J S Leeds

Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms

Patients with coeliac disease may have diarrhoea despite being on a gluten‐free diet.

The role of fecal elastase-1 in detecting exocrine pancreatic disease

Exocrine pancreatic disease is thought to be uncommon in clinical practice and usually secondary to excess alcohol intake. Although excess alcohol intake does account for many cases of exocrine pancreatic disease, other conditions are associated with exocrine pancreatic insufficiency and such dysfunction perhaps occurs more frequently than conventionally expected. A reliable, patient-friendly, cheap and easy to use test for exocrine pancreatic disease is yet to be established; however, in many countries the main (and often only available) method of assessment of exocrine pancreatic function is the fecal-elastase-1 test. This Review examines the role of fecal-elastase-1 testing in detecting exocrine pancreatic insufficiency in a number of gastrointestinal and nongastrointestinal conditions and determines the value of pancreatic enzyme supplementation in these settings.

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

Background:Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy.Methods:Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations.Results:We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin.Conclusions:In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

BACKGROUNDnCoeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics.nnnMETHODSnUnselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors.nnnRESULTSn4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk.nnnCONCLUSIONSnCoeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted.

Letter: bile acid malabsorption - what is the prevalence in patients with chronic diarrhoea?

We read with interest the article by Wilcox et al. Bile acid malabsorption (BAM) is a recognised cause of diarrhoea, however there remains a paucity of work systematically evaluating its prevalence in patients with chronic diarrhoea. 3 Our group recently investigated a cohort of patients with chronic diarrhoea, aiming to establish BAM prevalence and whether time delays were incurred in establishing a diagnosis. Ninety-two consecutive patients referred to a University hospital and fulfilling the British Society of Gastroenterology definition for chronic diarrhoea were retrospectively evaluated. All patients underwent haematological, biochemical and immunological testing prior to subsequent investigations. Investigations included bi-directional endoscopy, barium enema/swallow, abdominal ultrasound, CT imaging, SeHCAT scan, small bowel capsule endoscopy, MRI small bowel, glucose hydrogen breath tests and lactose hydrogen breath tests. Demographical data, results of subsequent investigations and diagnostic yields of differing tests were collected and compared using a Fisher’s exact test. Times to diagnosis comparisons were made using an unpaired t-test. Medical records were identified in 89 of 92 patients referred (mean age 50 years, range 18–86 years). Of these, 27% (24/89) had an organic cause for their diarrhoea identified (Table 1), with six patients having dual pathology. Inflammatory bowel disease was the most prevalent condition identified, with BAM prevalence being comparable to that of coeliac disease (P = 0.72). Despite comparable prevalence of BAM to coeliac disease, the mean time to diagnosis was significantly prolonged (248 days vs. 35 days, P = 0.04). Our findings highlight the importance of systematically evaluating patients with chronic diarrhoea, with an organic condition identified in 27%. In addition, we highlight how BAM prevalence may be similar to a well-established condition such as coeliac disease. Given the potential treatment options, highlighted in Wilcox et al.’s review, for BAM we would advocate increased availability of testing and earlier consideration of the diagnosis.

Outcomes after through-the-PEG tube placement of jejunal extensions: a case series from a single center.

1 PEG was first described by Gauderer et al and is used for providing long-term feeding. Enteral feeding is indicated in patients with functional GI tracts unable to meet nutritional requirements orally. PEG tube placement has several indications, with the strongest evidence in patients with acute dysphagic stroke and oropharyngeal malignancy. PEG feeding is not suitable for alldfor example, in those with gastroparesis in whom post-gastric or jejunal feeding is required to maintain adequate nutrition. Recurrent aspiration has been reported in up to 30% of PEG-fed individuals, with some evidence that jejunal feeding decreases the aspiration risk. However, this is a contentious issue because other studies show no advantage to this approach. Establishing stable access to the small bowel can be difficult, and placement of a percutaneous endoscopic jejunostomy (PEJ) tube challenging. A PEG with jejunal extension (PEG-J) is an alternative technique for patients who do not tolerate gastric feeding. Many methods of PEG-J tube placement have been reported, but no consensus on the most effective technique exists. Conventional techniques are time consuming, technically demanding, and generally require sedation, oral intubation, and fluoroscopic guidance. Most methods involve passing a guidewire or jejunal tube through the PEG tube and catching this in the stomach with a standard endoscope and forceps. The

PTH-142 The Role of Sehcat Scanning in Patients with Chronic Diarrhoea: Results from a new Service

Introduction Chronic diarrhoea is a common reason for referral to gastroenterology departments and often multiple investigations are undertaken. Bile acid malabsorption is an under recognised cause of chronic diarrhoea and currently occupies a lower tier in the investigatory pathway. SeHCaT scanning has been available in our region for the last 2 years and therefore the aim of this study was to investigate the role that this test has in such patients. Methods All patients referred for a SeHCaT scan were identified by searching by procedure in the Nuclear Medicine department. Patient demographics, indication, number of previous tests, surgical history and SeHCaT result were noted. The cut off for an abnormal test was < 15% retention at 7 days. Notes were reviewed to determine which patients had treatment and the response rate. In those with a negative result, the final diagnosis (if known) was recorded. Results 122 patients (95 female, median age 50 years) had undergone a SeHCaT scan for investigation of chronic diarrhoea during the period January 2011 to July 2012. 61/122 (50%) patients had a SeHCaT retention < 15% with 30 having retention values < 5%, 19 between 5.1 – 10% and 12 between 10.1 – 15%. An abnormal SeHCaT scan was associated with previous bowel surgery (Odds ratio 14.2, 95% CI 1.8–113.1, p = 0.002) but not gender (odds ratio 2.0 95% CI 0.8–4.7, p = ns) or previous cholecystectomy (odds ratio 1.2 95% CI 0.5–2.7, p = ns). 45/53 (84.9%) patients were commenced on bile acid sequestrants (mainly cholestyramine) with a good response to treatment. 13 patients were intolerant of cholestyramine and switched to colesevalam of which 10 have so far had clinical improvement. Prior to SeHCat scanning patients had undergone a median of 2.5 other investigations (range 0 – 9). Final diagnosis was bile acid diarrhoea (n = 61), irritable bowel syndrome (n = 34), malabsorption (n = 3), Crohns disease (n = 2), coeliac disease (n = 1), diverticular disease (n = 1), small bowel bacterial overgrowth (n = 1) and still being investigated (n = 19). Conclusion In patients with chronic diarrhoea, SeHCaT scanning has a high yield and is associated with good clinical response to treatment with cholestyramine. We did not find that previous cholecystectomy was a risk factor but confirm that bowel resection appears to be. Switching to colesevalam is effective when cholestyramine is not tolerated. Disclosure of Interest None Declared.

Utility of cyst fluid CEA cut-off of 192ng/ml in the diagnosis of mucinous cysts of the pancreas

Introduction The differentiation of mucinous from non-mucinous pancreatic cysts is important because of the malignant potential of the latter. EUS-FNA allows for high resolution imaging of pancreatic cysts as well as sampling for markers (CEA), cytology and a visual assessment of cyst content. The Cooperative cyst study found an elevated fluid CEA (>192 ng/ml) to be the single most accurate test in correctly predicting mucinous cysts with a sensitivity of 73%. The CEA value of 192ng/ml has subsequently been widely adopted as a definitive cut-off value. Methods The aims of the present study were to assess the utility of a cut-off value of 192 ng/ml in differentiating mucinous from non-mucinous pancreatic cysts and to compare this to general EUS assessment. IPMN and mucinous cyst adenoma/adenocarcinoma (MCA and MCAC) were considered separately. The study population comprised all the patients undergoing EUS-FNA at a tertiary centre for assessment of suspected pancreatic neoplastic cysts between June 2003 and April 2010. Results During this period 267 procedures were performed on 235 individuals, of whom 71 had a definitive diagnosis (60 resection histology, 5 histology, 6 malignant cytology), cystic degeneration of pancreatic adenocarcinoma (3) being excluded. 68 patients (51 females), (78 procedures) formed the study group. There were 25 mucinous cyst adenomas (11 MCA, 14 MCAC). There were 22 IPMN (2 malignant) and 21 non-mucinous cysts. For MCA/MCAC using a cut-off of 192 ng/ml the sensitivity, specificity, accuracy and NPV of detecting a mucinous lesion were 62.5%, 94.4%, 79.4%, 73.9%. Combining EUS morphology, cytology and visual assessment of aspirate (mucoid/non-mucoid) gave figures of 100%, 70.8%, 86%, 100%. The combination was significantly more sensitive p=0.007, but no significant difference in specificity. ROC area under the curve was numerically greater 0.861 versus 0.785 (not significant). For the IPMN patients the cut-off 192 ng/ml showed a sensitivity of 20% in the diagnosis of IPMN. EUS diagnosis had a sensitivity of 85%. Sensitivity of aspirate appearance: 87%, cytology: 50%; combining fluid appearance, EUS and cytology: 93%. Comparing the performance of CEA 192 versus combination in differentiating IPMN from non-mucinous cyst, ROC curve area was 0.864 versus 0.623 p =0.02. Conclusion A CEA cut-off of 192 ng/ml demonstrated good specificity and moderate sensitivity in the diagnosis of MCA, however it performed poorly in the diagnosis of IPMN. Combining EUS, aspirate appearance and cytology was significantly more sensitive in diagnosing mucinous cysts with a very high NPV.

PTU-088 Has the European Working Time Directive affected gastrointestinal trainees?

Introduction The European Working Time Directive (EWTD) came into force in August 2009 and dictates that junior doctors should not work >48u2005h on an average week. Many trusts have had to alter on call rotas to be compliant with the directive. Many trainees, particularly in procedure based specialities, have been concerned about the reduction in procedural training. Previous studies have mainly looked at number of hours worked and not the impact on number of procedures performed or new patients seen in outpatients. Our aim was to examine the effect of the EWTD on important training areas; number of colonoscopies performed, number of ERCPs performed and new outpatients seen by gastroenterology trainees. Methods Working hours changed from 56u2005h per week to 48u2005h per week in February 2009. In our unit, this was delivered by increasing numbers of days off during a full rota cycle without changing individual timetables. Personal logs and local IT systems were examined for 6u2005months prior to and for 6u2005months following the change to determine number of new patients seen in outpatients and number of colonoscopies/ERCPs performed. Only three of the trainees attended colonoscopy lists as the fourth post is a hepatology fellowship post and only two of the trainees performed ERCP. Both periods included the same amount of annual and study leave. Results From August 2008 to February 2009 the four trainees saw 602 new patients and were present at/performed 196 colonoscopies. The two trainees performing ERCP attended/performed 120 procedures during this period. From February 2009 to August 2009 there was a reduction in the number of colonoscopies attended/performed down to 160 (19.4% reduction, p=0.002). There was also a reduction in the number of new patients seen to 456 (24.3% reduction, p=0.01). There was a reduction in the number of ERCPs performed to 104 (13.3% reduction, p=0.1) but this was not statistically significant. Extrapolating these figures to a 5-year training programme, under the 48u2005h limit trainees would see 730 less new patients, perform 180 less colonoscopies and 80 less ERCPs. Each reductions of these accounts for around a least a year of training. Conclusion There has been significant impact of the EWTD on training in gastroenterology particularly in colonoscopy training and new patient assessment. ERCP may be impacted however the current numbers are too small. New models of training will be required to address this problem perhaps focusing on post training fellowships.

Radiofrequency ablation for management of malignant biliary obstruction: a single-center experience and review of the literature

ABSTRACT Background: Radiofrequency ablation (RFA) causes coagulative necrosis of tissue and may be beneficial prior to biliary stenting. We report our experience using RFA for malignant biliary obstruction and review the literature. Methods: Retrospective analysis of all patients undergoing RFA for malignant biliary obstruction over the last two years. Success, complications and re-intervention following RFA were assessed. Controls were age, sex and disease matched who had stenting alone. Results: 31 patients were included and 15 patients underwent biliary RFA prior to stenting (median age 78 years, 8 females). 14 patients had pancreatic cancer, 13 cholangiocarcinoma (6 hilar lesions) and 4 malignant disease invading the bile duct. Adverse events included acute pancreatitis (n = 2) and bacteremia in (n = 1). Median duration of intervention free survival was 220 days in the RFA group compared to 106.5 days in controls (hazard ratio 2.4, 95% CI 1.1 – 5.3, p = 0.025). Multivariable Cox proportional hazard analysis showed survival was associated with RFA (hazard ratio 2.55, 95% CI 1.09–5.96, p = 0.026) but not age, site or type of malignancy. Conclusion: Biliary RFA is a technically feasible with a low adverse event rate and is associated with increased survival. Multi-centre randomized controlled trials are required.