Predrag Jovanovic

FibroTest/Fibrosure for Significant Liver Fibrosis and Cirrhosis in Chronic Hepatitis B: A Meta-Analysis

OBJECTIVES:Extent of liver fibrosis is one of the most important factors in determining prognosis and the need for active treatment in chronic hepatitis B (CHB). Noninvasive alternatives such as FibroTest/Fibrosure (FT) have been developed in order to overcome the shortcomings of liver biopsy (LB). We aimed to systematically review studies describing the diagnostic accuracy of FT for predicting CHB-related fibrosis.METHODS:MEDLINE and EMBASE searches and hand searching methods were performed to identify studies that assessed the diagnostic accuracy of FibroTest in HB patients using LB as a reference standard. We used a hierarchical summary receiver operating curves model and the bivariate model to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity.RESULTS:We included 16 studies (N=2494) and 13 studies (N=1754) in the heterogenous meta-analysis for liver fibrosis and cirrhosis, respectively. The area under the hierarchical summary receiver operating curve for significant liver fibrosis and for all included studies was 0.84 (95% confidence interval (CI): 0.78–0.88). At the FT threshold of 0.48, the sensitivity, specificity, and diagnostic odds ratio (DOR) of FT for significant fibrosis were 61 (48–72%), 80 (72–86%), and 6.2% (3.3–11.9), respectively. The area under the hierarchical summary receiver operating curve for liver cirrhosis and for all included studies was 0.87 (95% CI: 0.85–0.90). At the FT threshold of 0.74, the sensitivity, specificity, and DOR of FT for cirrhosis were 62 (47–75%), 91 (88–93%), and 15.7% (8.6–28.8), respectively.CONCLUSIONS:FibroTest is of value in exclusion of patients with CHB-related cirrhosis, but has suboptimal accuracy in the detection of significant fibrosis and cirrhosis. It is necessary to further improve the test or combine it with other noninvasive modalities in order to improve accuracy.

Biochemical and ultrasound parameters may help predict the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with a firm clinical and biochemical suspicion for choledocholithiasis

BACKGROUND Prediction of the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected choledocholithiasis (CDL) remains a challenging task. AIMS We aimed to evaluate the predictive value of biochemical and ultrasound parameters and to create a corresponding model for prediction of the need for therapeutic ERCP. METHODS 203 consecutive patients referred to our center due to a firm clinical and/or biochemical suspicion for CDL. All patients underwent ERCP. Biochemical and ultrasound variables were analyzed. RESULTS The sample was divided into testing group (103; 50.7%) and validation group (100; 49.3%) which did not differ in their baseline characteristics. Elevated gamma glutamil transaminase (GGT), common bile duct (CBD) diameter and presence of hyperechoic structures in CBD were found to be significant predictors for presence of CBD stones on ERCP (p<0.05) in the testing group. We used these variables to construct a predictive model for the presence of CBD stones on ERCP. The model was tested on a second, validation group of patients using ROC analysis with the area under the ROC curve of 0.81 (%95 CI=0.75-0.86; p<0.001). We identified a threshold (0.86) above which, patients had a high probability (93.1%) for the need for interventional ERCP. CONCLUSION Our predictive model may help predict the need for therapeutic ERCP in patients with a suspicion for choledocholithiasis.

Minimally invasive treatment of pancreatic pseudocysts

A pancreatic pseudocyst (PPC) is typically a complication of acute and chronic pancreatitis, trauma or pancreatic duct obstruction. The diagnosis of PPC can be made if an acute fluid collection persists for 4 to 6 wk and is enveloped by a distinct wall. Most PPCs regress spontaneously and require no treatment, whereas some may persist and progress until complications occur. The decision whether to treat a patient who has a PPC, as well as when and with what treatment modalities, is a difficult one. PPCs can be treated with a variety of methods: percutaneous catheter drainage (PCD), endoscopic transpapillary or transmural drainage, laparoscopic surgery, or open pseudocystoenterostomy. The recent trend in the management of symptomatic PPC has moved toward less invasive approaches such as endoscopic- and image-guided PCD. The endoscopic approach is suitable because most PPCs lie adjacent to the stomach. The major advantage of the endoscopic approach is that it creates a permanent pseudocysto-gastric track with no spillage of pancreatic enzymes. However, given the drainage problems, the monitoring, catheter manipulation and the analysis of cystic content are very difficult or impossible to perform endoscopically, unlike in the PCD approach. Several conditions must be met to achieve the complete obliteration of the cyst cavity. Pancreatic duct anatomy is an important factor in the prognosis of the treatment outcome, and the recovery of disrupted pancreatic ducts is the main prognostic factor for successful treatment of PPC, regardless of the treatment method used. In this article, we review and evaluate the minimally invasive approaches in the management of PPCs.

Artificial neural network predicts the need for therapeutic ERCP in patients with suspected choledocholithiasis

BACKGROUND Selection of patients with the highest probability for therapeutic ERCP remains an important task in a clinical workup of patients with suspected choledocholithiasis (CDL). OBJECTIVE To determine whether an artificial neural network (ANN) model can improve the accuracy of selecting patients with a high probability of undergoing therapeutic ERCP among those with strong clinical suspicion of CDL and to compare it with our previously reported prediction model. DESIGN Prospective, observational study. SETTING Single, tertiary-care endoscopy center. PATIENTS Between January 2010 and September 2012, we prospectively recruited 291 consecutive patients who underwent ERCP after being referred to our center with firm suspicion for CDL. INTERVENTIONS Predictive scores for CDL based on a multivariate logistic regression model and ANN model. MAIN OUTCOME MEASUREMENTS The presence of common bile duct stones confirmed by ERCP. RESULTS There were 80.4% of patients with positive findings on ERCP. The area under the receiver-operating characteristic curve for our previously established multivariate logistic regression model was 0.787 (95% CI, 0.720-0.854; P < .001), whereas area under the curve for the ANN model was 0.884 (95% CI, 0.831-0.938; P < .001). The ANN model correctly classified 92.3% of patients with positive findings on ERCP and 69.6% patients with negative findings on ERCP. LIMITATIONS Only those variables believed to be related to the outcome of interest were included. The majority of patients in our sample had positive findings on ERCP. CONCLUSIONS An ANN model has better discriminant ability and accuracy than a multivariate logistic regression model in selecting patients for therapeutic ERCP.

Ulcerative colitis in the Tuzla region of Bosnia and Herzegovina between 1995 and 2006: epidemiological and clinical characteristics.

Background Bosnia and Herzegovina (B&H) is one of the Eastern European countries that lacks data on the epidemiology of ulcerative colitis (UC). Aims We aimed to assess the epidemiological and clinical characteristics of UC in Tuzla Canton of B&H during a 12-year period (1995–2006). Patients and methods We retrospectively evaluated hospital records of both UC inpatients and outpatients residing in Tuzla Canton of B&H (total of 496 280 inhabitants) between 1995 and 2006. Patients that firmly satisfied the diagnostic criteria for UC were included in the study. Incidence rates were calculated with age standardization using European population standards. Trends in incidence were evaluated as moving 3-year averages. Results During the observed period, 214 patients met the diagnostic criteria for UC. The average age-standardized incidence was found to be 3.43/105 inhabitants [95% confidence interval (CI) = 2.97–3.89], ranging from 0.22 to 7.44 per 105. The mean annual crude incidence in the last 5 years of study (2002–2006) was 5.55/105 (95% CI = 4.63–6.48). The prevalence of UC during the observed period was found to be 43.1/105 (95% CI = 37.3–48.8). The incidence of UC increased dramatically from the average of 1.01/105 in the period between 1995 and 1997 to 6.04/105 between 2004 and 2006, as did the number of colonoscopies performed, from 29 in 1995 to 850 in 2006. The average yearly incidence of confirmed UC cases detected on colonoscopy was 5.56 per 100 colonoscopies per year (95% CI = 4.81–6.30) and only 3.92 per 100 colonoscopies (95% CI = 3.26–4.57) in the last 5 years of the observed period. Conclusion Tuzla Canton of B&H is a region with an increasing incidence of UC, which is most likely a direct consequence of a wider use of colonoscopy. We believe that in the next few years, the incidence of UC in this region will probably reach the annual incidence rate of 6 per 105 inhabitants.

Preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: What can be done?

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography. The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis varies substantially and is reported around 1%-10%, although there are some reports with an incidence of around 30%. Usually, PEP is a mild or moderate pancreatitis, but in some instances it can be severe and fatal. Generally, it is defined as the onset of new pancreatic-type abdominal pain severe enough to require hospital admission or prolonged hospital stay with levels of serum amylase two to three times greater than normal, occurring 24 h after ERCP. Several methods have been adopted for preventing pancreatitis, such as pharmacological or endoscopic approaches. Regarding medical prevention, only non-steroidal anti-inflammatory drugs, namely diclofenac sodium and indomethacin, are recommended, but there are some other drugs which have some potential benefits in reducing the incidence of post-ERCP pancreatitis. Endoscopic preventive measures include cannulation (wire guided) and pancreatic stenting, while the adoption of the early pre-cut technique is still arguable. This review will attempt to present and discuss different ways of preventing post-ERCP pancreatitis.

Simple uninvestigated dyspepsia: age threshold for early endoscopy in Bosnia and Herzegovina.

Objective To establish an optimal age threshold for endoscopy referral in patients with simple uninvestigated dyspepsia in the setting of European developing country (Bosnia and Herzegovina) with low availability and high workload of endoscopy units. Methods We reviewed patient information on all upper endoscopies performed during a 6-year period (2000–2005). Different age thresholds were evaluated in terms of their predictive power for absence of malignancy. Results A total of 82 of 4403 (1.86%) dyspeptic patients had upper gastrointestinal (GI) malignancy. Age cutoffs of 40 years for men and 45 years for women had the best predictive power, without any cases of upper GI malignancies below those thresholds. Age cutoffs of 45 years for men and 50 years for women also had excellent negative predictive values (99.7 and 99.9%, respectively) with 1.45 and 0.98 cases of missed upper GI malignancies per 1000 endoscopies, respectively. A total of 1709 of 4403 (38.8%) of endoscopies might have been avoided in men of less than 45 and women of less than 50 with uninvestigated dyspepsia. Conclusion (i) Age thresholds for endoscopy referral are lower than in Western countries and should be different for men and women. (ii) Cutoff values of 40 and 45 years for men and women, respectively, are completely safe to use. (iii) Thresholds of 45 years for males and 50 years for females have a small level of risk of missing upper GI malignancy, but are acceptable to use in areas of low availability of endoscopy.

Online combination algorithm for non-invasive assessment of chronic hepatitis B related liver fibrosis and cirrhosis in resource-limited settings

OBJECTIVE The use of commercially available noninvasive markers for chronic hepatitis B (CHB) related fibrosis is not widely available in developing countries so clinicians in those countries frequently use free alternatives. We aimed to create an optimized algorithm for selection of patients with the highest probability for presence/absence of significant liver fibrosis and cirrhosis based on the use of multiple free scores. METHODS We evaluated six free noninvasive markers for CHB related fibrosis against liver biopsy and selected the best thresholds for prediction/exclusion of significant fibrosis and cirrhosis in CHB patients. Algorithm based on four scores and their corresponding thresholds was created. RESULTS The calculator based on developed algorithm can be found at http://www.chb-lfc.com. We evaluated 211 patients in main group and 65 patients in external validation group. We selected four scores for creation of combination algorithm. The algorithm was able to classify 123/211 (58.3%) patients with a 93.5% accuracy of correct classification for prediction of presence/absence of significant fibrosis in main group. In validation group, the algorithm was able to classify 48/65 (73.8%) of patients with 93.8% (45/48) overall accuracy. When used to predict presence/absence of cirrhosis, the algorithm was able to correctly classify 181/211 (85.8%) and 59/65 (90.8%) of patients in main and validation group, respectively, with an overall accuracy of 97.8% and 98.3%, respectively. CONCLUSION Developed algorithm based on routine laboratory tests is a usable, applicable and accurate tool for diagnosis of CHB related fibrosis and cirrhosis, suitable for resource-limited settings where more expensive modalities are unavailable.

Response to Munteanu et al.

Comment on FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: a meta- analysis.

Prognostic Significance of BCL-6 Protein and KI-67 Monoclonal Antibody in Large Cell B-lymphoma Treated with Polichemiotherapy with or without Addition of Rituximab

Introduction: Lymphomas are malignant neoplasms of lymphoid tissue characterized by heterogenecity in pathology and clinical symptomatology. Diffuse large cell lymphoma (DLCL) is the most common type of non-Hodgkins lymphoma (NHL), accounting for almost 35-40% of all cases of NHL. Aim: To analyse the expression of Ki-67 i bcl-6, in large cell lymphoma tissue, treated with CHOP and CHOP+R protocol, and to evaluate the level of therapeutic response and the duration of progression free survival of the disease in patients with diffuse large cell lymphoma, treated by therapeutic protocols CHOP and CHOP+R. Methods: For analysis of both Ki-67 and bcl-6 we used criterion for positivity of >10% expression in lymphoid tissue. Results: The median of precentual expression of bcl-6 in total sample was 15,5% with interquartile range of 5,5% and 54,5%, and with minimum of 0% and maximum of 99%. Considering the criterion of bcl-6 positivity with 10% positive lymphoma cells, in total sample there was 29/50 (48,3%) bcl-6 positive cells. Comparing the two different treatments, there was no difference in level of bcl-6 expression. (Mann-Whitney; U=398; p=0,44). There was also no difference in incidence of bcl-6 positive patients (considering the criterion of >10% expression) between two types of treatment (X2=0,60; df=1; p=0,44). The median value of procentual Ki-67 expression in total sample was 59% with interquartile range of 33% to 74%, and minimum from 11% to 96%. All the patients were Ki-67 positive, considering the criterion of >10% expression in lymphoid tissue. Compared within two therapeutic groups, there was no difference in level of Ki-67 expression (Mann-Whitney; U=403,5; p=0,49). Separate Cox analiysis for both treated groups of patients was made to evaluate the separate prognostic influence of bcl-6 and Ki-67 on the duration of progression free survival of the disease. In the group of patients treated with CHOP protocol niether bcl-6 (OR=0,99; %CI=0,96-1,02; p=0,44) nor Ki-67 (OR=0,99; %CI=0,97-1,02; p=0,60) showed significant influence on duration of progression free survival of the disease. In the group of patients treated with CHOP+R protocol, there was also no significant influence of bcl-6 (OR=0,93; %CI=0,82-1,07; p=0,32) and Ki-67 (OR=1,02; %CI=0,97-1,08; p=0,42) on duration of progression free survival. Conclusions: These data suggest that Ki-67 and bcl-6 expression in tumor tissue can not be used as indicators for the level of therapy response and progression-free period in large cell B-lymphoma treated with polichemiotherapy with or without addition of Rituximab.