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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

Cross-sectional imaging of gastric neoplasia.

The detection of gastric neoplasia has traditionally been limited to barium examination and direct visualization at endoscopy. The rapid development of techniques such as multidetector computed tomography (MDCT) and endoscopic ultrasound (EUS) has resulted in more accurate diagnosis and staging of gastric neoplasia. In this review we describe the normal anatomy of the stomach with multi-modality illustrations and review the imaging manifestations of gastric neoplasia, including adenocarcinoma, lymphoma, neuroendocrine and gastro-intestinal stromal tumours. We also describe the optimal techniques for up-to-date and accurate gastric imaging, outlining the role of MDCT and EUS.

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer.

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates.

Biliary brush cytology is the standard method of sampling a biliary stricture but has a low sensitivity for the detection of malignancy. We have previously shown that minichromosome maintenance (MCM) replication proteins (Mcm2-7) are markers of dysplasia and have utilised these novel biomarkers of growth for the diagnosis of cervical and bladder cancer. We aimed to determine if MCM proteins are dysregulated in malignant pancreaticobiliary disease and if levels in bile are a sensitive marker of malignancy. In 30 tissue specimens from patients with malignant/benign biliary strictures, we studied Mcm2 and -5 expression by immunohistochemistry. Bile samples were also collected prospectively at endoscopic retrograde cholangiopancreatography from 102 consecutive patients with biliary strictures of established (n=42) or indeterminate aetiology (n=60). Patients with indeterminate strictures also underwent brush cytology as part of standard practice. Bile sediment Mcm5 levels were analysed using an automated immunofluorometric assay. In benign biliary strictures, Mcm2 and -5 protein expression was confined to the basal epithelial proliferative compartment - in contrast to malignant strictures where expression was seen in all tissue layers. The percentage of nuclei positive for Mcm2 was higher in malignant tissue (median 76.5%, range 42-92%) than in benign tissue (median 5%, range 0-33%) (P<0.0005), with similar results for Mcm5. Minichromosome maintenance protein 5 levels in bile were significantly more sensitive than brush cytology (66 vs 20%; P=0.004) for the detection of malignancy in patients with an indeterminate stricture, with a comparable positive predictive value (97 vs 100%; P=ns). In this study, we demonstrate that Mcm5 in bile detected by a simple automated test is a more sensitive indicator of pancreaticobiliary malignancy than routine brush cytology.

EUS-guided tissue sampling: comparison of "dual sampling" (Trucut biopsy plus FNA) with "sequential sampling" (Trucut biopsy and then FNA as required).

BACKGROUND AND STUDY AIMS: Both endoscopic ultrasound- (EUS-) guided tissue sampling techniques, fine-needle aspiration (FNA) and Trucut biopsy, have advantages and limitations. The aim of this study was to develop a strategy of combining these two EUS-guided sampling techniques in order to maximize the diagnostic accuracy and minimize duplication. PATIENTS AND METHODS: In this multicenter study we performed "dual sampling" (i. e. with both FNA and Trucut biopsy) in 95 patients during phase 1 of the study and "sequential sampling" (i. e. performing FNA only when Trucut biopsy tissue cores were macroscopically inadequate) in 72 patients during phase 2. RESULTS: During the study period, 167/401 patients referred for EUS-guided sampling were eligible for the study; only solid lesions were included. In 143/167 patients (86 %), sampling was performed via the transesophageal or transgastric routes. When the dual sampling strategy was used, an accurate diagnosis was achieved in 78/95 patients by FNA, compared with 85/95 by Trucut biopsy ( P = 0.21). The combined accuracy of the dual sampling strategy was higher than FNA alone (88/95 vs. 78/95, P = 0.048), but was not significantly higher than Trucut biopsy alone (88/95 vs. 85/95, P = 0.61). Using the sequential sampling strategy, an accurate diagnosis was achieved in 66/72 patients (92 %) compared with 88/95 (93 %) for dual sampling ( P = 1.0), and 8/72 patients (11 %) had to undergo FNA after Trucut biopsy failed to obtain an adequate sample. One patient with mediastinal tuberculosis developed a cold abscess following Trucut biopsy. CONCLUSION: A sequential sampling strategy, in which EUS-guided Trucut biopsy is attempted first, and FNA performed only when Trucut biopsy fails to obtain a macroscopically adequate sample, achieves a diagnostic accuracy of 92 %, with 11 % of patients requiring both sampling procedures.

Systematic review: sphincter of Oddi dysfunction--non-invasive diagnostic methods and long-term outcome after endoscopic sphincterotomy.

BACKGROUND: Sphincter of Oddi dysfunction is a benign, functional gastrointestinal disorder for which invasive endoscopic therapy with potential complications is often recommended. AIMS: To review the available evidence regarding the diagnostic accuracy of non-invasive methods that have been used to establish the diagnosis and to estimate the long-term outcome after endoscopic sphincterotomy. METHODS: A systematic review of English language articles and abstracts containing relevant terms was performed. RESULTS: Non-invasive diagnostic methods are limited by their low sensitivity and specificity, especially in patients with Type III sphincter of Oddi dysfunction. Secretin-stimulated magnetic resonance cholangiopancreatography appears to be useful in excluding other potential causes of symptoms, and morphine-provocated hepatobiliary scintigraphy also warrants further study. Approximately 85%, 69% and 37%, of patients with biliary Types I, II and III sphincter of Oddi dysfunction, respectively, experience sustained benefit after endoscopic sphincterotomy. In pancreatic sphincter of Oddi dysfunction, approximately 75% of patients report symptomatic improvement after pancreatic sphincterotomy, but the studies have been non-controlled and heterogeneous. CONCLUSIONS: Patients with suspected sphincter of Oddi dysfunction, particularly those with biliary Type III, should be carefully evaluated before considering sphincter of Oddi manometry and endoscopic sphincterotomy. Further controlled trials are needed to justify the invasive management of patients with biliary Type III and pancreatic sphincter of Oddi dysfunction.

Biochemical markers of acute pancreatitis.

Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in "idiopathic" acute recurrent pancreatitis.