Nonalcoholic Fatty Liver Disease (NAFLD)-A New Cardiovascular Risk Factor in Peritoneal Dialysis Patients.

UNLABELLED: ♦ BACKGROUND: Recent investigations indicated that nonalcoholic fatty liver disease (NAFLD), a hepatic component of metabolic syndrome (MS), is associated with an increased risk of cardiovascular disease (CVD). Accordingly, we were interested in exploring the frequency of NAFLD in peritoneal dialysis (PD) patients and analyzing factors in PD patients associated with NAFLD occurrence. In addition, we were interested in investigating whether NAFLD is associated with higher CVD risk in our PD patients. ♦ METHODS: In the present cross-sectional study, we analyzed 58 PD patients. The controlled attenuation parameter (CAP) was used to detect and quantify liver steatosis with the help of transient elastography (TE) (FibroScan, Echosense SA, Paris, France). A carotid ultrasound was performed in all patients to measure carotid intimae media thickness (IMT) and plaque as surrogate measures of increased CVD risk, and we investigated their association with NAFLD. ♦ RESULTS: Nonalcoholic fatty liver disease was present in 74.1% of PD patients. Peritoneal dialysis/nonalcoholic fatty liver disease patients had statistically greater daily (136.5 ± 62.6 vs 93.6 ± 36.1; p = 0.02) and monthly (4,095.3 ± 1,877.7 vs 2,806.6 ± 1,083.2; p = 0.02) glucose load in comparison to the non-NAFLD/PD patients. In the next step, we were interested in analyzing what demographic and clinical characteristics in our PD patients are associated with a higher NAFLD occurrence. Presence of diabetes mellitus (DM), arterial hypertension (AH), dyslipidemia, body mass index > 25 kg/m(2), and daily glucose load > 100 g were associated with NAFLD occurrence. Peritoneal dialysis patients with NAFLD showed more carotid atherosclerosis than PD patients without NAFLD. In addition, CAP values (as indicator of liver steatosis) showed strong positive association with IMT (r = 0.801; p < 0.0001). Nonalcoholic fatty liver disease was a strong predictor of carotid atherosclerosis in PD patients. ♦ CONCLUSION: Nonalcoholic fatty liver disease is highly prevalent in PD patients. Peritoneal dialysis patients with NAFLD are at high risk of atherosclerosis. Assessment of NAFLD in PD patients may be helpful for CVD risk stratification.

[CANCER PATIENTS FOLLOW-UP ­ CROATIAN SOCIETY OF MEDICAL ONCOLOGY CLINICAL GUIDELINES Part III: neuroendocrine neoplasms, hepatocellular carcinoma, pancreatic cancer, cancer of the bile ducts]. / PRACENJE ONKOLOSKIH BOLESNIKA ­ KLINICKE PREPORUKE HRVATSKOG DRUSTVA ZA INTERNISTICKU ONKOLOGIJU HLZ-a III. dio: neuroendokrine neoplazme, hepatocelularni karcinom, rak gusterace, rak zucnih vodova.

The treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of individual oncological centers or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment, in patients with neuroendocrine neoplasms, hepatocellular carcinoma, pancreatic cancer and cancer of the bile ducts.

Clinical profile, natural history, and predictors of mortality in patients with acute-on-chronic liver failure (ACLF).

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 µmol/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.

Relationship between non-alcoholic fatty liver disease and MIA syndrome.

Non-alcoholic fatty liver disease (NAFLD) is an important factor in the pathogenesis of cardiovascular diseases in the general population. Recently, it has been shown that NAFLD is highly prevalent in chronic kidney disease (CKD) patients. Ninety-four hemodialysis (HD) patients were followed for a time period of 18 months or until death. Patient's survival rate was determined in relation to their nutritional and inflammatory state, and the presence of NAFLD. We also investigated the association between the presence of NAFLD and the patients' nutritional and inflammatory state. We did not find any significant association between the clinical parameters of nutritional status and the mortality rate. However, the mortality rate was statistically significantly higher in patients with low serum albumin and high high-sensitive C-reactive protein (hs-CRP) levels and in those who had NAFLD. Surprisingly, patients who had received enteral nutrition did not have a better survival rate. The severity of liver steatosis was negatively correlated with the serum albumin levels, while it was positively correlated with hs-CRP values. Furthermore, serum albumin levels showed a negative correlation with hs-CRP levels. We did not find any significant association between the presence of NAFLD and clinical parameters of nutrition. We have shown that NAFLD could be one more possible example of reverse epidemiology in patients undergoing HD. NAFLD may be the missing link that causally ties malnutrition, inflammation, and atherosclerosis syndrome to the morbidity and mortality in patients undergoing HD.

Epidemiology of Acute Pancreatitis in the North Adriatic Region of Croatia during the Last Ten Years.

Introduction. Several European studies have reported an increase in the incidence rate of acute pancreatitis (AP). Therefore, we studied the incidence rate of AP in the North Adriatic Region in Croatia, as well as epidemiological analysis concerning etiology, age, gender, and severity of disease. Methods. We analyzed 922 patients with confirmed diagnosis of AP (history, clinical and laboratory findings, and imaging methods) admitted to our hospital during a ten-year period (2000-2009). Epidemiological analysis was carried out focusing on incidence, demographic data, and etiology, as well as severity of the disease based on the Ranson and APACHE II scores. Results. The incidence rate varied from 24 to 35/100 000 inhabitants annually. Mean age was 60 ± 16 years. There were 53% men and 47% women among the patients. Most frequent etiologies of AP were biliary stones in 60% and alcohol abuse in 19% of patients. According to the Ranson and APACHE II scores, pancreatitis was considered to be severe in 50% and 43% of the cases, respectively. Conclusion. In our region the incidence of AP was around 30 per 100,000 population per year during the ten-year period studied. The mean age at admission was 60 years and etiology was predominantly biliary. In our region, we have shown epidemiological characteristics of AP typical for Mediterranean countries.

Nutritional support in patients with colorectal cancer during chemotherapy: does it work?

BACKGROUND/AIMS: Early intervention with nutritional supplementation has been shown to halt malnutrition and may improve outcome in some patients with colorectal cancer. The aim of this study was to investigate whether dietary counseling, oral nutrition and megestrol acetate during chemotherapy affected nutritional status and survival in patients with advanced disease. METHODOLOGY: Six hundred and twenty-eight patients with colorectal advanced disease were included in the study from January 2000 through December 2009 and divided into one of two groups. Group I consisted of 315 patients who were monitored prospectively and were given nutritional support. Group II included 313 patients without nutritional counseling and support. After the completion of chemotherapy all patients were evaluated (BMI, NST, Appetite Loss Scale and ECOG). RESULTS: After the completion of chemotherapy, there were lower proportions of patients in Group I with a BMI<20, NST>=5, loss of appetite and decreased weight gain. Nutritional counseling and supplemental feeding temporarily halted weight loss and improved appetite. This improvement may have implications for patient survival. Patients with early nutritional support lived 19.1 months while patients in the control group had a survival of 12.4 months (p=0.022). CONCLUSIONS: This study demonstrated that concurrent individualized dietary counseling and nutritional support are effective in improving nutritional status thereby lessening chemotherapy-induced morbidity.

[Acute-on-chronic liver failure (ACLF)--a new entity in hepatology?]. / Acute-on-chronic liver failure (ACLF)--novi entitet u hepatologiji?

Recently, acute-on-chronic liver failure has been recognized as a specific and unique clinical form of liver failure (usually related to acute insult) in patients with previously known or unknown compensated chronic liver disease. Its main feature is the reversibility, and high short-mortality due to multiorgan failure (MOF) in the absence of liver support system devices and/or liver transplantation. This article aims to introduce the definition and better understanding of this newly developed and unique profile of liver failure.

Etiology and oncogenesis of pancreatic carcinoma.

Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis.

Clinical utility of red cell distribution width in alcoholic and non-alcoholic liver cirrhosis.

Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as apart of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value < 130 g/L in men and < 120 g/L in women, which were hospitalized in our Division in a period between 2006 and 2008. Patients were divided in two groups; in first were patients with alcoholic liver cirrhosis, and in second with non-alcoholic cirrhosis. Severity of disease was determined according to Child-Pugh score. Red blood cells distribution width Normal reference range is 11-15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn't find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p > 0.05) and we didn't proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p = 0.915) nor in group of patients with non-alcoholic cirrhosis (p = 0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease.

Effects of nutritional support in patients with colorectal cancer during chemotherapy.

Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline. Early intervention with nutritional supplementation has been shown to halt malnutrition, and may improve outcome in some patients. In our study we tried to assess the influence of nutritional support (counseling, oral liquids, megestrol acetate) on nutritional status and symptoms prevalence in patients with colorectal cancer during chemotherapy. Group I consisted of 215 (55%) patients with medium age 68 +/- 2.6 years who were monitored prospectively and were given nutritional support. Group II included 173 (45%) patients (medium age 67 +/- 2.9 years) without the proper nutritional counseling, in whom the data were collected retrospectively during a 6 years period of time. After evaluation Nottingham Screening Tool Score, Appetite Loss Scale and Karnofsky Performance Status) all patients in the group I received nutritional counseling, 153 of them (72%) were taking form of enteral food supplement and 103 (48%) patients were using megestrol acetate. Evaluating the initial risk measurements according to BMI, decrease in weight gain and NST, we did not find any significant difference between the two groups. After chemotherapy completion, patients in group I had a 15.3% drop of those who's BMI was < 20.65% patients increased their body weight, with an average weight gain of 1.5 kg (0.6-2.8 kg). Contrary, in group II we found increase in weight loss > or = 2 kg/month in 39% of patients. The appetite improvement was detected on Appetite Loss Scale from 3.1 (pre-chemotherapy) to 4.7 (post-chemotherapy) in group I, especially in those receiving megestrol acetate. In both groups Karnofsky Performance Status didn't change significantly reflecting the impact of the disease itself and chemotherapy procedures to the patient's condition. Nutritional counseling, supplemental feeding and pharmacological support do temporarily stop weight loss and improve appetite, social life and quality of life in those groups of patients. However, this improvement have no implications on patients KPS and course of their disease.

[C-reactive protein and lactate dehydrogenase as single prognostic factors of severity in acute pancreatitis]. / C-reaktivni protein i laktat dehidrogenaza kao samostalni prognosticki cimbenici tezine akutnog pankreatitisa.

Ranson and Glasgow scores are routinely used for prediction of severity in acute pancreatitis. We undertook a prospective study to investigate the role of lactate dehydrogenase (LDH) and C-reactive protein (CRP) as potential single predictors of severity in acute pancreatitis. In our study we included 100 patients with diagnosis of acute pancreatitis admitted to our hospital during last two years. The inclusion criteria consisted of a combination of clinical features, a typical case history, elevation of serum pancreatic enzymes and diagnosis confirmed by imaging studies (ultrasound or computerised tomography). We used Ranson score for assesment of severity and compared it with single parameters as LDH and CRP on the first and the third day after admission. Cut off values for predicting local and systemic complications were > or =3 for Ranson score, 320 IU for LDH and 5 mg/L for CRP. Ranson score showed highest sensitivity in the prediction of local and systemic complication of acute pancreatitis. Specificity and diagnostic accuracy were highest for LDH on the first day (67.74; 57%). Diagnostic accuracy for Ranson score and CRP on the third day after admission was around 50%. We can conclude that LDH and CRP are available, simple and economical biochemical parameters that can help us predict complications of acute pancreatitis in the early phase of the disease. They showed similar diagnostic accuracy as the far more clinically used Ranson score.

The role of nonenhanced magnetic resonance imaging in the early assessment of acute pancreatitis.

BACKGROUND AND AIMS: Computed tomography (CT), especially contrast-enhanced CT (CECT), provides important information on the severity and prognosis of acute pancreatitis (AP). Magnetic resonance imaging (MRI) has become a useful tool as an alternative to CT in the assessment of AP. The primary aim of our study was to determine the diagnostic value of nonenhanced MRI (NEMRI) to assess severity and predict outcome in patients with AP from the third to fifth day after admission. We also correlated MRI findings with CT and biochemical parameters. PATIENTS AND METHODS: The study included 101 patients (49 men, 52 women, median age 62 yr, range 20-82) with a diagnosis of AP admitted to our hospital between January 1, 2004 and June 31, 2005. The inclusion criteria consisted of a combination of clinical features, a typical case history, elevation of serum pancreatic enzymes, and diagnosis confirmed by imaging studies. Contrast-enhanced spiral CT exams were performed in all patients from the third to fifth day after admission, and Balthazar grade and CT severity index were calculated. All patients underwent NEMRI, and MR severity index (MRSI) was calculated. We also performed magnetic resonance cholangiopancreatography (MRCP) in all patients to detect bile duct lithiasis. RESULTS: Significant correlation between CECT and NEMRI was found for Balthazar grade (P<0.001) and the assessment of pancreatic necrosis (P<0.001), as well as between the combined severity indices (rho=0.819, P<0.001). MRSI correlated with Ranson score (rho=0.656, P<0.01), C-reactive protein (CRP) levels 48 h after admission (rho=0.502, P<0.01), appearance of systemic complications (rho=0.576, P<0.01), and length of hospital stay (rho=0.484, P<0.01). Considering the Atlanta criteria as the gold standard and the Ranson score, no difference in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the two methods was observed. Comparing the group of patients with presumed acute pancreatic hemorrhage with the group of patients with severe AP, we found a significantly higher APACHE II score on the first day (P<0.05), that the development of systemic complications was more frequent (P < 0.05), and that the hospital stay and ICU management of patients with MRI signs of pancreatic hemorrhage tended to be longer. CONCLUSION: NEMRI is comparable to CECT in the early assessment of the severity of AP, and both methods are equally efficient in predicting local and systemic complications of AP. MRI has a potential advantage over CT in detecting bile duct lithiasis and pancreatic hemorrhage.