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Background Spontaneous bacterial peritonitis (SBP) is associated with a high mortality. The aim was to investigate whether bacterial deoxyribonucleic acid (bactDNA) could offer an accurate identification of pathogens and to explore its prognostic role during and early after an SBP episode. Methods Consecutive patients with SBP (SBP-group) and patients with decompensated cirrhosis without SBP/bacterascites (control-group) were enrolled. Standard culture methodology was used to isolate and identify pathogens from blood and ascitic fluid (AF). The SeptiFast test was used to identify bactDNA directly from AF. Results Fifty-five patients, median age 60 (interquartile range [IQR] 53-74), model-for-end-stage liver disease (MELD) score 18 (IQR 13-29), with SBP were prospectively included. AF cultures were positive in 52.7% (17.2% drug-resistant bacteria) and bactDNA in 29.1% (58.2% combined sensitivity). BactDNA results were 84.6% concordant with AF cultures. Three patients had positive bactDNA in the culture-negative SBP-group. BactDNA was negative in all 36 of the control group (100% specificity). In multivariate analysis for 7-day survival, factors adversely affecting outcome were MELD (P=0.049) and C-reactive protein (P=0.012). After patients who died during the first week post-admission were excluded, patients with positive bactDNA had a poor prognosis compared to those with a negative test (log-rank P=0.005). Variables independently associated with 30-day mortality were neutrophil-to-lymphocyte ratio (P=0.011) and positive bactDNA (P=0.020). Conclusions No evidence was found for the usefulness of bactDNA to improve bacterial identification during an SBP episode. However, bactDNA was a predictor of 30-day mortality in the subset of patients who recovered from the infection episode.

BACKGROUND: Cholangiocarcinoma is a very aggressive tumor with poor survival. Therefore, early diagnosis and surgical resection are of paramount importance. Its diagnosis is difficult because access to the tumor is not easy. Biopsy is possible only for intrahepatic cholangiocarcinoma, which accounts for 10% of cases. Routine brush cytology from endoscopic retrograde cholangiopancreatography (ERCP) has a high specificity of 100% but unfortunately a low sensitivity of 30%. In this review we briefly describe new diagnostic techniques applicable to ERCP brush cytology specimens and targeting the genetic background of the disease, in particular fluorescence in situ hybridization (FISH) and digital image analysis (DIA). DATE SOURCES: The PubMed database up to 2011 was used for the retrieval of relevant articles. The search terms FISH, fluorescence in situ hybridization, DIA, digital image analysis and cholangiocarcinoma were used. Both original and review articles were used. RESULTS: FISH identifies cells with chromosomal abnormalities, mainly numerical aberrations, using a mixture of fluorescence-labeled probes. FISH offers a higher sensitivity than routine cytology, retaining a high level of specificity The DIA criterion for malignancy is demonstration of aneuploidy. This technique increases the sensitivity to 40%, but the specificity remains low. Preliminary data from application to other tumors suggest that combination of FISH and DIA may be of further benefit. CONCLUSIONS: The new techniques offer a significantly enhanced diagnostic efficacy in the evaluation of ERCP brush specimens. Apart from contributing to a more timely diagnosis, their wider application to cholangiocarcinoma may also facilitate the genetic study of the disease and add to our understanding of oncogenesis at the molecular level, with the prospect of identifying targets for novel therapeutic interventions. (Hepatobiliary Pancreat Dis Int 2012;11:349-359)

Background: There is evidence that in cirrhotic patients, certain hemodynamic parameters, such as blood pressure and heart rate, are related to the severity of liver disease. This study investigated whether non-invasive 24-hour ambulatory blood pressure and heart rate are more closely associated with markers of liver disease severity than conventional office measurements. Methods: Ambulatory patients with cirrhosis underwent office blood pressure and heart rate measurements, 24-hour ambulatory blood pressure monitoring and blood laboratory tests. Results: Fifty-one patients (32 men, mean age 57.4 +/- 11.3 years) completed the study. Twenty six patients had compensated liver cirrhosis (group A) and 25 patients had more advanced liver disease (group B). Group A and B patients differed significantly both in ambulatory asleep diastolic blood pressure (p < 0.05) and office diastolic blood pressure (p < 0.01), which were lower in more advanced liver disease. Office blood pressure and heart rate correlations were similar to or even stronger than ambulatory ones. Ambulatory blood pressure and heart rate awake-asleep variation (dipping) showed a relatively flat pattern as markers of liver dysfunction were deteriorating. The strongest correlations were found with both ambulatory and office heart rate, which increased as indicators of severity of liver disease were worsening. Conclusions: Heart rate seems to be a more reliable marker of ongoing liver dysfunction than blood pressure. Evaluation of blood pressure and heart rate with 24-hour ambulatory measurement does not seem to offer more information than conventional office measurements.

Acute exacerbations in HBeAg negative patients with chronic hepatitis 8 virus (HBV) infection are invariably associated with concurrent increases in the index of IgM class antibodies against the core protein (anti-HBc) of the virus. This study aimed to investigate whether this was related to the clearance of variants from the quasispecies pool and the appearance of new ones, with aminoacid substitutions in well recognized B-cell epitopes. In this study, 5 HBeAg negative patients (A to E) with 13 sequential serum samples (A1-A2, B1-B2-B3, C1-C2, D1-D2-D3, E1-E2-E3) were investigated after amplification of the entire core encoding region followed by cloning/sequencing studies. The sequences at different time points were compared with those from a single HBeAg positive patient with no apparent acute exacerbations. The results from sequence comparison showed that virus variants emerged in all (A2, B3, C2, D3, E2, and E3) but two (B2 and D2) subsequent sera with amino-acid substitutions affecting B-cell epitopes. It is concluded that the rise in the values of IgM anti-HBc may be attributed to the alteration of the antigenic epitopes leading to new antibody production in the majority of the cases. However, it appears that increases in IgM anti-HBc indexes in a few cases may relate to other possible mechanisms which are discussed. J. Med. Virol. 81:34-41, 2009. (c) 2008 Wiley-Liss, Inc.

Extranodal NK/T cell lymphoma, ‘nasal type,’ is a rare clinicopathological entity in Europe. The main clinical features are nasal congestion, sore throat, dysphagia and epistaxis, due to a destructive mass involving the midline facial tissues. Pathologically, lymphoma cells exhibit angioinvasion, angiodestruction and coagulative necrosis. We report the case of a patient who presented with fever, dyspnea, nasal congestion, headache, distention of right nasal turbinates and exophytic lower leg ulcerating lesions. A CT scan of visceral scull demonstrated a filling mass of right frontal, ethmoidal and maxillary sinuses with erosion of the wall of right maxillary sinus and ventral portion of the diaphragm. A biopsy was performed in the skin lesion and showed an angioinvasive NK/T cell lymphoma CD56 negative with clonal rearrangement of the T-cell-receptor gamma gene. Up to our knowledge, this is a rare immunophenotype for NK/T-cell, ‘nasal type,’ lymphomas. However, the lymphoma may be classified as extranodal NK/T cell lymphoma, ‘nasal type,’ due to typical clinical presentation, radiologic findings and pathological characteristics of polymorphism, angioinvasion, angiodestruction and coagulative necrosis.

Background: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. Methods: A prospective study was conducted over a 6-month period. All patients consecutively admitted were enrolled in the study. Analysis included: (1) an evaluation of the frequency of ADR-related hospital admissions and their causality, severity, and preventability; (2) a description of the type of drugs involved; (3) a report of the most common clinical manifestations related to these ADRs; and (4) an assessment of the factors that were predictive of ADRs. Results: Seventy of the 548 admissions (12.8%) were related to an ADR. Hemorrhage represented the most common ADR (37.3%), followed by metabolic and renal events (10.8% each). The drugs most often involved were non-steroid anti-inflammatory drugs (NSAIDs), followed by diuretics, aspirin, oral anticoagulants, and oral hypoglycemic agents, A comparison between ADR and non-ADR-related admissions showed that mean number of medications and age were significantly higher for patients admitted for an ADR than for those who were not. Gender, chronic disease at admission, days of hospitalization, cognitive impairment, renal insufficiency, physical activity impairment, and use of psychoactive drugs did not differ between the two groups. In the multivariate analysis, number of drugs was the only independent predictor of ADR-related hospital admission (OR = 1.064, 95% CI 1.019-1.109). In 13 of 70 (18.6%) ADR-related hospital admissions, ADRs were coded as severe. Conclusions: ADRs are common causes of hospital admissions and may have important consequences. The most important determinant for ADR-related hospital admissions is the number of drugs taken. (C) 2008 European Federation of Internal Medicine. Published by Elsevier B.V. All rights

AIM: To evaluate survival rate and clinical outcome of cholangiocarcinoma. METHODS: The medical records of 34 patients with cholangiocarcinoma, seen at a single hospital between the years 1999-2006, were retrospectively reviewed. RESULTS: Thirty-four patients with a median age of 75 years were included. Seventeen (50%) had painless jaundice at presentation. Sixteen (47.1%) were perihilar, 15 (44.1%) extrahepatic and three (8.8%) intrahepatic. Endoscopic retrograde cholangiography (ERCP) and/or magnetic resonance cholangiography (MRCP) were used for the diagnosis. Pathologic confirmation was obtained in seven and positive cytological examination in three. Thirteen patients had co-morbidities (38.2%). Four cases were managed with complete surgical resection. All the rest of the cases (30) were characterized as non-resectable due to advanced stage of the disease. Palliative biliary drainage was performed in 26/30 (86.6%). The mean follow-up was 32 mo (95% CI, 20-43 mo). Overall median survival was 8.7 mo (95% CI, 2-16 mo). The probability of 1-year, 2-year and 3-year survival was 46%, 20% and 7%, respectively. The survival was slightly longer in patients who underwent resection compared to those who did not, but this difference failed to reach statistical significance. Patients who underwent biliary drainage had an advantage in survival compared to those who did not (probability of survival 53% vs 0% at 1 year, respectively, P = 0.038). CONCLUSION: Patients with cholangiocarcinoma were usually elderly with co-morbidities and/or advanced disease at presentation. Even though a slight amelioration in survival with palliative biliary drainage was observed, patients had dismal outcome without resection of the tumor. (C) 2008 The WJG Press. All rights reserved.

Background Hepatic granulomas have been reported in 2-15% of unselected liver biopsies, with a wide clinical profile responsible for their presence. To date, no series concerning the prevalence and the etiology of granulomas from Greece has been reported. Objectives To evaluate the prevalence and the etiology of hepatic granulomas and to investigate whether there has been an alteration in distribution of diagnoses in our compared with those published so far in the literature. Study The results of liver biopsy specimens performed in a Department of Medicine, between 1999 and 2004, were retrospectively reviewed and the cases revealing hepatic granulomas had their medical notes and the liver biopsies recorded. Results Over the study period, 1768 liver biopsies were performed. Hepatic granulomas were identified in 66 (3.7%). Of those, 51 were female with a mean age of 57 years (range 34-74 years) and 15 were male with a mean age of 42 years (range 18-78 years). Autoimmune liver diseases including primary biliary cirrhosis, overlap syndrome and autoimmune hepatitis accounted for the majority of cases (68%), followed by sarcoidosis (7.5%), chronic hepatitis B virus and hepatitis C virus infection (Z5%), idiopathic (6%), drugs (3%) and other miscellaneous causes (Z5%). Conclusions Our series showed that autoimmune liver diseases, mainly primary billary cirrhosis was the most common cause of granuloma formation, a finding rather similar to that stated in the studies from Western countries. A rather small number of idiopathic cases were recorded. Chronic viral hepatitis and sarcoldosis rates were equal, a finding possibly reflecting a fairly high proportion of viral hepatitis in our sample.