Challenges in diagnosis of pancreatic cancer

Pancreatic cancer is a growing source of cancer related death, yet has poor survival rates which have not improved in the last few decades. Its high mortality rate is attributed to pancreatic cancer biology, difficulty in early diagnosis and the lack of standardised international guidelines in assessing suspicious pancreatic masses. This review aims to provide an update in the current state of play in pancreatic cancer diagnosis and to evaluate the benefits and limitations of available diagnostic technology. The main modalities discussed are imaging with computed tomography, magnetic resonance imaging, endoscopic ultrasound and positron emission tomography and tissue acquisition with fine needle aspiration. We also review the improvements in the techniques used for tissue acquisition and the opportunity for personalised cancer medicine. Screening of high risk individuals, promising biomarkers and common mimickers of pancreatic cancer are also explored, as well as suggestions for future research directions to allow for earlier detection of pancreatic cancer. Timely and accurate diagnosis of pancreatic cancer can lead to improvements in the current poor outcome of this disease.

Macrophage inhibitory cytokine-1/growth differentiation factor-15 in premalignant and neoplastic tumours in a high-risk pancreatic cancer cohort

BACKGROUND Pancreatic cancer(PC)is a leading cause of cancer related mortality worldwide,with poor survival due to late diagnosis.Currently,biomarkers have limited use in early diagnosis of PC.Macrophage inhibitory cytokine-1 or growth differentiation factor-15(MIC-1/GDF15)has been implicated as a potential serum biomarker in PC and other malignancies.AIM To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program.METHODS A feasibility prospective single centre cohort study was performed.Participants recruited for yearly surveillance with endoscopic ultrasound(EUS)had serial fasting blood samples collected before EUS for MIC-1/GDF15,C-reactive protein and carbohydrate antigen 19-9.Patients were stratified into five groups based on EUS findings:Normal;pancreatic cysts,branch-duct intraductal papillary mucinous neoplasm;diffuse non-specific abnormalities;and neoplastic tumours.MIC-1/GDF15 serum levels were quantified using ELISA.Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging(MRI)or computed tomography.RESULTS One hundred twenty participants were prospectively recruited from 2011-2018.Forty-seven participants(39.2%)had an abnormal EUS and five participants(4.2%)were diagnosed with neoplastic tumours,three by EUS(two pancreatic and one liver)and two by MRI/computed tomography(breast cancer,bladder cancer),which were performed for follow up of abnormal EUS.Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis[area under curve(AUC)=0.814,P=0.023].Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm(AUC=0.644)and neoplastic tumours noted on EUS(AUC=0.793),however this was not significant(P=0.188 and 0.081 respectively).Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS(P=0.213).Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours(Median=1039.6,interquartile range=727.0-1977.7)compared to those diagnosed with a benign lesion(Median=570.1,interquartile range=460.7-865.2)on EUS and MRI(P=0.012).CONCLUSION In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC.Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15.Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.

Review of screening for pancreatic cancer in high risk individuals

Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival.Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation.Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer.Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups.This article reviews high-risk groups,screening methods,and current screening programs and their results.

Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket?

Pancreatic cancer(PC)is a leading cause of cancer related mortality on a global scale.The disease itself is associated with a dismal prognosis,partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis.To combat this,there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma.Currently,serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker.In the search for a biomarker that is both sensitive and specific for the diagnosis of PC,there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC.Currently,promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA(miRNA)in serum and circulating tumour cells.Both these modalities,although in their infancy and yet to be widely accepted into routine clinical practice,possess merit in the early detection of PC.We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC(serum,urinary,salivary,faecal,pancreatic juice and biliary fluid).

Clinical predictors for sessile serrated polyposis syndrome:A case control study

AIM To compared individuals with serrated polyposis syndrome (SPS) to those with sessile serrated adenoma (SSA) and adenomas in the setting of endoscopists with high adenoma detection rates at a secondary and tertiary academic centre.METHODS Retrospectively we collated the clinical,endoscopic and histological features of all patients with SPS at St Vincent's public and private hospital in the last 3 years.Patients were identified by searching through 2 pathology databases.Variables explored included smoking status,symptoms,and family history of concurrent colorectal cancer,number and location of polyps.Patients with SPS were matched to two cohorts (1) patients with SSA not meeting World Health Organization (WHO) criteria for SPS over 3 years; and (2) patients with exclusively adenomas.The control cases were also matched according to gender and endoscopist.Adenoma detection rates ranged from 25% to 40%.RESULTS Forty patients with SPS were identified and matched with 40 patients in each control group.In total 15452 colonoscopies were performed over the study period which amounts to a prevalence of 1: 384 patients (0.26%) with SPS.Fourteen patients (35%) required more than 1 year to accumulate enough polyps to reach WHO criteria for SPS.The diagnosis of SPS was largely incidental and 5% SPS patients were diagnosed with colorectal cancer over 3 years.The chance of detecting a meta-synchronous adenoma was similar in those with SPS(42%) and those with SSA(55%),P = 0.49.The majority of patients(75%) meeting criteria for SPS were women.The mean age of those with SPS (45 years) was significantly lower than both cohorts with SSA(57 years) and adenomas(63 years),P = 0.01.On univariate analysis cigarette exposure,firstdegree family history of colorectal cancer and a high BMI weren't significantly more associated with SPS compared to patients with SSA or patients with adenomas.However,patients with SPS (97%) and patients with SSAs not meeting SPS criteria(98%) were significantly more likely to be Caucasian compared to patients with adenomas (79%),P = 0.01.CONCLUSION The prevalence of SPS in our study was 0.26%.The vast majority of patients diagnosed with SPS were women.As a group,they were significantly younger compared to patients with SSA not meeting WHO criteria and patients with adenomatous polyps by more than a decade.Patients with SPS were no more likely to have a first degree relative with colorectal cancer or smoking history than the other two groups.Patients with serrated polyps were more likely to be Caucasian than patients with adenomas.