Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Role of acid suppression in the development and progression of dysplasia in patients with Barrett's esophagus.

Barrett's esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression.

Discriminatory ability of calcaneal quantitative ultrasound in the assessment of bone status in patients with inflammatory bowel disease.

A high incidence of bone disease in patients with inflammatory bowel disease (IBD) requires frequent monitoring of skeletal status and, for that reason, evaluation of radiation-free technology is an issue of interest. Our objective was to appraise the parameters of calcaneal quantitative ultrasound (QUS): broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI), and establish their t-score values to investigate discriminatory ability of QUS in IBD patients with metabolic bone disease. The study included 126 patients (Crohn's disease [n = 94] and ulcerative colitis [n = 32]), and 228 age- and sex-matched healthy volunteers. Bone status was evaluated on the same day by calcaneal QUS and dual-energy x-ray absorptiometry (DXA) at spine (L1-L4) and total hip. All QUS measurements were lower in patients compared with healthy controls (BUA p < 0.001; SOS p < 0.001; QUI p < 0.001) and correlated significantly but inversely with disease duration (r = -0.3, p = 0.002). There was no difference with respect to type of disease (Crohn's disease or ulcerative colitis) or corticosteroid therapy. All three QUS t-scores were significantly lower in patients who had previously sustained fragile fractures (n = 28) than in those without fracture in their history (n = 98) (t-scores: BUA -2.0 vs. -1.3, p = 0.008; SOS -2.1 vs. -1.4, p = 0.02: QUI -2.3 vs. -1.5, p = 0.009). Axial DXA was not significantly different between the fracture and nonfracture patients (-1.7 vs. -1.2, p = 0.1), whereas total hip DXA showed a discriminatory power between the two (-1.6 vs. -0.7, p = 0.001). Patients with t-score < -1.0 scanned by DXA were classified as bone disease. The sensitivity of QUS to identify bone disease was 93% and specificity 63%. The sensitivity of QUS to detect osteopenia was 84% and 72% for osteoporosis. Alternatively, lower negative QUS t-score cutoff

Lactobacillus acidophilus as a cause of liver abscess in a NOD2/CARD15-positive patient with Crohn's disease.

INTRODUCTION: The development of a fistula and/or an abscess are major complications in patients with Crohn's disease. An abscess can involve any of the major viscera, including the liver and spleen. CASE REPORT: A 27-year-old male patient with a 6-month history of NOD2/CARD15-positive Crohn's disease with stenosis of the terminal ileum, previously treated with corticosteroids, was admitted with fever, chills, diarrhea, fatigue and cachexia. Diagnostic work-up revealed sepsis, an abscess in the right hepatic lobe, multiple abdominal collections and right-sided pleural effusion. It was felt that his poor general condition prevented surgical intervention and complex conservative treatment was initiated. It consisted of total parenteral nutrition, antibiotics, percutaneous drainage of the liver abscess, and thoracocentesis. Pus and blood cultures showed Lactobacillus acidophilus. There was a gradual improvement in the patient's condition and the liver abscess decreased in diameter from 14 to 2 cm. Aminosalicylates and enteral nutrition were gradually introduced. The patient was discharged after 9 weeks in good general condition. CONCLUSION: Although extremely rarely, L. acidophilus can cause hepatic abscess and sepsis. This can be explained by immunologic incompetence due to corticosteroid treatment of Crohn's disease.

Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease.

INTRODUCTION: Interferon gamma is a potent proinflammatory cytokine implicated in the inflammation of Crohn's disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe CD. METHODS: A total of 133 patients with Crohn's disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI < or =150). RESULTS: There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated. CONCLUSION: Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Benign mesenchymal liver hamartoma in an adult male: a case report and review of the literature.

Mesenchymal hamartoma of the liver is an uncommon benign lesion seen almost exclusively in children younger than two years of age. The first case was reported in 1903, and until now fewer than 200 cases have been reported. A 38-year-old male complaining of dull subcostal pain lasting for almost 10 months was found on abdominal ultrasound to have a focal lesion of the liver. He was referred to our Unit where imaging procedures (ultrasound and computed tomography) revealed a solid lesion, 8 centimeters in diameter, located in the IVb and V segments of the liver. There were no clear margins between the lesion and the gallbladder wall. Alpha-fetoprotein and carcinoembryonic antigen were within normal limits and carbohydrate antigen 19-9 was minimally elevated. There was no evidence of metastatic disease. Ultrasound-guided biopsy of the lesion was done and pathology report of a biopsy specimen suggested that the tumor was probably a benign mesenchymal hamartoma. The patient underwent a formal bi-segmentectomy (IVb and V segments) with cholecystectomy. Definitive pathology report confirmed the diagnosis of a benign mesenchymal hamartoma.

Dynamics of serum hepatitis C virus load and quasispecies complexity during antiviral therapy in patients with chronic hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) infection is a dynamic process during which viral genetic variants continuously develop as a result of the virus adaptation to the host's immune system. The level of viremia and the complexity of the hypervariable region 1 (HVR 1) quasispecies of hepatitis C virus during antiviral therapy reflect the dynamic balance between the viral and host components in response to therapy. OBJECTIVE: The aim of the study was to evaluate the dynamics of HCV viremia and the complexity of the HVR 1 quasispecies during the induction phase of a triple combination therapy regimen in nonresponders to earlier anti-HCV treatment. STUDY DESIGN: Ten patients with chronic hepatitis C undergoing antiviral combination therapy with interferon-alpha, ribavirin, and amantadine were studied. The serum HCV RNA level was monitored by a quantitative RT-PCR assay up to 3 months after start of treatment. The HVR 1 quasispecies complexity was analysed by an "in house" nested RT-PCR mediated single-strand conformation polymorphism (SSCP) assay. RESULTS: Baseline serum HCV RNA levels ranged from 1.94x10(6) to 5.53x10(6) copies/ml. In all patients, HCV subtype 1b was found. At the start of therapy, the SSCP assay revealed a high complexity pattern (at least six SSCP bands) in all patients. None of the patients responded within 4 weeks of treatment, however, the serum HCV RNA level decreased by one to two logs in eight patients. At week 4 after start of treatment, there was a decrease of SSCP bands in five patients. In four patients, SSCP bands remained unchanged and in one patient SSCP bands increased. At month 3 after start of treatment, serum HCV RNA was not detectable in one patient. CONCLUSION: Because of the low number of patients involved in this study, prediction of therapeutical success based on the quasispecies complexity was not possible. Larger studies are urgently needed.

Hypervariable region 1 of hepatitis C virus genome and response to interferon therapy.

The relationship between the complexity of the hypervariable region 1 (HVR1) quasispecies of hepatitis C virus (HCV) and responsiveness to interferon-alpha (IFN) therapy was studied in patients with chronic hepatitis C. Twelve HCV-RNA-positive patients were treated daily with high dose IFN and ribavirin for 4 weeks, and then with IFN 3 MIU (Million International Units) TIW (three times per week) and ribavirin for 6 months. The HVR1 quasispecies complexity was analyzed by nested polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP). The baseline HCV-RNA levels in the study group ranged from 10(6) to 10(7) copies/ml. All patients exhibited HCV genotype 1 b. Initial SSCP analysis revealed four (33.3%) patients with a low complexity pattern (SSCP bands < or =4) and eight (66.6%) patients with high complexity pattern (SSCP bands >4). After 4 weeks of IFN therapy, one patient became HCV negative, and among those remaining positive, the HCV-RNA levels decreased by 2 to 3 logs and the number of SSCP decreased by 2 to 3 bands per sample. After 6 months of IFN therapy, five (41.7%) patients became HCV-RNA-negative. Seven (58.3%) patients did not respond to IFN therapy with sustained viral load from 10(3) to 10(5) copies/ml, and high complexity SSCP patterns. Our data support the HVR quasispecies complexity to be an independent predictive factor for IFN responsiveness in patients infected with HCV.

[Pseudomyxoma peritonei associated with splenic mucinous epithelial cysts--case report]. / Pseudomiksom peritoneuma s pridruzenim mucinoznim epitelnim cistama slezene--prikaz bolesnika.

A massive gelatinous ascites occurred in a 60-year-old patient, with no primary tumor found in the clinical work-up. The malignant cells were not found in the cytological examination of ascites. Explorative laparotomy revealed a gelatinous mass of 14 kg, a cystic tumor of the omentum and an identical cystic tumor of the spleen's lower pole. It was a well differentiated mucinous cystadenocarcinoma, most likely originating in the appendix. Most interesting is the involvement of the spleen with mucinous epithelial cysts, described as a rare finding associated with pseudomyxoma.

Quantitative tissue carcinoembryonic antigen (T CEA) assay as a screening test for severe dysplasia in colorectal adenomas.

Relationship between the serum (S CEA) and the tissue (T CEA) carcinoembryonic antigen concentrations with regard to the degree of dysplasia in colorectal adenomas was investigated. Our study included 56 single or multiple colorectal adenomas in 46 patients. The measurements of T CEA concentrations were performed using the quantitative CEA-EIA method (Abbott) modified for wet tissue, obtained from heads of the adenomas. As a control point the mucosa near adenoma and the rectal mucosa were used. Our results suggest that the T CEA concentrations from the head of the adenoma demonstrate a highly significant difference between mild and severe dysplasia (P < 0.001), between mild dysplasia and invasive adenocarcinoma (P < 0.001) and a significant difference between mild and moderate dysplasia (P < 0.05). On the other hand, the S CEA concentrations corresponding to these cases showed no such differences. In conclusion, we suggest the quantitative measurement of T CEA concentrations as a screening test for severe dysplasia in colorectal adenomas.

[Palliative treatment of malignant esophageal obstruction with a new endoscopically administered self-expanding nitinol stent: case report]. / Palijativni pristup malignoj opstrukciji jednjaka endoskopskom primjenom novog samosireceg (self-expanding) nitinolskog stenta; prikaz bolesnice.

The endoscopic methods of palliative treatment in malignant esophageal stenoses caused by neoplasm which have been performed so far unfortunately do not provide permanently satisfying results. The implantation of self-expanding stents with the purpose of removing malignant esophageal obstructions has recently become the most acceptable method of treatment. By using that method it is possible to reduce or even completely remove difficulties in swallowing. In that way a significant improvement in life quality of patients with inoperable esophageal cancer is possible. The various types of metal endoprostheses used for the palliative treatment of esophageal malignant stenoses are described in this paper. Here is also presented a case of nitinol stent implantation in a 50 year old woman suffering from esophageal cancer. This type of therapeutic treatment has been applied in Croatia for first time.

[Treatment of malignant bile duct obstruction with a metal stent. Case report]. / Rjesenje maligne opstrukcije zucovoda metalnim stentom. Prikaz slucaja.

In the case report we describe endoscopic implantation of endoprosthesis in the periampullar area in a 87 year old female patient with obstructive jaundice and cholangitis caused by pancreatic tumour. This is the first time that this procedure was successfully performed in Croatia.

Serum selenium concentration in patients with liver cirrhosis and hepatocellular carcinoma.

The aim of the study was to investigate the serum selenium concentration in patients with liver cirrhosis and hepatocellular carcinoma. A total of 59 patients, 49 with liver cirrhosis and 10 with liver cirrhosis and coexistent hepatocellular carcinoma, as well as 202 healthy volunteers entered the study. In the patients with liver cirrhosis and in those with liver cirrhosis and coexistent hepatocellular carcinoma, serum selenium concentrations were significantly lower (39.28 +/- 13.99 and 42.00 +/- 10.59 g/L, respectively), when compared to the group of healthy volunteers (66. 79 +/- 9.13 g/L) (p < 0.001). There was no significant difference in serum selenium concentrations between the two patient groups. In the group of patients with liver cirrhosis positive correlation was found between serum selenium and albumin concentrations, and negative correlation between serum selenium and bilirubin (p < 0.05 and p < 0.01, respectively). There was no correlation of serum selenium concentration with fibrinogen and prothrombin time. Results of the study suggested the possible important nutritive and protective role of selenium in the patients with liver cirrhosis and coexistent hepatocellular carcinoma, as well as the potential need of selenium supplementation in these patients.