Liver and spleen stiffness and their ratio assessed by real-time two dimensional-shear wave elastography in patients with liver fibrosis and cirrhosis due to chronic viral hepatitis.

OBJECTIVES: To investigate the performance of real-time 2D shear wave elastography (RT 2D-SWE) for non-invasive staging of liver disease in patients with chronic viral hepatitis (CVH). MATERIALS AND METHODS: Naive CVH patients underwent liver (LS) and spleen stiffness (SS) measurements by an intercostal approach. Patients with ALT >3× upper limit of normal, cholestasis as revealed by dilated intrahepatic biliary tree, and liver congestion were excluded. Results were expressed in kPa and compared to histological stage (Ishak) of liver fibrosis (LF). Patients with decompensated liver cirrhosis (LC) were diagnosed using standard clinical, ultrasound, and endoscopic criteria. RESULTS: Of 123 patients, LS was successfully measured in 79.7% and SS in 53.7%. LS accurately differentiated between liver disease stages, with cut-off values of 8.1 (AUC 0.991) for F ≥ 3, 10.8 kPa (AUC 0.954) for F ≥ 5, and 27 kPa (AUC 0.961) for decompensated LC. SS was significantly different between non-cirrhotic stages (F0-4) and LC (cut-off 24 kPa; AUC 0.821). While both LS and SS increased with liver disease progression, the difference between them decreased, as reflected by the stiffness ratio index. CONCLUSIONS: RT 2D-SWE can accurately differentiate between the stages of LF, and can distinguish LF from LC and compensated from decompensated LC. KEY POINTS: • RT 2D-SWE is an accurate method for assessment of liver fibrosis. • RT 2D-SWE is applicable in 80% of patients with chronic viral hepatitis. • RT 2D-SWE accurately differentiates compensated from decompensated liver cirrhosis. • Both liver and spleen stiffness increase with progression of liver fibrosis. • In cirrhosis, the difference between liver and spleen stiffness decreases.

Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis.

AIM: Primary: to evaluate predictivity of liver stiffness (LS), spleen stiffness (SS), and their ratio assessed by real-time 2D shear wave elastography (RT-2D-SWE) for adverse outcomes (hepatic decompensation, hepatocellular carcinoma or death; "event") in compensated liver cirrhosis (LC) patients. Secondary: to evaluate ability of these measures to discriminate between cirrhotic patients with/without esophageal varices (EV). METHODS: Predictivity of LS, SS, and LS/SS was assessed in a retrospectively analyzed cohort of compensated LC patients (follow-up cohort) and through comparison with incident patients with decompensated cirrhosis (DC) (cross-sectional cohort). Both cohorts were used to evaluate diagnostic properties regarding EV. RESULTS: In the follow-up cohort (n=44) 18 patients (40.9%) experienced an "event" over a median period of 28 months. LS≥21.5 kPa at baseline was independently associated with 3.4-fold (95% confidence interval [CI] 1.16-10.4, P=0.026) higher risk of event. Association between SS and outcomes was weaker (P=0.056), while there was no association between LS/SS ratio and outcomes. Patients with DC (n=43) had higher LS (35.3 vs 18.3 kPa, adjusted difference 65%, 95% CI 43%-90%; P<0.001) than compensated patients at baseline. Adjusted odds of EV increased by 13% (95% CI 7.0%-20.0%; Plt;0.001) with 1 kPa increase in LS. At cut-offs of 19.7 and 30.3 kPa, LS and SS had 90% and 86.6% negative predictive value, respectively, to exclude EV in compensated patients. CONCLUSION: This is the first evaluation of RT-2D-SWE as a prognostic tool in LC. Although preliminary and gathered in a limited sample, our data emphasize the potential of LS to be a reliable predictor of clinical outcomes and the presence of EV in LC patients.

[LOW SPECIFICITY OF PLATELET TO SPLEEN RATIO FOR NONINVASIVE PREDIC- TION AND CHARACTERIZATION OF ESOPHAGEAL VARICES IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS]. / OMJER BROJA TROMBOCITA I VELICINE SLEZENE IMA NISKU SPECIFICNOST U NEINVAZIVNOJ PREDIKCIJI I KARAKTERIZACIJI VARIKOZITETA JEDNJAKA KOD BOLESNIKA S ALKOHOLNOM CIROZOM JETRE.

Diagnosis of esophageal varices (EV) is based upon endoscopic examination, which is a rather unpleasant method that carries a certain risk of complications. For that reason, efforts have been made to develop noninvasive methods for characterization of EV. The aim of this study was to explore the value of platelet count to spleen size ratio (PSR) for noninvasive prediction and characterization of EV in patients with alcoholic liver cirrhosis (ALC). One hundred and seventeen patients (20 females and 97 males, mean age 60.7) with ALC were included in our research. All patients underwent endoscopic examination upon which the EV were classified as small (< 5 mm), large (> 5 mm), or absent. Spleen size (bipolar diameter in mm) was assessed by ultrasound. Platelet count to spleen diameter ratio was calculated and the values obtained were compared to the presence, size and risk of bleeding from EV as defined by endoscopy. No significant difference in PSR could be found between patients without and with EV (1.341 ± 0.725 vs. 1.053 ± 0.636, respectively; p = 0.06). The PSR was significantly different between the patients with small and large EV (1.103 ± 0.689 vs. 0.876 ± 0.314; p < 0.05) with a cut-off value of 1.141 (sensitivity 94.7%, specificity 38.2%, AUROC = 0.656; p = 0.042). The value of PSR below 1.182 pointed to patients at risk from variceal bleeding with 91.7% sensitivity and 38.5% specificity (AUROC = 0.625, p = 0.035). Based on our results, it is not possible to recommend the use of PSR as the exclusive noninvasive indicator for the presence, size and bleeding risk from EV due to its low specificity for these categories in patients with ALC.

Etiology and epidemiology of obstructive jaundice in Continental Croatia.

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.

[The role of biologic therapy in the treatment of extraintestinal manifestations and complications of inflammatory bowel disease]. / Uloga bioloske terapije u lijecenju ekstraintestinalnih manifestacija i komplikacija upalnih bolesti crijeva.

Extraintestinal manifestations occur in about 35% of patients with inflammatory bowel diseases (IBD). Most frequently affected are bones and joints, skin, eyes, liver and biliary ducts. Extraintestinal manifestations of IBD are divided in two groups: reactive manifestations which depend on activity of IBD--peripheral arthritis, erythema nodosum, aphthous stomatitis, episcleritis and other manifestations which are independent on activity of IBD--pyoderma gangrenosum, uveitis, axial arthropathy, primary sclerosing cholangitis (PSC). Most affected are bones and joints. Symptoms vary from mild arthralgia to severe arthritis with painful swallowing of joints. They occur in about 5-10% of patients with ulcerative colitis (UC) and in 10-20% of patients with Crohn's disease (CD). Both peripheral and axial joints can be affected. According to available data, most patients with active IBD and concomitant arthritis have benefit from infliximab therapy. Infliximab is also effective in maintenance of remission in group of patients with spondyloarthropathy. Adalimumab showed similar efficacy in treatment of ankylosing spondylitis, but there are still no data about efficacy of adalimumab in treatment of patients with IBD and concomitant arthritis. Primary sclerosing cholangitis, autoimmune hepatitis, cholestasis, cholelithiasis and elevation of aminotransferase are also considered to be extraintestinal manifestations of IBD. Most frequent is PSC which affects usually patients with UC (7.5% of patients). Course of liver disease is completely independent on activity of IBD, and destruction of biliary ducts is usually irreversible and refractory on treatment and most of the patients need liver transplantation. Anti-TNF therapy is also ineffective in treatment of PSC and has no impact on disease course and outcome. However, there is no contraindication for anti-TNF therapy of concomitant active IBD in this group of patients. Erythema nodosum (EN) and pyoderma gangrenosum (PG) are usual skin manifestations of IBD. Erythema nodosum occurs in about 3-20%, and pyoderma gangrenosum in about 0.5-20% of patients with IBD. Infliximab is proven to be effective in treatment of PG, but there is still not enough evidence on efficacy of anti-TNF drugs in treatment of EN and other rare skin manifestations of IBD. About 2-5% of patients with IBD have also some ophthalmological disorder. Symptoms vary from mild conjunctivitis to severe inflammation of eye membranes--iritis, episcleritis, scleritis and uveitis. It seems that infliximab and adalimumab can diminish uveitis and scleritis in patients with different autoimmune disorders and IBD. According to guidelines of American Gastroenterology Association (AGA), in group of patients with CD, infliximab is indicated in treatment of spondyloarthropathies, arthritis, arthralgia, pyoderma gangrenosum, erythema nodosum, uveitis and other ophthalmological manifestations of IBD except optical neuritis which can worse or be consequence of anti-TNF treatment. Similar indications exist for use of adalimumab except in case of erythema nodosum. In group of patients with extraintestinal manifestations of UC, infliximab is indicated in treatment of spondyloarthropathies and pyoderma gangrenosum. Complications of IBD are fistulas (perianal and non-perianal), stenosis and strictures, abscesses, bowel perforations, gastrointestinal bleeding and development of different malignomas. Anti-TNF drugs are proven to be effective and indicated only for treatment of perianal fistulas in patients with Crohn's disease. In group of patients with UC, there are only few case reports on beneficial effect of infliximab in treating chronic pouchitis and infliximab in treatment of these patients still cannot be recommended.

[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.

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.

Prevention of peritoneal carcinomatosis in mice by combining hyperthermal intraperitoneal chemotherapy with the water extract from Burr parsley (Caucalis platycarpos L.).

The presence of peritoneal carcinomatosis arising from gastrointestinal and gynecologic tumors is associated with a poor prognosis. Animal models of peritoneal carcinomatosis are important in the evaluation of new treatment modalities. The purpose of this study was to investigate the effect of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in an animal model of induced peritoneal carcinomatosis in the mouse. For induction of peritoneal carcinomatosis, cells from transplantable mammary carcinoma (MCa) were implanted intraperitoneally in CBA mice. Seven or 3 days before implantation of MCa cells (5 x 10 (3)) the mice were injected with lyophilized water extract from CAUCALIS PLATYCARPOS L. (CPL; 200 mg . kg (-1)) into the abdominal cavity. Immediately after implantation of MCa cells in the abdominal cavity, mice were treated two times with 2 mL of saline that was heated either at 37 degrees C or 43 degrees C (hyperthermal treatment) and cytostatics (doxorubicin 20 mg . kg (-1), cisplatin 10 mg . kg (-1), mitomycin 5 mg . kg (-1), 5-FU 150 mg . kg (-1)). We followed the survival of animals and the side effects appearing with different forms of treatment. CPL increased the life span of mice with peritoneal carcinomatosis without hyperthermal treatment (ILS% = 32.55 %) but showed no effect on the life span of mice with hyperthermal treatment (ILS% = 1.44). Combined treatment with CPL and cytostatics (CIS, DOX, and MIT) significantly affected the development of peritoneal carcinomatosis and increased the survival of mice (ILS% - 37 degrees C = 144.17, 415.46, and 124.13, ILS% - 43 degrees C = 311.42, 200.74, and 138.33, respectively). However, intraperitoneal chemotherapy with 5-FU alone resulted in greater survival time of mice than the treatment with 5-FU + CPL. Results suggest the synergistic effect of hyperthermia, chemotherapy, and immunotherapy. CPL significantly increases the antitumor activity of the hyperthermic chemotherapy and the survival rate of mice with peritoneal carcinomatosis. The stimulative effect of CPL on immunomodulation may be a possible mechanism which protects mice from developing peritoneal carcinomatosis and reduces the side effects of chemotherapy, increasing the life span of mice.

Biliary brush cytology for the diagnosis of malignancy: a single center experience.

Differentiation between benign and malignant biliary strictures is critical to the provision of adequate treatment. Brush cytology during the endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly used method for obtaining tissue confirmation of the nature of biliary strictures. It's specificity is remarkably high but reported sensitivities for the diagnosis of malignancy are low. Aim of our study was to assess sensitivity and specificity of biliary brush cytology in our institution, to find out main causes of false negative diagnoses and to confirm impression that the team approach has impact on sensitivity. Gold standard for diagnosis was definitive surgical histology or adequate clinical follow up for minimum of six month. Direct smears made by cytotechnician at the endoscopy room, and stained according to Papanicolaou and May-Grünwald Giemsa (MGG) were examined for well-recognized features of malignancy on conventional smears as a part of diagnostic routine. Cytologic diagnoses were benign, atypical/reactive, suspicious for malignancy and malignant. Of 143 brushings with available definitive diagnosis 36 (25%) had malignant cytologic diagnosis and 91(63.6%) were classified as benign, 3 were atypical/reactive and 13 suspicious for malignancy with 20 "false-negative" cases. When specimens with atypical and suspicious cytology were excluded from data analysis sensitivity was 64% and specificity was 100% and when suspicious findings were taken into account as true positives sensitivity rose to 71%. We find that biliary brush cytology, although mainly depending on the skill of endoscopist, as well as the experience of the cytologist, is a valuable method for obtaining accurate tissue diagnosis of biliary strictures, thus solving eternal diagnostic dilemma: benign or malignant.

Endoscopic ultrasound in solid pancreatic masses--current state and review of the literature.

Some 25 years ago endoscopic ultrasound (EUS) was introduced in clinical practice for better visualization of pancreas. At the time of introduction EUS was superior to other methods in detection of pancreatic masses allowing tissue diagnosis by later introduced EUS-guided fine needle aspiration (FNA). During the time EUS was improved, electronic probes replaced mechanical probes adding ability of color Doppler, power Doppler, contrast enhanced endosonography as well as EUS elastography analysis. Meanwhile, CT technology has also experienced significant improvements raising the question whether EUS has lost ground in diagnostics of solid pancreatic masses. The aim of this review was to discuss the current evidence of clinical impact of EUS and EUS-FNA in evaluation of solid pancreatic masses with special emphasis on differentiation between benign and malignant pancreatic lesions. According to the literature, the detection of small pancreatic tumors, preoperative localization of pancreatic endocrine tumors and tissue sampling by fine-needle aspiration of pancreatic masses in cases with therapeutic consequences are considered firm indications for EUS. Cytological tissue analysis remains undisputed in differentiation benign from malignant lesions, but the question when FNA is needed is discussed. Color Doppler, power Doppler, contrast enhanced endosonography and especially elastography are also discussed as tools that are bringing additional information in evaluation of pancreatic masses, however insufficient for definitive judgment of the lesion's nature. Pancreatic cancer staging as indication for EUS is discussed controversially, inconsistent results and conflicting evidence in literature making adequate conclusion impossible. However, this indicates that at least the role of EUS is no longer undisputed in this matter. Resuming the role of EUS we can state that despite some controversies EUS is very valuable method in evaluation of solid pancreatic masses and with EUS guided FNA is nowadays by far the best method for obtaining tissue diagnosis.

Insulin-like growth factor 2 binding protein 3 expression on endoscopic ultrasound guided fine needle aspiration specimens in pancreatic ductal adenocarcinoma.

BACKGROUND: Despite numerous investigations, we still do not have a specific marker for pancreatic ductal adenocarcinoma. Only guideline-recommended biomarker for pancreatic ductal adenocarcinoma is the CA19-9, but it is also present in other gastrointestinal diseases. IMP3 is a new potential biomarker that is over-expressed in some cancers. The aims of our study were (1) to assess IMP3 in benign pancreatic lesions and pancreatic cancer, and (2) to estimate its concentrations in localized and advanced pancreatic cancer. PATIENTS AND METHODS: Seventy-five patients with solid pancreatic lesions who underwent EUS-FNA were included. Patients were divided into three groups: benign lesions, cancer localized only on the pancreas, and patients with advanced pancreatic cancer (locally advanced or with distal metastases). Immunoreactivity of IMP3 was assessed on cytological smears sampled by endoscopic ultrasound. RESULTS: IMP3 was expressed in 89% of the patients with pancreatic cancer and not in benign lesions. Stronger expression of IMP3 protein and stage of the pancreatic cancer was statistically significant. IMP3 was expressed in all localized cancers and in 85% of patients with advanced pancreatic cancer. In the subgroup with locally advanced cancer, IMP3 was expressed in 88%, and in 83% of patients in the subgroup with distal metastasis (P = 0.007). In the present study, sensitivity was 89%, specificity 100%, with positive predictive value of 100% and negative predictive value of 63%. CONCLUSION: There is a positive correlation between IMP3 expression and TNM stages of the pancreatic cancer. Higher expression of IMP3 on EUS-FNA specimens can suggest poorer prognosis.

Prevention of peritoneal carcinomatosis in mice with combination hyperthermal intraperitoneal chemotherapy and IL-2.

PURPOSE: The purpose of this study was to investigate the effect of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse model of induced peritoneal carcinomatosis. MATERIAL AND METHODS: Peritoneal carcinomatosis in mice was produced by intraperitoneal implantation of MCa cells (5 x 10(3)). Interleukin-2 (4.1 x 10(4) IU/mouse) was injected into the abdominal cavity of mice at day 7 and 3 before implantation of tumour cells. Immediately after implantation of MCa cells mice were treated twice with 2 ml of saline that was heated either at 37 degrees C or 43 degrees C and cytostatics (doxorubicin 20 mg kg(-1), cisplatin 10 mg kg(-1), mitomycin 5 mg kg(-1), or 5-FU 150 mg kg(-1)). We followed the survival of animals and side effects appearing with different forms of treatment. RESULTS: Combined treatment with Interleukin-2 (IL-2) and cytostatics (5-FU, CIS or MIT) significantly affected the development of peritoneal carcinomatosis and increased the survival of mice (ILS% - 37 degrees C = 29.88, 199.32, and 108.52, ILS% - 43 degrees C = 62.69, 260.50, and 178.05, respectively). However, intraperitoneal chemotherapy on survival time of mice with DOX + IL-2 was ineffective as compared with DOX alone. CONCLUSION: We would like to stress that treatment with IL-2 prior to tumour diagnosis is not clinically practical, rather, the manuscript attempts to describe an experimental proof of principle. Results suggest the synergistic effect of hyperthermia, chemotherapy and immunotherapy; IL-2 significantly increases antitumor activity of hyperthermic chemotherapy and survival rate of mice with peritoneal carcinomatosis.

The association between upper gastrointestinal lesions and high-sensitivity C-reactive protein in coronary artery disease patients.

BACKGROUND: Although high-sensitivity C-reactive protein (hs-CRP) testing is not specific for coronary atherosclerosis, elevated hs-CRP is recently accepted as an independent predictor of future cardiovascular events. Also, a connection between upper gastrointestinal lesions (UGILs) and coronary artery disease (CAD) has been observed. The authors hypothesized that UGILs increase hs-CRP in CAD patients. MATERIAL/METHODS: One hundred fifty patients with stable CAD were enrolled in the study. Demographic and clinical variables and chronic medication used were gathered from a structured questionnaire. UGIL severity was determined by a modified Lanza score, H. pylori status by histology of the gastric mucosa, and the severity of CAD by a modified Gensini score. Independent correlation between hs-CRP and UGIL was tested by logistic regression analysis. RESULTS: The overall hs-CRP value was higher in patients with UGIL than in those with normal endoscopic results (8.14+/-4.53 mg/l vs. 4.64+/-3.06 mg/l, P<0.0001). hs-CRP level positively correlated with UGIL severity (r=0.434, P<0.0001). Correlation between UGIL and hs-CRP level remained significant after adjustment for coronary risk factors, medication used, CAD severity, and H. pylori status (standardized coefficient beta=1.272, P<0.0001). However, when hs-CRP level was used as a categorical variable, multivariate analysis revealed independent correlation only between UGIL and hs-CRP categories > or =6.1 mg/l. CONCLUSIONS: Elevated hs-CRP levels may be predictive of UGIL; thus endoscopy should be considered in CAD patients with elevated hs-CRP even with no dyspeptic symptoms. Because CRP plays an active role in atherothrombosis, UGILs with subsequent elevated CRP levels could increase cardiovascular risk in those patients.

[Video capsule endoscopy--preliminary experience in university hospital setting]. / Endoskopska kapsula za tanko crijevo--pocetna iskustva u klinickoj bolnici.

INTRODUCTION: The use of video capsule endoscopy (VCE) started in late 2001 when it was approved by the Food and Drug Administration (FDA). Since then, we are able to visualize small bowel mucosa with a minimally invasive technique, very comfortable for patients, with very few complications and without the need of hospitalization. At Dubrava University Hospital, we have been using VCE since October 2006, and by February 2008 we examined 30 patients. AIM: The aim of the study was to present our preliminary results in the use of VCE during a period of one year and five months. We also report indications and contraindications for VCE, and patient preparation. METHODS: In this retrospective study we reviewed records on 30 patients that had undergone VCE at Dubrava University Hospital, Zagreb, Croatia, between October 2006 and February 2008. The indications for VCE were restricted to the investigation of obscure gastrointestinal bleeding (OGIB) (n = 10), iron deficiency anemia (n = 2), suspected Crohn's disease (n = 1), assessment of known small bowel Crohn's disease (n = 5), unexplained diarrhea (n = 6), chronic abdominal pain (n = 3), suspected ganglioneurinoma (n = 1) and suspected polyposis syndrome (n = 2). To be eligible for VCE, patients had to have previously undergone usual diagnostic methods of upper endoscopy, colonoscopy and small bowel follow-through, without discovering the cause of their symptoms. Before swallowing the capsule, patients were instructed not to eat anything the day before VCE and to drink 4 L of liquids, and additional 2 L magnesium sulfate. In all patients we used Olympus EndoCapsule Software (Tokyo, Japan). Results were interpreted by one specialist, gastroenterologist. RESULTS: Definitive diagnosis was made in 15 patients. Suspect findings were noted in 2 patients, whereas no diagnosis could be established in 13 patients. According to our experience, VCE is a promising new method that has a high diagnostic yield in patients with OGIB and known Crohn's disease. Use of VCE enabled definitive diagnosis to be made in 6 of 10 patients with OGIB after all previously used diagnostic methods had failed to reveal any pathological finding. In the group of OGIB patients, angiodysplasia was the most common findings (4 of 10 patients). In the group of patients with Crohn's disease, progression of the disease to neotherminal ileum was recorded in 3 of 5 patients. Our experience also confirmed the VCE to be a very safe method; capsule retention was recorded in only one patient. DISCUSSION: Although VCE enabled us to visualize the small bowel mucosa and therefore helped us establish the diagnosis in cases where other diagnostic methods had failed, it still has some important limitations, the major one being the impossibility to take biopsies and to perform any therapeutic procedures. However, it has a high diagnostic yield in cases of OGIB and Crohn's disease, is very comfortable for patients, and has a low incidence of complications (capsule retention). When making definitive diagnosis, one should always consider patient's history and physical examination findings as well as other possible causes of small bowel mucosal impairment. CONCLUSION: VCE is a promising new technique that has a high diagnostic yield in patients with OGIB and Crohn's disease. However, more studies need to be done to establish definitive indications, cost-effectiveness and the best way of patient preparation for VCE.

[Color Doppler ultrasound of the liver circulation]. / Dopler jetrene cirkulacije.

Color Doppler Ultrasound (CDUS) is a valuable method for evaluation of morphological and hemodynamic changes of liver circulation occurring in various pathological conditions. In some of these conditions CDUS has a decisive diagnostic role, thus making further, potentially harmful invasive diagnostic procedures unnecessary. Except for the analysis of vascular liver diseases, as well as repercussions of circulatory impairment to the liver, utilization of CDUS provides valuable information for characterization of diffuse parenchymal and focal liver lesions. CDUS has advantages as compared to the other imaging modalities as it is widely available and noninvasive. The possible disadvantage is not related to the method itself, but is due to lack of expertise, i.e. training of the operator. In this article we review the present position of CDUS in evaluation of impairment of liver circulation: disorders of the venous outflow from the liver (Budd-Chiari syndrome, right-sided heart diseases, veno-occlusive disease), disorders of/in liver parenchyma (vascular anomalies-fistulae, solid tumors, circulatory changes that occur in diffuse liver diseases) and obstruction of the blood inflow to the liver (stenosis and thrombosis of hepatic artery and portal vein).

Informed consent for gastrointestinal endoscopy: a view of endoscopists in Croatia.

BACKGROUND/AIM: There are many differences and deficiencies in the process of informed consent. The aim of this study was to get the view of gastrointestinal endoscopists in Croatia on obtaining patients' consent before endoscopic procedures. METHODS: During the 2004 annual meeting of the Croatian Society of Gastroenterology, endoscopists were asked to answer a questionnaire according to common clinical practice in affiliated institutions. It included questions on endoscopists' experience and education in medical ethics, as well as on the nature and quality of information given to patients and their opinion on proposed measures for improvement of the informed consent process. RESULTS: The questionnaire was distributed to 96 endoscopists attending the meeting and the response rate was 54% (52/96). In only 50% of institutions was the obtained consent written and potential complications of endoscopic procedures are occasionally given to the patient. In the minority of cases the patient is provided with information about alternative diagnostic tests and/or treatment options, and the information about mortality rate was almost never discussed. CONCLUSIONS: In Croatia, the process of informed consent for endoscopy needs improvement and should be regarded against the background of education in medical ethics, regional burden in endoscopic practice and appropriateness of by-laws and local guidelines.

The utilization of antibiotics in the management of acute pancreatitis--experience from one transitional country university hospital.

The aim of the study was to analyze the evidence-based use of antibiotic therapy in the treatment of acute pancreatitis and to identify factors influencing the introduction of antibiotic therapy in the setting of transitional country clinical hospital. This retrospective study was conducted at Department of Internal Medicine at University Hospital Dubrava in Zagreb, Croatia. Data were collected from hospital records of patients treated for acute pancreatitis from January 1st, 2005 till December 31st, 2005. Data collected from patients' histories were compared with indications for antibiotic treatment and antibiotics with demonstrated therapeutic efficacy in acute pancreatitis which were obtained from published literature. Logistic regression was used to identify factors with a significant impact on deciding on the introduction of antibiotic therapy, and multivariate analysis was used to identify factors with a significant impact on the cost of treatment. Statistical significance was set at p < 0.05. Antibiotic therapy was used in 67.7% of patients with acute pancreatitis. Combination of amoxicillin plus clavulanic acid was most frequently administered, either as monotherapy or in combination with metronidazole and/or gentamicin (37.3%), followed by cefuroxime (32.8%) and cefoperazone (26.9%). The choice of antibiotic was appropriate in 35.8% of study patients; however in 29.9% of patients who were administered antibiotics had no indication for this therapy; and 46.9% of patients who had indications for receiving antibiotic therapy didn't receive it. In the groups of patients treated with antibiotics, the cost of treatment was significantly higher compared to groups of patients who were not treated with antibiotics (p = 0.0035; p = 0.0026). In addition to antibiotic therapy, the cost of treatment was significantly influenced by the length of hospital stay and treatment at intensive care unit. The use of antibiotics in the setting of transitional country university hospital in patients with acute pancreatitis is not evidence-based. Decision on the introduction of antibiotic therapy is not based on objective parameters of disease severity or evidence of therapeutic efficacy of particular antibiotics. The cost of treatment is significantly increased by the use of antibiotic therapy.

[Gastroduodenal mucosal lesions and coronary atherosclerosis severity in patients with coronary artery disease]. / Ostecenje gastroduodenalne sluznice i tezina koronarne ateroskleroze u bolesnika s koronarnom bolescu srca.

AIM: Due to high metabolic activity and oxygen demands, ischemia of gastroduodenal (GD) mucosa is an important factor in the pathogenesis of its impairment. Comparing the degree of coronary atherosclerosis, for evaluation of severity of atherosclerosis, with the prevalence and severity of GD mucosal lesions, we wanted to investigate the possible ischemia of GD mucosa could contribute to its impairment. PATIENTS AND METHODS: This prospective study included 150 coronary artery disease (CAD) patients, 109 (72.7%) male and 41 (27.3%) female, average age 62.61 +/- 10.23 years. We noted clinical and anthropometric parameters, standard laboratory findings, treatment until inclusion into the study and standard cardiovascular risk factors. The severity of CAD was assessed by several parameters: 1) number of coronary arteries affected with atherosclerosis, 2) modified Gensa score, and 3) number of coronary arteries with stenosis > 50%. The severity of GD mucosal lesions was assessed by modified Lanza score, and Helicobacter pylori infection was confirmed by biopsy and pathohistological analysis of GD mucosa. Predictive value of different independent factors regarding the presence of GD mucosal lesions was assessed by multivariate analysis. RESULTS: The severity of CAD in patients with or without GD mucosal lesions did not differ by any of used scoring methods: 1) number of coronary arteries affected by atherosclerosis (2.15 +/- 0.85 vs. 2.00 +/- 0.87, p = 0.292), 2) modified Gensa score (71.22 +/- 51.78 vs. 69.89 +/- 54.18, p = 0.881), 3) number of coronary arteries with stenosis > 50% (3.89 +/- 2.05 vs. 3.47 +/- 2.25, p = 0.244). We also noticed that there had been no correlation between severity of CAD and severity of GD mucosal lesions. Correlation of number of coronary arteries affected with atherosclerosis with Lanza score resulted in r = 0.029, p = 0.721, correlation of Genza score with Lanza score resulted in r = 0.019, p = 0.082, and correlation of the number of coronary arteries with stenosis > 50% with Lanza score resulted in r = 0.079, p = 0.337. CONCLUSION: According to available method for evaluating the severity of CAD, in CAD patients ischemia has no or very minor role in pathogenesis of GD mucosa impairment.

Albi Score as a Predictor of Survival in Patients with Compensated Cirrhosis Resected for Hepatocellular Carcinoma: Exploratory Evaluation in Relationship to Palbi and Meld Liver Function Scores.

The aim of the study was to explore predictive value of the ALBI, PALBI and MELD scores on survival in patients resected for hepatocellular carcinoma with compensated liver cirrhosis and no macrovascular infiltration. In this retrospective study, longitudinal survival analysis was performed. We analyzed patient/tumor characteristics and MELD, ALBI and PALBI scores as liver function tests for predicting survival outcome. Survival was analyzed from the date of liver resection until death, liver transplantation, or end of follow-up. Patients were stratified for age, cirrhosis etiology, presence of esophageal varices, hepatocellular carcinoma stage, microvascular invasion, histologic differentiation, and resection margins. We identified 38 patients (alcoholic cirrhosis in 84.2% of patients) resected over an 8-year period. Median preoperative MELD score was 8, ALBI score -2.63, and PALBI score -2.38. During the follow-up period, 24 patients died. Estimated median survival time was 36 months. Microvascular invasion was observed in 33 patients. Higher ALBI score was associated with 23.1% higher relative risk of death. PALBI score was associated with 12.1% higher relative risk of death, whereas MELD score was not associated with the risk of death. In conclusion, ALBI score demonstrated significant predictive capabilities for survival in patients with compensated cirrhosis resected for hepatocellular carcinoma.