TORADOL (ketorolac) linked to Recurrence Prevention
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I too just listened to Dr. Retsky's presentation. Excellent. Seems so logical with the data he presented that an NSAID is a no brainer pre cancer surgery...it really should be standard protocol for bc surgery. One cannot argue with the relapse trend/data post mx that he presents.
I so wish I knew this information when I had my mx in 2013. If I decide on reconstruction, I'll be definitely pushing for NSAID pre incision...I know it's not cancer surgery but it could induce a relapse if the inflammation data is sound.
I'm very thankful he shared the dosing and timing
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Stephy from the article about Forget's study. " Postoperative analgesia was intravenous piritramide titrated(not available in the USA) until visual analog scale scores were below 4. All patients received acetaminophen during the first 48 hours and oral diclofenac(Voltaren in USA) 50 mg twice daily for 3 days as necessary."
Rainey good luck
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Rainey and Solfeo, I went back and reread scanned the article on Forget's 2010 study. I thought it best to just post it b/c it's short.
"June 10, 2010 — Surgery to remove solid tumors can trigger metastatic spread. A groundbreaking analysis by Patrice Forget, MD, and colleagues from the Université catholique de Louvain, in Louvain-la-Neuve, Belgium, suggests that using different intraoperative analgesics for cancer surgery can reduce this risk.
We cannot ignore the possibility that anesthesia may contribute to the recurrence of cancer months or even years after cancer surgery.
"" frameborder="0" marginwidth="0" marginheight="0" scrolling="no" style="border: 0px currentColor; border-image: none; vertical-align: bottom;">An editorial by James G. Bovill MD, PhD, from Leiden University in the Netherlands, which accompanies the paper published in the June issue of Anesthesia & Analgesia, raises the broader question of whether inhaled anesthesia might trigger the growth of microscopic primary tumors even after surgery unrelated to cancer.
"Even though the evidence is inconclusive and at times conflicting, we cannot ignore the possibility that anesthesia may contribute to the recurrence of cancer months or even years after cancer surgery," Dr. Bovill writes in the editorial. "Less clear, but equally worrying, is the possibility that anesthesia could activate dormant cancer cells in an individual undergoing noncancer surgery, with the development of an overt cancer that otherwise might never have materialized in the lifetime of that individual," he adds.
Review of Mastectomy PatientsIn the new analysis, the Belgian team, headed by Dr. Forget, reviewed the medical records of 327 consecutive patients who had undergone mastectomy with axillary dissection between February 2003 and September 2008.
All mastectomies were performed by the same surgeon and jointly followed by this surgeon and the same oncologist, who used chemotherapy, radiotherapy, and endocrine therapy in accordance with the 9th and 10th St. Gallen expert consensus guidelines.
"" frameborder="0" marginwidth="0" marginheight="0" scrolling="no" style="border: 0px currentColor; border-image: none; vertical-align: bottom;">The main objective of the study was to determine the effect, if any, of the administration of different intraoperative analgesics (sufentanil, ketamine, clonidine, and ketorolac) on cancer recurrence after mastectomy. The primary end point was length of recurrence-free survival.
Dr. Forget told Medscape Oncology that "the most important finding was the suggestion that intraoperative ketorolac given before surgery decreases relapse risk. The other analgesics have no detectable impact."
All patients had general anesthesia induced with sufentanil (0.0 to 0.2 μg/kg) and a hypnotic, sodium thiopental (4 mg/kg) or propofol (2 to 3 mg/kg). Anesthesia was maintained with a continuous infusion of propofol plus sevoflurane or desflurane in an oxygen/air mixture.
Intraoperative analgesia was chosen by the 2 anesthesiologists in charge: sufentanil (total dose, 0.0 to 0.5 μg/kg), preincisional clonidine (0 to 6 μg/kg), and preincisional ketamine (0.0 to 0.5 mg/kg), or preincisional ketorolac (20 mg intravenously in patients weighing <60 kg, 30 mg in patients weighing >60 kg).
Postoperative analgesia was intravenous piritramide titrated until visual analog scale scores were below 4. All patients received acetaminophen during the first 48 hours and oral diclofenac 50 mg twice daily for 3 days as necessary.Importantly, no opioids were given during or after surgery.
Median follow-up was 27.3 months. After adjustment for age, histologic grade, and lymph node involvement, the researchers found that intraoperative administration of ketorolac was associated with a significantly lower risk for cancer recurrence (6% vs 17%; P = .019).
Sufentanil, clonidine, and ketamine had no significant effect on cancer recurrence rates.
The authors note that, "in contrast to previous data suggesting a negative influence of opioids on cancer-related immunity," in this study, sufentanil (given preoperatively) had no deleterious effect on cancer recurrence. "One reason may be the doses used in our patients, which are relatively small in comparison to those in other series. This is consistent with the fact that opioid-induced immunosuppression is dose dependent,"(emphasis mine) they add.
Dr. Forget said that "intraoperative analgesics have a great influence on anticancer immunity. These effects must be evaluated before concluding the effect on the outcome. Such studies add a rationale for the use of nonsteroidal anti-inflammatory drugs [NSAIDs] in cancer patients [experiencing pain], but must be confirmed."
Oncologists must have an interest in the possible long-term impact of intraoperative analgesics.
"These data are not definitive evidence, mostly because of the retrospective nonrandomized design of the study," Dr. Forget continued. "But the change is that prospective studies are now clearly needed. Anesthesiologists, surgeons, and oncologists must have an interest in the possible long-term impact of intraoperative analgesics."
This conclusion was strengthened by a review article by Antje Gottschalk, MD, and colleagues published in the same issue of Anesthesia & Analgesia, which examined the role of the perioperative period in recurrence after cancer surgery. Dr. Gottschalk is from the Department of Anesthesia at the University of Virginia in Charlottesville.
The authors of the review note that surgery creates "profound metabolic, neuroendocrine, inflammatory, and immunological stress," increasing mediators that can upregulate major promalignant pathways and disrupt normal tumor homeostasis.
After reviewing clinical and preclinical data on the possible effects of type of anesthesia on that process, Gottschalk et al conclude that "beneficial approaches might include a selection of induction drugs such as propofol, minimizing the use of volatile anesthetics and the coadministration of cyclooxygenase antagonists with systemic opioids." They and Dr. Forget suggest more use of regional anesthesia.
When NSAID Administered Is Important
Interestingly, Dr. Forget's data suggest that when the NSAID is given matters as much as whether it is given. Breast cancer recurrence was lower in patients given preincisional ketorolac but not in those who received postoperative diclofenac.
Dr. Bovill notes in his editorial that surgery inhibits natural killer (NK) cells, the only cells able to recognize and lyse cells lacking self HLA-1 molecules. NK cells are the first line of defense against primary tumors and the metastatic spread of established tumors.
Inhaled anesthetics reduce NK activity, he points out.
Regarding the Forget study, Dr. Bovill writes that despite the fact that it was a retrospective nonrandom study in which patients received a number of other drugs, "the analysis of their data is sufficiently robust that the implications of their findings cannot be ignored."
Dr. Forget cautioned that "the possibility that perioperative management may alter the rate or incidence of recurrence is tremendously exciting, but much more research is needed for this possibility to be conclusively demonstrated."
http://www.medscape.com/viewarticle/723293
Link that's in the topic box.
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Importantly, no opioids were given during or after surgery.
I find that interesting.
How cool Retsky dropped in!
Dr. Bovill notes in his editorial that surgery inhibits natural killer (NK) cells...
This is why I try to avoid surgery. And on other threads ladies chastise saying that there is no proof that surgery effects our immune systems. LOL
But it is quite a different ball of wax to think that IF we have surgeries, we can make choices that will improve our outcome. Super cool.
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Mea Culpa, Mea Culpa, Mea Maxima Culpa ---Means forgive me. Today I heard Rainey and Solfeo say they asked for no opiods. Well I knew I hadn't suggested that, but couldn't locate the source. I went looking in the Forget article. In Forget's study Sufentanil is the opiod used during surgery. On the first page of the thread, I described Sufentanil as the granddaddy of Fentanyl. Much stronger. The Study/article does reference opiod having an impact on cancer related immunity. I missed it. However, you all got it. What Forget points out is that opiod induced immunity is dose dependent. and in the Forget study it did not have a deleterious effect on recurrence. The addition of Toradol allows for a reduction of opiods. Until further research is in I would suggest they're be a balance. Surgery done without an opiod is hmmmmm brutal. Harsh word, but applicable.
" The authors note that, "in contrast to previous data suggesting a negative influence of opioids on cancer-related immunity," in this study, sufentanil (given preoperatively) had no deleterious effect on cancer recurrence. "One reason may be the doses used in our patients, which are relatively small in comparison to those in other series. This is consistent with the fact that opioid-induced immunosuppression is dose dependent," they add.
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Falleaves. Please, Sift through your material and see what you have on opiods and immunity. I know you referenced either here or in a PM. I remember you saying something, and it flew by me (again forgive me). It is something we need to address here b/c it's part and parcel of why Toradol is important and why we need to keep studying.
To the team............
Toradol-------whatever this is we need to know it.
1. It is a good pain reliever in it's own right. In certain circumstances, it can be used without an opiod.
2. Potential to reduce recurrence
3. Combined with an opiod intraoperatively, the opiod dose may be effectively reduced with still allowing good anesthesia control. Thus, limiting the immune response caused by opiods.
Brain is on fumes now................. but we have more work to do. We need the research on opiod induced immunity stuff.
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I had my surgery a year ago at UCSF, my dr was Dr. Laura Esserman who's co- director of the UCSF comprehensive cancer center, I have no idea what was used on me..,never even thought about it as I had a mastectomy 25 yrs ago and whatever they gave me, I'm obviously still here. Should I be worried now ????? Can what they gave me cause a recurrence? Do I need to call UCSF and if so 1 yr later what can I do about what they gave me if it was the wrong thing. I know I had no pain. I try to be as on top of stuff as I can but I never heard anything about this before. Do I need to call the hospital? What I want to know is if they put me at risk, and is this a legal issue
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Sula, No it's not a legal issue...sorry, I may have PM'd you inadvertently. My fingers were flying fast and furiously trying to Pm everyone that has posted here while Dr. Retsky was here. This is early research. It's compelling. But your docs gave you anesthesia according to accepted practice. You'd have to read from the beginning to understand. The topic box covers the initial reason I started the thread. Accepted practice may change. Were just trying to be on the right side of the change.
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WE Need a Reality Break !
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All right, I did watch the talk--very helpful (among other reasons, because it taught me how to pronounce "Forget" and "ketoralac." Sas-Schatzi, you are getting some idea of how we non-scientists process this information.
Fallleaves, thanks for your good thoughts.
A little intimidating to think that I will be meeting the anesthesiologist right before surgery, dressed in a gown, and bald unless I can get them to give me a surgical cap. Not ideal circumstances, eh? But Retzsky's talk was compelling, and I've read all the relevant studies. I'm pretty sure they will give me ketoralac, though less sure they'll do so pre-incision. I will be very clear that I want opiods minimized. Suspect surgeon is not on board with paravertebral block but will bring up.
Thanks for laying things out so clearly above.
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Go girl, Have it your way, praying for you HUGS,
BTW it was Retsky on the phone that corrected me about how to say Forget. Didn't admit I also thought he was a woman---Patrice.
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Dr. Retsky what do you prefer we call you Dr or Michael. I never said Congratulations on being a survivor. YAY. Hope you come back. They're still questions on Page 9. Seriously, when did you recognize the paradigm could change? I loved how you introduced your thoughts about how important the recognition of Toradol could be. It' was as much fun as the first chapter of Da Vinci Code.
I was going to post some fireworks for your survivorship, but remembered 3-2-1
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Dr. Retsky-
We just want to thank you for taking the time to come here and answer some of the questions our community has! We appreciate your input, and value the knowledge you've shared, both in your original study and here on our boards!
The Mods
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Solfeo check Dr Retsky's response on page 9 re dose. We'll wait a few days and see if he checks in again. Solfeo. I was in a rare mood, played detective finding him, who would guess he'd answer his own phone, chat, and come. The stars aligned.
When's your surgery? falleaves already started anew thread on the paravertebral block. I can't link a the moment.
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I am in a lot of pain the drugs of choice I have is toradol and morphine I said no morphine but the toradol every 6 hours isn't cutting it hoping to feel better tomorrow but this has been a rough night without the morphine I'm going to be honest
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double mastectomy with tissue expanders was feeling ok but once that toradol starts wearing off I'm hurting I have no idea what else to ask for
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Stephy Forget study groups did use an opiod. Just a smaller dose. AND the drug was stronger than Morphine. Consider this---- a body under stress produces chemicals that support inflammation. That is opposite than what you are trying to do. Consider taking as ordered or you could take half dose.
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ok thanks maybe I will ask for half dose I don't want to cause more stress ony body toradol is doing the trick now I will see how I feel in a few hours..thank you!
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stephy in Forget'smstudy generic Voltaren was used and a an opiod not available in this country. Check page 10. I posted re: what was used . It's directly after the article.
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Stephy, solfeo dead on right. working on something working on something bbL
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yes I found that out the hard way waited 6 hours between doses and was in pain my back also hurts from the block i will ask for a reduced dose of morphine in a few hours not good for my body to suffer through pain..thanks for all the input ladies
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Well something is seriously wrong here. Went to the article again and there is a statement. that is clearly wrong. " Importantly, no opioids were given during or after surgery" That is a direct quote from the article. But Sufentanil was used pre-incision & intraoperatively, and a drug piritramide(not available in USA--similar to a metabolite of Demerol) was used post op. Forget's statement clearly identified opiods were used.
Big error in the article, maybe that's why I didn't catch the no opiod thing before b/c I knew Sufentanil was an opiod. Well this is a mess. Hmmmmm I'm guessing all the medical people were reading the drugs and others were reading the no opiod statement.
I sent a email to Retsky. Hmm 5(6 pre publication) years.......no one caught the discrepancy. That's a worry.
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Stephy, Take your Toradol on a scheduled basis. Call in the morning if you need something stronger.
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toradol not cutting it
may take morphine if I can't sleep cancer sucks! Thank go it's gone out of my body 5 lymoh nodes were taken all clear very good news0 -
Stephy have you got morphine at home right now? If so take it as prescribed. You would be 500x's less than what was used in the forget study.
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final decision was norco to hopefull last me through the night and take the edge off
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Uncontrolled pain is not good. We can deal with studies tomorrow.
You are putting yourself at risk when pain is uncontrolled. Every system goes on alert when pain is out of control. Cortisol is increased & epinephrine, the inflammatory process aflame, set up for infection. If you have morphine on hand and you are in severe pain> 7 or you feel like wolves are gnawing on your chest and your alive. That's uncontrolled pain.
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Norco is hydrocodone and acteominophen ---good drug. Do you have it or does someone have to get it from the pharmacy?
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Stephy sticking here until, your settled.
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Late for the Q&A
Steph, I agree with Ms. Sass. Take your Norco
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