Drug Reduces Risk of Serious Pancreatic Surgery Complication

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Pictured: Peter Allen

Surgical oncologist Peter Allen

Pancreatic surgery to treat cancer and other conditions is a difficult operation that carries significant risks, both during the procedure and while the patient recovers. Up to half of patients develop serious complications and 2 to 4 percent do not survive the procedure — one of the highest mortality rates for any operation.

One common complication is leakage of fluid from the pancreas after the surgery, often in large amounts that can cause an abscess and lead to infection and sepsis. This leakage doubles the risk of death and results in longer hospital stays while the fluid is drained. Many patients even have to be readmitted to alleviate this grave complication.

Now Memorial Sloan Kettering clinical researchers have shown that a new drug could dramatically reduce the rate of leakage. Patients receiving the drug, pasireotide, in a phase 3 clinical trial had their rate of serious complication due to leakage cut in half, and significantly fewer had to be readmitted to the hospital.

“This could be a major advance that will change the practice of pancreatic surgery, given the complications that still exist,” says surgical oncologist Peter Allen, Associate Director of the David M. Rubenstein Center for Pancreatic Cancer Research, who led the study. “Pancreatic leak is the Achilles’ heel of this operation, and one of the few remaining difficult complications of any surgery.”

Results of the trial were recently published in the New England Journal of Medicine.

Blocking Leakage at the Secretion Source

Pasireotide appears to prevent leakage by binding to receptors in pancreatic cells, blocking the secretion of digestive enzymes. Normally, Dr. Allen explains, these secretions go into the intestine to break down food, but when they leak into the abdominal cavity during or after surgery, they cause serious problems. This abnormal conduit between pancreas and abdominal cavity is called a pancreatic fistula.

“The pancreas can secrete up to a liter of fluid a day, so when that’s leaking into your abdominal cavity, it can build up very fast,” he says. “We have put to drains in to remove the fluid, sometimes through multiple invasive procedures, and it can be months before the fistula will heal.”

Previous studies in the United States and Europe had tried blocking pancreatic secretion with a drug called octreotide, with mixed results. Octreotide does not seem to bind effectively with critical receptors in the pancreas that control secretion, and the drug does not stay active long enough.

Pasireotide, a newer version of this class of drug, was shown in laboratory and animal studies to be superior both in binding and in staying active longer. Manufactured by Novartis, it was already approved by the Food and Drug Administration in 2012 for the treatment of Cushing’s disease, a condition in which pituitary tumors cause the adrenal gland to secrete too much cortisol.

Because of this promise, Dr. Allen and colleagues designed a clinical trial to test whether pasireotide could block pancreatic secretions and prevent leakage. They randomly assigned 300 Memorial Sloan Kettering patients to receive either pasireotide or a placebo, injected twice daily beginning the morning of the surgery and continuing for seven days. The study was double-blinded, meaning that neither patient nor medical staff knew who received the drug.

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Striking Outcome

Results suggested pasireotide is effective at blocking secretion and reducing complications. Of the 300 patients in the study, the researchers focused on the 45 who had pancreatic leakage, and within this group noted whose leakage was severe enough to require insertion of a drain. Patients receiving the drug required this intervention at a lower rate (9 percent) than those who received the placebo (21 percent). Those receiving the drug were also less likely to need hospital readmission. The pasireotide group had a readmission rate of 17 percent compared with a rate of 29 percent for the placebo group.

“Avoiding readmission is going to significantly reduce cost of care for any patient, in addition to improving quality of life,” Dr. Allen explains. “I’ve already had innumerable surgeons from around the country contacting me [who are] very interested in the effect of this drug and wondering when they will be able to give it to their patients.”

Dr. Allen says that he hopes pasireotide will be eligible for administration outside a clinical trial soon, although this depends partly on the FDA approval process for use in pancreatic surgery. “The placebo and the double-blinding lend a lot of strength to the study and make us feel very confident in the validity of the results,” he says.

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Comments

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Always great to hear these findings, as the Pancreas is very difficult to treat, given the location in the body. Have been a patient of Dr. Allen for several years, diagnosed with precancerous lesions, that have been stable for sometime. It's a "watch & wait" situation with a slim chance of becoming malignant. God Bless the wonderful work you do at MSKCC. June Fay

After being diagnosed With a rare Adrenal Tumor in 2011 ,I was fortunate to be referred to Dr. Allen, He is calm , confident , experienced and very knowledgeable. At the time I had no idea how prominent he was.
My surgery went great , no complications. I owe my life to Dr. Allen and his amazing staff. I've been cancer free and was truly blessed. Michael Fasano

My dad just got a major surgery .and there has been several complicarion.
His had several opening in the past 2 week .fever and infection are happenning.
To where i get scared on a daily basis...would like to take him where the best expierience doctors for pancriatic cancer .please what should i do for the best of my father..they are doing all they can .but they have drawn to this is the last thing they can do..
Look forward for the right expert decisión. And a piece of mind confort
We are in florida..

Michelle, thank you for reaching out. If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment.

As you mentioned that you are in Florida, you might contact the Moffit Cancer Center in Tampa, which is an NCI-Designated Cancer Center:

http://www.cancer.gov/researchandfunding/extramural/cancercenters/find-…

For questions about pancreatic cancer treatment, you also can call the National Cancer Institute’s Cancer Information Service at 800-4CANCER (800-422-6237). To learn more about the CIS, including Live Chat help and how to send them an email message, go to http://www.cancer.gov/aboutnci/cis/page3.

42 year old brother in Australia just diagnosed with pancreatic cancer. Would like his records reviewed by memorial Sloan Kettering doctors. Please advise.

My husband had pancreatic stents placed just 2-3 weeks ago about 2 months after gall bladder removal. He is back in the hospital now because of infection fever and Nassau and throwing up. CT scan shows major fluid build up since surgery. What is preferred treatment? In these situations you feel powerless and as if you must accept treatment offered. While at the same time wondering if you are losing a chance for recovery by not reaching out to experts like Sloan Kettering or other top places. When situation is acute can help be gotten? How to inquire for help?

Sir my 22year daughter went hospital and Doctor put something in her stomach thurgh her mouth she came home and midnight she went to hospital say her stomach hurt she went through all scanning /X-ray finally Doctor found her pancreas got puncture during test from the pancreas tail and drew little fluid so she is still in hospital and not allow to eat till pancreas get back to normal her test was positive she don't have sign off cancer or other related just little fluid drew I'm so worried about my daughter is she gonna get well soon thanks

Dear Kuldip, we are sorry to hear about your daughter. We recommend you discuss your concerns with her physician. Thank your for reaching out to us.

I had a distal pancreotomy and removal of spleen 4 eeeks ago. I came home with two drains, one has since been removed. I ran a low grade fever after I came home but my surgeon didn't think I needed an antibiotic until the second week. I had lots of pain, I pass about 30-40 cc a day. Do you think I will be able to have the drain removed soon? Fever is gone

Dear Judy, you should discuss this with someone in your surgeon’s office. Thank you for your comment, and best wishes to you.

Thank you for your reply. I am now almost 8 weeks out of surgery (distal pancreotomy and splenectomy with complications) and have a pancreatic fistula. Pet scan was clear but due to the fact I had two out of 26 lymph nodes with cancer I will need chemo and radiation. I came out of the hospital with two drains in me, now I still have one. Doctors don't want to do chemo until fistula heals and I have no drain due to risk of infection. What go you think? Thankd

nephew survived being shot 14 times. Been in the hospital since 7/28/17 and has recovered nicely with the exception of the symptoms from damage to the pancreas that has created the fluid in the abdomen. He is being treated in Moses Cone Hospital in Greensboro, NC and had some unsuccessful procedures done. Has 2 drain tubes and a pouch on an opening in his stomach which will not heal due to the collection of fluid. A stint was put in also so that was not successful. Was advised today they will look at other options of maybe reducing his food intake and putting him back on liquid meal. Is the pasireotide available yet? If not I would like to get your advise on other options to discuss with the trauma team at the hospital or things I should consider. Unfortunately he is to ill to travel out of the state.

Dear Tracy, we’re very sorry to hear about all that your nephew has been through. Pasireotide is currently FDA approved for the treatment of a hormone disorder called Cushing’s disease. In the clinical trial discussed in this story, doctors used the drug in another way — to prevent leakage of fluid in the pancreas. We recommend that you discuss this with your nephew’s medical team. Thank you for your comment, and best wishes to you and your family.

Hello,

I'm a 26 yo female who they discovered an incidental 5cm pancreatic mass on. 4 weeks ago I had a spleen preserving distal pancreatectomy and lap chole (incidental gallstones. joy. -__-). Since then, I have been readmitted to the hospital twice for fluid build up and possible infection. They removed a liter of fluid from my chest cavity and they can see there is a small (4-5 cm ish) build up of leaked pancreatic fluid that they can't remove without another surgery. They do not think my pancreas is still leaking so they just have me on heavy duty IV antibiotics. I'm just curious how long it will take to feel normal? Will my body just absorb the fluid from my pancreas? The drug you're talking about here...that's simply to prevent the initial leak...correct? Or would it help me get rid of the build up I already have there?

Thanks :)
Nat

Dear Nat, we’re sorry to hear about what you’re going through. We recommend that you discuss this with your doctor or nurse. Thank you for your comment and best wishes to you on your recovery.

Hello, my mom was a very healthy 65 years old before her surgery. Dr found a pancreatic mass and did a whipple surgery. She had a major leak and 2 more surgeries to fix the complications. She stayed almost 4 months after surgery. Now she ended up with a pancreatic drain. She is getting worse and worse every day . Complaining of sever back pain, stomach pain nausea she got readmited to ho the hospital few times after surgery sofar,, what is concerning that there was some pus in the pancreatic drain bag and I contacted her sugeon ,, they keep saying everything is okay but my mom's symptoms getting worse day by day,,, i feel so helpless to see my mom suffering every day ,,,don't know what to do,,

Dear Zia, we are very sorry to hear about what your mom is going through. If she would like to come to MSK for a consultation, you can make an appointment online or call 800-525-2225. Thank you for your comment and best wishes to both of you.