Postoperative pancreatic fistula (POPF) remains the major cause of morbidity after pancreatic resection, affecting up to 41% of cases. With the recent development of a consensus definition of POPF, there has been a large number of reports examining various risk factors, prediction models, and mitigation strategies for this costly complication. Despite these strategies, the rates of POPF have not significantly diminished. Here, we review the literature and evidence regarding both traditional and emerging concepts in POPF prediction, prevention, and management. In particular, we review the evidence for the association between postoperative pancreatitis and POPF, and present a novel proposed mechanism for the development of POPF.

Pancreatic cancer has poor survival despite modern-day advances in its management. At present, there are no available biomarkers that can predict chemotherapy response or help inform prognosis. In more recent years, there has been increased interest in potential inflammatory biomarkers, with studies revealing a worse prognosis of patients with a higher neutrophil-to-lymphocyte ratio in a range of tumour types. Our aim was to assess the role of three inflammatory biomarkers in peripheral blood in predicting chemotherapy response in patients with earlier disease treated with neoadjuvant chemotherapy and as a prognostic marker in all patients that underwent surgery for pancreatic cancer. Using retrospective records, we discovered that patients with a higher neutrophil-to-lymphocyte ratio (>5) at the time of diagnosis had worse median overall survival than those with ratios ≤5 at 13 and 32.4 months (p = 0.001, HR 2.43), respectively. We were able to appreciate a correlation between a higher platelet-to-lymphocyte ratio and increased residual tumour in the histopathological specimen in patients receiving neoadjuvant chemotherapy; however, the association was weak (p = 0.03, coefficient 0.21). Due to the dynamic relationship between the immune system and pancreatic cancer, it is unsurprising that immune markers may be useful as potential biomarkers; however, larger prospective studies are needed to validate these findings.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors in the world. Currently, there are no approved targeted therapies for PDAC. Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are known to be a major driver of PDAC progression, but it was considered an undruggable target until recently. Moreover, PDAC also suffers from drug delivery issues due to the highly fibrotic tumor microenvironment. In this perspective, we provide an overview of recent developments in targeting mutant KRAS and strategies to overcome drug delivery issues (e.g., nanoparticle delivery). Overall, we propose that the antitumor effects from novel KRAS inhibitors along with strategies to overcome drug delivery issues could be a new therapeutic way forward in PDAC.

Pancreatic cancer is known to have the lowest survival outcomes among all major cancers, and unfortunately, this has only been marginally improved over last four decades. The innate characteristics of pancreatic cancer include an aggressive and fast-growing nature from powerful driver mutations, a highly defensive tumor microenvironment and the upregulation of advantageous survival pathways such as autophagy. Autophagy involves targeted degradation of proteins and organelles to provide a secondary source of cellular supplies to maintain cell growth. Elevated autophagic activity in pancreatic cancer is recognized as a major survival pathway as it provides a plethora of support for tumors by supplying vital resources, maintaining tumour survival under the stressful microenvironment and promoting other pathways involved in tumour progression and metastasis. The combination of these features is unique to pancreatic cancer and present significant resistance to chemotherapeutic strategies, thus, indicating a need for further investigation into therapies targeting this crucial pathway. This review will outline the autophagy pathway and its regulation, in addition to the genetic landscape and tumor microenvironment that contribute to pancreatic cancer severity. Moreover, this review will also discuss the mechanisms of novel therapeutic strategies that inhibit autophagy and how they could be used to suppress tumor progression.