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Biliary microbiome altered after neoadjuvant therapy for pancreatic cancer

The biliary microbiome – the collection of bacteria present in the bile ducts – was altered in patients who received neoadjuvant therapy prior to undergoing surgery for pancreatic cancer, according to new research published in The Official Journal of the International Hepato Pancreato Biliary Association (HPB). 

Additionally, 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 study researcher Sanjay Reddy, MD, FACS, assistant professor of the Department of Surgical Oncology at Fox Chase. “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 Reddy, pancreatic tumours 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 hypothesised that the environment the pancreatic cancer sits in – its microbiome – is affected by preoperative stenting and exposure to antibiotics,” Reddy said. “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.”

To explore this issue further, Reddy and colleagues studied patients who underwent pancreatoduodenectomy from 2007 to 2017 at Fox Chase.

Eighty-three patients received neoadjuvant therapy – chemotherapy or chemoradiation – and 89 underwent surgery alone.

All patients had operative bile samples taken and analysed.

Patients who had neoadjuvant therapy were about twice as likely to have two forms of bacteria in their bile: Enterococci (22 percent vs. 45 percent) and Klebsiella (19 percent vs. 37 percent).

In addition, patients treated with neoadjuvant therapy were significantly more likely to have resistance to cephalosporins compared with patients who had surgery alone.

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," Reddy said. “Prophylactic antibiotics given at the time of surgery should be geared towards covering a broad spectrum of organisms to provide adequate coverage.

According to Reddy, it is currently unknown whether the length of exposure to the stent or what type of stent – plastic versus metal – might play a role.

“The benefit of metal stents are longevity, with those stents lasting for months,” Reddy said. “Plastic stents on the other hand have to be replaced more frequently, and can have more issues with occlusion.”

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

Source: Fox Chase Cancer Center

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