Milutin Bulajic

Helicobacter pylori and the risk of benign and malignant biliary tract disease.

BACKGROUND The etiology of tumors arising in the biliary tract remains unclear. Several previous studies have detected Helicobacter pylori organisms in bile from patients with gallstones or cholecystitis. The objective of this study was to determine whether there is an association between H. pylori in bile and biliary tract carcinoma. METHODS The authors used polymerase chain reaction (PCR) assays to detect the presence of H. pylori in the stomach and bile from 89 patients: Sixty-three disease free patients had biliary calculi, 15 patients had carcinoma of the biliary tract, and 11 patients had neither gallstones nor carcinoma. Bile was considered to contain H. pylori only if the results of PCR determinations were positive in two or more samples assayed independently in two separate laboratories. RESULTS There was a strong association between the presence of H. pylori in the stomach and in the bile (P < or = 0.01). Biliary H. pylori was associated with age but not with gender, and it was associated strongly with the clinical diagnosis. Patients with gallstones were 3.5 times as likely to have H. pylori in the bile compared with patients in a control group (95% confidence interval [95%CI], 0.8-15.8; P = 0.100), and H. pylori was 9.9 times more frequent in patients with biliary tract carcinoma compared with patients in the control group (95%CI, 1.4-70.5; P = 0.022). CONCLUSIONS There is a strong association between biliary tract carcinoma and H. pylori in bile. If these results are confirmed by prospective studies, H. pylori may be responsible for a significant proportion of malignant biliary tract disease.Helicobacter pylori and the Risk of Benign and Malignant Biliary Tract Disease In a recent paper concerning the role of Helicobacter pylori in benign and malignant biliary tract diseases, Bulajic et al. analyzed the bile of 89 patients using the polymerase chain reaction. Sixty-three patients had biliary calculi (gallstones), 15 patients had carcinoma of the biliary tract, and 11 patients had neither gallstones nor carcinoma. Bulajic et al. found that patients with gallstones were 3.5 times more likely to have H. pylori in their bile than were patients in the control group and that the biliary presence of H. pylori was 9.9 times more common in patients with biliary tract carcinoma than in control group patients. It was concluded that there is a strong association between biliary tract carcinoma and the presence of H. pylori in bile and that H. pylori may be responsible for a significant proportion of malignant biliary tract diseases. We would like to comment on and question these findings. The results reported by Bulajic et al. are in disagreement with the results reported by the same authors in a previous paper, which stated that the prevalence of H. pylori in the bile of patients with benign diseases of the biliary tract is not significantly different from the prevalence of H. pylori in the bile of patients with normal findings on endoscopic retrograde cholangiopancreatography (ERCP). The prevalence of H. pylori in the bile of a normal population appears to be difficult to assess. In fact, in a larger series, Figura et al. reported an H. pylori infection rate of 82.1% in 112 patients with gallstones, compared with 80.3% in 112 control patients (P not significant). The low prevalence of H. pylori (14%) reported by Bulajic et al. for their control group probably was the result of a bias; the control group was small (n 11) compared with the control group studied by Figura et al. The resulting error may have influenced the results and conclusions reported by Bulajic et al. regarding the role of H. pylori in the onset of malignant biliary tract diseases. In particular, biliary malignancies cannot be considered as a single entity. In our previous studies of 51 consecutive patients with gallbladder carcinoma (11 men and 40 women; mean age, 69.4 years) who were found during a study of 2750 patients who had undergone surgery for biliary tract diseases, we observed that 48 patients had gallstones, which were asymptomatic in 25 cases. Of the 16 patients with nonsquamous gallbladder carcinoma (13 with adenocarcinoma, 1 with papillary adenocarcinoma, and 2 with poorly differentiated adenocarcinoma), 14 had cholesterol or combination stones, 1 had black mud, and 1 (the patient with papillary adenocarcinoma) had no stones. Stones were larger than 15 mm in 9 cases and smaller in 6 cases. The mean time between documentation of lithiasis and surgery was 16.3 years. Bile culture was positive in 24% of patients, and pancreatobiliary reflux was evident in 16.6% of patients. All patients with squamous cell carcinoma (n 5) had cholesterol stones larger than 15 mm. For this group, the mean time between documentation of lithiasis and surgery was 31.6 years (P 0.002). For all patients in this group, bile culture was negative and pancreatobiliary reflux was not evident. On the basis of current data, instead of classifying biliary malignancies 656

Helicobacter pyloriand the risk of benign and malignant biliary tract disease: Helicobacter pyloriin Biliary Carcinoma

The etiology of tumors arising in the biliary tract remains unclear. Several previous studies have detected Helicobacter pylori organisms in bile from patients with gallstones or cholecystitis. The objective of this study was to determine whether there is an association between H. pylori in bile and biliary tract carcinoma.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas

BACKGROUND The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.BACKGROUND The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma.

Background:Helicobacter pylori has been suggested to be involved in pancreatic diseases, namely autoimmune pancreatitis and pancreatic carcinoma. We investigated the presence of conserved sequences of Helicobacter in pancreatic tissue and pancreatic juice from patients with chronic nonautoimmune and autoimmune pancreatitis as well as pancreatic ductal adenocarcinoma (PDAC). Methods: 35 pancreatic juices collected during routine endoscopic retrograde cholangiopancreatography and 30 pancreatic tissues were studied. Nested PCR was used to detect H. pylori in the isolated DNA samples. In order to exclude a methodological bias, the samples were analyzed blindly in 2 different laboratories using either conventional or LightCycler PCR for H. pylori urease A and 16S ribosomal DNA. Results: In the pancreas of 11 patients with autoimmune pancreatitis, no H. pylori DNA could be detected. Further, in none of the other tissue samples of chronic pancreatitis or PDAC could we detect any Helicobacter sequences. Out of the pancreatic juice samples, none demonstrated either of the 2 Helicobacter gene sequences investigated. Conclusion: Despite good scientific reasoning for an involvement of Helicobacter in pancreatic diseases, a direct infection of the microbial agent seems unlikely. Rather, the pathomechanism must involve molecular mimicry in autoimmune pancreatitis, or the transformation of nitric food constituents to nitrosamines in pancreatic cancer.

Ttv infection in colorectal cancer tissues and normal mucosa

Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg and the Molecular Gastroenterology Unit,Deutsches Krebsforschungszentrum, Heidelberg, GermanyDear Sir,Genetic modifications and environmental factors are presentlyseen as the key factors in the etiology of colorectal cancer,

Helicobacter pylori in Colorectal Carcinoma Tissue

Helicobacter pylori ([1][1]) is associated with the development of chronic gastritis, peptic ulcer, and gastric adenocarcinoma ([2][2]-[4][3]). Previous studies reported positive ([5][4], [6][5]) and negative ([7][6], [8][7]) associations between infection and colorectal neoplasia. Recent reports

Clinical outcome in patients with hilar malignant strictures type II Bismuth-Corlette treated by minimally invasive unilateral versus bilateral endoscopic biliary drainage

BACKGROUND Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors. The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II. METHODS During a 3-year period, a total of 49 patients with hilar tumors (Bismuth-Corlette type II) were referred for endoscopic treatment, following the criteria of unresectability. Ultrasound, computed tomography scan and magnetic resonance cholangiopancreatography (MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography (ERCP). The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected. Mechanical bile duct dilation was performed, followed by plastic stent placement only in the liver lobe which was previously opacified. The procedures were performed under conscious sedation. The patients were followed up for the next 12 months with a stent exchange every 3 months. Primary outcome was assessed by patient survival in the first 12 months after the procedure. RESULTS All 49 patients were treated with ERCP while 39 (79.59%) had successful stent placement. Among these, 32 had hilar cholangiocarcinoma (82%) and 7 (18%) had gallbladder cancer. Two groups of patients had Bismuth II strictures: A, 21 patients (54%) with unilateral contrast injection and drainage, and B, 18 (46%) with bilateral contrast injection and drainage. A total of 57 plastic stents were used (10 Fr, 89%; 11.5 Fr, 11%). Group B showed a lower bilirubin level 7 days after the procedure (P=0.008). Early complications were cholangitis (3 patients, 2 in group A and 1 in group B) and acute pancreatitis (2 patients, 1 each in A and B) with no statistical difference between the groups. Late complications were stent migration (5 patients, 1 in A and 4 in B) and stent clogging (6 patients, 2 in A and 4 in B) showing a significant difference between the groups (P<0.01). The first stent replacement after 3 months was successful in 87% of patients (four died due to disease progression and one due to cardiopulmonary insufficiency) showing no statistical difference between the groups. At 6 months follow-up, 72% patients survived, with no statistical difference between the groups. A final follow-up (12 months) showed the survival rate of 18% (4 patients from group A and 3 from group B) (P>0.05). CONCLUSIONS A minimally invasive approach, based on the criterion that every bile duct being opacified needs to be drained, is associated with a lower incidence of early complications. Considering that the clinical outcome measured by bilirubin level was lower in patients with bilateral drainage 7 days after the procedure, we assumed that drainage of 50% or more of the liver volume leads to sufficient drainage effectiveness.

Helicobacter pylori and pancreatic diseases

A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecular mimicry between H. pylori α-carbonic anhydrase (α-CA) and human CA type II, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal and acinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pancreatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the genesis of such conditions could have a substantial impact on healthcare.

Predictors of endoscopic treatment outcome in the management of biliary complications after orthotopic liver transplantation.

Background and aims The most common complications after liver transplantation nowadays affect the biliary tract. We carried out a retrospective study to identify predictors of endoscopic treatment outcome in the management of post-transplantation biliary complications. Methods Data from all patients with post-transplantation biliary complications subjected to endoscopic treatment at the University of Udine between 2000 and 2012 were extracted. To identify predictors of endoscopic treatment outcome, a logistic regression analysis was carried out. Cox modeling was used to identify factors associated with mortality. Results We identified 142 patients who developed biliary complications: 83 of these patients had a successful endoscopic therapy, whereas 45 had a failure. Fourteen patients, who developed nonanastomotic biliary stricture, were excluded from the analysis. Patients with biliary complications who had pretransplant Model for End-Stage Liver Disease score more than 10 [odds ratio (OR) 3.88; 95% confidence interval (CI) 1.16–12.95; P=0.03] and stent retention time more than 12 months (OR 6.45; 95% CI 2.14–19.42; P<0.01) were less likely to respond to endoscopic therapy. In contrast, both dilatation and stenting procedures (OR 0.10; 95% CI 0.03–0.30; P<0.01) and 10 Fr diameter stent placement (OR 0.21; 95% CI 0.07–0.70; P=0.01) predicted favorable endoscopic treatment outcome. Time to the occurrence of biliary complications of more than 3 months [hazard ratio (HR) 0.24; 95% CI 0.10–0.56] and placement of five or more stents (HR 0.31; 95% CI 0.12–0.79) were found to be protective against mortality, whereas hepatic artery thrombosis was a significant risk factor for mortality (HR 13.88; 95% CI 4.08–47.25). Conclusion We found endoscopic treatment to be less effective in patients with pretransplant Model for End-Stage Liver Disease score more than 10 and stent retention time more than 12, whereas dilatation and stenting procedure and 10 Fr diameter stent placement predicted a favorable outcome.

The weekend effect in patients hospitalized for upper gastrointestinal bleeding: A single-center 10-year experience

Objective This study was conducted to assess the possible weekend effect in patients with upper gastrointestinal bleeding (UGIB) on the basis of a 10-year single-center experience in Serbia. Materials and methods A retrospective analysis of hospital records in the University Clinic ‘Dr Dragisa Misovic-Dedinje’, Belgrade, Serbia, from 2002 to 2012 was conducted. Patients admitted for UGIB were identified, and data on demographic characteristics, symptoms, drug use, alcohol abuse, diagnosis and treatment were collected. Univariate and multivariate logistic regression were used to assess the association between weekend admission and the occurrence of rebleeding and in-hospital mortality. Results Analyses included 493 patients. Rebleeding occurred significantly more frequently on weekends (45.7 vs. 32.7%, P=0.004). Weekend admission [odds ratio (OR)=1.78; 95% confidence interval (CI): 1.15–2.74], older age (OR=1.02; 95% CI: 1.00–1.03), and the presence of both melaena and hematemesis (OR=2.29; 95% CI: 1.29–4.07) were associated with the occurrence of rebleeding. No difference between weekend and weekday admissions was observed for the in-hospital mortality rate (6.9% vs. 6.0%, P=0.70). Older age (OR=1.14; 95% CI: 1.08–1.20), presentation with melaena and hematemesis (OR=4.12; 95% CI: 1.56–10.90) and need for surgical treatment (OR=5.16; 95% CI: 1.61–16.53) were significant predictors of all-cause mortality. Patients with nonvariceal bleeding had significantly higher rebleeding rates on weekends (44 vs. 32.3%, P=0.013). Conclusion There was no significant weekend effect in the mortality of patients admitted for UGIB, irrespective of the source of bleeding. Increased attention to older patients presenting with a more severe clinical picture is needed to prolong survival and prevent rebleeding.