This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites.

A gallbladder polyp is an elevation of the gallbladder mucosa that protrudes into the gallbladder lumen. Gallbladder polyps have an estimated prevalence in adults of between 0.3%-12.3%. However, only 5% of polyps are considered to be “true” gallbladder polyps, meaning that they are malignant or have malignant potential. The main radiological modality used for diagnosing and surveilling gallbladder polyps is transabdominal ultrasonography. However, evidence shows that other modalities such as endoscopic ultrasound may improve diagnostic accuracy. These are discussed in turn during the course of this review. Current guidelines recommend cholecystectomy for gallbladder polyps sized 10 mm and greater, although this threshold is lowered when other risk factors are identified. The evidence behind this practice is relatively low quality. This review identifies current gaps in the available evidence and highlights the necessity for further research to enable better decision making regarding which patients should undergo cholecystectomy, and/or radiological follow-up.

Serum biomarkers of iron status and risk of primary liver cancer: A systematic review and meta-analysis.

Purpose To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. Methods A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. Results In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13-3.38) but not adjusted (HR 1.70 95% CI 0.95-3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. Conclusions In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival.

Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in pancreatic ductal adenocarcinoma (PDAC). We undertook a systematic review and meta‐analysis of immune cell infiltration, measured by immunohistochemistry (IHC), as a prognostic biomarker in PDAC. All other IHC prognostic biomarkers in PDAC were also summarised. MEDLINE, EMBASE and Web of Science were searched between 1998 and 2018. Studies investigating IHC biomarkers and prognosis in PDAC were included. REMARK score and Newcastle–Ottawa scale were used for qualitative analysis. Random‐effects meta‐analyses were used to pool results, where possible. Twenty‐six articles studied immune cell infiltration IHC biomarkers and PDAC prognosis. Meta‐analysis found high infiltration with CD4 (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.51–0.83.) and CD8 (HR = 0.68, 95% CI = 0.55–0.84.) T‐lymphocytes associated with better disease‐free survival. Reduced overall survival was associated with high CD163 (HR = 1.62, 95% CI = 1.03–2.56). Infiltration of CD3, CD20, FoxP3 and CD68 cells, and PD‐L1 expression was not prognostic. In total, 708 prognostic biomarkers were identified in 1101 studies. In summary, high CD4 and CD8 infiltration are associated with better disease‐free survival in PDAC. Increased CD163 is adversely prognostic. Despite the publication of 708 IHC prognostic biomarkers in PDAC, none has been validated for clinical use. Further research should focus on reproducibility of prognostic biomarkers in PDAC in order to achieve this.