Milan Kujundžić

Results of National Colorectal Cancer Screening Program in Croatia (2007-2011).

AIM To study the epidemiologic indicators of uptake and characteristic colonoscopic findings in the Croatian National Colorectal Cancer Screening Program. METHODS Colorectal cancer (CRC) was the second leading cause of cancer mortality in men (n = 1063, 49.77/100,000), as well as women (n = 803, 34.89/100,000) in Croatia in 2009. The Croatian National CRC Screening Program was established by the Ministry of Health and Social Welfare, and its implementation started in September, 2007. The coordinators were recruited in each county institute of public health with an obligation to provide fecal occult blood testing (FOBT) to the participants, followed by colonoscopy in all positive cases. The FOBT was performed by hypersensitive guaiac-based Hemognost card test (Biognost, Zagreb). The test and short questionnaire were delivered to the home addresses of all citizens aged 50-74 years consecutively during a 3-year period. Each participant was required to complete the questionnaire and send it together with the stool specimen on three test cards back to the institute for further analysis. About 4% FOBT positive cases are expected in normal risk populations. A descriptive analysis was performed. RESULTS A total of 1,056,694 individuals (born between 1933-1945 and 1952-1957) were invited to screening by the end of September 2011. In total, 210,239 (19.9%) persons returned the envelope with a completed questionnaire, and 181,102 of them returned it with a correctly placed stool specimen on FOBT cards. Until now, 12,477 (6.9%), FOBT-positive patients have been found, which is at the upper limit of the expected values in European Guidelines for Quality Assurance in CRC Screening and Diagnosis [European Union (EU) Guidelines]. Colonoscopy was performed in 8541 cases (uptake 66%). Screening has identified CRC in 472 patients (5.5% of colonoscopied, 3.8% of FOBT-positive, and 0.26% of all screened individuals). This is also in the expected range according to EU Guidelines. Polyps were found and removed in 3329 (39% of colonoscopied) patients. The largest number of polyps were found in the left half of the colon: 64% (19%, 37% and 8% in the rectum, sigma, and descendens, respectively). The other 36% were detected in the proximal part (17% in the transverse colon and 19% in ceco-ascending colon). Small polyps in the rectum (5-10 mm in diameter), sigmoid and descending colon were histologically found to be tubular adenomas in 60% of cases, with a low degree of dysplasia, and 40% were classified as hyperplastic. Polyps of this size in the transverse or ceco-ascending colon in almost 20% had a histologically villous component, but still had a low degree of dysplasia. Polyps sized 10-20 mm in diameter were in 43% cases tubulovillous, and among them, 32% had areas with a high degree of dysplasia, especially those polyps in the ceco-ascending or transverse part. The characteristics of the Croatian CRC Screening National Program in the first 3 years were as follows: relatively low percentage of returned FOBT, higher number of FOBT-positive persons but still in the range for population-based programs, and higher number of pathologic findings (polyps and cancers). CONCLUSION These results suggest a need for intervention strategies that include organizational changes and educational activities to improve awareness of CRC screening usefulness and increase participation rates.

Efficacy of Interferon-α in the Treatment of Chronic Hepatitis C in Dialysis Patients: Two Therapeutic Protocols Compared

Background: Data on the efficacy of particular therapeutic protocols of interferon-α (IFN-α) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary. Aim: To compare the efficacy of two different therapeutic protocols for HD patients. Patients and Methods: 15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-α 3 × 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-α 3 × 5 MU/week for 3 months, then 1 × 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection. Results: ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR [50% (4/8) vs. 28.5% (2/7)] and lower drop-out rate [0% (0/8) vs. 28.5% (2/7)] were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05). Conclusion: Therapy with IFN-α 3 × 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.

Leukotriene receptor antagonists as potential steroid sparing agents in a patient with serosal eosinophilic gastroenteritis

Eosinophilic gastroenteritis is a heterogeneous and uncommon disorder characterised by eosinophilic inflammation of the gastrointestinal tissues. The location and depth of infiltration determine its various manifestations and later serve as the basis for its classification as mucosal, muscular, and serosal forms of eosinophilic gastroenteritis. The gold standard for diagnosis is an endoscopic biopsy showing prominent tissue eosinophilia. Gastrointestinal mucosal involvement causes malabsorption, protein losing enteropathy, and diarrhoea. Infiltration of the muscular layer of the bowel wall may cause gastric outlet or small bowel obstruction. Serosal involvement causes exudative ascites rich in eosinophils; this is the least common form and is usually diagnosed by laparoscopic examination and biopsy of the whole intestinal wall. …

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%; P < 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.

No adverse effect of ABVD chemotherapy in a patient with chronic hepatitis C and Hodgkin’s disease

SummaryThere is insufficient information on the effects of chemotherapy protocols for Hodgkin’s disease (HD) and the course of coexisting hepatitis C virus (HCV) infection. A single literature case reported a patient with HD who developed fulminant hepatitis and hepatic coma after receiving chemotherapy. The case described here is of a female patient previously exposed to prolonged war stress, complicated by intravenous drug abuse and chronic hepatitis C. One year after diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II, clinical stage IIIB). The patient received six cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete remission of HD. There was no hepatitis flare either during or after chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on the course of HCV infection in this patient who was successfully treated for HD. Because concurrent HCV infection and HD is extremely rare, we discuss here the possibility of the synergistic contribution of chronic war stress and hepatitis C infection in the pathogenesis of HD.

Treatment of Pancreatic Diseases

Treatment of acute pancreatitis should be started as early as possible because fluid resuscitation in the first 24 h is of the utmost importance. Pain should be alleviated and early changes to nutrition considered. Antibiotics should not be introduced unless signs of systemic inflammatory response syndrome with suspicion of infection, concomitant biliary infection, or another organ infection are present. Various local complications can occur, which may be treated conservatively, minimally invasively, or surgically. Early endoscopic biliary decompression should be considered in patients with biliary pancreatitis. For chronic pancreatitis, lifestyle modifications should be encouraged, and pain relief medications should be gradually introduced. Patients with obstructive forms of chronic pancreatitis might benefit from endoscopic treatment, whereas surgical treatment should be considered for patients with disabling pain that cannot be controlled by medical treatment and is refractory to endoscopic treatment. Pancreatic exocrine insufficiency is often difficult to define and should be treated with pancreatic enzyme replacement therapy. Pancreatic cancer has a poor prognosis, and its management depends on the disease stage. Generally, in cases of resectable illness, surgery should be considered, with postoperative chemotherapy. Locally advanced disease (unresectable) can be treated with chemo(radio)therapy or stereotactic body radiotherapy; the best supportive care should be offered to patients with poor performance status. Systemic chemotherapy should be considered for patients with metastatic disease, and supportive care and palliative treatment should be provided.

Diagnostic specificity and sensitivity of PIVKAII, GP3, CSTB, SCCA1 and HGF for the diagnosis of hepatocellular carcinoma in patients with alcoholic liver cirrhosis:

Introduction Despite some new treatment possibilities, the improvement in survival rate for hepatocellular carcinoma (HCC) patients is still poor due to late diagnosis. The aim of this study was to investigate the diagnostic sensitivity and specificity of protein induced by vitamin K absence or antagonist-II (PIVKAII), Glypican-3 (GP3), Cystatin B (CSTB), squamous cell carcinoma antigen 1 (SCCA1) and hepatocyte growth factor (HGF) as potential tumour markers for HCC in patients with alcoholic liver cirrhosis (ALC) using imaging techniques (MSCT and MRI) as reference standards. Patients and methods Eighty-three participants were included: 20 healthy volunteers, 31 patients with ALC and 32 patients with HCC. Peripheral blood sampling was performed for each participant, and serum concentrations of PIVKAII, GP3, CSTB, SCCA1 and HGF were determined using commercial ELISA kits. Results Only serum concentrations of PIVKAII were significantly higher in HCC patients as compared with ALC and healthy controls (cut-off: 2.06 µg/L; AUC: 0.903), whereas individual diagnostic performance of other individual compounds was inadequate. The ‘best’ combination of tumour markers in our study includes all tested markers with AUC of 0.967. Conclusion While novel diagnostic tumour markers are urgently needed, the examined potential tumour markers, with the exception of PIVKAII seem to be inadequate for diagnosing HCC in ALC. Furthermore, probably the future is in finding the best optimal combination of tumour markers for diagnosing HCC based on cost-effectiveness.

Therapeutic dilemmas in patient with perianal Crohn's disease and corticosteroid dependent difficult-to-control asthma

Dear Sir, We present a 53 years old woman who suffered from endogenous difficult-to-control asthma from young adult age, with need of chronic use of oral corticosteroid therapy (metilprednisolone 16–24 mg/day > 50% year) together with treatment of high doses of inhaled corticosteroids and daily requirement of long acting beta 2 agonist. Despite therapy, asthma was poorly controlled with FEV1 20%. In the year 2008 perianal Crohns disease was diagnosed in this patient. She had a history of asthma since young adult age that had been poorly controlled, with need of chronic use of oral corticosteroid therapy. She reported daily symptoms and almost nightly nocturnal awakenings due to shortness of breath, which were temporarily relieved with bronchodilators. She had had several exacerbations of asthma in the past 2 years requiring hospitalization. Her past medical history was negative for perennial allergies. She was a lifelong nonsmoker and denied any illicit drug use. Current pulmonary medication included: metilprednisolone 16–24 mg/day, fluticasone/salmeterol 500 ug/50 ug twice daily, montelukast 10 mg once daily and salbutamol on an as-needed basis which she was currently using three …

The use of color doppler flow imaging in the diagnosis of acute alcoholic hepatitis: Evidence of intrahepatic arterial dilatation

Abstract Objective: In this article, a color Doppler flow imaging investigation was performed to demonstrate the segmental arterial dilatation within the liver parenchyma of patients with acute alcoholic hepatitis and to compare these findings with those obtained in a group of patients with alcoholic liver disease, but without clinical and biochemical parameters suggesting acute hepatitis. Methods: Color Doppler flow imaging was performed in 59 patients with a previously established diagnosis of alcoholic disease of the liver. Among those patients, 25 fulfilled physical and biochemical criteria of acute alcoholic hepatitis. Ultrasound scans were performed by two independent, equally skilled investigators with a 3.5 MHz transducer. Based on a previous observation, special attention was given to whether a intrahepatic arterial dilatation was present. Results: Of the 59 patients with alcoholic liver disease, intrahepatic arterial dilatation was seen in 29 (49.2%) patients. In 27 of 29 patients (93.1%) with intrahepatic arterial dilatation the arterial nature of one of the vessels was confirmed by pulsed-Doppler flowmetry. Intrahepatic arterial dilatation was observed in 22 of 25 (88.0%) patients with acute alcoholic hepatitis. Among the 34 patients with advanced alcoholic liver disease, but without physical and biochemical evidence of acute hepatitis, the presence of intrahepatic arterial dilatation was found in 7 (20.6%) patients. A systolic hepatic bruit was heard in 19 of 25 (76.0%) patients with acute alcoholic hepatitis, all of whom had intrahepatic arterial dilatation. Comparing patients with acute alcoholic hepatitis who had intrahepatic arterial dilatation with those who had not, significant difference was found with respect to the values of serum bilirubin and aspartate transaminase. For technical reasons an accurate and reproducible measurement of hepatic artery resistive index (RI) was possible in 41 (69.5%) patients (18 patients with and 23 patients without acute alcoholic hepatitis). For the 18 patients with acute alcoholic hepatitis, the mean RI was 0.74 ± 0.08, a level that was significantly lower than that observed in the 23 patients without physical and biochemical findings of acute alcoholic hepatitis (0.85 ± 0.05); P