The Microbiome of Pancreatic Cancer: "PANDEMIC" Study

Overview

Microbiome in patients affected by pancreatic ductal adenocarcinoma may present specific and identifiable patterns. These variations could affect the surgical outcome and increase the risk of life-threatening infections supported by multidrug-resistant bacteria. The identification of microbial signatures with tumor specificity may have a potential role in postoperative risk stratification. Variation of pancreatic, intestinal or bile microbiome and their relationship can be investigated and measured as promising tools in order to predict and overcome the clinical and infectious burden imposed by MDR infections. The prospect of a potential role for probiotics to promote competition against the pathogens and to improve the gastrointestinal barrier integrity has also been raised. Moreover, if the bacterial composition in human PDAC was confirmed to be distinct from that of the normal pancreas, microbiome variation could be used as a potential biomarker, to assess the potential for malignancy in precursor neoplastic lesions. However, we believe that a preliminary and explorative study is necessary. The study aims to outline the pancreatic microbiome of patients who undergo upfront PD for resectable PDAC and to characterize the possible association between bacterial composition and the occurrence of post-operative complications, particularly POPF and IC.

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.