Hypertriglyceridemia-induced pancreatitis treated with continuous insulin infusion-Case series.

OBJECTIVE: There are no definitive treatment guidelines for hypertriglyceridemia (HTG)-induced acute pancreatitis (AP). The aim of this retrospective study was to evaluate the efficacy of insulin in decreasing triglyceride (TG) levels in patients with HTG-induced AP. DESIGN: We included 17 cases of HTG-induced AP treated with continuous insulin aspart for 4 days. PATIENTS: Fifteen patients were male, two were female. The mean TG level at admission was 56.53 ± 25.29 mmol/L. The mean APACHE II score was 10.2 ± 5.7, Ranson 4.2 ± 1.7 and Balthazar 6.5 ± 2.6, implying a severe form of the disease. METHODS: In an 8-year period, 17 patients with a diagnosis of HTG-induced AP were treated with a continuous infusion of 5% dextrose and insulin aspart in an attempt to lower TG levels. TG levels were assessed on admission, the second and fourth day of therapy. The patient outcome, complications and recurrence of AP were monitored. RESULTS: A significant reduction of TG levels was observed in all patients on Day 4. All patients survived, with one forming a giant pseudocyst as a disease complication, one needing haemodialyses treatment due to an acute kidney injury, and one developing acute respiratory distress syndrome that required mechanical ventilation for 4 days. All patients recovered completely. CONCLUSION: Our study showed that continuous insulin aspart infusion decreases TG levels in HTG-induced AP from a mean TG level of 56.53 mmol/L on Day 1 to 21.75 mmol/L on Day 2 and finally to 6.86 mmol/L on Day 4. We consider this therapy very efficient, safe, simple to administer and monitor.

Klatskin-Mimicking Lesions.

Altemeier-Klatskin tumor is a perihilar cholangiocarcinoma that occurs within 2 cm of the confluence of the right and left hepatic duct at the hepatic hilum and accounts for 50-70% of all cholangiocarcinomas cases. Although imaging techniques have come very far today, this entity can still be very challenging to diagnose as there are many lesions that can mimic Klatskin tumor. In this review, we will present the most common Klatskin-mimicking lesions.

NAFLD, Insulin Resistance, and Diabetes Mellitus Type 2.

Nonalcoholic fatty liver disease is a condition defined by fat accumulation in hepatocytes not promoted by excessive alcohol consumption. It is highly prevalent and is strongly associated with insulin resistance, metabolic syndrome, and diabetes type II. Insulin resistance plays a crucial role in the multifactorial etiopathogenesis of this condition leading to accumulation of free fatty acids in the liver cells, thus causing lipotoxicity, inflammation, and fibrosis. In this review, we will focus on currently known pathogenesis of nonalcoholic fatty liver disease. Numerous investigation strategies are available to establish the diagnosis, from biochemical markers and ultrasound to various molecular and advanced imaging techniques and liver biopsy. Prevention is crucial. However, effective and promising therapies are strongly demanded.

Gastroesophageal variceal bleeding - An overview of current treatment options.

Gastroesophageal variceal hemorrhage is the most important clinical event that results from portal hypertension. It is a lifethreatening condition that demands rapid and efficient treatment. The first step in bleeding control is hemodynamic stabilization and pharmacological treatment, which includes administration of vasoactive drugs and short-term antibiotic prophylaxis. After initial hemodynamic stabilization, endoscopic therapy should be performed. The first choice of endoscopic treatment for esophageal bleeding is endoscopic variceal ligation (EVL), or endoscopic injection sclerotherapy (EIS) if EVL cannot be performed. Several rescue therapies, such as application of balloon tamponade, a selfexpandable metal stent (SEMS), or a transjugular intrahepatic portosystemic shunt (TIPS), are available in cases of resistant variceal bleeding that cannot be controlled with endoscopic therapies. Gastric varices have a lower incidence than esophageal varices, but bleeding from gastric varices is associated with higher mortality and morbidity rates. The first-line treatment, as with esophageal variceal bleeding, is stabilization of the patient. After that, control of bleeding can be attempted. Optimal management of gastric variceal bleeding is not yet standardized due to diverse underlying pathologies and the lack of large, randomized controlled trials. Among endoscopic techniques, endoscopic variceal obturation (EVO) has been acknowledged as reliable. Among rescue therapies, balloon-occluded retrograde transvenous obliteration (B-RTO) of gastric varices and TIPS are the most common techniques.

Common Bile Duct Stricture After Laparoscopic Cholecystectomy: Case Report

Despite progress in laparoscopic surgery and increasing surgical experience, the incidence of bile duct injury during laparoscopic cholecystectomy fails to fall below 0.3%-0.6% and it is still higher than those recorded in the era of open cholecystectomy. Bile duct injuries belong to the most serious complications of abdominal surgery in general and often end up with liver transplantation as the only hope for cure. We present a case of a 78-year-old jaundiced male patient who sustained common hepatic duct injury during laparoscopic cholecystectomy eight months earlier. Exploratory laparotomy, ERCP and MRCP revealed a metal clip placed just below hepatic duct confluence and causing stricture of bile duct with dilatation of bile ducts proximal to the level of stenosis (Strasberg classification type E3 injury). Repair of the injury was performed by creating termino-lateral hepaticojejunostomy between the right and left hepatic ducts and retrocolic Roux en-Y jejunal limb. By presenting this case, we wish to emphasize the importance of timely conversion and execution of intraoperative cholangiography in all cases when identification of the structures of Calot's triangle is not clear enough. Successful treatment of bile duct injury is only possible with joint approach of radiologist, gastroenterologist and experienced hepatobiliary surgeon.

Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

Bismuth-based quadruple therapy modified with moxifloxacin for Helicobacter pylori eradication.

BACKGROUND: The aim of this study was to evaluate the efficacy, tolerability and safety of modified bismuth-based quadruple therapy for the second-line eradication treatment of Helicobacter pylori (H. pylori) infection. METHODS: Out of 758 patients treated between January 2010 and December 2015, 155 patients (20.45%) remained H. pylori positive after the first line treatment and received the second-line treatment consisting of colloidal bismuth subcitrate (240 mg twice daily), pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily) and moxifloxacin (400 mg once daily) for 14 days. Six weeks after the completion of treatment patients were retested for the presence of H. pylori infection with 13C urea breath test. RESULTS: Out of 155 patients, 142 patients completed their second-line regimens. 13 patients were excluded from the study: 4 experienced adverse effects that have led to discontinuation of treatment, 5 were lost to follow-up and 4 complied poorly with medication. The eradication rates were 80.64% (125/155) and 88.02% (125/142) according to intention-to-treat and per-protocol analyses. Compliance with the therapy was 89%. CONCLUSIONS: Moxifloxacin in modified bismuth-based quadruple therapy was found to be effective and safe with good drug compliance; therefore it may be an acceptable alternative to other second-line eradication protocols.

What is the Right Therapeutic Approach to Biliary Choledochal Cyst?

We report a case of biliary cyst type II which, independently of its a priori benign nature, caused numerous complications such as recurrent cholangitis and pancreatitis, as well as subsequent hepatic fibrosis and the potential danger of choledochocele perforation. Although they are benign, biliary/choledochal cysts can cause numerous disorders such as cholestasis, leading to cholangitis and pancreatitis and biliary sepsis, and due to chronic inflammation of the biliary system even cholangiocarcinogenesis. Our findings showed that sometimes this type of biliary cyst (according to the available literature the rarest and most benign type), as well as type I cyst, should undergo timely radical excision. In our patient, timely choledochocele resection would have certainly contributed to the reduction of subsequent complications, as well as to obviating repeated invasive diagnostic and surgical procedures.

[Croatian guidelines for diagnostics and treatments of Helicobacter pylori infection]. / Hrvatski postupnik za dijagnostiku i terapiju infekcije Helicobacterom pylori.

In the past 30-year period of investigations, the crucial role of Helicobacter pylori in chronic gastritis, gastric and duodenal ulcer development, and subsequently in gastric cancer and MALT lymphoma pathogenesis, has been recognized. During the first meeting of European Helicobacter Study Group in 1996 in Maastricht, the first recommendations for diagnostics and treatments of Helicobacter pylori infection were published, later reviewed in 2000, 2007 and 2010. The first meeting of Croatian doctors focusing on the same topics, but suitable to specific national circumstances, was held as early as 1998. The need for updating the old guidelines has emerged during the last years. The working expert group of gastroenterologists was formed and gathered on Consesus Conference in December 2012 in Zagreb, to arrive to current guidelines for the clinical management of Helicobacter pylori infection in Croatia. The following topics relating to Helicobacter pylori infection were examined: 1. indications and contraindications for diagnostics and treatments; 2. diagnostic methods and 3. treatments applicable in our country.

Do gender and age influence the frequency of Helicobacter pylori infection?

BACKGROUND: (13)C urea breath test (UBT) is a noninvasive method for detection of Helicobacter pylori (H. pylori) infection. The aim of this study was to determine age and gender differences in patients with positive UBT. PATIENTS AND METHODS: During the period 2008-2011, a total of 3,000 patients, who did not receive Hp eradication therapy before our study, underwent UBT in Laboratory of Clinical Hospital Sveti Duh. Data were analyzed according to age and gender. RESULTS: A total of 1,400 patients were positive (47 %), 670 males and 730 females (the male/female ratio for positive UBT was 0.92). The male predominance was found in people born between 1930 and 1939, 1940 and 1949, and 1960 and 1969, respectively. The majority infected are born between from 1940 and 1979, with the highest point from 1950-1969. CONCLUSIONS: Our study results confirm the importance of epidemiologic characteristics of Hp infection in our region.

Acute oxcarbazepine-induced hepatotoxicity in a patient susceptible to developing drug-induced liver injury.

Oxcarbazepine (OXC) is generally accepted as a drug without risk of severe drug-induced hepatotoxicity, but according to recently reported pharmacovigilance data this statement has been challenged. However, in the literature there have been no reports of acute OXC-induced hepatotoxicity without systemic manifestations of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome. We present a female with seizures one month after delivery who had borderline elevated liver enzymes prior to the initiation of OXC treatment. Two weeks after introducing OXC, highly elevated liver enzymes were found. After discontinuation of OXC the enzymes continued to rise for another week, and afterward gradually decreased. The causal relationship with OXC intake was determined to be highly probable. Two years later, the transitory elevation of liver enzymes was observed during the treatment of acute tonsilopharingitis with amoxicillin + clavulanic acid. The repeated elevation of liver enzymes related to use of different drugs might indicate patients susceptibility for drug induced liver injuries. We suggest that monitoring of liver function tests would be clinically rational for early detection of acute OXC-induced liver hepatotoxicity in the patients with clinical and/or laboratory features which might be interpreted as possible risk factors of the increased susceptibility to drug induced liver injuries.

[Croatian consensus on the treatment of inflammatory bowel diseases with biologic therapy]. / Hrvatski konsenzus o lijecenju upalnih bolesti crijeva bioloskom terapijom.

Introduction of biologic therapy in clinical practice represented significant progress in the treatment of inflammatory bowel diseases (IBD) because of its proven efficacy and due to the fact that biologics are the first drugs used in the treatment of IBD that can change the natural course of this diseases. At the same time, biologics are very expensive drugs with complex mechanism of action and important side effects and their use requires evidence-based clinical guidelines. These were the reasons that Referral Center of the Croatian Ministry of Health for IBD and the IBD Section of the Croatian Society of Gastroenterology organised Croatian consensus conference that defined guidelines for the treatment of IBD with anti-TNF drugs. The text below includes definitions of IBD, general principles of IBD therapy, comments on the importance of mucosal healing, analysis of reasons for nonresponse and loss of response to anti-TNF drugs, recommendation for the duration of anti-TNF therapy, rules of screening for opportunistic infections prior to anti-TNF therapy, comments on the problems with reproduction in IBD and finally guidelines for the treatment of various phenotypes of IBD including extraintestinal manifestations with anti-TNF therapy.

[Pharmacology of biologic medications]. / Farmakologija bioloskih lijekova.

Two major types of inflammatory bowel diseases (IBD) are Crohn's disease (CD) and ulcerative colitis (UC). Insights into their pathophysiology and inflammatory cascade have lead to the discovery of medications that can have a selective effect on a particular molecule or signal pathway and correct an imbalance in pro- and anti-inflammatory mediators. The first to be developed were the TNF-alpha antagonists, soluble receptors like etanercept and monoclonal antibodies. Infliximab has been approved worldwide for treatment of moderate to severe and active fistulizing forms of Crohn's disease, as well as for severe forms of ulcerative colitis in adults who do not react to full and adequate corticosteroid and/or immunosuppressive therapy, i.e. for patients who have problems with or medical contraindications to such therapy and for treatments of severe forms of active disease in children. Adalimumab can be applied in cases when antibodies develop as a reaction to infliximab, leading to reduced drug efficacy and allergic reactions. According to the available data from preclinical tests and earlier phases of clinical tests, potential candidates for new biological medications in treating IBDs are another TNF-alpha antagonist (certolizumab), inhibitors of Th1 polarisation (fontolizumab, ustekinumab) and selective adhesion-molecule inhibitors (natalizumab).

Quantitative analysis of troponin I serum values in patients with acute cholecystitis.

The diagnosis and staging of acute cholecystitis, upon a lot of diagnostic methods and some scoring systems, is still a great clinical problem. The aim of the study was to investigate if serum Troponin I is elevated in patients with acute cholecystitis. Following informed consent, 65 patients with clinical and laboratory signs of acute cholecystitis were enrolled. All patients had measured serum Troponin I level and an abdominal ultrasound was done before definitive treatment was performed. Increased serum Troponin I level was found in most patients with severe form of acute cholecystitis (p < 0.00001). It reached sensitivity of 94.5% and specificity of 57.1% of this test. In multiple regression analysis Troponin I significantly correlated (p < 0.05) with the serum aspartate aminotransferase (r = 0.27), gamma-glutamyl transferase (r = 0.25) and gallbladder wall (> 6 mm) thickness (r = 0.58). Our study confirms that in most patients with severe and acute cholecystitis, serum Troponin I is increased. Troponin I level is in a lower range than it would be in patients with cardiac muscle damage or necrosis. Measuring serum Troponin I is a fast, reliable and widely performed test that could, with other routinely measured parameters, help in early diagnosis of the severe form of acute cholecystitis.

Celiac disease and fulminant T lymphoma detected too late in a 35-year-old female patient: case report.

UNLABELLED: Celiac disease is the most common chronic gastroenterological autoimmune disease characterized by gluten intolerance. The diagnosis of celiac disease and enteropathy-associated T cell lymphoma is often made when it is too late.Case report describes a 35-year-old female patient managed for one year under the diagnosis of inflammatory bowel disease and admitted to our hospital for exacerbation of the underlying disease. However, inflammatory bowel disease was ruled out by diagnostic work-up, while the clinical picture and the findings obtained raised suspicion of lymphoma. The patient's condition was additionally complicated by fulminant course of the disease and ileus. CONCLUSION: Early diagnosis and appropriate treatment of the disease, and follow up of family members are crucial to prevent intestinal lymphoma development.

Second-line treatment for Helicobacter pylori infection based on moxifloxacin triple therapy: a randomized controlled trial.

BACKGROUND: In eradication of Helicobacter pylori infection, standard quadruple second-line therapy consisting of proton pump inhibitor (PPI), bismuth, metronidazole and tetracycline often fails and shows poor patient compliance. The aim of our study was to evaluate the efficacy and tolerability of moxifloxacin-based triple therapy as an alternative second-line protocol. METHODS: A total of 160 patients, in whom the initial standard PPI triple therapy had failed to eradicate H. pylori infection, were included in the study. The initial H. pylori status was assessed using the (13)C-urea breath test. Patients were randomized to one of the following 7-day treatment regimens: (1) OMM: omeprazole 20 mg twice a day, moxifloxacin 400 mg/day, metronidazole 500 mg three times a day; and (2) OBMT: omeprazole 20 mg twice a day, colloidal bismuth subcitrate 120 mg four times a day, metronidazole 500 mg three times a day, tetracycline 500 mg four times a day. Patient compliance and adverse events were evaluated one week after completion of therapy. H. pylori status was re-assessed with the (13)C-urea breath test six weeks after the end of therapy. RESULTS: The eradication rates were 73.2% (60/82) and 78.9% (60/76) with moxifloxacin-based triple therapy, and 53.8% (42/78) and 64.6% (42/65) with bismuth-based quadruple therapy, by intention-to-treat (p = 0.018) and per-protocol (p = 0.088) analyses, respectively. Adverse events/intolerability were described in 12/82 patients in the OMM group and 18/78 patients in the OBMT group. Compliance with treatment was 92.7% in the OMM group and 83.3% in the OBMT group. CONCLUSION: Moxifloxacin-based triple therapy is a highly effective second-line eradication treatment in H. pylori infection. Because of its high levels of safety and tolerability, this protocol represents an adequate alternative to the standard bismuth-based quadruple therapy.

Impaired esophageal function in patients with irritable bowel syndrome.

The aim of the study was to determine prevalence of the signs and symptoms related to esophageal dysfunction in irritable bowel syndrome (IBS) patients, and to investigate sensorimotor function impairment based on the esophageal manometry study, thus to determine the correlation between them. The study included 30 patients with IBS, 14 of them with diarrhea (IBSd) and 16 with constipation (IBSc) as a predominant discomfort. Control group consisted of 30 healthy subjects. The patients were included in the study on the basis of the Rome criteria for IBS. In addition to thorough history and physical examination patient underwent esophagogastroduodenoscopy and esophageal manometry. The values of esophageal manometry obtained in healthy subjects served as controls in manometry studies. The patients with IBS suffered a great number of both colonic and extracolonic signs and symptoms, however, there was no statistically significant difference in the prevalence of particular symptoms between the two patient subgroups. In comparison with healthy subjects, the patients suffering from IBS showed pathologically altered values in the majority of parameters of esophageal motility. Comparison of the two subgroups of IBS patients according to esophageal motility characteristics yielded differences in only few of them. The results obtained in the study could explain why the patients with IBS quite commonly complain of the symptoms related to upper gastrointestinal tract, such as heartburn and chest pain of noncardiac genesis. The results also suggest that the IBS might be associated with considerably more extensive smooth muscle or innervation changes than presumed before.

Lower gastrointestinal disorders in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal system characterized by abdominal pain related to bowel emptying, defecation impairment and abdominal distention. The aim of the study was to objectify lower gastrointestinal system disturbances in IBS patients. Thirty IBS patients and 30 healthy subjects were included in the study. IBS patients were divided into two subgroups: IBS with predominant diarrhea (IBSd) and IBS with predominant constipation (IBSc). All study subjects underwent physical examination (including digitorectal examination), standard laboratory testing and anorectal manometry. Endoscopy was performed only in group of IBS patients. A statistically significant difference was recorded in most manometric parameters between healthy subjects and IBS patients, which was even more pronounced in IBSd patients. Study results showed that the intestinal motility disorder underlying IBS could be objectified by use of anorectal manometry.

Seroprevalence of Helicobacter pylori infection in dyspeptic patients.

The objective of the study was to assess the effect of age on the seroprevalence of Helicobacter (H.) pylori infection in dyspeptic patients. The results obtained in the patient group were compared with findings on the seroprevalence of H. pylori infection in 2051 blood donors. Serum samples were tested by the commercial ELISA and CFT assays according to manufacturer's instructions. The mean seroprevalence of H. pylori infection as determined by ELISA/CFT was 64.0%/51.7% in the group of blood donors and 92.3%/89.5% in the group of dyspeptic patients. Study results indicated a higher prevalence of H. pylori infection in dyspeptic patients as compared with blood donors in all age groups. In the patient S group, H. pylori seroprevalence was not age dependent.

[Is there any connection between angiotensin converting enzyme activity and liver cirrhosis of alcoholic genesis?]. / Postoji li povezanost izmedu serumske aktivnosti angiotenzin konvertirajuceg enzima i jetrene ciroze alkoholne geneze?

UNLABELLED: The objective of this study was to assess the serum angiotensin converting enzyme (ACE) activity in patients with liver cirrhosis caused by chronic alcohol consumption, in order to get better insight into the function of the renin-angiotensin system. PATIENTS AND METHODS: Serum level of ACE activity was measured by Neels spectrophotometry in 35 alcoholic liver cirrhosis patients classified according to Child-Pugh-Turcotte criteria and 35 dyspeptic patients with any liver disease excluded (control group). RESULTS: Serum values of ACE were statistically significantly higher (p < 0.00001) in the group of liver cirrhosis patients (x = 250.16 +/- 85.5 nmol) than in the control group (x = 115.88 +/- 58.19 nmol). The highest levels of ACE were measured in class B group of liver cirrhosis patients vs. class A and class B groups (p < 0.013). CONCLUSION: It is concluded that liver cirrhosis patients have elevated ACE levels, which coud be useful in the diagnosis and follow up of these patients.