Mindfulness-based cognitive therapy in functional dyspepsia: A pilot randomized trial.

BACKGROUND AND AIM: Patients with functional dyspepsia (FD) often have concomitant anxiety and depression. Mindfulness-based cognitive therapy (MBCT) combines the principles of cognitive behavioral therapy and mindfulness. It is a group-based therapy and has been shown to be efficacious in functional gastrointestinal disorders. There are no randomized controlled trials (RCTs) evaluating MBCT in FD. We aimed to evaluate feasibility and efficacy of MBCT in FD management. METHODS: We performed a mixed-method single-center pilot randomized trial of 28 patients fulfilling ROME-III criteria for FD. Fifteen patients were randomized to an 8-week MBCT program while 13 underwent treatment-as-usual (TAU). Patients completed questionnaires at baseline and at week 8. Two focus-groups were conducted. Feasibility of recruitment, acceptability of randomization, procedures and intervention, handout compliance and feasibility of quantitative measures were assessed. The primary outcome was subjective-clinical-assessment of FD symptoms (SCA-FD). Secondary outcome measures included Short-form Nepean Dyspepsia Index (SF-NDI), subjective-clinical-assessment of general health (SCA-GH), EuroQoL-Visual Analog Scale (EuroQoL-VAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21). RESULTS: Twelve of 15 patients in the MBCT group completed the program. There was a trend towards symptom improvement, with 90% in the MBCT group reporting improvement in SCA-FD compared with 45% in TAU(P = 0.063). Patients who underwent MBCT reported greater improvement in SF-NDI (mean change: -8.8 (SD: 7.5) vs -0.7 (7.2), P = 0.018) and DASS-21 (-19.8 (29.5) vs -5.5 (6.6) P = 0.13) compared with TAU. There was no difference in SCA-GH and EuroQoL-VAS. Based on SCA-FD improvement, the eventual RCT will require 50 patients (25 in each group). CONCLUSIONS: Mindfulness-based cognitive therapy is likely efficacious for FD, and it would be feasible to conduct a RCT.

Role of fluorescence in situ hybridization in diagnosing cholangiocarcinoma in indeterminate biliary strictures.

BACKGROUND AND AIM: Brush cytology, the conventional method to diagnose cholangiocarcinoma, has been plagued by low diagnostic sensitivity and false-negative results. This paper aims to study the clinical utility of fluorescence in situ hybridization (FISH) in enhancing identification of malignant biliary strictures. METHODS: Brush cytologic specimens collected from endoscopic retrograde cholangiopancreatography for biliary strictures in a tertiary hospital in Singapore from March 2013 to July 2015 were examined by FISH technique using UroVysion probe set in this study. RESULTS: Thirty patients were chosen with five patients having multiple FISH performed due to indeterminate results. The diagnoses for biliary strictures were 13 (43.3%) cholangiocarcinomas, seven (23.3%) pancreatic cancers, seven (23.3%) benign biliary strictures, and three (10%) primary sclerosing cholangitis. Conventional brush cytology had sensitivity of 53.8% with specificity of 82.4%. FISH had sensitivity of 30.8% with specificity of 100%. When FISH results were interpreted in cases with negative or atypical brush cytology, two patients had positive FISH results and cholangiocarcinomas. Based on this pilot study, FISH increased sensitivity of brush cytology in detection of cholangiocarcinoma from 53.8% to 69.2% while preserving specificity of 82.4%. CONCLUSION: Compared with conventional cytology with low sensitivity, FISH may help to increase sensitivity on top of brush cytology while maintaining high specificity.

Factors influencing treatment outcome in patients with gastroesophageal reflux disease: outcome of a prospective pragmatic trial in Asian patients.

BACKGROUND: Predicting response to proton pump inhibitor (PPI) treatment can aid the effective management of gastroesophageal reflux disease (GERD). The aim was to investigate the predictors of symptomatic response to pantoprazole in Asian patients with GERD; the first study of its kind in Asian patients. METHODS: Asian patients with GERD symptoms (N = 209) received pantoprazole 40 mg daily for 8 weeks in a multinational, prospective, open-label study. Response was assessed using ReQuest™. Baseline and demographic factors were examined using logistic regression to determine if they were related to treatment response. RESULTS: Response rates were 44.3% (Week 4) and 63.6% (Week 8) in Asian patients versus 60.7% (P < 0.001) and 72.2% (P = 0.010) for the rest of the world. Higher response rates at 8 weeks occurred in patients with erosive reflux disease (ERD; 71.3%) versus those with non-erosive reflux disease (NERD) at baseline (48.5%). The presence of ERD (P = 0.0143) and lower ReQuest™-GI scores at baseline (P = 0.0222) were associated with response. Improvements in quality of life (QoL) and anxiety and depression at 4 and 8 weeks were associated with treatment response (both P < 0.0001). Patient satisfaction correlated with treatment response (P < 0.0001), and improvement in anxiety and depression (P < 0.0001) and QoL (P < 0.0001). CONCLUSIONS: Asian patients with GERD, especially those with NERD, may have lower response rates to PPIs than Western populations. ERD and less severe gastrointestinal symptoms may help to predict symptomatic responses to PPIs in Asian patients. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT00312806.

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Autoimmune pancreatitis masquerading as pancreatic cancer.

Video 1Pursuit of a pancreatic mass: autoimmune pancreatitis mimicking pancreatic cancer. EUS features of autoimmune pancreatitis in an older man who presented with obstructive jaundice and pancreatic mass.

Does the advent of endoscopic ultrasound (EUS) sound the death knell for endoscopic retrograde cholangiopancreatography (ERCP)?

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) has been the premier diagnostic and therapeutic endoscopic procedure in the management of pancreatic and biliary diseases (PBD). The use of endoscopic ultrasound (EUS), including EUS-guided fine needle aspiration (FNA), of pancreatic and biliary tumours has become more widely available in the last decade and has gradually replaced diagnostic ERCP. Together with EUS, other imaging modalities like magnetic resonance cholangiopancreatography (MRCP) have resulted in a decrease in the number of ERCPs. With the advent of interventional EUS, ERCP is at risk of being completely eclipsed. METHODS: A search of all relevant articles on EUS and ERCP from Medline and peer-reviewed journals. RESULTS: This review article examines the exact place of ERCP and EUS and their relative contributions in the management algorithm of PBD. CONCLUSION: Although diagnostic EUS, including EUS-guided FNA, is well established in the evaluation of PBD, interventional EUS is still in its infancy and its true potential is unknown. Therefore, therapeutic ERCP still has a vital, albeit smaller role to play in the treatment of pancreatic and biliary diseases.

Ampullary carcinoma: effect of preoperative biliary drainage on surgical outcome.

AIM: To evaluate the influence of preoperative biliary drainage on morbidity and mortality after surgical resection for ampullary carcinoma. METHODS: We analyzed retrospectively data for 82 patients who underwent potentially curative surgery for ampullary carcinoma between September 1993 and July 2007 at the Singapore General Hospital, a tertiary referral hospital. Diagnosis of ampullary carcinoma was confirmed histologically. Thirty-five patients underwent preoperative biliary drainage (PBD group), and 47 were not drained (non-PBD group). The mode of biliary drainage was endoscopic retrograde cholangiopancreatography (n = 33) or percutaneous biliary drainage (n = 2). The following parameters were analyzed: wound infection, intra-abdominal abscess, intra-abdominal or gastrointestinal bleeding, septicemia, biliary or pancreatic leakage, pancreatitis, gastroparesis, and re-operation rate. Mortality was assessed at 30 d (hospital mortality) and also long-term. The statistical endpoint of this study was patient survival after surgery. RESULTS: The groups were well matched for demographic criteria, clinical presentation and operative characteristics, except for lower hemoglobin in the non-PBD group (10.9 +/- 1.6 vs 11.8 +/- 1.6 in the PBD group). Of the parameters assessing postoperative morbidity, incidence of wound infection was significantly less in the PBD than the non-PBD group [1 (2.9%) vs 12 (25.5%)]. However, the rest of the parameters did not differ significantly between the groups, i.e. sepsis [10 (28.6%) vs 14 (29.8%)], intra-abdominal bleeding [1 (2.9%) vs 5 (10.6%)], intra-abdominal abscess [1 (2.9%) vs 8 (17%)], gastrointestinal bleeding [3 (8.6%) vs 5 (10.6%)], pancreatic leakage [2 (5.7%) vs 3 (6.4%)], biliary leakage [2 (5.7%) vs 3 (6.4%)], pancreatitis [2 (5.7%) vs 2 (4.3%)], gastroparesis [6 (17.1%) vs 10 (21.3%)], need for blood transfusion [10 (28.6%) vs 17 (36.2%)] and re-operation rate [1 (2.9%) vs 5 (10.6%)]. There was no early mortality in either group. Median survival was 44 mo (95% CI: 34.2-53.8) in the PBD group and 41 mo (95% CI: 27.7-54.3; P = 0.86) in the non-PBD group. CONCLUSION: Biliary drainage before surgery for ampullary cancer significantly reduced postoperative wound infection. Overall mortality was not influenced by preoperative drainage.

Pancreatic cysts: a proposed management algorithm based on current evidence.

BACKGROUND: Currently, the management strategy of pancreatic cyst (PC) remains controversial because of the inability to diagnose this type of cyst accurately and the limited knowledge of its natural history. Previously, many clinicians have advocated an aggressive resectional policy. This approach is no longer appropriate, and the number of PCs detected incidentally has increased. This study reviews the present literature and attempts to provide a management algorithm of pancreatic cysts based on currently available evidence. METHODS: A Medline search was conducted to identify studies investigating PC, with particular emphasis placed on studies addressing its diagnosis and management. Additional articles were obtained from the reference lists of key articles and recent reviews. COMMENTS: Based on current evidence, the optimal management of PC remains an art and should be individualized based on the risk-benefit ratio of surgery, which is influenced by multiple factors, such as the patient's potential life expectancy, surgical risk; and malignant potential of the cyst. Our proposed management algorithm is based on an individual's predicted risk-benefit ratio of surgery. Prospective evaluation of the algorithm is needed to determine its integrity.

Duodenal EUS to identify thickening of the extrahepatic biliary tree wall in primary sclerosing cholangitis.

BACKGROUND: Diagnosing primary sclerosing cholangitis (PSC) is problematic and requires meeting a burden of proof through clinical, biochemical, radiologic, and histological features. Endoscopic ultrasound yields detailed images of the extrahepatic biliary tree, but its value in contributing to the diagnosis of this condition is unknown. OBJECTIVES: To determine the potential for transduodenal EUS to detect common bile duct wall thickening in PSC. DESIGN: A prospective, controlled study with retrospective, blinded data analysis. SETTING: Single tertiary referral center for inflammatory bowel disease and EUS. PATIENTS: Four groups of patients were assessed with radial endosonography: PSC (n = 9); inflammatory bowel disease (IBD) with abnormal liver blood tests (n = 21); choledocholithiasis (n = 15); and normal controls (n = 50). Measurements were made of the common bile duct diameter and wall thickness. INTERVENTIONS: Transduodenal radial EUS of the biliary tree. MAIN OUTCOME MEASUREMENTS: Common bile duct diameter and wall thickness. RESULTS: The mean diameter (SD) of the common bile duct for the PSC, IBD, choledocholithiasis, and normal control groups measured 8.9 mm (2.8), 5.4 mm (1.7), 7.2 mm (2.2), and 5.0 mm (1.9), respectively (PSC and choledocholithiasis groups compared to the IBD group, P < .05 for a single test of hypothesis, but correction for the multiple testing of data removed this significance; normal control group P < .005). Mean ductal wall thickness (SD) was 2.5 mm (0.8) for the PSC group, 0.7 mm (0.4) for the IBD group, 0.8 mm (0.4) for the choledocholithiasis group, and 0.8 mm (0.4) for the normal control group, respectively (PSC group compared to the other 3 groups, P < .005). LIMITATIONS: Assessment of intrahepatic PSC is problematic. CONCLUSION: Thickening (>1.5 mm) of the common bile duct wall is seen in patients with PSC but not in those with apparently uncomplicated IBD or choledocholithiasis. The results of this study suggest that standard endosonography contributes to the imaging and potentially to the diagnosis of PSC.

Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody.

AIMS: This study aims to examine the genomic variants of the 'a' epitope in chronic hepatitis B virus (HBV) carriers positive for both hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). METHODS: Eighteen HBV carriers were studied. Hepatitis B virus (HBV) DNA was extracted and the 'a' epitope region was amplified and sequenced. RESULTS: Eighteen Chinese asymptomatic HBV carriers were studied. There were 13 patients who were positive for both HBsAg and anti-HBs. Of these, one patient had only wild-type HBV, three had a viral mixture, and five had only 'a' epitope variant HBV. Of the three patients with a viral mixture, all had variants in the less conserved region (123-137). Of the five patients with pure HBsAg mutants, three had variants in the less conserved region while two had variants in the highly conserved region. In this study with a limited number of patients, the serum alanine aminotransferase (ALT) levels were higher in patients with wild-type HBV, compared with those with either 'a' epitope variants or a viral mixture consisting of wild type and variants. CONCLUSION: Eight of the nine (89%) patients positive for both HBsAg and anti-HBs harbored an 'a' epitope variant. The lower ALT levels seen in patients who had either pure 'a' epitope variant or a mixture of wild type and mutants suggest that a closer monitoring of these 'a' epitope variants should be required, as patients carrying these infectious viral strains may remain asymptomatic.

Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti-HBs and anti-HBc.

BACKGROUND AND AIMS: Mutations on the a-determinant of hepatitis B virus surface antigen (HBsAg), capable of escaping detection and vaccination, are identified in HBsAg-positive/anti-HBs-positive vaccinated infants. We studied the prevalence of these mutants in HBsAg-negative/anti-HBc-positive chronic HBV carriers and patients with hepatocellular carcinoma (HCC). METHODS: DNA sequence coding for the antigenic a-determinant of HBsAg was amplified from either HCC genomic DNA or serum samples of the selected patients and sequenced. The replicative mutant genomes were reconstituted in vitro and their reactivity to commercial kits measured. RESULTS: Mutations within and/or outside the a-determinant were identified in patients seronegative for HBsAg. They were then reconstituted in vitro and transiently transfected into HepG2 cells. Culture medium containing secreted HBV viral particles was collected and assayed for their binding to commercial kits. Drastic decrease of reactivity to these kits was seen with most of the identified mutations, including those located outside the a-determinant. CONCLUSION: The existence of a more complex antigenic structure of HBsAg is indicated by the decreased reactivity to detection of mutations, some of which are outside the a-determinant, escape vaccination and may persist in seronegative patients. The high proportion of HBsAg mutants that are integrated in HCC genomes suggests a role of these mutants in hepatocarcinogenesis, possibly leading to mutant HBV-related HCC.