TORADOL (ketorolac) linked to Recurrence Prevention

Fallleaves · January 2016

Hi Grammy3x, I looked for a comprehensive review of various opioids and their effects on immunity and cancer, but couldn't find anything. Here's a pretty extensive general overview of different opioids, though: ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555047/)

Most of the opioid studies are on morphine, which is still the heavy hitter, used during surgery and for postsurgical and chronic pain management. The studies indicate that morphine is immunosuppressive, but have shown conflicting results regarding morphine's effect on tumor growth and metastasis. Of the many synthetic opioids, fentanyl seems to be the most studied, along with the much stronger sufentanil, both of which are used during surgery and for postsurgical and chronic pain relief. They have also been shown to be immunosuppressive (http://www.ncbi.nlm.nih.gov/pubmed/15249732), although I did find one study that showed fentanyl promoted NK cell cytoxicity (http://journals.lww.com/anesthesia-analgesia/Abstr...). I also ran across this study, which indicated that fentanyl used for postoperative analgesia in mastectomy patients promoted factors associated with metastasis and recurrence, but that the effects were greatly diminished by the addition of a NSAID called flurbiprofen. (http://onlinelibrary.wiley.com/doi/10.1111/papr.12...) (Honestly, every time I read flurbiprofen, I think of flubber....)

The synthetic opioids I have read positive things about are Tramadol and buprenorphine. Tramadol may actually stimulate NK cell activity and prevent metastasis. (Discussed in the opioids section of this paper:http://bja.oxfordjournals.org/content/105/2/106.fu...) In a rat model buprenorphine was able to prevent the surgical stress response (which decreases NK cell activity and promotes tumor metastasis), while fentanyl and morphine did not (http://www.ncbi.nlm.nih.gov/pubmed/17291715).

Happy New Year everybody!

solfeo · January 2016

Hi kids, I'm still here!

Glad to be reminded that tramadol may promote NK cell activity. After making it through the recovery from BMX with only Tylenol and NSAIDS, I've found myself on tramadol the last couple of weeks due to a yoga injury. I've been afraid to take it as much as I need it, so only do so when I'm desperate. I remembered that tramadol was better, but I'm just so overwhelmed with research right now and what seems like endless contradictions in the science of breast cancer, that I'm afraid to put anything in my mouth anymore.

Fallleaves · January 2016

Hi Solfeo, great to see you on here! Sorry you had an injury, but good on you for doing the yoga (looks like you are working all the angles to stay healthy!) Hope you heal up very soon, and your New Year is wonderful!

solfeo · January 2016

Well, I would have been doing yoga if I didn't hurt myself the first time. haha! Thanks Fall - and a great 2016 to you too...

Fallleaves · January 2016

The very first time? Oh nooo...that really sucks!

sas-schatzi · January 2016

SOLFEOOOOOOOOOOOOOoooooooooo. Yay doing good! Except for Yoga. Can empathize. Swimming's my trick. The stroke that works well for my spinal problems is --Backstroke. Every time I get in the routine something interferes. Like two falls a couple a weeks a part on first one shoulder, then the other. Wiped out months. Then decide I want to lengthen the pool year after 22 years of having a pool, I install solar pool heating. ChChing$$$. We have the most cloudy days EVER.

Seriously though Happy New Year.

sas-schatzi · January 2016

Been meaning to write a synopsis of what occurred since the beginning of this thread. Many were involved. The uniqueness can't be compared.

I found Dr Retsky's and Dr Forget's study's as a result of a statement on the Port thread. That statement from another member said NSAIDS should never be used around surgery time. Not faulting the member. I thought 'yes that is the prevailing thought'. When I read words like never or always they trigger a response. Pavlov conditioning. I went on a search. Came across Retsky's & Forget's research. Changed my world. Started the thread.

Fairly soon Stephmom--Stephy, Solfeo, geewhiz, PeaceStrength and Rainnyc joined. I did a search on BCO engine and found Falleaves had done a thread. Went looking for her. Coincident to that time 123Justme joined, energetic and thriving on research. Falls chimed in with her old thread and much new information. Falls, and 123JM have been a researchers dream as compatriots. And in the background, Is Loveroflife(Loverly).

What happened after that was the uniqueness. Solfeo, Rainny, Stephy were going for surgery. It became more than an esoteric discussion. Each was seeking to prevent recurrence. They read everything. Here. Everything that Falls had on the other Toradol thread. Everything Falls had gathered on opiod and block links.

Each tried to do it.

The risk was all the research is not proven. Each felt that they wanted to risk it. Toradol, no opiods, and blocks.

They're was much discussion early on about the risk of a bleed with Toradol as a NSAID. the literature showed that bleeding wasn't an absolute risk. The pediatric studies where bleeding was a critical risk in tonsillectomies showed that bleeding minimal and that an NSAID could be used safely i.e Ibuprofen. They're was a study on Reduction Mammoplasties that showed Toradol risk. Overall it determined there was some risk, but didn't contraindicated it's use.

Stephy was the first to have surgery. Low and behold she has a bleed. The origin of her bleed is undetermined. But it was intense time for all off us.

Two more seeking the same path and the first to go, has a bleed.

Rainnyc and Solfeo followed, but with concern. Each had uncomplicated paths.

If you look at the three's self reports it becomes a microcosm of the macro world of science. They covered the spectrum of the studies. I think all involved understand.

Falls, 123, and I linked all the studies in the topic boxes. Very busy topic boxes. They will be relevant for awhile i.e. a few years. But for anyone wanting to know, they have much to work with, that they don't have to seek on their own.

We were privileged to have Dr. Retsky and Dr Forget come here. Never has that happened on BCO that I know of. Thank you to both of them. Their effort in this area of research is continuing.

I contacted Dr. Retsky at the moment that I felt I had to seek counsel. He came within the hour. Bless him. He then brought Dr Forget here. They only were here briefly, but the door is open and I'm sure they are watching.

Solfeo had a question for Forget. Forget's response to Solfeo's question to me was perfect. But I had worked the OR, his response did cover everything. Solfeo was not convinced. It took me a bit to figure out why she had questions versus my concurrence. Her challenge of his response was perfect b/c she was the patient. She didn't have the insider's knowledge of the OR(operating room/anesthesia). Her questions were excellent, and should be considered by all patients.

Just this week I took a risk and posted on the Jan. 2016 Surgery thread. Have thought long and hard about what do we do with this informationthat we have gathered here. Ethical conundrum. Do we make those that haven't had surgery yet, aware they're may be a better way? Do we let them find their own way? Have felt guilt that time has lapsed and they're surgical groups, that could have been made aware.

Thankful, that all have contributed.

grandma3X · January 2016

Sassy - I'm from the Jan. 2016 surgery group and was not aware of any of this until you posted it, so thank you. I have since asked my surgeon for the PVB and she agreed. I also will talk to her by phone this week about non-narcotic alternatives to pain control. I think you should continue to post for every new month. I'm not totally convinced that morphine directly promotes cancer progression, but the side effects of opioates are enough to make me think that they should be used only if necessary for break-through pain.

Fallleaves · January 2016

Sassy, very nice synopsis. I agree, there has been an amazing synergy on this thread. Also agree with Grandma3x that you should continue to post on the surgery group threads for each new month. Anesthesia is an afterthought for probably the majority of people going into surgery. Many people see their anesthesiologist for the first time right before they go into surgery, and then there's no choice offered. I still don't know what anesthesia I got. (All I know is what I asked NOT to get!) I think it is very valuable for people going into surgery to know they DO have choices, so they can discuss them with their doctors ahead of time.

rainnyc · January 2016

I agree with what Fallleaves just said. I only knew about this because the thread was so active in the couple of weeks before my surgery. Even armed with that information--and I am not in the medical field and even reading the medical articles was only able to form an imperfect understanding of the issues involved--it was very difficult to bring this to the attention of the surgeon and anesthesiologist, whom I met only minutes before the surgery. It needs to be linked to the first page of that very helpful thread about preparing for surgery. I was very grateful for this thread though I wasn't able to get everything I asked for. With reconstructive surgery coming up (I hope) once I heal from radiation, I know that I have at least one more surgery in my future.

Fallleaves · January 2016

Sass, I ran across a small study comparing the impacts of IV morphine, tramadol and ketorolac on the immune functioning of mastectomy patients. Ketorolac was the least immunosuppressive (morphine was most immunosuppressive and tramadol was in the middle). http://www.ncbi.nlm.nih.gov/pubmed/26710216 This is just the abstract, I can't access the full text ($)

Should it go on one of the threads?

solfeo · January 2016

Awesome summary!

All I know is that I walked out of the hospital 4 hours after my BMX and I felt great, and except for the inconvenience of the drains my recovery was relatively easy. That benefit alone has me never wanting opiates in surgery again. The ketorolac caused no problems at all during or after surgery. Why would I not want to use it even if there is only a slight chance it reduces risk of recurrence? I don't think any one thing alone causes recurrence. It's a synergy of events. I believe you have to go at it from every direction possible and chip away at the risk until it's as close to gone as you can get.

sas-schatzi · January 2016

Good. Glad you are happy with the summary.

Falls, I think it would be a good to add that abstract to the topic boxes.

Leslie13 · January 2016

I had my BMX 3 1/2 months ago. I'm having a hip replacement in a month. Much sooner than ideal, but my hip is bone on bone and I can barely walk.

Should I be asking for Torodal during anesthesia? I'm still at risk for post surgical metastasis, and immune system is stressed from the other surgery. I sleep 9-10 hours a night and am often fatigued.

I've also been on Opiates since my cancer dx. I developed an Opioid dependency in the last years of my career, so I could keep going through the Arthritic pain. Back surgery in my early 30's started chronic pain and I used NSAIDS like candy. I developed Diverticulitis 15 years later (10 years ago) and ended up with a bowel resection to remove a bad part of my colon. Also was told to NOT use NSAIDS.

My back and a bad hip kept me from being able to sit, stand or walk very long, so I was miserable the last 5 years I worked. My PCP had me on Opiates so I could keep going. My left hip was botched when replaced in 2010 so I didn't return to work. I've used Buphrenorphine much of the time since to treat chronic pain and reduce opiate dependency. But it isn't nearly as effective to me as regular opiates, and can really block the effectiveness of anesthesia when you have surgery. I've found this out the hard way. Even an Opiate dependency can be problematic, as they don't want to give you the amounts you need for pain control in recovery

So I'm very confused with this info as to how to handle my pain. I don't think asking for Torodal is a problem, as short term use is OK. Should I get back on Buphrenorphine as soon as I can? Having this goofy ILC, where standard chemo doesn't work, but the cancer has to metastasize to receive the right medications is frustrating

Fallleaves · January 2016

Hi Leslie,

I'm sorry you are having to have another surgery so soon, and sorry you have been dealing with so much pain. I hope this hip surgery goes much better than the last.

Can you schedule a one on one with the anesthesiologist or at least contact that person through email? I think you should try discussing your concerns with the anesthesiologist well ahead of your surgery, because you might have some back and forth.

I'm not at all familiar with hip replacement surgery, but I did find this review of methods of reducing postoperative pain in knee and hip replacement. It has a few things you might want to discuss with the anesthesiologist.

http://www.practicalpainmanagement.com/pain/myofas...

This article mentions:

1) periarticular injections that include the local anesthetic ropivicaine mixed with epinephrine and ketorolac. "the local anesthetic mixture significantly reduced opioid consumption over 48 hours postoperatively (P=0.003). The local anesthetic group also reported lower mean VAS pain scores at rest (P=0.01) and during exercise on POD 1 (P=0.008) and on POD 2 (P=0.02), as well as less postoperative nausea (P=0.011) compared to the control group.¹³"

2) peripheral femoral block (FNB). "A continuous ropivacaine FNB with a fentanyl PCA (patient controlled analgesia) was compared with PCA alone. The control had a higher total opioid consumption (P<0.001) and required more PCA dose increases compared to the FNB group. Those with an FNB, however, experienced lower ROM in both flexion and extension. Similarly, when levobupivacaine FNB with patient-controlled epidural analgesia (PCEA) was compared with PCEA alone, the FNB group had lower VAS scores from 0 to 24 hours (P<0.001), and 24 to 48 hours (P=0.025). Patients receiving FNB also experienced significantly less nausea (P<0.001), vomiting (P=0.033), and demand for rescue antiemetics."

Nerve blocks (regional anesthesia) may reduce the stress response associated with surgery that suppresses the immune system, and some studies have shown reduced recurrence of breast cancer with the use of paravertebral nerve blocks (this is the thread on that: https://community.breastcancer.org/forum/73/topics...).

3) celecoxib, an anti-inflammatory (COX2 inhibitor/NSAID), reduced the need for postsurgical opioids

Celecoxib is being studied for a beneficial effect on breast cancer, as BC strongly expresses COX2, so definitely won't hurt in that regard.

4) gabapentin and pregabalin, are thought to reduce the need for opioids, and reduce chronic postsurgical pain. But this may be more for knee replacement than hip surgery.

A few other things:

If you are getting spinal anesthesia, this study indicated that unilateral spinal anesthesia was better than conventional bilateral spinal anesthesia in preventing a surgical stress response when undergoing hip replacement. This could be beneficial to you because the stress response is thought to drive cancer progression.

http://www.ncbi.nlm.nih.gov/pubmed/25410068

You might want to ask about having dexmedetimidine added to the mix. It was seen to be cardioprotective in this study of patients with coronary heart disease undergoing hip replacement http://www.ncbi.nlm.nih.gov/pubmed/25132247 (however it does have the effect of lowering blood pressure), and in this study of children with cancer, presurgical administration of dex reduced the stress response and immunosuppression. http://www.ncbi.nlm.nih.gov/pubmed/25932229 Also, this study of breast cancer surgeries showed dex lowered postoperative opioid consumption and nausea and vomiting. http://www.ncbi.nlm.nih.gov/pubmed/26694929

Tramadol is another alternative that may be less immunosuppressive than other opioids, as seen in this study of gastric cancer patients:http://www.ncbi.nlm.nih.gov/pubmed/25885721

If you can use buprenorphine again that would be good too. This study (in rats) showed buprenorphine prevented the surgical stress response on the neuroendocrine and immune systems. http://www.ncbi.nlm.nih.gov/pubmed/17291715

Anyway, I just want to wish you luck with your surgery. Hope you can have a good discussion with your anesthesiologist beforehand!

sas-schatzi · January 2016

Leslie What Falleaves has bought forward is very good. Amazing. But you have to study. You have to read. You have to search. It's so hard. Never depend on just one search or study.

They're is a bigger reason why I say don't depend on what we say or discuss. We are at a crossroads in knowledge. What is exciting based on our research or many, may in a few years be proven false.

You are in a hard situation based on history. But it can be dealt with. Consider genetics. I was thought to be strange on anesthesia. Finally, learned I had a rare metabolism. of drugs. If the Anesthiologists had applied the concepts of my rare metabolism, they wouldn't of raised certain questions.

sas-schatzi · January 2016

Ad a drug checker _-------------Genelex

Smaarty · March 2016

bump

sas-schatzi · March 2016

Bump

sas-schatzi · April 2016

Hi, All, received this from Dr. Retsky

Look at this video from my coauthor Vikas Sukhatme. He is academic dean at Beth Israel Deaconess Medical Center at Harvard. A very smart guy. OK to circulate.

Michael

https://www.youtube.com/watch?v=H8zVrYEW8vE&feature=youtu.be

____________________________________________________

This is an amazing video presentation. The fella is brilliant and he makes the info so easy.

Every concern that we went through in the summer and into the fall for our small group, is addressed in this video.

What I think anyone trying to digest this info should request of their doc is to review this video. Then give a solid reason why not, if you are willing to take the risk of a bleed.

Folks with the knowledge that we gained last year, by talking it out, and flying by the seat of our pants came to the same conclusions that Dr. Retsky, Dr, Forget, and Dr. Sukhatme, we did good. Our research and conclusions were good. Yes, it needs to be confirmed by a prospective study. I hate the thought of a prospective study when the results mean that recurrence could be avoided by a simple < 10$ IV push pre-op.

Way back when I said that being on the right side of the change when change is occurring is the side we want to be on.

Dr. Forget has a study going in Belgium. Dr. Retsky is working on getting something approved in two other areas.

As Dr. Retsky has said feel free to share the link.

jojo9999 · April 2016

wow, great ideas. I just donated!

What about an observational study on recurrence rates for women who had mastectomy with and without reconstruction? I wonder if the surgery from reconstruction could put into action the inflamation behind this theory. Thoughts?

sas-schatzi · April 2016

Hi Jojo, The recommendation is for ketorolac for any subsequent surgery. Since generally there are not the subsequent surgeries for non reconstructors, it would seem it would be easy to sort them out.

peacestrength · April 2016

Sas...love this thread. Thanks for posting the video...going to watch it soon.

sas-schatzi · April 2016

Hi peace, I enjoyed it too. I learned so much and met some great folks. It was so intense, I think I still haven't recovered. Haven't studied that hard in a while.

Did you have your surgery? The video is good. Dr. V takes the difficult material and makes it easy to understand. I apparently misheard that Jennifer was Dr V wife. She was a friend of his wife's.

peacestrength · April 2016

Sas, watched video and helpful how he narrows it down in "practical" language. No decision on reconstruction yet...thanks for asking.

Mominator · April 2016

Hi Sassy, I just posted a link to the video on my Twitter and Facebook accounts to help spread the word.

Dr. V thinks that this could help patients with all types of cancers. Amazing. He considers this similar to hand washing in the 1880s to prevent fever in women delivering babies, a change which eventually led to handwashing and sterilization in all areas of medicine. Truly paradigm shifting!

sas-schatzi · April 2016

Mominator Go to the topic box and look for Dr Patrice Forget's study. Then Dr Michael Retsky. Dr, V was a co-author with Dr. Retsky on Retsky's study.

The brilliant young doctoral student doing his thesis that Dr. V referred to was Dr. Forget.

Both Dr. Forget (forshey) and Dr. Retsky have been here in our little pond

sas-schatzi · April 2016

Keep Dr. Forget in your prayers. Remember he's in Brussels. We pm'd the day after the attack. It was brief. I worry b/c of the way he worded his response. It was brief. But I would only chose that phrasing if I were very worried.

sas-schatzi · April 2016

Hi folks did a thread that incorporates all the threads. It's self explanatory I hope. Please, give it a read and let me know what I can fix

Hootie hoo, Hope everyone's doing well. YAY, been meaning to do this for awhile.

https://community.breastcancer.org/forum/73/topics/843381?page=1#post_4691605

Oh yeah, I was tapped out on a name. Any ideas. Mods will change it if I ask sweetly.

sas-schatzi · May 2016

Trying to post the link from the previous post to each surgery group, and now sticking around for questions. Posted this today on the June surgery thread. Sent it to the Docs for review.

Falls and 123, consider make a plug for your threads. I know pushy, pushy.

Hope all are doing well solfeo, Stephy, rainnyc, geewhiz, Loverly, and anyone I missed hugs sassy

////////////////////////////////////////////////////////////////////////////////////////////////////////////////////

Thought I'd drop this post here. It was written to the June 2016 surgery group:

To all. Check back to the post on Toradol and NSAIDS. Please, view Dr. V's video. He explains about the use of Ketorolac/toradol pre-incision. That's just the intro. If you follow all the links you will find the definitive studies and the work we all did last summer......................On the lumpectomy & rads versus mx and adjuvant. Is the most controversial of any subject. I think it's the SEER study that says the lumpectomy & Rads group do well, BUT it's how the MBC group fits into the story gets murky. Please, view Dr. V's study and then read my Toradol thread from last summer.

They're many elements that are the bases for consideration at the time of surgery time. It is known that the act of surgery causes the body's response of inflammation. That cascade of chemicals that are produced in the inflammatory response can cause 1. circulating tumor cells that are released from the tumor site to lodge at a distant point an stimulated to grow, and 2. cells that were released earlier that were dormant at a distant site are stimulated to grow.

This is the idea behind the interruption of the inflammatory cascade by the use of ketorolac/ Toradol. Not sure when inflammation was seen to be such a problem i.e what year, but Dr. Patrice Forget's first retrospective study done in 2010, looked at the drugs that were used at the time of surgery to see if the any connection could be found.

This was a highly unique situation of 325 patients at one hospital that had the same group of anesthesia docs and same surgeon(s). The finding was that ketorolac was the common drug in the group that had the longest time to reoccurrence or no recurrence. Dr. Forget then did a second retrospective study on a cohort of 725. The same finding. This was remarkable. It's earthmoving. Then Dr. Retsky did a study that looked at what was being done worldwide. There was more data worldwide supporting Forget's study in recognizing interference with the inflammatory cascade was a key connection. Though the connection to ketorolac was made by Dr.Forget, Dr. Retsky saw the immense meaning. Dr. Retsky 's study is a wild ride in the science behind Forget's discovery.

Dr. V from the video, was a co-author with Dr. Retsky. All the data that Dr. V uses in his video is from their study and Dr. Forget's study.

Dr. Forget has a prospective(double blinded) study going on in Brussels now. Dr Retsky is trying to get one going in Africa now.

The reason Dr. Retsky is in Africa is that blacks have a higher incidence(nearly exclusive) rate of triple negative patients. If ketorolac does in fact reduce reoccurrence it will be known pretty quickly b/c TNBC has the highest early reoccurrence rate. For Africa this would be revolutionary( the world too) b/c they don't have the medical resources that the developed world has. Ketorolac cost less than 10$.

I could go on for a very long time. I'm hoping this is enough to convince you of the importance of studying yourself, and then talking with your docs about ketorolac pre-incision. In the link to the topic box i have described how to use the info there. There are two posts that pull all the need to consider info & links to take to your docs. Our team from last summer did some very very intense work to put it all together to make it simpler for anyone reading this.

It has become my mission to try and make people aware of this research. If you and your physician choose not to do it b/c this is retrospective research, I get that. But the research is so compelling, don't discard it without a serious look.

Plus, there is compelling research about blocks and opiods. All the links are there.

I'm going to send this off to Dr. Retsky and Dr. Forget and see if they agree as to how I've stated this. Always like to check the facts I'll post back if they have any comments.

Okay, off the soap box

TORADOL (ketorolac) linked to Recurrence Prevention

Comments

Categories