Biliary papillomatosis.

Biliary papillomatosis (BP) is a rare disorder of the biliary tract characterized by the presence of multiple papillary adenomas spread along the biliary tree. Although benign, it carries a significant risk of malignant transformation. Due to low sensitivity and specificity of conventional radiologic modalities, the diagnosis as well as estimation of disease extent is difficult. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreaticography (ERCP) are superior although direct peroral cholangioscopy (POC) is currently the most accurate diagnostic method. Mainly because it provides more detailed information and makes targeted histological diagnosis possible. The treatment of biliary papillomatosis consists of surgical resection, liver transplantation (LT) or a combination of both. Unfortunately, the recurrence rate after radical surgery without LT remains high due to the diffuse distribution of the disease.

The role of extracorporeal shock wave lithotripsy in the treatment of chronic pancreatitis.

Pain is the most frequent symptom in chronic pancreatitis (CP) and has an important impact on quality of life. One of its major pathophysiological mechanisms is ductal hypertension, caused by main pancreatic duct stones and/or strictures. In this article, we focus on extracorporeal shock wave lithotripsy (ESWL) as a treatment for main pancreatic duct stones, which have been reported in >50% of CP patients. ESWL uses acoustic pulses to generate compressive stress on the stones, resulting in their gradual fragmentation. In patients with radiopaque obstructive main pancreatic duct (MPD) stones larger than 5 mm, located in the pancreas head or body, ESWL improves ductal clearance, thereby relieving pain and improving quality of life. In case of insufficient ductal clearance or the presence of an MPD stricture, ESWL can be followed by endoscopic retrograde cholangiopancreatography (ERCP) to increase success rate. Alternatively, direct pancreaticoscopy with intracorporeal lithotripsy or surgery can be performed.

Evaluating the accuracy of three international guidelines in identifying the risk of malignancy in pancreatic cysts: a retrospective analysis of a surgical treated population.

BACKGROUND AND STUDY AIMS: The international consensus Fukuoka guideline (Fukuoka ICG), The European evidence-based guideline on pancreatic cystic neoplasms (European EBG) and the American Gastroenterological Association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts (AGA IG) are 3 frequently cited guidelines for the risk stratification of neoplastic pancreatic cysts. The aim of this study was to assess the accuracy of detecting malignant cysts by strictly applying these guidelines retrospectively to a cohort of surgically resected pancreatic cysts. PATIENTS AND METHODS: 72 resected cysts were included in the analysis. Invasive carcinoma, high grade dysplasia and neuro-endocrine tumour were considered as "malignant cysts" for the purpose of the study. RESULTS: 32% of the resected cysts were malignant. The analysis showed that the Fukuoka ICG, European EBG and AGA IG had a sensitivity of 66,8%, 95,5%, 80%; a specificity of 26,8%, 11,3%, 43,8%; a positive predictive value of 31,8%, 35%, 47,1% and a negative predicted value of 61,1%, 83,3%, 77,8% respectively. The missed malignancy rate was respectively 11,3%, 1,5%, 7,7% and surgical overtreatment was respectively 48,4%, 59,1%, 34,6%. CONCLUSION: In this retrospective analysis, the European EBG had the lowest rate of missed malignancy at the expense of a high number of "unnecessary" resections. The Fukuoka ICG had the highest number of missed malignancy. The AGA IG showed the lowest rate of unnecessary surgery at the cost of a high number of missed malignancy. There is need to develop better biomarkers to predict the risk of malignancy.

Risk factors for bleeding and clinical implications in patients undergoing liver transplantation.

INTRODUCTION: Advanced liver disease is characterized by prolonged global coagulation tests such as prothrombin time (PT). Using Model of End-stage Liver Disease (MELD) score-based allocation, many current transplant recipients show advanced end-stage liver disease with an elevated international normalized ratio (INR). The relationship between abnormalities in coagulation tests and the risk of bleeding has been recently challenged among liver disease patients. In this study we reassessed risk factors for bleeding and the clinical implications for patients who underwent orthotopic liver transplantation (OLT). METHODS: We studied OLT patients between 2005 and 2011 excluding combined transplantations, retransplantations, or cases due to acute liver failure. We collected prospectively pre-OLT, during OLT, and post-OLT clinical and biochemical data to assess the risk for bleeding using linear regression models. RESULTS: The strongest predictor of overall survival among 286 patients with a mean follow-up of 32 months was the number of blood transfusions (P = .005). The risk factor for bleeding during surgery investigated by multivariate analysis only showed the INR (P < .001) and the presence of ascites (P = .003) to independently correlate with the amount of blood transfusion. Receiver operation characteristics (ROC) analysis performed to determine the risk for massive blood transfusion (more than 6 units) revealed a cut-off value for INR ≥ 1.6. Appreciation of the operative field by the surgeon during the intervention as "wet" versus "dry", amounts of blood transfusion and fresh frozen plasma, and stay in the intensive care unit (ICU) and in the hospital were all significantly different (P < .001) for patients with INR <1.6 versus INR ≥ 1.6. CONCLUSIONS: Bleeding during OLT affects the outcome. The risk is independently influenced by the presence of ascites (probably reflecting the degree portal hypertension) and an INR ≥ 1.6. To improve survival after OLT therapeutic interventions should be further explored to reduce the need for blood transfusions.

Molecular classification of hepatocellular carcinoma anno 2011.

Hepatocellular carcinoma has an increasing incidence and high mortality. Treatment options are limited if the disease is not diagnosed in its early stage. The natural course of the disease is aggressive but not always predictable. Molecular profiling is a promising tool for classification in order to optimize prognosis prediction and treatment for an individual patient. In the last decade a large amount of studies has been conducted to better classify hepatocellular carcinomas. The focus of this review is on implications of molecular classification for prognosis and therapeutic decision making in HCC patients. Most studies used microarray technique for genome wide profiling, but other methods to detect genomic changes and microRNA are gaining interest. The whole genome profiling studies identified differences in affected signalling and tried to relate this to prognosis. Some common subgroups were identified, such as the proliferation cluster and the beta-catenin cluster. However, there is still little overlap between most studies. Better study design and bio-informatical analysis might help in this context.

Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces.

BACKGROUND: Severe duodeno-gastro-oesophageal reflux (DGOR) is a risk factor for oesophagitis and Barrett's oesophagus. Patients with non-erosive reflux disease (NERD) have a slight increase in DGOR. Patients with gastro-oesophageal reflux disease (GORD), who are taking proton pump inhibitors (PPIs), still have reflux but of weakly acidic pH and persistence of bile. In these two groups of patients, heartburn might be due to increased oesophageal mucosal permeability and dilated intercellular spaces (DIS). We aimed to assess whether experimental short exposure of the oesophageal mucosa to bile acids, in low concentrations (at acidic, weakly acidic and neutral conditions) can increase mucosal permeability and provoke DIS. METHODS: Rabbit oesophageal mucosa was studied in diffusion and Ussing chambers. We assessed the effects of different solutions containing bile acids, applied to the mucosal side, on transepithelial electrical resistance (R(T)) and permeability to fluorescein. The diameter of intercellular spaces was assessed by using transmission electron microscopy. RESULTS: Incubation of oesophageal mucosa with acidic solutions (pH 2.0) containing a range of bile acids (0.5-5 mmol/l) markedly decreased R(T) and increased mucosal permeability. Weakly acidic solutions (pH 5.0), and to some extent neutral solutions (pH 7.4), containing some bile acids also decreased R(T) and increased permeability, although the effects were much less marked and in some combinations no effect was seen. Exposure to bile acids provoked DIS in acid and weakly acidic conditions but not in neutral (pH 7.4) solutions. CONCLUSIONS: Experimental short exposure of the oesophageal mucosa to solutions with a bile acid concentration and acidity similar to that observed in the gastric contents of patients with NERD or ERD, and who are taking PPIs, may impair oesophageal mucosal integrity and even induce dilated intercellular spaces. Such a situation could, theoretically, underlie the occurrence and/or persistence of symptoms in these patients.

Nutcracker oesophagus: association with chest pain and dysphagia controlling for gastro-oesophageal reflux.

BACKGROUND: The association between nutcracker oesophagus, gastro-oesophageal reflux and their symptoms is controversial. AIM: To evaluate the association of nutcracker oesophagus with chest pain and dysphagia controlling for gastro-oesophageal reflux. METHODS: From a database of 935 consecutive patients investigated with oesophageal manometry and pH-metry, we selected all patients with nutcracker oesophagus including diffuse and segmental patterns. Patients with normal oesophageal peristalsis served as controls. Symptoms assessment, manometry testing and 24h oesophageal pH monitoring off acid-suppressive medications were performed following a standardized protocol. The associations between nutcracker oesophagus and symptoms were assessed by logistic regression analysis. RESULTS: Nutcracker oesophagus was found in 60 patients (6.4%), of which 30 had diffuse nutcracker oesophagus and 30 had segmental nutcracker oesophagus. The control group was composed by 656 patients with normal oesophageal peristalsis. Diffuse nutcracker oesophagus was associated with chest pain (odds ratio 4.3; 95% CI 1.9-9.9; P<0.0001) and dysphagia (odds ratio 5.3; 95% CI 2.3-12.2; P<0.0001), whereas segmental nutcracker oesophagus was associated with chest pain (odds ratio 2.8; 95% CI 1.1-6.9; P=0.026), controlling for total oesophageal acid exposure, age, sex and lower oesophageal sphincter (LOS) pressure. CONCLUSION: This study suggests that both diffuse and segmental nutcracker oesophagus should be regarded as meaningful abnormalities and not mere manometric curiosities.