David Westaby

Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction

BACKGROUNDnIn unresectable malignant bile duct obstruction in a patient with a life expectancy longer than 3 months, the use of self-expandable metal stents (SEMSs) is the standard technique to ensure continued biliary drainage. As many as 50% of patients with SEMSs will present with stent occlusion within 6 months. Changes to stent design and composition and concomitant therapy have failed to improve stent patency; therefore, alternative techniques to safely prolong stent patency are required.nnnOBJECTIVEnTo demonstrate the safety of endobiliary bipolar radiofrequency ablation (RFA) in patients with malignant biliary obstruction and to report the 90-day biliary patency of this novel procedure.nnnDESIGNnOpen-label pilot study.nnnSETTINGnSingle tertiary care unit.nnnPATIENTSnA total of 22 patients with unresectable malignant bile duct obstruction.nnnINTERVENTIONSnBipolar RFA within the bile duct.nnnMAIN OUTCOME MEASUREMENTSnImmediate and 30-day complications and 90-day stent patency.nnnRESULTSnA total of 22 patients (16 pancreatic, 6 cholangiocarcinoma) were recruited between January 2009 and April 2010. Deployment of an RFA catheter was successful in 21 patients. SEMS placement was achieved in all cases of successful RFA catheter deployment. One patient failed to demonstrate successful biliary decompression after SEMS placement and died within 90 days. All other patients maintained stent patency at 30 days. One patient had asymptomatic biochemical pancreatitis, 2 patients required percutaneous gallbladder drainage, and 1 patient developed rigors. At 90-day follow-up, 1 additional patient had died with a patent stent, and 3 patients had occluded biliary stents.nnnLIMITATIONSnCohort study.nnnCONCLUSIONSnEndobiliary RFA treatment appears to be safe. Randomized studies with prolonged follow-up are warranted.

The provision of a percutaneously placed enteral tube feeding service

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.

Percutaneous endoscopic gastrostomy (PEG) feeding

#### Summary pointsnnPercutaneous 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.nn#### Sources and selection criteriannWe searched the Cochrane database of systematic reviews and did a PubMed search (from January 1980 until January 2010) using the keywords “percutaneous endoscopic …

Elevated Levels of Neutrophil Gelatinase-Associated Lipocalin in Bile From Patients With Malignant Pancreatobiliary Disease

OBJECTIVES: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.METHODS: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).RESULTS: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. 480u2009ng/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.CONCLUSIONS:NGAL in bile is a novel potential biomarker to help distinguish benign from malignant biliary obstruction.

Analysis of Endoscopic Radiofrequency Ablation of Biliary Malignant Strictures in Pancreatic Cancer Suggests Potential Survival Benefit

AbstractBackgroundPancreatic 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.AimTo analyze the clinical efficacy of endobiliary RFA.MethodsnRetrospective 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.ResultsRFA and control groups were closely matched—ASA 2.35xa0±xa00.65 versus 2.54xa0±xa00.50, pxa0=xa00.086; metastases 9/23 (39.1xa0%) versus 18/46 (39.1xa0%), pxa0=xa00.800; chemotherapy 16/23 (69.6xa0%) versus 24/46 (52.2xa0%), pxa0=xa00.203. Median survival in RFA group was 226xa0days (IQR 140–526xa0days) versus 123.5xa0days (IQR 44–328xa0days) in controls (pxa0=xa00.010). RFA was independently predictive of survival at 90xa0days (OR 21.07, 95xa0% CI 1.45–306.64, pxa0=xa00.026) and 180xa0days (OR 4.48, 95xa0% CI 1.04–19.30, pxa0=xa00.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects.ConclusionsEndoscopic 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.

Endoscopic radiofrequency ablation for cholangiocarcinoma.

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.

Metabolic profiling of bile in cholangiocarcinoma using in vitro magnetic resonance spectroscopy

OBJECTIVESnCholangiocarcinoma (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.nnnMETHODSnMagnetic 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.nnnRESULTSnUnivariate 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). 7 beta 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).nnnCONCLUSIONSnThese 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.

Diagnostic utility of single-user peroral cholangioscopy in sclerosing cholangitis.

Abstract Objective. To evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) in patients with sclerosing cholangitis. Methods. 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. Results. 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). Conclusions. 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.

National survey evaluating service provision for percutaneous endoscopic gastrostomy within the UK

Abstract Objectives. 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. Materials and methods. The British Society of Gastroenterology (BSG) approached all NHS hospitals providing an endoscopy service (n = 260). A custom designed web-based questionnaire was circulated. Results. 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 inserting >150). 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). Conclusion. 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.

The palliation of cholangiocarcinoma.

Purpose of reviewCholangiocarcinoma 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 findingsFor 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. SummaryThe 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.