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Descriptive morphological studies of the normal heart are lacking. Previous autopsy studies have focused mainly on heart weight. We characterize the normal heart by providing normal dimensions of the atria, ventricles, valves and sub-epicardial fat, comparing the findings in terms of sex, age and body measurements.From 3602 referrals to our cardiovascular pathology unit, pathological criteria used for the classification of a morphologically normal heart were a weight of below 500 grams in males, and below 400 grams in females. Diseased hearts were excluded on anatomical and histological evaluation.We diagnosed 1062 morphologically normal hearts. Mean age at death was 34±12, with a male predominance (701, 66%). Age was similar in females and males (35±13 vs 34±12). Females had a significantly lower heart weight (285±55 vs 374±64). Sex was an independent predictor of most measurements. The atrial and ventricular cavities were significantly larger in males. All ventricular measurements of muscle thickness were larger in males. All valvular circumferences were larger in males. In contrast, sub-epicardial fat was significantly thicker in females in 6 of 7 regions. This is the first study to provide a calculator to give expected values according to sex, age, height and weight.Major differences between the sexes exist in the morphologically normal heart. These variations should be considered when assessing cardiac structure in imaging for risk stratification and diagnosis in the cardiomyopathies, as well as in treatment outcomes.

Pancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression. To analyze the clinical efficacy of endobiliary RFA. Retrospective case–control analysis was carried out for 23 patients with surgically unresectable pancreatic carcinoma and malignant biliary obstruction undergoing endoscopic RFA and SEMS insertion and 46 controls (SEMS insertion alone) in a single tertiary care center. Controls were stringently matched for age, sex, metastases, ASA/comorbidities. Survival, morbidity, and stent patency rates were assessed. RFA and control groups were closely matched—ASA 2.35 ± 0.65 versus 2.54 ± 0.50, p = 0.086; metastases 9/23 (39.1 %) versus 18/46 (39.1 %), p = 0.800; chemotherapy 16/23 (69.6 %) versus 24/46 (52.2 %), p = 0.203. Median survival in RFA group was 226 days (IQR 140–526 days) versus 123.5 days (IQR 44–328 days) in controls (p = 0.010). RFA was independently predictive of survival at 90 days (OR 21.07, 95 % CI 1.45–306.64, p = 0.026) and 180 days (OR 4.48, 95 % CI 1.04–19.30, p = 0.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects. Endoscopic RFA is a safe and efficacious adjunctive treatment in patients with advanced pancreatic malignancy and biliary obstruction and may confer early survival benefit. Randomized prospective clinical trials of this new modality are mandated.

Purpose of review To describe the use of endobiliary radiofrequency ablation (RFA) in the treatment of malignant disease of the bile duct and offer a comprehensive review of the emerging evidence on the safety and effectiveness of this new technique. Recent findings Ex-vivo and in-vivo porcine studies have been reported, confirming the feasibility of the technique, gathering preliminary safety data and defining appropriate power settings for human studies. Moderate-sized case series have now reported the use of RFA in mixed cohorts of human individuals with pancreatic cancer, cholangiocarcinoma and other malignant diseases of the bile duct. Endoscopic and percutaneous approaches have both been investigated. Small case series of blocked self-expanding metal stent clearance using RFA have been published. Summary Intraductal RFA, via both endoscopic and percutaneous approaches, is feasible. Complication rates appear to be comparable with the current standard endoscopic and percutaneous approaches to palliation of malignant strictures of the bile duct. The current body of literature is germinal, but warrants the further investigation of planned clinical trials.

BACKGROUND AND AIM We aimed to evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) for indeterminate biliary lesions and its usefulness in electrohydraulic lithotripsy (EHL) of biliary stones not amenable to conventional endoscopic therapy. PATIENTS AND METHODS All patients undergoing SpyGlass SOC in four UK tertiary centres between 2008 and 2010 were retrospectively enrolled. Patients were followed up until death or the last clinic visit until May 2011. The operating characteristics of SOC for detecting malignant lesions and the stone clearance rate after SOC-guided EHL were calculated. RESULTS A total of 165 patients underwent 179 SOC procedures. Sixty-six percent were referred for indeterminate biliary strictures, 13% for filling defects and 21% for SOC-guided EHL. Cannulation with the SOC system was successful in 95% but visualization was inadequate in 13%. Primary sclerosing cholangitis was a risk factor for failed cannulation and conscious sedation (vs. general anaesthesia) for inadequate visualization (P

Accurate differentiation between benign and malignant causes of biliary obstruction remains challenging and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers. Our aim was to apply a proteomic approach to identify a potential biomarker in bile that differentiates between malignant and benign disease, and to assess its diagnostic accuracy. Neutrophil gelatinase-associated lipocalin (NGAL) is multi-functional protein, released from activated neutrophils, with roles in inflammation, immune function, and carcinogenesis. It has not previously been described in bile.Bile, urine, and serum were collected prospectively from 38 patients undergoing endoscopic retrograde cholangiopancreatography ("discovery" cohort); 22 had benign and 16 had malignant pancreatobiliary disease. Initially, label-free proteomics and immunoblotting were performed in samples from a subset of these patients. Enzyme-linked immunosorbent assay was then performed for NGAL as a potential biomarker on all samples in this cohort. The diagnostic performance of biliary NGAL was then validated in a second, independent group ("validation" cohort) of 21 patients with pancreatobiliary disease (benign n=14, malignant n=7).NGAL levels were significantly raised in bile from the malignant disease group, compared with bile from the benign disease group in the discovery cohort (median 1,556 vs. 480 ng/ml, P=0.007). Biliary NGAL levels had a receiver operating characteristic area under curve of 0.76, sensitivity 94%, specificity 55%, positive predictive value 60%, and negative predictive value 92% for distinguishing malignant from benign causes. Biliary NGAL was independent of serum biochemistry and carbohydrate antigen 19-9 (CA 19-9) in differentiating between underlying benign and malignant disease. No significant differences in serum and urine NGAL levels were found between benign and malignant disease. Combining biliary NGAL and serum CA 19-9 improved diagnostic accuracy for malignancy (sensitivity 85%, specificity 82%, positive predictive value 79%, and negative predictive value 87%). The diagnostic accuracy of biliary NGAL was confirmed in the second independent validation cohort.NGAL in bile is a novel potential biomarker to help distinguish benign from malignant biliary obstruction.

Background The optimal endoscopic investigation of diarrhea in patients under age 50 without specific features of right-sided colonic/ileal disease is inadequately defined. Objective To assess the potential additional yield of colonoscopy over flexible sigmoidoscopy (FS) in this group. Design Retrospective cohort study. Setting Two teaching hospital endoscopy units. Patients This study involved all patients under age 50 who had a colonoscopy between 1997 and 2007 to investigate diarrhea, without high-risk features of right-sided colonic/ileal disease, inflammatory bowel disease (IBD), or rectal bleeding. Intervention Colonoscopy and biopsy. Main Outcome Measurements Diagnostic yield of colonoscopy over FS with biopsy. Results Colonoscopic appearances were abnormal in 126 of 625 eligible patients (20%); 72% of abnormalities were within reach of FS. The most common endoscopic abnormality was suspected inflammation in 60 patients (10% overall), reportedly confined to the proximal colon or ileum in 22 patients (37% of this group). Histology from areas of suspected inflammation revealed features of IBD in 68% of patients, but results were normal in the remainder. In the 22 patients with suspected isolated proximal disease, 8 patients (36%) had normal histology results, and a further 6 had left-side colon biopsies demonstrating IBD. In patients with macroscopically normal colons, histological evidence of IBD or microscopic colitis occurred in 14 and 12 patients, respectively, with changes in the left side of the colon in 93% of patients. In this patient group, 85% of IBD or microscopic colitis could have been detected by FS and biopsy. The negative predictive value of FS with biopsy was 98% for IBD and 99% for microscopic colitis. Limitations Retrospective study. Conclusion FS is adequate for the investigation of diarrhea in patients under age 50 who lack other features, but its yield depends on biopsy of the left side of the colon.

The use of temporary prophylactic pancreatic duct (PD) stents in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in high-risk patients has been shown to be effective in multiple trials. However, there are limited data on the clinical implications of PD stents and their impact on practice outside of the trial setting. The utility of prophylactic pancreatic stenting was evaluated in a retrospective analysis of 1,000 consecutive ERCPs performed in a single tertiary referral pancreatobiliary center over a 24-month period, based upon a predetermined protocol to identify patients at high risk of postprocedure pancreatitis. One thousand procedures performed in 688 patients were studied. Sixty-one patients were considered for stent placement and stents were successfully placed in 58 cases. The overall rate of post-ERCP pancreatitis in our study population was 3.6%. The rate of pancreatitis in the stented patients was considered high at 22.4%, but the majority (69%) were classified as mild and there were no reported severe episodes. This compares to pancreatitis in the nonstented group, in whom the majority (73.9%) experienced either moderate or severe episodes. A strategy of prophylactic PD stents in this study has eliminated severe post-ERCP pancreatitis in high-risk patients. However, the high pancreatitis rate in stented patients may represent the cost to achieve this, while stent type and size employed are likely contributing factors. To maximize the benefits of PD stenting, there is a need to identify and treat all those considered at high risk.

Aim: To describe the clinical features and treatment schedules of a series of 5 patients with esophageal lichen planus (LP). To review the literature on esophageal LP. Background: LP, a common papulosquamous dermatologic condition, can present to the gastroenterologist with esophageal involvement. This is rare and occurs in a distinct population of LP patients. Disease at this site is frequently refractory to conventional treatment. Case Series: Between 2001 to 2007, 5 female patients were diagnosed with esophageal LP. They all had esophageal strictures which were treated with a combination of balloon dilatation and intralesional triamcinolone. Therapeutic intervention was covered with oral steroids before and after the procedure. Symptoms tended to recur, necessitating repeat procedures. The average interval between treatments was 8.3 months. Conclusions: Intralesional triamcinolone and balloon dilatation produced good symptomatic relief in these 5 patients with esophageal LP. This was generally maintained for several months. We reviewed 35 cases of symptomatic esophageal LP in the English literature. Esophageal LP seems to have a striking predilection for middle-aged women, particularly those with disease at other mucosal sites. A range of systemic immunosuppressants and esophageal-directed therapies has been tried.

Summary Background : The primary therapeutic goals in patients with gastroduodenal obstruction secondary to advanced malignancy are the re-introduction of an enteral diet and early discharge. The endoscopic placement of expandable metal stents has been proposed as an alternative technique for palliation in patients not suitable for surgery. Aim : To review our experience with gastroduodenal metal stent insertion for the palliation of malignant gastric and duodenal obstruction. Methods : A retrospective review was conducted of the notes of all patients who underwent gastroduodenal stent insertion in our unit. Results : Forty patients (mean age, 64.5 years; range, 34–93 years) underwent insertion of an enteral stent for malignant gastroduodenal obstruction. The primary tumour was gastric in 20 patients, pancreatico-biliary in 15 and metastatic in five. A stent was successfully placed in all cases. Thirty-two patients have subsequently died, the median (range) survival being 7 weeks (1 week to 10 months). Thirty-three patients (82.5%) were discharged from hospital. During follow-up, 12 patients (30%) returned to a solid diet, 20 (50%) required a soft diet, six (15%) tolerated liquids and two (5%) were unable to tolerate any enteral nutrition. Conclusion : The use of enteral stents achieves good palliation, allowing discharge from hospital and re-introduction of an enteral diet.

Background: Endoscopic balloon dilatation (EBD) of the sphincter of Oddi has been proposed as an alternative therapy with possible advantages, as compared with endoscopic sphincterotomy (ES), for removal of bile duct stones. Patients and methods: In a randomised study, we compared the efficacy and complication rate of the two techniques in 202 patients with common bile duct stones. Patients were followed up for 12 months. Results: A total of 103 patients were randomised to the EBD group and 99 to the ES group. Overall duct clearance was 87.1% and did not differ between the two groups (EBD 87.4%; ES 86.9%). The complication rate at 24 hours was 6.8% in the EBD group and 3.0% in the ES group (NS). Complications during follow up were 11.7% and 15.2% respectively (NS). A multivariate logistic regression analysis showed only the size of the largest stone to be predictive of success for either technique. Conclusion: Endoscopic balloon dilatation offers no significant advantage over the well established technique of endoscopic sphincterotomy for the removal of bile duct stones.

To evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) in patients with sclerosing cholangitis.All patients with sclerosing cholangitis who underwent SOC procedures due to suspicious biliary strictures, in one Swedish and four UK tertiary centers in 2008-2012, were retrospectively enrolled. For each SOC procedure in sclerosing cholangitis, another one attempted due to a single biliary stricture in the same center and calendar year was randomly selected as control. Patients were followed up until death or last clinic visit until November 2012.Fifty-four SOC procedures were attempted in 52 sclerosing cholangitis patients (48 with primary sclerosing cholangitis, 4 with IgG4-related sclerosing cholangitis). Cannulation with the SOC system failed more frequently in sclerosing cholangitis (15% vs. 2% in controls; p = 0.015). The sensitivity, specificity, and accuracy of SOC (including tissue sampling) for cancer diagnosis were similar in sclerosing cholangitis and controls (50% vs. 55%, 100% vs. 97%, and 88% vs. 80%, respectively) with largely overlapping confidence intervals. Adverse events were more common in sclerosing cholangitis, due to an increased frequency of cholangitis (11% vs. 2% in controls; p = 0.051).SOC is equally accurate in cancer diagnosis in sclerosing cholangitis and patients with single biliary strictures. However, cholangioscope insertion may be hampered by bile duct narrowing and post-SOC cholangitis is more common in sclerosing cholangitis.

BackgroundMalnutrition is a common management problem in patients with cystic fibrosis (CF). Various approaches to supplemental nutrition by both parenteral and enteral routes have been used.AimTo analyse the efficacy and acceptability of supplemental overnight feeding using a percutaneous endoscopic gastrostomy (PEG) in patients with CF.Patients53 patients with CF (43 adults; age >17 years) with severe pulmonary disease.MethodsThe technical success and complications of PEG insertion were documented together with changes in nutritional and pulmonary status of the cohort.ResultsPEG tubes were successfully inserted in all patients, with immediate complications (respiratory depression) in two (4%) and late complications in 13 (25%). Feeding was well tolerated by 50/51 (98%) of the cohort during a mean (SEM) follow up of 14.5 (2.1) months. The adult cohort had a significant increase in weight and body mass index at six months which was maintained at 12 months. Serum albumin concentration remained stable at six months but had fallen by 12 months, although the differences were not statistically significant. These results were reflected in the paediatric cohort. Pulmonary function in those followed up for one year had apparently stabilised, but the number of admissions to hospital over the year before and the year after PEG did not change. Half of the cohort were accepted for heart-lung/lung transplantation, the improvement in nutritional status being a prerequisite for this.ConclusionSupplemental PEG tube feeding is well tolerated and results in a significant improvement in nutritional status and an apparent stabilisation of pulmonary function in severely malnourished CF patients with advanced pulmonary disease.

Background and Study Aims: Treatment options for un-resectable hepatic hilar strictures include percutaneous or endoscopic stent insertion, using either standard Teflon or self-expanding metal endoprostheses. The use of Teflon stents is complicated by stent migration and high occlusion rates. Published series of endoscopically placed metal stents have not concentrated on their use in the treatment of high-grade hilar strictures (Bismuth grades II and III). We therefore undertook a prospective and open pilot study to evaluate the efficacy of endoscopically placed metal endoprostheses in the palliation of jaundice due to high-grade hilar strictures. Patients and Methods: Self-expanding metal stents were placed endoscopically in 17 patients (nine women, eight men; median age 64 years, range 33-77). Of the 17 malignancies 11 patients (65%) had a diagnosis of cholan-giocarcinoma, and 12 (71%) had Bismuth grade III strictures. Results: The stents were inserted successfully in all 17 patients. Adequate drainage, as demonstrated by a significant reduction in bilirubin, was achieved in 15 (88 %); the two patients in whom drainage failed had extensive intrahepatic disease. Early complications (cholangitis) developed in one patient (6%), and there were seven late complications (41 %) in five patients (four occluded stents and three cases of duodenal compression). The stent patency appeared to be prolonged (median stent patency 12 months, range 1.5-24 months, in patients surviving five months or more). The median survival was ten months (range 1-48 months) after stent insertion. All of the patients died during follow-up. Conclusions: These results suggest that endoscopically placed metal stents offer effective palliation for high-grade hilar malignancies, although controlled trials comparing the use of metal and Teflon endoprostheses in this patient group are required.

Purpose of review Cholangiocarcinoma is the second most common primary liver tumour, worldwide. Its incidence and mortality are rising, the cause of which is unclear. Cholangiocarcinoma usually presents late, with obstructive jaundice, malaise, weight loss and discomfort. For most patients, complete surgical resection, the only potential cure, is not possible. Survival length and palliation of symptoms become paramount and often this centres on restoration of bile flow to relieve jaundice and improve general well being. There are now multiple options to achieve this goal and emerging evidence supports certain methods over others. Recent findings For advanced cholangiocarcinoma, endoscopic biliary stenting has become an established treatment. Recent evidence supports the use of metal stents over plastic to improve survival and stent patency. Locoregional therapies, such as radiofrequency ablation, transarterial chemoembolisation and radiotherapy have shown promise in preliminary studies. Landmark studies have established the use of cisplatin and gemcitabine as first-line chemotherapy in advanced cholangiocarcinoma. Summary The rise in incidence of advanced cholangiocarcinoma, has necessitated the development of novel therapies to optimize palliation. This article discusses the current options for palliation of cholangiocarcinoma, including stenting, locoregional therapy, surgery, endoscopic ultrasound and palliative chemotherapy.

Percutaneous endoscopic gastrostomy (PEG) feeding has a significant morbidity and mortality associated with the procedure. Patient selection, procedural volume, timing of insertion and aftercare may have a direct bearing on mortality. We aimed to establish whether variation in PEG practice exists within the UK.The British Society of Gastroenterology (BSG) approached all NHS hospitals providing an endoscopy service (n = 260). A custom designed web-based questionnaire was circulated.The response rate was 83% (n = 215); 57% were Joint Advisory Group (JAG) accredited; 33% (70/215) of hospitals inserted more than 75 PEGs a year (4 hospitals inserting150). Stroke and neurodegenerative conditions were the main indications for PEG insertion. However, 36% (77/215) of hospitals inserted PEGs for dementia. PEG insertion timings varied: 33% (72/215) had a strict policy of waiting more than 2 weeks from referral to insertion, 14% (30/215) performed immediately and 34% (74/215) determined the time delay depending on the underlying condition. Local guidelines for PEG insertion existed in 87% (186/215) of hospitals and 78% (168/215) had access to radiologically inserted gastrostomies. Prophylactic antibiotics were used in 93% (201/215) of hospitals. Only 64% (137/215) had a dedicated PEG aftercare service. This was significantly lower in non-JAG accredited units (p = 0.008).This National BSG survey demonstrates variations in practice particularly with regards to PEG insertion in patients with dementia, the timing of PEG insertion and PEG aftercare. These variations in practice may be important factors accounting for the significant morbidity and mortality associated with this procedure.

It has been postulated that the adverse metabolic effects of beta-adrenergic blockade with propranolol in cirrhosis may be related to altered delivery and utilisation of oxygen, particularly in patients with advanced alcoholic liver disease (ALD). Consequently, in 10 patients with decompensated ALD, we assessed (a) systemic and hepatic oxygen delivery (DO2), extraction ratio (%O2E) and consumption (VO2), (b) myocardial VO2 (assessed by the rate-pressure product [RPP], together with full systemic and splanchnic haemodynamics) and (c) hepatic redox state (HRS), measured indirectly by the arterial ketone body ratio (KBR i.e. ratio of acetoacetate/beta-hydroxybutyrate), prior to and following intravenous propranolol (0.1-2 mg/kg). Results are expressed as mean +/- S.E.M. Propranolol reduced DO2 (700 +/- 33 vs. 583 +/- 32 ml/min/m2, p0.05) and myocardial VO2 (RPP 72 vs. 58, p0.05). The %O2E increased however, (18.5 +/- 1.3 vs. 22.6 +/- 1.6%, p0.05), resulting in unaltered systemic VO2 (127 +/- 7.3 vs. 131 +/- 6.9 ml/min/m2, p0.10). Similarly hepatic VO2 did not change. KBR was not altered (0.44 +/- 0.08 vs. 0.48 +/- 0.07), and in fact improved in two patients (Child C12 and C13) from 0.17 to 0.34 and 0.12 to 0.27, respectively. In conclusion, the results of this study suggest that an underlying O2 debt exists in patients with advanced alcoholic cirrhosis and that beta-adrenergic blockade with propranolol 'normalises' the O2 supply-consumption relationship resulting in more efficient O2 utilisation without adversely affecting HRS. The mechanism of this action may be related to the antagonism of beta 2-mediated arteriovenous shunting resulting in appropriate blood redistribution.

In order to determine the incidence of infection following sclerotherapy and the role of antimicrobial prophylaxis, a prospective randomized control study was performed comparing i.v. imipenem/cilastatin, with an infusion of dextrose-saline as a control group. One hundred patients with bleeding esophageal varices were included. All episodes of infection were documented during admission to the unit. Ninety-seven patients were evaluable. Post-sclerotherapy bacteremia developed in six (5.6%) of 107 sclerotherapy sessions in the control group and one (1.1%) of the 88 sclerotherapy sessions in the imipenem/cilastatin group (P < or = 0.1, NS): six of these seven post-sclerotherapy bacteremias occurred after emergency sclerotherapy. Infection within 7 days of the procedure was documented after 43 (22.1%) of the 195 sclerotherapy sessions, 18 (20.5%) in the imipenem/cilastatin group and 25 (23.4%) in the control group (P = NS). These infections were significantly more common after emergency sclerotherapy, 40 (34.8%) of 115 sessions, than after elective sclerotherapy, three (3.8%) of 80 sessions (P < or = 0.0001). A short prophylactic antibiotic regime does not reduce the risk of early bacteremia or the frequency of infection after sclerotherapy. The higher risk of infection after emergency sclerotherapy may be therefore related more to the gastrointestinal hemorrhage and its associated effects than to sclerotherapy.

There is overwhelming evidence that the maintenance of enteral feeding is beneficial in patients in whom oral access has been diminished or lost. Short-term enteral access is usually achieved via naso-enteral tube placement. For longer term tube feeding there are recognised advantages for enteral feeding tubes placed percutaneously. The provision of a percutaneous enteral tube feeding service should be within the remit of the hospital nutrition support team (NST). This designated team should provide a framework for patient selection, pre-assessment and post-procedural care. Close working relations with community-based services should be established. An accredited therapeutic endoscopist should be a member of the NST and direct the technical aspects of the service. Every endoscopy unit in an acute hospital setting should provide a basic percutaneous endoscopic gastrostomy (PEG) service. This should include provision for fitting a PEG jejunal extension (PEGJ) if required. Specialist units should be identified where a more comprehensive service is provided, including direct jejunal placement (DPEJ), as well as radiological and laparoscopically placed tubes. Good understanding of the indications for percutaneous enteral tube feeding will prevent inappropriate procedures and ensure that the correct feeding route is selected at the appropriate time. Each unit should adopt and become familiar with a limited range of PEG tube equipment. Careful adherence to the important technical details of tube insertion will reduce peri-procedural complications. Post-procedural complications remain relatively common, however, and an awareness of the correct approach to managing them is essential for all clinicians involved in providing a percutaneous enteral tube feeding service. Finally, ethical considerations should always be taken into account when considering long-term enteral feeding, especially for patients with a poor quality of life.

Objectives Cholangiocarcinoma (CCA) has a poor prognosis and its aetiology is inadequately understood. Magnetic resonance spectroscopy (MRS) of bile may provide insights into the pathogenesis of CCA and help identify novel diagnostic biomarkers. The aim of this study was to compare the chemical composition of bile from patients with CCA with that of bile from patients with benign biliary disease. Methods Magnetic resonance spectra were acquired from the bile of five CCA patients and compared with MRS of control bile from patients with benign biliary disease (seven with gallstones, eight with sphincter of Oddi dysfunction [SOD], five with primary sclerosing cholangitis [PSC]). Metabolic profiles were compared using both univariate and multivariate pattern-recognition analysis. Results Univariate analysis showed that levels of glycine-conjugated bile acids were significantly increased in patients with CCA, compared with the benign disease groups ( P = 0.002). 7β primary bile acids were significantly increased ( P = 0.030) and biliary phosphatidylcholine (PtC) levels were reduced ( P = 0.010) in bile from patients with CCA compared with bile from gallstone patients. These compounds were also of primary importance in the multivariate analysis: the cohorts were differentiated by partial least squares discriminant analysis (PLS-DA). Conclusions These preliminary data suggest that altered bile acid and PtC metabolism play an important role in CCA aetiopathogenesis and that specific metabolites may have potential as future biomarkers.

Summary points Percutaneous endoscopic gastrostomy (PEG) feeding, introduced into clinical practice in 1980,1 is now established as an effective way of providing enteral feeding to patients who have functionally normal gastrointestinal tracts but who cannot meet their nutritional needs because of inadequate oral intake.2 It is the preferred method of feeding when nutritional intake is likely to be inadequate for more than four to six weeks, and when enteral feeding is likely to prevent further weight loss, correct nutritional deficiencies, and stop the decline in quality of life in patients caused by insufficient nutritional intake.3 4 The beneficial effects of gastrostomy feeding on morbidity and mortality have been described only in certain subgroups of patients.5 6 Randomised studies in patients after stroke who received gastrostomy feeding have shown improved nutritional outcomes, higher likelihood of survival, and earlier discharge.6 7 However, gastrostomy tubes are increasingly being requested and inserted for indications where long term outcomes are uncertain.8 In this review we discuss the indications for, controversies surrounding, and complications of gastrostomy feeding and provide practical advice on the management of percutaneous endoscopic gastrostomies. #### Sources and selection criteria We searched the Cochrane database of systematic reviews and did a PubMed search (from January 1980 until January 2010) using the keywords “percutaneous endoscopic …

Objectives A small group of cystic fibrosis (CF) patients develop symptomatic pancreatitis. The clinical characteristics of these cases are not well documented in the literature. Most cases are in pancreatic sufficient (PS) patients, but it is not clear whether pancreatitis does occur in pancreatic insufficient (PI) patients. There is no information on how the group with PS and pancreatitis differs from the group with PS that does not develop pancreatitis. Methods The Royal Brompton Hospital database of adult CF patients was searched to identify all patients with symptomatic pancreatitis. Clinical details were taken from the case notes. PS pancreatitis patients were then compared with an age- and sex-matched PS control group drawn from the database. Results Sixteen patients (9 males) had suffered symptomatic pancreatitis, representing 1.6% of the total database. The mean age at CF diagnosis was 18.7 years, and at presentation with pancreatitis it was 28.8 years. Twelve were PS at diagnosis of CF. At presentation with pancreatitis, seven patients were PS and at the most recent follow-up or death, two remained PS. There was a median of three hospital admissions with pancreatitis. Eight cases developed pancreatic or hepatobiliary complications. In the comparison of pancreatitis patients with controls, there was no difference in survival but pancreatitis patients were significantly more likely to develop PI status. Mild CF transmembrane conductance regulator mutations in general, and R117H in particular, were found more often in pancreatitis patients. Conclusions Symptomatic pancreatitis is a significant problem in 1-2% of patients with CF. These patients are PS at birth but are more likely to develop late PI status than PS patients without pancreatitis. R117H may be associated with this phenotype.

Summary Background Infliximab is used for treatment of Crohn’s disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC). Aim To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC. Methods A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres. Results Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4–59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8–13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media. Conclusion Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC.

The enthusiasm for injection sclerotherapy over the last decade has almost certainly surpassed what was justified on the basis of objective evidence. This was most clearly emphasized by the widespread adoption of prophylactic sclerotherapy after the report of the first two trials, even though enough was known of the natural history of variceal hemorrhage in patients with cirrhosis to warrant caution. The use of sclerotherapy for an episode of variceal hemorrhage represents the role most supported by the available data. Diagnostic endoscopy, as an integral part of management, provides the optimum time to intervene with sclerotherapy. Sclerotherapy can then provide hemostasis in patients who are actively bleeding and prevent early rebleeding in those in whom bleeding has stopped spontaneously. The progression to long-term injection sclerotherapy is of proven benefit; however, doubts exist concerning the need for the intensive regimens currently in use. The continued use of long-term injection sclerotherapy is dependent not only on additional investigations, but also on the accumulating evidence arising from comparative studies encompassing other available therapy.

Hemodynamic changes induced by a single, total paracentesis were evaluated in 21 patients with tense ascites from whom 4 to 16 L of ascites were drained over 2 to 8 hr with no serious complications. At 60 min, compared to baseline, there was an increase in cardiac output (7.7 +/- 0.5 to 8.5 +/- 0.6 L/min, p less than 0.02) and a tendency for right atrial pressure to decrease (9.3 +/- 0.8 to 7.50 +/- 0.8 mm Hg, NS), with no change in pulmonary capillary wedge pressure (10.9 +/- 0.9 to 10.7 +/- 0.9 mm Hg). Between 3 and 12 hr later, there was a drop in right atrial pressure, pulmonary capillary wedge pressure and cardiac output to 5.6 +/- 0.6 (p less than 0.02), 7.2 +/- 0.8 mm Hg (p less than 0.002) and 7.2 +/- 0.6 L/min (NS) respectively, indicative of the development of relative hypovolemia and suggesting that therapeutic plasma expansion is appropriate at this time. Two-dimensional echocardiography before paracentesis (n = 8) showed a reduction in the right to left atrium area ratio as compared with values in patients with minimal ascites (0.54 +/- 0.04 vs 0.82 +/- 0.02, p less than 0.0001). This technique may help in identifying patients with right atrial compression caused by tense ascites.

This trial was carried out to assess the value of propranolol for the prevention of recurrent variceal bleeding in patients with well-compensated cirrhosis. We also compared propranolol therapy to long-term injection sclerotherapy. One hundred and eight patients, in whom the original variceal hemorrhage stopped spontaneously (before diagnostic endoscopy) and without sclerotherapy or surgical intervention, were included. All were Pugh grade A or B; 55% had alcoholic cirrhosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long-term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long-term sclerotherapy. Follow-up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long-term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (p less than 0.20). On an intention-to-treat basis, the risk of bleeding expressed per patient-month of follow-up was similar for the two groups, at 0.05 and 0.037, respectively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p less than 0.40). Stepwise regression analysis of possible factors predicting further bleeding in patients taking propranolol selected only two variables--the pretreatment pulse rate and the extent of pulse-rate reduction in response to propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

The past decade saw the emergence of sclerotherapy and vasoactive pharmacologic agents as alternatives to surgery in the prevention and treatment of variceal haemorrhage. Despite encouraging results from clinical trials with regard to the prevention of rebleeding, these modalities of therapy have made no major impact on survival. This failure to alter radically the clinical outcome results from the fact that in many patients with cirrhosis death is primarily related to the degree of hepatic decompensation rather than the prevention or control of variceal bleeding. Advances in our knowledge of vasoactive mediators, receptor function, and altered vascular reactivity have provided increased insight into the circulatory disturbances that characterise cirrhosis and portal hypertension. Earlier and more aggressive pharmacologic intervention with single or combination drug therapy may inhibit fibrogenesis, reduce portal vascular resistance, and improve liver function and therefore provide effective prophylaxis against variceal haemorrhage. The emergence of reliable prognostic indices for variceal bleeding should help identify patients at risk who would benefit from prophylaxis with either drugs or sclerotherapy. Transplantation will be increasingly considered in the patient at high risk of recurrent bleeding before the stage of severe hepatic decompensation (the risks of the transplant then become very much greater), as the definitive means for reducing mortality in cirrhosis and portal hypertension.

Mo1391 The Usefulness of Concurrent Use of Fully Covered Self-Expandable Metal Stentsand Plastic Stentsin Benign Pancreatic Ductal Stricture Dongwook Oh*, Sang Soo Lee, Tae Jun Song, Do Hyun Park, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (the Republic of) Background and Aims: Recently, fully covered self-expandable metal stents (FCSEMSs) has been used for pancreatic ductal strictures in chronic pancreatitis. However, distal stent migration and stent-induced ductal stricture are not uncommon. The purpose of this study was to investigate the feasibility, efficacy, safety of concurrent use ofFCSEMSsand plastic stentsin patients with benign pancreatic ductal stricture. Patients and Methods: We retrospectively reviewed the data of 18 patients who received endoscopic treatment with concurrent FCSEMSsand plastic stents for the benign pancreatic ductal stricture between August 2011 and November 2013. Additional plastic stents, which were longer than FCSEMSs, were inserted through FCSEMSs lumen. Results: Stents placement was successful through the major (nZ11) or minor papilla (nZ7). All patients could achieve pain relief after stents placement. In all patients,stents could be easily removed median 181 days (range from 68 to 181days) after stents insertion. There was no distal or proximal stent migration. Ductal stricture was resolved in 16 (88.9%) patients. During follow-up periods (median 527 days, range from 127 to 963 days), stent-induced ductal stricture did not developed after stent removal. Conclusions: The concurrent use of FCSEMSs and plastic stentsmay be safeand effective in the treatment of benign pancreatic ductal stricture. Baseline characteristics

Autopsy and imaging studies show that liver involvement is common in cystic fibrosis. However, complications of chronic liver disease including portal hypertension and variceal bleeding are infrequently encountered, and the degree to which variceal hemorrhage affects prognosis in cystic fibrosis is unclear. This uncertainty has lead to debate as to whether liver transplantation is indicated in these patients. We describe a case series of 18 patients and compare their survival with a control group of cystic fibrosis patients without liver disease. The median age at first bleed was 20.0 years (range 9.7-30.9). The median survival after first bleed was 8.4 years, compared to 13.0 years in the control group (P = 0.15). A total of 14 patients have died, 9 from respiratory disease with no discernable contribution from their liver disease. Liver disease contributed to 4 deaths. Only 1 patient suffered a fatal hemorrhage, which may have been either variceal or bronchial in origin. Long-term survival is a frequent occurrence in patients with cystic fibrosis who suffer variceal hemorrhage, and age at death is comparable to the general cystic fibrosis population. In conclusion, this suggests that liver transplantation is not indicated in these patients without additional features of liver decompensation.

Recent advances in the treatment of cardiorespiratory complications in patients with cystic fibrosis (CF) have improved median survival and resulted in gastrointestinal complications becoming more evident.1,2 The distal intestinal obstruction syndrome (DIOS) develops due to the accumulation of viscid muco-faeculent material in the terminal ileum and right hemicolon.3 Reduced intestinal water content, lower luminal acidity of the foregut, and accumulation of intraluminal macromolecules contribute to the development of DIOS.4 Typically, patients develop progressive symptoms and signs of small bowel obstruction. A plain abdominal x ray will reveal dilated loops of centrally placed small bowel, with faecal loading at the terminal ileum and right hemicolon (see fig 1). Most cases will respond to the aggressive use of laxative agents administered orally and rectally, intravenous hydration, pancreatic supplements, and N -acetylcysteine (Parvolex) and gastrografin (meglumine diatrizoate) orally or per rectum.5–8 Surgical decompression has been reserved for refractory cases but carries a …

Introduction Choledocholithiasis is the commonest indication for endoscopic retrograde cholangiopancreatography (ERCP). ERCP carries substantial risk of complication when compared to other endoscopic modalities. The identification of key performance indicators (KPIs) in colonoscopy practice and implementation of related standards has driven quality assurance in the UK and elsewhere. The failure to establish similar contemporary, meaningful and measurable KPIs in ERCP has hampered the development of national standards. We aimed to quantify current performance in a potential new endoscopic KPI: the complete clearance of CBD stones at first ERCP. Methods Seven centres participated – four secondary and three tertiary HPB units. All patients undergoing first ERCP for confirmed or suspected choledocholithiasis over a twelve month period were included and data were analysed on an intention to treat basis. The primary endpoint was complete clearance of bile duct stones. Failure to clear stones was defined as i) persisting stones reported ii) placement of biliary endoprosthesis, even if considered precautionary. Secondary endpoints were CBD cannulation, successful biliary decompression and complications. Outcomes were analysed by unit and by consultant clinician performing the procedure. Results 1178 patients were included in the study. 20 consultant endoscopists carried out or supervised the procedures. Overall, deep biliary cannulation was achieved in 1074/1178 (91%, range for seven units 82–96%). Complete bile duct clearance at first ERCP was achieved in 861/1178 (73%, 65–81%). Conclusion We investigated the outcome of 1178 ERCP procedures, representing real-life practice in the UK. Duct clearance was possible at first ERCP in almost three quarters of patients. There were significant differences in performance between units and individual operators. The reasons for this are not fully elucidated. The primary endpoint of this study has strengths as a potential KPI. It is clearly defined, measurable on an intention to treat basis and is strongly focused on patient outcome. In addition, it quantifies performance in the commonest indication for ERCP, stone extraction, which is undertaken in all ERCP units. Disclosure of Interest None Declared.

Endoscopic therapy and in particular endoscopic variceal banding ligation, in experienced hands, is the treatment of choice for acute variceal bleeding which remains a major cause of death in patients with cirrhosis and portal hypertension. Pharmacological therapy with Glypressin or somatostatin can be useful to gain time when the endoscopic expertise is not available or to help to obtain a clearer endoscopic view. Transjugular intrahepatic porto-systemic stent shunt is currently used for endoscopic failures, producing similar results with the surgical portacaval shunts. Which one of the two should be preferred, since they both work best in relatively compensated patients, should be a balance between the available surgical and radiological expertise, the urgency of the situation and the expected course of the disease.

Background: If areas of specialized intestinal metaplasia (SIM) or dysplasia in Barrett's esophagus can be identified at endoscopy, the number of biopsies could be reduced and the sensitivity of biopsy surveillance would increase. It has been suggested that methylene blue (MB) dye staining may be useful for this purpose. Methods: Nine patients were prospectively studied with Barrett's esophagus. Staining involved sequential spraying of 10% N-acetylcysteine, 0.5% MB and water. Quadrantic biopsies were obtained from Barrett's epithelium and collected in separate containers depending on whether they were taken from stained or unstained areas. Seven patients undergoing yearly surveillance were asked to compare the discomfort of this endoscopy with that of previous surveillance endoscopies. Biopsies were analyzed for the presence and the percentage of SIM and dysplasia by a nonblinded pathologist. Results: MB staining prolonged endoscopy by a mean of 8 minutes (47% increase in procedure time) and was associated with significant vomiting during the procedure in 2 patients. Staining was observed in all 9 patients. All 7 patients undergoing yearly endoscopic surveillance indicated more discomfort with endoscopy plus MB staining. Of 37 biopsies from stained mucosa, 20 contained SIM; of 23 from unstained mucosa, 15 contained SIM (57% sensitivity, 32% specificity for MB staining). Conclusions: In this small, nonblinded study MB staining was associated with prolongation of endoscopy, increased patient discomfort, and potentially serious complications and was neither very sensitive nor specific for SIM. It is our recommendation that this technique should not be routinely used in endoscopic surveillance of patients with Barrett's esophagus. Further studies of MB staining are needed. (Gastrointest Endosc 2001;53:333-5.)