Feature

Neoadjuvant therapy may alter biliary microbiome in patients with pancreatic cancer

Sanjay S. Reddy, MD, FACS
Sanjay S. Reddy

Patients with pancreatic cancer who received neoadjuvant therapy before pancreatoduodenectomy exhibited biliary microbiome alterations, according to study results.

“This study shows that proper antibiotic prophylaxis in this patient population is important,” Sanjay S. Reddy, MD, FACS, assistant professor in the department of surgical oncology at Fox Chase Cancer Center, said in a press release. “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.”

Investigators compared data on 83 patients treated with neoadjuvant therapy before surgery for pancreatic cancer with that of 89 patients who underwent surgery alone between 2007 and 2017. Researchers analyzed bile samples from all patients.

According to study results, patients who received neoadjuvant therapy were approximately twice as likely to have Enterococci (22% vs. 45%) and Klebsiella (19% vs. 37%) in bile compared with patients who underwent surgery alone. Moreover, those treated with neoadjuvant therapy were significantly more likely to be resistant to cephalosporins than those who went directly to surgery (76% vs. 60%; P < .05).

The groups demonstrated similar incidence of surgical site infections and clinically relevant postoperative pancreatic fistulas.

HemOnc Today spoke with Reddy about the study, the clinical implications of the findings and what subsequent research may entail.

Question: What prompted this research?

Answer : The concept of the microbiome and cancer has been studied across various disease sites. My interest in this topic began with the idea of multimodality therapy with chemotherapy, radiation and surgery, and how various treatments can play a role in the microbiome of our patients. We wanted to investigate if altering the microbiome affects the cancer, complications, leak rate and wound infections.

Q: How did you conduct the study and what did you find?

A: This retrospective study included patients at our institution between 2007 and 2017. We compared one group of patients with pancreatic cancer who underwent surgery and did not undergo preoperative therapy with another group who underwent neoadjuvant therapy and then surgery. We found that patients who underwent neoadjuvant therapy were more likely to have two bacteria — Enterococci and Klebsiella — in their bile duct cultures. We also found that resistance to cephalosporins was much more common among those who underwent neoadjuvant chemotherapy. However, neoadjuvant therapy did not increase patients’ risk for infection or clinically relevant postoperative pancreatic fistula.

Q: Were you surprised by any of your findings?

A: I expected to find that if patients had their bile ducts manipulated, which they often do in the neoadjuvant population, that by stirring the pot, different organisms would be present. However, I was surprised that resistance to cephalosporins was more common in the neoadjuvant group.

Q: What are the clinical implications of your findings?

A: With pancreatic surgery, we are always concerned about wound infections, either superficial or deep, and the development of pancreatic fistulas. Tailoring antibiotics for adequate coverage is important, and we need to know what things we do that can change the flora. This study shows that choosing antibiotics wisely in the beginning is important. Treating patients with neoadjuvant therapy does not necessarily mean we are placing our patients at higher risk.

Q: Do you have plans for subsequent research on this?

A: Yes. The tough part here is understanding whether the stent involved played a role. For example, sometimes we use metal stents and other times we use plastic stents. I am curious to know if using multiple stent exchanges with plastic is better than one stent exchange if we use metal. I am also curious to see if we send off cultures at the time of stent placement, whether those organisms that grow match up with what we find in the operating room. Stay tuned. – by Jennifer Southall

Reference:

Goel N, et al. HPB (Oxford). 2019;doi:10.1016/j.hpb.2019.04.005.

For more information:

Sanjay S. Reddy, MD, FACS, can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111; email: sanjay.reddy@fccc.edu.

Disclosure: Reddy reports no relevant financial disclosures.

Sanjay S. Reddy, MD, FACS
Sanjay S. Reddy

Patients with pancreatic cancer who received neoadjuvant therapy before pancreatoduodenectomy exhibited biliary microbiome alterations, according to study results.

“This study shows that proper antibiotic prophylaxis in this patient population is important,” Sanjay S. Reddy, MD, FACS, assistant professor in the department of surgical oncology at Fox Chase Cancer Center, said in a press release. “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.”

Investigators compared data on 83 patients treated with neoadjuvant therapy before surgery for pancreatic cancer with that of 89 patients who underwent surgery alone between 2007 and 2017. Researchers analyzed bile samples from all patients.

According to study results, patients who received neoadjuvant therapy were approximately twice as likely to have Enterococci (22% vs. 45%) and Klebsiella (19% vs. 37%) in bile compared with patients who underwent surgery alone. Moreover, those treated with neoadjuvant therapy were significantly more likely to be resistant to cephalosporins than those who went directly to surgery (76% vs. 60%; P < .05).

The groups demonstrated similar incidence of surgical site infections and clinically relevant postoperative pancreatic fistulas.

HemOnc Today spoke with Reddy about the study, the clinical implications of the findings and what subsequent research may entail.

Question: What prompted this research?

Answer : The concept of the microbiome and cancer has been studied across various disease sites. My interest in this topic began with the idea of multimodality therapy with chemotherapy, radiation and surgery, and how various treatments can play a role in the microbiome of our patients. We wanted to investigate if altering the microbiome affects the cancer, complications, leak rate and wound infections.

Q: How did you conduct the study and what did you find?

A: This retrospective study included patients at our institution between 2007 and 2017. We compared one group of patients with pancreatic cancer who underwent surgery and did not undergo preoperative therapy with another group who underwent neoadjuvant therapy and then surgery. We found that patients who underwent neoadjuvant therapy were more likely to have two bacteria — Enterococci and Klebsiella — in their bile duct cultures. We also found that resistance to cephalosporins was much more common among those who underwent neoadjuvant chemotherapy. However, neoadjuvant therapy did not increase patients’ risk for infection or clinically relevant postoperative pancreatic fistula.

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Q: Were you surprised by any of your findings?

A: I expected to find that if patients had their bile ducts manipulated, which they often do in the neoadjuvant population, that by stirring the pot, different organisms would be present. However, I was surprised that resistance to cephalosporins was more common in the neoadjuvant group.

Q: What are the clinical implications of your findings?

A: With pancreatic surgery, we are always concerned about wound infections, either superficial or deep, and the development of pancreatic fistulas. Tailoring antibiotics for adequate coverage is important, and we need to know what things we do that can change the flora. This study shows that choosing antibiotics wisely in the beginning is important. Treating patients with neoadjuvant therapy does not necessarily mean we are placing our patients at higher risk.

Q: Do you have plans for subsequent research on this?

A: Yes. The tough part here is understanding whether the stent involved played a role. For example, sometimes we use metal stents and other times we use plastic stents. I am curious to know if using multiple stent exchanges with plastic is better than one stent exchange if we use metal. I am also curious to see if we send off cultures at the time of stent placement, whether those organisms that grow match up with what we find in the operating room. Stay tuned. – by Jennifer Southall

Reference:

Goel N, et al. HPB (Oxford). 2019;doi:10.1016/j.hpb.2019.04.005.

For more information:

Sanjay S. Reddy, MD, FACS, can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111; email: sanjay.reddy@fccc.edu.

Disclosure: Reddy reports no relevant financial disclosures.

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