The Microbiome of Pancreatic Cancer: "PANDEMIC" Study

Pancreatic cancer is predicted to become the second leading cause of cancer-related death in the western world by 2030. Patients still have a poor prognosis, and a complete surgical resection provides the only potential for long-term cure of pancreatic ductal adenocarcinoma (PDAC) with a 5-year survival of only around 20%. In addition, despite all the advances and technical modifications developed during this past decade, pancreatic surgery is still hampered by considerable postoperative morbidity. Postoperative pancreatic fistula (POPF), with a range of incidence between 3-45%, and the infectious complications (IC) that occur in nearly one-third of the patients are still the more frequent and dreadful complications after pancreatic resection. Moreover, in patients submitted to pancreaticoduodenectomy (PD), the constantly growing presence of multidrug-resistant (MDR) bacteria increases the morbidity and mortality rate. Those complications may also limit access to adjuvant chemotherapy and result in higher costs and longer hospitalization. The high clinical burden of pancreatic surgery, associated with the overall poor outcome of PDAC and worldwide diffusion of antibiotic resistance, suggest the urgent need to enhance our knowledge on new and modifiable risk factors able to affect the surgical, the infectious and the oncological outcomes. The alteration of the microbiome recently emerged as a contributor to oncogenesis, as a risk factor for postoperative morbidity in many intestinal tract malignancies and as one of the leading causes of colonization by resistant pathogenic bacteria. Recent evidence suggests that the pancreas also harbors its microbiome and in PDAC this is markedly more abundant and with different patterns compared to a normal pancreas in both mice and humans. However, the intestinal and PDAC microbiome have never been compared in humans. Alteration of the microbiome induces an adaptive immune suppression and promotes an inflammatory status. Growing literature evidence shows that the microbiome accounts for local and systemic microenvironment changes. These alterations, characterized by immune suppression and selection of potentially pathogenic bacteria, may lead both to adverse outcomes after surgical treatment and to the overgrowth of multidrug-resistant flora. Nevertheless, the etiologic relationship between intrapancreatic microbiota and postoperative complications in PDAC patients subjected to surgery has not yet been described.