Pancreatic Cancer: From Detection, Pathophysiology to Therapeutic Approaches

Dear Colleagues,

Pancreatic cancer continues to represent one of the most aggressive human malignancies, with early local and systemic invasions, poor response to current chemotherapy, and usual failure of the surgical resection to offer local control of the disease. The significant disease burden of pancreatic cancer is related to its increasing incidence, from 337,871 new cases in 2012 to 548,782 predicted new cases in 2030, associated with a dismal five-year overall survival of only 5%.

The scientific community invested significant human and financial resources in fundamental and clinical research to improve clinical outcomes of patients with pancreatic cancer. Despite progress in the development of surgical techniques, intensive care, chemotherapy, and radiotherapy, with better understanding of pathological molecular processes inside pancreatic ductal adenocarcinomas, significant clinical benefits are lacking. 

Significant refinements of the surgical techniques were proposed during the last decade, such as superior mesenteric artery (SMA) first approach in pancreaticoduodenectomy and antegrade pancreaticosplenectomy for body and tail tumors. The main objective of these techniques is an anatomically diven dissection, in the embryological planes, with central vascular ligation of the corresponding arteries. The SMA first approach pancreaticoduodenectomy seems to be associated with better postoperative outcomes, such as blood loss, transfusions requirements, pancreatic fistula and delayed gastric emptying, and better long-term oncological outcomes (local and metastatic recurrence rate).

A better understanding of the surgical anatomy of the pancreas resulted in development of the mesopancreas and first jejunal trunk concepts. We proposed the term ‘first jejunopancreatic vein,’ which is concordant with the current principles of radical pancreatic head resection. The mesopancreas, or the retroportal lamina, although appealing, proved to be an anatomically incorrect term, different from the total mesorectum and complete mesocolic excision principles.

Neoadjuvant therapy is increasingly used in clinical practice, not only to convert to resection locally advanced or borderline resectable cases, but also to improve outcomes in resectable pancreatic cancer. Although FOLFIRINOX is the most frequently used chemotherapeutic regimen, the role of chemoradiation therapy or other antineoplastic agents (e.g., gemcitabine-based protocols) remains to be defined.

Ablative therapies, in the form of thermal (radiofrequency, microwave or high intensity focused ultrasound ablation) and non-thermal methods (irreversible electroporation or photodynamic therapy), are proposed to improve local control for patients with locally advanced disease. Although these methods are widely used in different solid organ cancers, in pancreatic malignancies they are associated with significant complications which prevented their wide adoption.

MicroRNAs are small fragments of 19-25 nucleotides which form single-stranded noncoding RNA, and represent one of the most ample gene regulatory molecules. miR-21, miR23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, miR-1301 represent promising biomarkers for diagnosis and prognosis of patients with pancreatic cancer.

The epithelial to mesenchymal transition is a key step for systemic invasion of pancreatic cancer, being associated with characteristics of cancer stem cells and resistance to standard chemotherapy. Nowadays, a significant number of studies are investigating the benefits of targeting epithelial to mesenchymal transition in patients with pancreatic cancer, through hedgehog signaling inhibition, Gamma-secretase/Notch signaling pathway inhibition, Wnt signaling blocking, or anti cancer stem cells therapies.

Immunotherapy is a very promising field for tumors with high invasiveness, and targets the heterogeneous pancreatic ductal adenocarcinoma immunosuppressive microenvironment. Currently many ongoing trials are available, but clear evidence is lacking. 

In conclusion, the area of pancreatic oncology is facing dramatic changes and opportunities, with many promises for our patients but few certainties.

Dr. Ionut Negoi
Guest Editor

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• pancreatic cancer
• pancreatic ductal adenocarcinoma
• pancreatectomy
• translational research
• surgical technique