new endoscopic weight-loss techniques and devices, based on evidence-based medicine principles.

Symptomatic Uncomplicated Diverticular Disease (SUDD) is the most common clinical form of Diverticular Disease (DD). The therapy should be aimed at reducing both the intensity and frequency of symptoms as well as preventing complications. The pharmacological treatments include fibers, not absorbable antibiotics (for example rifaximin), anti-inflammatory drugs (for example 5-amino-salycilic acid) and probiotics, alone or in combination with other drugs. Although some of these treatments seem to be effective in treating SUDD, but their efficacy in preventing complications of the disease is still uncertain. It has been hypothesized that microbial imbalance associated with bacterial overgrowth of the colon, may be the key to the development of diverticular disease (DD). Therefore, drugs that can manipulate gut microbiota such as probiotics or rifaximine are considered as a potential key therapy. Rifaximine is able to modulate the intestinal ecosystem, restoring eubiosis. Traditionally, DD of the colon is thought to be related to low grade of inflammation. By analogy with other inflammatory bowel diseases mesalazine has been studied also in DD. There are several evidences that may support the use of mesalazine in the SUDD. Unfortunately, mesalazine cannot be used to prevent diverticulitis because of the paucity of high-quality studies. Currently, mesalazine has a limited place for the management of SUDD. In SUDD probiotics have been proven as an effective therapy in reducing abdominal symptoms, but unfortunately there has been limited number of relevant studies regarding efficacy of this therapy.

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To assess the diagnostic accuracy of contrast‐enhanced ultrasound (CEUS) for the diagnosis of HCC of any size and at any stage in people with chronic advanced liver disease.

In this session different issues for the diagnosis of diverticular disease (DD) were considered including “Biomarkers”, “Computer tomography”, “Ultrasonography in detecting acute diverticulitis”, “Endoscopy” and “The DICA classification: a new predictive tool in managing diverticular disease”. Most patients affected by DD suffer from recurrent attacks of abdominal pain without evidence of an active inflammatory process, causing a difficult differential diagnosis with other intestinal conditions. Several biomarkers, serological, fecal, urinary and genetic were considered, but recent studies confirmed that only CRP and fecal calprotectin are matching with the criteria for an ideal biomarker for DD. Colonoscopy still remains the gold standard for the diagnosis of DD, playing a key role in many clinical settings, such as colonic diverticular bleeding, or to differentiate inflammatory bowel disease (IBD) and segmental colitis associated with diverticulosis (SCAD); Moreover, in 2015 has been developed the DICA (Diverticular Inflammation and Complication Assessment) endoscopic classification that considers 10 different parameters, each one with a score, and the sum of items scores represents the severity of the disease; in this way the endoscopic exam would be able to predict the outcome of DD for each patient. On the other hand, computer tomography (CT) is the gold standard for acute diverticulitis (AD) with an excellent sensitivity and specificity; recently, metanalysis of prospective studies have shown that intestinal ultrasonography (IUS) and CT have the same sensitivity for the diagnosis of an AD and the advantage is that IUS is less expensive, non-invasive and easily accessible.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the beneficial and harmful effects of pegylated interferon for patients with acute hepatitis C.

BACKGROUND/OBJECTIVES: There is substantial evidence of superiority of enteral nutrition (EN) to parenteral nutrition in acute pancreatitis (AP) treatment, but few studies evaluated its effectiveness compared to no intervention. The objective of our trial was to compare the effects of EN to a nil-by-mouth (NBM) regimen in patients with AP. METHODS: Patients with AP were randomized to receive either EN via a nasojejunal tube initiated within 24 h of admission or no nutritional support. Systemic inflammatory response syndrome (SIRS) was assessed as the primary outcome. Secondary outcomes included mortality, organ failure, local complications, infected pancreatic necrosis, surgical interventions, length of hospital stay, adverse events and inflammatory response intensity. Outcomes were compared using Student's t-test and Mann- Whitney U test as appropriate. RESULTS: 214 patients were randomized in total, 107 to each group. SIRS occurrence was similar between groups, with 48 (45%) versus 51 (48%), respectively (RR 0.94 ; 95% CI 0.71-1.26). No significant reduction of persistent organ failure (RR 0.81 ; 95% CI 0.52-1.27) and mortality (RR 0.59 ; 95% CI 0.28-1.23) was present in the EN group. There were no significant differences in other outcomes between the groups. When analyzing the occurrence of SIRS and mortality in subgroup of patients with severe disease no significant differences were noted. CONCLUSION: Our results showed no significant reduction of persistent organ failure and mortality in patients with AP receiving early EN compared to patients treated with no nutritional support (NCT01965873).

Obesity represents a major global challenge from both healthcare and economic perspectives. Although lifestyle modifications aimed at reducing calorie intake and increasing energy expenditure remain the cornerstone of obesity management, pharmacotherapy can serve as a useful adjunct. Until recently, orlistat was the only medication registered for the treatment of obesity in the European Union (EU). A deeper understanding of the complexity of energy homeostasis has resulted in new pharmacological options for weight reduction. In 2015, two new antiobesity drugs were approved in the EU. These are a fixed combination of naltrexone/bupropion (Mysimba®) and liraglutide at a dose of 3.0 mg (Saxenda®). In addition, lorcaserin (Belviq®) and a fixed combination of phentermine/topiramate (Qsymia®) were introduced into the US market in 2012. However, the European Medicines Agency did not approve their use in the EU. The burden of previous weight loss agents that have been withdrawn due to safety concerns underlines the need for caution and close follow-up of patients undergoing pharmacological interventions for obesity treatment. This article provides an overview of the efficacy and safety of currently available weight loss pharmacotherapies.

Purpose:The aim of our trial is to assess the potential beneficial andharmful effects of a balanced crystalloid solution (Plasmayte) compared tonormal saline in the early treatment of patients with acute pancreatitis.Materials and methods:Consecutive patients with a diagnosis ofacute pancreatitis admitted at our hospital will be randomly assigned toreceive a balanced crytalloid solution as an initial bolus od 10 ml/kg bodyweight within 60 min after randomization and then continued at a rate of3.0 ml/kg body weight/h during the next 72 hours, or normal salineadministered in an identical manner. In cases of severe hypovolaemiabolus doses may be repeated and the administration offluid will becontinued at a rate of 3.5 ml/kg/h with the possibility of potential increaseto a maximum of 5.0 ml/kg/h. Clinical assessment with systemic inflam-matory response syndrome (SIRS) parameters and laboratory parametersincluding pH, bicarbonates, white blood cells count, hematocrit, blood ureanitrogen, creatinine, sodium, potassium, C-reactive protein, procalcitonin, and lactate levels will be assessed 8-12, 24, 48, and 72 hours afterrandomization.All patients (age 18 years) with a diagnosis of acute pancreatitisdefined according to the Revised Atlanta criteria, regardless of etiology andseverity of disease, who present at our hospital within 48 hours from onsetof symptoms will be included in the trial. Exclusion criteria: chronicpancreatitis, liver cirrhosis (Child-Pugh B and C), chronic hearth failure(NYHA>II), acute coronary syndrome, cardiovascular intervention within60 days before randomization, COPD on home oxigenator or acute exac-erbation of COPD, chronic kidney disease (eGFR

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To assess the diagnostic accuracy of abdominal ultrasound and alpha‐fetoprotein (AFP), alone or in combination, for the diagnosis of hepatocellular carcinoma (HCC) of any size and at any stage in people with chronic advanced liver disease, either in a surveillance programme or in a clinical setting.

Sustav mjera za ostvarivanje i unapređenje sveobuhvatne kvalitete zdravstvene zaštite u Republici Hrvatskoj te implementacija i praćenje obveznih indikatora kvalitete za bolničke zdravstvene ustanove definirani su putem zakonskih propisa. Pokazatelji (indikatori) kvalitete kvantitativna su osnova za analizu, praćenje i poboljšanje. Oni definiraju kako, kada i gdje skupljati podatke te se na temelju analize tih podataka može uvidjeti što treba promijeniti u dosadašnjoj praksi i kako unaprijediti trenutačni postupak koji će time dati bolje i učinkovitije rezultate. Indikatorima kvalitete može se ocijeniti kvaliteta rada u zdravstvenom sustavu. Agencija za kvalitetu i akreditaciju u zdravstvu i socijalnoj skrbi unaprijedila je sustav praćenja kvalitete zdravstvene skrbi i sigurnosti pacijenta sukladno međunarodnim kriterijima, a na temelju svojih zakonskih obveza i nadležnosti. Osim obveznog praćenja indikatora kvalitete koji je određen nacionalnim zakonodavstvom, pri čemu je stimulacija prvenstveno na ustanovi da učini određene promjene za poboljšanje, Hrvatski zavod za zdravstveno osiguranje započeo je 2015. s projektom praćenja uspješnosti i kvalitete rada bolnica. Pokazatelji rada bolničkih zdravstvenih ustanova doneseni su s ciljem svojevrsnog „nagrađivanja” ustanova, a uključuju odabrane ključne pokazatelje uspješnosti (key performance indicators, KPI) i pokazatelje kvalitete (quality indicators, QI).

Aim: To assess the measures of disease frequency and determine the clinical features of primary biliary cholangitis (PBC) in two Croatian regions. Methods Databases of two tertiary hospitals, one located in the continental and one in the coastal region of Croatia, were retrospectively searched for PBC patients diagnosed from 2007 to 2018. Epidemiologic data analysis was restricted to patients from each hospital’s catchment area. We analyzed factors related to response to therapy and event-free survival (EFS), defined as absence of ascites, variceal bleeding, encephalopathy, hepatocellular carcinoma, liver transplantation (LT), or death. In addition, we determined clinical and demographic data of transplanted PBC patients. ----- Results: Out of 83 PBC patients, 86.7% were female, with a median age at diagnosis of 55 years. Average PBC incidence for the 11-year period was 0.79 and 0.89 per 100 000 population, whereas the point prevalence on December 31, 2017 was 11.5 and 12.5 in the continental and coastal region, respectively. Of 76 patients with complete medical records, 21% had an advanced disease stage, 31.6% had an associated autoimmune condition, and all received ursodeoxycholic acid. EFS rate at 5 years was 95.8%. In an age and sex-adjusted multivariate Cox regression model, the only factor significantly associated with inferior EFS was no response to therapy (HR = 18.4; P = 0.018). Of all Croatian patients who underwent LT, 3.8% had PBC, with the survival rate at 5 years after LT of 93.4%. ----- Conclusion: This study gives pioneer insights into the epidemiological and clinical data on PBC in Croatia, thus complementing the PBC map of Southeast Europe.

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To assess the diagnostic accuracy of multidetector, multiphasic contrast‐enhanced computed tomography (CT) for the diagnosis of hepatocellular carcinoma (HCC) of any size and at any stage in people with chronic advanced liver disease.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

Diabetic gastroparesis (DGP), a delay in gastric emptying without obstruction to outflow as a complication of diabetes, typically develops after at least 10 years of diabetes. Cardinal symptoms include nausea, vomiting, early satiety, bloating, and upper abdominal pain. The aim of DGP treatment is to alleviate the severity and frequency of symptoms, improve the level of gastric emptying, ameliorate the patient's nutritional status and to optimize glycemic control. In the treatment of chronic drug-refractory nausea and vomiting secondary to DGP, gastric electrical stimulation (GES) such as Enterra Therapy System (Medtronic Inc., Minneapolis, MN, USA) can be considered. It is well established that diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) requiring renal replacement therapy. The exact prevalence of patients with severe DGP and ESRD is not known; however, finding a therapeutic approach to these patients, particularly those whose gastroparesis symptoms preclude them from undergoing kidney transplant procedure, represents a huge challenge. Our experience suggests that GES implantation can be an effective treatment modality for type 1 diabetic patients on peritoneal dialysis (PD) who are simultaneous pancreas-kidney transplantation candidates, by improving the severity and frequency of gastroparesis symptoms and eventually ensuring their optimal nutritional and fluid intake.

With the increasing incidence of obesity and metabolic syndrome the incidence of nonalcoholic fatty liver ­disease (NAFLD) is increasing as well. These patients have a significant risk of progression to the end-stage liver disease, but also these patients are at increased risk of developing hepatocellular carcinoma. In recent years there is a growing ­number of publications that support the idea that NAFLD is not just a disease that is limited to the liver, but is associated with a number of extrahepatic manifestations. For example, NAFLD increases the risk of type 2 diabetes mellitus, cardiovascular diseases and chronic kidney disease. Consequently NAFLD has become a growing public health problem. A number of sub-specialists as well as primary care physicians should be aware of these potential extrahepatic associations, given the availability of numerous methods for screening in clinical practice. The above approach is important in order to recognize potentially modifiable events in the early stages, and thus manage them and at least prevent the progression of certain diseases.

Introduction: Acute Pancreatitis (AP) is the most frequent complication after Endoscopic Retrograde Cholangiopancreatography (ERCP). Some prophylactic strategies are the use of pancreatic stents or peri-procedural nonsteroidal anti-inflammatory drugs (NSAIDs). Statins are widely used lipid-lowering drugs. Recent studies suggest that chronic statin intake may be associated to a lower incidence of AP. Methods: Our aim is to investigate whether chronic statin and/or acetylsalicylic acid (ASA) intake is associated to a lower incidence of PEP. Stark project is an international, multicenter, prospective, cohort study, developed under the auspices of “Pancreas 2000”. Consecutive patients undergoing ERCP in seven european centers, older than 18, were included prospectively. Demographic and medical data were retrieved by anamnesis. Patients were followed-up to detect those with PEP. The sample size was estimated to be 1, 016 participants. A univariate analysis and multivariate analysis (binary logistic regression) were performed. Results: 1150 patients were included. Mean age was 68.4 years (SD 14.5). 561 (48.8%) patients were female. 70 patients developed post-ERCP-AP (PEP) (6.1%) ; 25 patients (8.1%) under chronic statin treatment versus 45 patients (5.4%) who do not (p= 0.086). Multivariate analysis showed an aOR of 1.679 (0.941-2.994), p 0.079 for PEP incidence in statin users. Regarding ASA consumption, 11 patients (6.6%) under ASA treatment versus 59 patients (6%) who were not consuming ASA, developed PEP (p= 0.753). Multivariate analysis showed an aOR of 1.017 (0.487-2.127), p=0.963 for PEP incidence among ASA users. Conclusion: Our data suggest that chronic statin and/or ASA intake isnt statistically associated to an increase incidence of PEP.

Background Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, either secondary to superimposed liver injury or due to extrahepatic precipitating factors such as infection culminating in the end-organ dysfunction. Its main features are reversibility and high short-term mortality due to multiorgan failure (MOF). We aimed to analyze the clinical, laboratory, and etiological predictors of mortality and outcome in patients with ACLF. Methods We evaluated 1215 patients with chronic liver disease; 90 patients met the criteria for ACLF. Results The most common cause of underlying chronic liver disease was alcohol, and the most common acute insult (AI) in those patients was superadded alcoholic hepatitis. In all, 50% of all patients died within 30 days (71.1 % within the first 14 days after admission). MOF was the cause of death in 70 % of cases. On multivariate analysis, high serum potassium, serum creatinine higher than 90 mu mol/L, and C-reactive protein > 30 mg/L were found to be independent baseline predictors of mortality. APACHE II (Acute Physiology and Chronic Health Evaluation II) score was the best predictor of short-term mortality (area under the curve (AUC), 0.878). MOF was a valuable predictor of mortality (AUC, 0.923); 33 of 35 patients who had MOF at admission died. Presence of positive systemic inflammatory response syndrome criteria at admission was also correlated with in-hospital mortality (AUC, 0.742). Conclusion ACLF is a serious condition with high short-term mortality. Because ACLF is reversible, it is necessary to identify at-risk patients as soon as possible to treat acute events in a timely manner.