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

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

Novel biomarkers and endoscopic techniques for diagnosing pancreaticobiliary malignancy

The UK incidence of pancreatic ductal adenocarcinoma is 9 per 100,000 population, and biliary tract cancer occurs at a rate of 1-2 per 100,000. The incidence of both cancers is increasing annually and these tumours continue to be diagnosed late and at an advanced stage, limiting options for curative treatment. Population-based screening programmes do not exist for these cancers, and diagnosis currently is dependent on symptom recognition, but often symptoms are not present until the disease is advanced. Recently, a number of promising blood and urine biomarkers have been described for pancreaticobiliary malignancy and are summarised in this review. Novel endoscopic techniques such as single-operator cholangioscopy and confocal endomicroscopy have been used in some centres to enhance standard endoscopic diagnostic techniques and are also evaluated in this review

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology

Background: Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2–7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples. methods: Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture. Collected samples were frozen at −80 °C. The supernatant was washed and lysed cells incubated with HRP-labelled anti-MCM5 mouse monoclonal antibody. Test positivity was determined by optical density absorbance. Patients underwent biliary brush cytology or additional investigations as per clinical routine. results: Ninety-seven patients were included in the study; 50 had malignant strictures. Median age was 65 years (range 21–94) and 51 were male. Compared with final diagnosis the MCM5 assay had a sensitivity for malignancy of 65.4% compared with 25.0% for cytology. In the 72 patients with paired MCM5 assay and biliary brush cytology, MCM5 demonstrated an improved sensitivity (55.6% vs 25.0%; P=0.0002) for the detection of malignancy. conclusions: Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology

Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint.

PURPOSE: Cdc7 is a serine/threonine kinase which is responsible for the 'firing' of replication origins leading to initiation of DNA replication. Inhibition or depletion of Cdc7 in normal cells triggers a DNA origin activation checkpoint causing a reversible G1 arrest. Here we investigate Cdc7 as a novel therapeutic target in pancreatic cancer. EXPERIMENTAL DESIGN: Cdc7 target validation was performed by immunoexpression profiling in a cohort of 73 patients with pancreatic adenocarcinoma including 24 controls. Secondly Cdc7 kinase was targeted in Capan-1 and PANC-1 pancreatic cancer cell line models using either an siRNA against Cdc7 or alternatively a small molecule inhibitor (SMI) of Cdc7 (PHA-767491). RESULTS: Cdc7 was significantly overexpressed in pancreatic adenocarcinoma compared to benign pancreatic tissue (median LI 34.3% vs. 1.3%; P<0.0001). Cdc7 knockdown using siRNA in Capan-1 and PANC-1 cells resulted in marked apoptotic cell death when compared with control cells. A prominent sub-G1 peak was seen on flow cytometry (sub-G1 51% vs. 3% and 45% vs. 0.7% in Capan-1 and PANC-1 cells, respectively). Annexin V labelling confirmed apoptosis in 64% vs. 11% and 75% vs. 8%, respectively. Western blotting showed cleavage of PARP-1 and caspase-3 and presence of γH2A.X. TUNEL assay showed strong staining in treated cells. These results were mirrored following Cdc7 kinase inhibition with PHA-767491. CONCLUSIONS: Our findings show that Cdc7 is a potent anti-cancer target in pancreatic adenocarcinoma and that Cdc7 immunoexpression levels might be used as a companion diagnostic to predict response to therapeutic siRNAs or SMIs directed against this kinase

Effect of concrete slats, three mat types and out-wintering pads on performance and welfare of finishing beef steers

peer-reviewedBackground The objective was to investigate the effect of placing mats on concrete slatted floors on performance, behaviour, hoof condition, dirt scores, physiological and immunological variables of beef steers, and to compare responses with animals on out-wintering pads. Continental crossbred beef steers [n = 360; mean (±SD) initial live weight 539 kg (42.2)] were blocked by breed and live weight and randomly assigned to one of five treatments; (1) Concrete slats alone, (2) Mat 1 (Natural Rubber structure) (Durapak Rubber Products), (3) Mat 2 (Natural rubber structure) (EasyFix), (4) Mat 3 (modified ethylene vinyl acetate (EVA) foam structure) and (5) Out-wintering pads (OWP’s). Results Animals on the OWPs had a greater (P  0.05) as the other treatments. Animals on the OWPs had reduced lying percentage time compared with all the other treatments. Dry matter (DM) intake was greater for animals on the OWPs compared with all the other treatments. Carcass weight, kill out proportion, carcass fat score, carcass composition score, FCR and physiological responses were similar (P > 0.05) among treatments. No incidence of laminitis was observed among treatments. The number of hoof lesions was greater on all mat types (P < 0.05) compared with concrete slats and OWP treatments. Dirt scores were greater (P < 0.05) for animals on OWPs when measured on days 42, 84, 105, 126 and 150 compared with animals on slats. Conclusions Under the conditions adopted for the present study, there was no evidence to suggest that animals housed on bare concrete slats were disadvantaged in respect of animal welfare compared with animals housed on other floor types. It is concluded that the welfare of steers was not adversely affected by slats compared with different mat types or OWPs

Sociodemographic Trends in the Incidence of Pancreatic and Biliary Tract Cancer in UK Primary Care

The UK incidence of pancreatic ductal adenocarcinoma (PDAC) is approximately 9/100,000 population compared with 1-2/100,000 for biliary tract cancer (BTC). This study explores the incidence of these cancers over time and the influence of socio-demographic and geographic factors in a UK primary care cohort

Systematic review of novel ablative methods in locally advanced pancreatic cancer

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Current standard therapy is limited to chemotherapy or chemoradiotherapy. Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed. Thermal and laser based ablative techniques are widely used in many solid organ malignancies. Initial studies in the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high quality imaging such as computed tomography and intraoperative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety. We conducted a systematic review of the literature up to October 2013. Initial studies suggest that ablative therapies may confer an additional survival benefit over best supportive care but randomised studies are required to validate these findings

Endoscopic versus percutaneous drainage of symptomatic pancreatic fluid collections: a 14-year experience from a tertiary hepatobiliary centre

INTRODUCTION: Endoscopic transmural drainage (ED) or percutaneous drainage (PD) has mostly replaced surgery for the initial management of patients with symptomatic pancreatic fluid collections (PFCs). This study aimed to compare outcomes for patients undergoing ED or PD of symptomatic PFCs. METHODS: Between January 2000 and December 2013, all patients who required PD or ED of a PFC were included. Rates of treatment success, length of hospital stay, adverse events, re-interventions and length of follow-up were recorded retrospectively in all cases. RESULTS: In total, 164 patients were included in the study; 109 patients underwent ED; and 55 had PD alone. During the 14-year study period, the incidence of ED increased and PD fell. In the 109 patients who were managed by ED, treatment success was considerably higher than in those managed by PD (70 vs. 31 %). Rates of procedural adverse events were higher in the ED cohort compared to the PD group (10 vs. 1 %), but patients managed by ED required fewer interventions (median of 1.8 vs. 3.3) had lower rates of residual collections (21 vs. 67 %) and need for surgical intervention (4 vs. 11 %). In the ED group, treatment success was similar for walled-off pancreatic necrosis (WOPN) and pseudocysts (67 vs. 72 %, P = 0.77). There were no procedure-related deaths. CONCLUSION: Compared with PD, ED of symptomatic PFCs was associated with higher rates of treatment success, lower rates of re-intervention, including surgery and shorter lengths of hospital stay. Outcomes in WOPN were comparable to those in patients with pseudocysts