5-Aminolevulinic acid for fluorescence-guided surgery in pancreatic cancer: Cellular transport and fluorescence quantification studies.

5-Aminolevulinic acid (ALA) is a potential contrast agent for fluorescence-guided surgery in pancreatic ductal adenocarcinoma (PDAC). However, factors influencing ALA uptake in PDAC have not been adequately assessed. We investigated ALA-induced porphyrin fluorescence in PDAC cell lines CFPAC-1 and PANC-1 and pancreatic ductal cell line H6c7 following incubation with 0.25-1.0 mM ALA for 4-48 h. Fluorescence was assessed qualitatively by microscopy and quantitatively by plate reader and flow cytometry. Haem biosynthesis enzymes and transporters were measured by quantitative polymerase chain reaction (qPCR). CFPAC-1 cells exhibited intense fluorescence under microscopy at low concentrations whereas PANC-1 cells and pancreatic ductal cell line H6c7 showed much lower fluorescence. Quantitative fluorescence studies demonstrated fluorescence saturation in the two PDAC cell lines at 0.5 mM ALA, whereas H6c7 cells showed increasing fluorescence with increasing ALA. Based on the PDAC:H6c7 fluorescence ratio studies, lower ALA concentrations provide better contrast between PDAC and benign pancreatic cells. Studies with qPCR showed upregulation of ALA influx transporter PEPT1 in CFPAC-1, whereas PANC-1 upregulated the efflux transporter ABCG2. We conclude that PEPT1 and ABCG2 expression may be key contributory factors for variability in ALA-induced fluorescence in PDAC.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

Risk of malignancy in resected pancreatic mucinous cystic neoplasms.

BACKGROUND: Pancreatic mucinous cystic neoplasms (MCNs) are rare mucin-producing cystic tumours defined by the presence of ovarian-type stroma. MCNs have a malignant potential and thus surgery is frequently performed. The aim of this cohort study was to define better the criteria for surgical resection in patients with MCN. METHODS: This multicentre retrospective study included all resected MCNs between 2003 and 2015 in participating centres. Lesions without ovarian-type stroma were excluded. Patient characteristics, preoperative findings, histopathology findings and follow-up data were recorded. RESULTS: The study included 211 patients; their median age was 53 (range 18-82) years, and 202 (95·7 per cent) were women. Median preoperative tumour size was 55 (range 12-230) mm. Thirty-four of the 211 (16·1 per cent) were malignant, and high-grade dysplasia (HGD) was found in a further 13 (6·2 per cent). One-third of MCNs in men were associated with invasive cancer, compared with 15·3 per cent in women. Five cases of malignant transformation occurred in MCNs smaller than 4 cm. All cases of malignancy or HGD were associated with symptoms or features of concern on preoperative cross-sectional imaging. In multivariable analysis, raised carbohydrate antigen 19-9 (odds ratio (OR) 10·54, 95 per cent c.i. 2·85 to 218·23; P < 0·001), tumour size (OR 4·23, 3·02 to 11·03; P = 0·001), mural nodules (OR 3·55, 1·31 to 20·55; P = 0·002) and weight loss (OR 3·40, 2·34 to 12·34; P = 0·034) were independent factors predictive of malignant transformation. CONCLUSIONS: Small indeterminate MCNs with no symptoms or features of concern may safely be observed as they have a low risk of malignant transformation.

The endoscopist and malignant and non-malignant biliary obstruction.

Patients with biliary strictures often represent a diagnostic and therapeutic challenge, due to the site and complexity of biliary obstruction and wide differential diagnosis. Multidisciplinary decision making is required to reach an accurate and timely diagnosis and to plan optimal care. Developments in endoscopic ultrasound and peroral cholangioscopy have advanced the diagnostic yield of biliary endoscopy, and novel optical imaging techniques are emerging. Endoscopic approaches to biliary drainage are preferred in most scenarios, and recent advances in therapeutic endoscopic ultrasound allow drainage where the previous alternatives were only percutaneous or surgical. Here we review recent advances in endoscopic practice for the diagnosis and management of biliary strictures. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.

Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.

Advanced Endoscopic Imaging Techniques for the Study of Colonic Mucosa in Patients with Inflammatory Bowel Disease.

BACKGROUND: Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) associated with colorectal cancer risk in long-standing diseases. In order to assess the colonic mucosa and to discover dysplastic or neoplastic lesions, advanced endoscopic techniques are needed. Such techniques are detailed in this review: chromoendoscopy, autofluorescence imaging (AFI), narrow band imaging (NBI), i-SCAN, Fujinon Intelligent Color Enhancement (FICE) and confocal laser endomicroscopy (CLE). AIM: The aim of the review is to describe and establish the clinical impact of advanced endoscopic techniques, that could be used in IBD patients'examination in order to assess mucosal healing, microscopic inflammation, dysplasia or neoplasia. MATERIALS AND METHODS: A literature research about new endoscopic approaches of patients with IBD was made. RESULTS: A lot of studies have been performed to reveal which imaging technique might be used for IBD surveillance. Regarding dysplasia or neoplasia detection and mucosal healing or inflammation assessment, CE proved to be superior to white light endoscopy (WLE), while NBI and AFI did not show an encouraging result. I-SCAN did not improve the colonoscopy quality while FICE has been used in a few studies. CLE could be used to characterize a lesion, providing the same results as conventional histology. CONCLUSION: At the moment, CE is the only technique which has been included in guidelines for IBD surveillance. CLE can be used to assess any lesion detected with WLE during surveillance, while the other imaging techniques require.more studies to determine their efficacy or inefficacy.

Modeling of coastal water contamination in Fortaleza (Northeastern Brazil).

An important tool in environmental management projects and studies due to the complexity of environmental systems, environmental modeling makes it possible to integrate many variables and processes, thereby providing a dynamic view of systems. In this study the bacteriological quality of the coastal waters of Fortaleza (a state capital in Northeastern Brazil) was modeled considering multiple contamination sources. Using the software SisBaHiA, the dispersion of thermotolerant coliforms and Escherichia coli from three sources of contamination (local rivers, storm drains and submarine outfall) was analyzed. The models took into account variations in bacterial decay due to solar radiation and other environmental factors. Fecal pollution discharged from rivers and storm drains is transported westward by coastal currents, contaminating strips of beach water to the left of each storm drain or river. Exception to this condition only occurs on beaches protected by the breakwater of the harbor, where counterclockwise vortexes reverse this behavior. The results of the models were consistent with field measurements taken during the dry and the rainy season. Our results show that the submarine outfall plume was over 2 km from the nearest beach. The storm drains and the Maceió stream are the main factors responsible for the poor water quality on the waterfront of Fortaleza. The depollution of these sources would generate considerable social, health and economic gains for the region.

Experience of propofol sedation in a UK ERCP practice: lessons for service provision.

OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) in the UK has been historically performed under conscious sedation. However, given the increasing complexity of cases, the role of propofol-assisted ERCP (propERCP) is increasing. We describe our experience of propERCP and highlight the importance of this service. DESIGN: Our prospective ERCP database was interrogated between January 2013 and January 2014. Data collection included procedural information, patient demographics, American Association of Anaesthesiologists (ASA) status, Cotton grade of endoscopic difficulty and endoscopic and anaesthetic complications. Comparison was made with patients undergoing conscious sedation ERCP (sedERCP). RESULTS: 744 ERCPs were performed in 629 patients (53% male). 161 ERCPs were performed under propofol. PropERCP patients were younger compared with the sedERCP group (54 vs 66 years, p<0.0001) but ASA grade 1-2 status was similar (84% vs 78%, p=0.6). An increased number of Cotton grade 3-4 ERCPs were performed in the propERCP group (64% vs 34%, p<0.0001). Indications for propERCP included sphincter of Oddi manometry (27%), previously poorly tolerated sedERCP (26%), cholangioscopy (21%) and patient request (8%). 77% of cases were elective, 12% were urgent day-case transfers and 11% were urgent inpatients. 59% of cases were tertiary referrals. ERCP was completed successfully in 95% of cases. Anaesthetic and endoscopic complications were comparable between the two groups (5% and 7% vs 3% and 5%). Where sedERCP had been unsuccessful due to patient intolerance, the procedure was completed successfully using propofol. CONCLUSIONS: PropERCP is safe and is associated with high endoscopic success. The need for propERCP is likely to increase given patient preference and the high proportion of complex procedures being undertaken. All endoscopy units should look to incorporate propofol-assisted endoscopy into aspects of their services.

Evaluation in pre-diagnosis samples discounts ICAM-1 and TIMP-1 as biomarkers for earlier diagnosis of pancreatic cancer.

Circulating intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been widely proposed as potential diagnostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). We report on serum protein levels prior to clinical presentation of pancreatic cancer. Serum ICAM-1 and TIMP-1 were measured by ELISA in two case­control sets: 1) samples from patients diagnosed with pancreatic cancer (n = 40), chronic pancreatitis (n = 20), benign jaundice due to gall stones (n = 20) and healthy subjects (n = 20); 2) a preclinical set from the UK Collaborative Trial of Ovarian Cancer Screening biobank of samples collected from 27 post-menopausal women 0­12 months prior to diagnosis of pancreatic cancer and controls matched for date of donation and centre. Levels of ICAM-1 and TIMP-1 were significantly elevated in set 1 in PDAC patients with jaundice compared to PDAC patients without jaundice and both proteins were elevated in patients with jaundice due to gall stones. Neither protein was elevated in samples taken 0­12 months prior to PDAC diagnosis compared to non-cancer control samples. In conclusion, evaluation in pre-diagnosis samples discounts ICAM-1 and TIMP-1 as biomarkers for earlier diagnosis of pancreatic cancer. Failure to account for obstructive jaundice may have contributed to the previous promise of these candidate biomarkers. BIOLOGICAL SIGNIFICANCE: Pancreatic cancer is usually diagnosed when at an advanced stage which greatly limits therapeutic options. Biomarkers that could facilitate earlier diagnosis are urgently sought.

A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTC) are often diagnosed late and at an advanced stage. Population-based screening programmes do not exist and diagnosis is primarily dependent on symptom recognition. Recently symptom-based cancer decision support tools (CDSTs) have been introduced into primary care practices throughout the UK to support general practitioners (GPs) in identifying patients with suspected PDAC. However, future refinement of these tools to improve their diagnostic accuracy is likely to be necessary. SETTING: The Health Improvement Network (THIN) is a primary care database, which includes more than 11 million electronic patient records, from 562 GP practices in the UK. PARTICIPANTS: All patients with a diagnosis of PDAC or BTC between 2000 and 2010 were included in the study along with six matched controls; 2773 patients with PDAC, 848 patients with BTC and 15,395 controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary aim of this study was to determine the early symptom profiles of PDAC and BTC. Secondary aims included comparing early symptom trends between BTC and PDAC, defining symptom onset in PDAC and evaluating trends in routine blood tests nearest to the time of diagnosis. RESULTS: In the year prior to diagnosis, patients with PDAC visited their GP on a median of 18 (IQR 11-27) occasions. PDAC was associated with 11 alarm symptoms and BTC with 8. Back pain (OR 1.33 (95% CI 1.18 to 1.49) p<0.001), lethargy (1.42 (95% CI 1.25 to 1.62) p<0.001) and new onset diabetes (OR 2.46 (95% CI 2.16 to 2.80)) were identified as unique features of PDAC. CONCLUSIONS: PDAC and BTC are associated with numerous early alarm symptoms. CDSTs are therefore likely to be useful in identifying these tumours at an early stage. Inclusion of unique symptoms, symptoms with an early onset and routinely performed blood tests is likely to further improve the sensitivity of these tools.

Toxicity effects of hazardous and noxious substances (HNS) to marine organisms: acute and chronic toxicity of p-xylene to the amphipod Gammarus locusta.

Despite the recent focus on hazardous and noxious substances (HNS) spills preparedness and responses, much remains to be done regarding the threat posed by HNS spills on marine biota. Among the identified priority HNS, p-xylene was selected to conduct ecotoxicological assays. The aim of this study was to assess the performance of the amphipod Gammarus locusta under acute and chronic exposure to p-xylene simulating conditions of a spill incident. In the acute exposure (96 h) the p-xylene LC50 was estimated. In the chronic bioassay (36 d), an integration of organism-level endpoints (survival, growth rate, and sex ratio) with biochemical markers indicative of oxidative stress including catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD) activities and lipid peroxidation (LPO) levels was determined. The aim was to increase the xylene ecotoxicological database and better predict its impact in aquatic environments. p-Xylene induced several chronic toxicity effects in G. locusta. Significant alterations in antioxidant enzymes and lipid peroxidation levels as well as growth rate and biased sex-ratio were observed. p-Xylene significantly affected the activities of CAT, SOD, and GST in G. locusta and produced oxidative damage by increasing levels of LPO in males. Further, impacts in key ecological endpoints, that is, growth and sex ratio, were noted that might be indicative of potential effects at the population level in a spill scenario. The present data may be useful to assist relevant bodies in preparedness and response to HNS spills.

Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort.

OBJECTIVES: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS: Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1-107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS: Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P<0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02). CONCLUSIONS: Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

Update on the management of cholangiocarcinoma.

Cholangiocarcinoma (CC) is a rare cancer arising from the epithelium of the biliary tree, anywhere from the small peripheral hepatic ducts to the distal common bile duct. Classification systems for CC typically group tumours by anatomical location into intrahepatic, hilar or extrahepatic subtypes. Surgical resection or liver transplantation remains the only curative therapy for CC, but up to 80% of patients present with advanced, irresectable disease. Unresectable CC remains resistant to many chemotherapeutic agents, although gemcitabine, particularly in combination with other agents, has been shown to improve overall survival. Ongoing investigation of biological agents has also yielded some promising results. Several novel interventional and endoscopic techniques for the diagnosis and management of non-operable CC have been developed: initial results show improvements in symptoms and progression-free survival, but further randomised studies are required to establish their role in the management of CC.

Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer.

BACKGROUND: Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin. METHODS: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg(-1) verteporfin. After 60-90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently. RESULTS: In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm(3) at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy. CONCLUSIONS: Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.

A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC). METHODS: We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322. RESULTS: The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively. CONCLUSION: Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.

Apical MUC1 expression revealed on the foveolar epithelium in H. pylori gastritis.

BACKGROUND: The membrane mucin MUC1 is altered in its pattern of expression in cancer, and also in other pathological situations, including Helicobacter pylori gastritis. Here we investigate the basis for the loss of apical staining of the gastric foveolar epithelium in H. pylori gastritis. METHODS: MUC1 was examined in the gastric antrum from cases of H. pylori gastritis and normal controls. We used tissue sections that were either treated or not treated with periodate to effect deglycosylation, and the monoclonal antibodies LICRLonM8, MUSE-11, CT2 and BC2. RESULTS: We show that the epitopes on the TR domain of MUC1 are partially cryptic due to glycosylation and that MUC1 is present on the apical surface of the gastric foveolar epithelium of gastritis patients. CONCLUSION: This observation suggests that there is no substantial loss of the mucin domain of MUC1 from the apical surface in gastritis, as suggested by others, but rather the H. pylori influences the glycosylation of MUC1. This paper highlights the issue of epitope specificity of monoclonal antibodies directed against disease-associated markers, specifically when they are glycoproteins, as is the case for many cancer markers.

A combination of serum leucine-rich α-2-glycoprotein 1, CA19-9 and interleukin-6 differentiate biliary tract cancer from benign biliary strictures.

BACKGROUND: Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) as they lack diagnostic accuracy. METHODS: Two-dimensional difference gel electrophoresis and tandem mass spectrometry were used to profile immunodepleted serum samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated cholangitis and healthy volunteers. The serum levels of one candidate protein, leucine-rich α-2-glycoprotein (LRG1), were verified in individual samples using enzyme-linked immunosorbent assay and compared with serum levels of CA19-9, bilirubin, interleukin-6 (IL-6) and other inflammatory markers. RESULTS: We report increased LRG1, CA19-9 and IL-6 levels in serum from patients with BTC compared with benign disease and healthy controls. Immunohistochemical analysis also demonstrated increased staining of LRG1 in BTC compared with cholangiocytes in benign biliary disease. The combination of receiver operating characteristic (ROC) curves for LRG1, CA19-9 and IL-6 demonstrated an area under the ROC curve of 0.98. In addition, raised LRG1 and CA19-9 were found to be independent predictors of BTC in the presence of elevated bilirubin, C-reactive protein and alkaline phosphatase. CONCLUSION: These results suggest LRG1, CA19-9 and IL-6 as useful markers for the diagnosis of BTC, particularly in high-risk patients with PSC.

Review article: surgical, neo-adjuvant and adjuvant management strategies in biliary tract cancer.

BACKGROUND: The majority of patients with cholangiocarcinoma present with advanced, irresectable tumours associated with poor prognosis. The incidence and mortality rates associated with cholangiocarcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection and treatment of residual lesions. AIM: To review the current evidence base for surgical, adjuvant and neo-adjuvant techniques in the management of cholangiocarcinoma. METHODS: A search strategy incorporating PubMed/Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation, in various combinations, was employed. RESULTS: Data on neo-adjuvant and adjuvant techniques remain limited, and much of the literature concerns palliation of inoperable disease. The only opportunity for long-term survival remains surgical resection with negative pathological margins or liver transplantation, both of which remain possible in only a minority of selected patients. Neo-adjuvant and adjuvant techniques currently provide only limited success in improving survival. CONCLUSIONS: The development of novel strategies and treatment techniques is crucial. However, the shortage of randomised controlled trials is compounded by the low feasibility of conducting adequately powered trials in liver surgery, due to the large sample sizes that are required.

Development of a questionnaire (EORTC module) to measure quality of life in patients with cholangiocarcinoma and gallbladder cancer, the EORTC QLQ-BIL21.

BACKGROUND: Quality of life measurement in cholangiocarcinoma and gallbladder cancer involves the assessment of patient-reported issues related to the symptoms, disease and treatment of these tumours. This study describes the development of the disease-specific quality of life (QoL) questionnaire for patients with cholangiocarcinoma and gallbladder cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30 core cancer questionnaire. METHODS: Phases 1-3 of the guidelines for module development published by the EORTC were followed, with adaptations for incorporation of questions from existing modules. RESULTS: A total of 47 QoL issues (questions) were identified; 44 questions from the two related validated questionnaires, the EORTC QLQ-PAN26 (pancreatic module) and the EORTC QLQ-LMC21 (liver metastases module), two from the Functional Assessment of Cancer Therapy hepatobiliary module questionnaire in the literature search and one from healthcare professional interviews. Following phase 1 and 2 interviews with patients (n=101) and health care professionals (n=6), a 23-question provisional questionnaire was formulated. There were five questions from PAN26, 15 from LMC21 and three extra questions. In phase 3, the provisional item list was pre-tested in 52 patients in four languages and this resulted in a 21-item module. CONCLUSION: This is the only disease-specific QoL questionnaire for patients with cholangiocarcinoma and gallbladder cancer, and initial assessments show it to be accurate and acceptable to patients in reflecting QoL in these diseases.

Drainage and bypass procedures for palliation of malignant diseases of the upper gastrointestinal tract.

Malignant diseases of the upper gastrointestinal tract are common and often diagnosed at a point when the opportunity for curative surgical resection has passed. Symptoms of luminal obstruction include nausea, vomiting, weight loss, pain, pruritus and jaundice. The median survival of patients who cannot be cured surgically is extremely short, with a duration of only a few months. Effective palliative techniques with a low morbidity and associated mortality are required. The length of hospital stay, rapid recovery and reduction in recurrent symptoms are important factors for patients and doctors to consider when planning treatment. Traditionally, surgical techniques were used, but in the last 20 years the availability of both endoscopic and interventional radiological procedures has increased. Furthermore, advances in technology such as the development of self-expanding metal stents and covered stent designs have provided more therapeutic options for the endoscopist and radiologist. Here we discuss the available treatments for the palliation of gastric outlet and biliary tract obstruction and the evidence for the respective approaches.