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Biliary Microbiome Altered in Patients Undergoing Surgery After Neoadjuvant Therapy for Pancreatic Cancer

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Key Points

  • Patients who had neoadjuvant therapy were about twice as likely to have two forms of bacteria in their bile: Enterococci (22% vs 45%) and Klebsiella (19% vs 37%).
  • Of patients with bactobilia, resistance to cephalosporins was more common in those who received neoadjuvant therapy (76 vs 60%).
  • Despite these differences, no difference in the incidence of surgical site infections or clinically relevant postoperative pancreatic fistulas occurred between the two study groups.

The biliary microbiome was altered in patients who received neoadjuvant therapy prior to undergoing surgery for pancreatic cancer, according to a study published by Goel et al in HPBAdditionally, more bacteria in patients who underwent surgery after neoadjuvant therapy were resistant to cephalosporins, a form of broad-spectrum antibiotics, compared with patients who were treated with surgery alone.

“This study shows that proper antibiotic prophylaxis in this patient population is important,” said coauthor Sanjay Reddy, MD, FACS, Assistant Professor in the Department of Surgical Oncology at Fox Chase Cancer Center. “Right now, the reflex is often to just use antibiotic ‘X’ as prophylaxis, but the study shows that is it important to know which antibiotics work and which do not.”

According to Dr. Reddy, pancreatic tumors will often compress the bile ducts, obstructing bile from flowing freely. Undergoing a biliary stent procedure can alleviate the compression, allowing bile to properly drain.

“We hypothesized that the environment the pancreatic cancer sits in—its microbiome—is affected by preoperative stenting and exposure to antibiotics,” said Dr. Reddy. “Manipulation of the biliary tract through stenting—more commonly used with neoadjuvant treatment—alters the biome by allowing intestinal bacteria to enter the biliary system. Exposure to multiple courses of antibiotics leads to more resistant organism in the biliary flora.”

Study Methods

To explore this issue further, researchers studied patients who underwent pancreatoduodenectomy from 2007 to 2017 at Fox Chase. Eighty-three patients received neoadjuvant therapy (either chemotherapy or chemoradiation) and 89 underwent surgery alone. All patients had operative bile samples taken and analyzed.

Findings

Patients who had neoadjuvant therapy were about twice as likely to have two forms of bacteria in their bile: Enterococci (22% vs 45%) and Klebsiella (19% vs 37%). Of patients with bactobilia, resistance to cephalosporins was more common in those who received neoadjuvant therapy (76 vs 60%, P < .05).

Despite these differences, no difference in the incidence of surgical site infections or clinically relevant postoperative pancreatic fistulas occurred between the two study groups.

“This showed that the biliary microbiome is altered with neoadjuvant treatments and biliary stenting,” said Dr. Reddy. “Prophylactic antibiotics given at the time of surgery should be geared towards covering a broad spectrum of organisms to provide adequate coverage.”

According to Dr. Reddy, it is currently unknown whether the length of exposure to the stent or type of stent—plastic vs metal—may play a role. “The benefit of metal stents [is] longevity…” he said. “Plastic stents, on the other hand, have to be replaced more frequently, and can have more issues with occlusion.”

In the future, Dr. Reddy plans to study the biliary microbiome in relation to stent type and duration, and whether the stents that are changed more frequently are harboring more difficult-to-treat bacteria.

Disclosure: For full disclosures of the study authors, visit hpbonline.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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