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.

Minimally invasive aortic valve surgery

Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replace- ment is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper stemotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease.