TORADOL (ketorolac) linked to Recurrence Prevention
Comments
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I'm sorry, Sas. I completely misspoke in my prior post, which I've deleted.
Here's what I should have posted: Although not related to recurrence, migraine sufferers should consider requesting Toradol to avoid triggering migraines, too. Immediately following my LX, I had some of the worst migraines of my life. I mentioned it the next time I saw my neurologist. While I was in her office, she went on the computer to look up my records to see the meds that had been used during surgery (when I was not given Toradol) and said the meds I received are known to trigger migraines. She said that if I ever had surgery again, I should request Toradol instead.
So, if I had to do it again, I would now have 2 reasons for requesting Toradol!
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Chicago, Thanks for clarifying. Hugs
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Expert opinion on micro environment of BC:
http://scienceblog.cancerresearchuk.org/2011/11/16/expert-opinion-professor-fran-balkwill/0 -
YAY, Wonder if you will be given Toradol preincision? Maximum dose amounts is 6 over 48 hrs(?) . otherwise the negative consequences of Toradol can begin. (still sleepy). No idea if Tylenol interrupts the inflammatory cascade like NSAIDS do. Tylenol is an antiinflammatory, but I don't know if it has the same affect on the cascade. Our 123, has posted a couple of articles about Ibuprofen. Give them a read if you can.
Where are you located Solfeo? Type of Center---NCCN, large teaching hospital, Community based hospital, Timbucktu? Reason we would expect a NCCN center to be looking at the NSAIDS based on study reports. But if you are in Timbucktu, then word is spreading faster OR you have docs that are right up their study reading YAY.
Ask for Toradol preincision
Post op ask your doc about why they used Toradol the way they do? It's be kind of cool if you could tell them you are familiar with Retsky's and Forget's studies.THANK YOU BUNCHES for letting us know Solfeo, Please keep us up to date now and down the road. What's your hormone status?
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So cool Solfeo!! Baby steps in awareness!
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123 would you mind seeing what you can find about Tylenol's affect on the cascade Thanks?
Falleaves your work on toradol and opiods. How does it plug into this particular discussion?
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From Medscape:
MECHANISM OF ACTION
The exact mechanism by which acetaminophen produces its analgesic and antipyretic effects remains undefined. The primary mechanism of action is believed to be inhibition of cyclooxygenase (COX), with a predominant effect on COX-2. Inhibition of COX enzymes prevents the metabolism of arachidonic acid to prostaglandin H2, an unstable intermediate byproduct which is converted to pro-inflammatory compounds. In the central nervous system, inhibition of COX enzymes reduces concentrations of prostaglandin E2, which lowers the hypothalamic set-point to reduce fever, and activation of descending inhibitory serotonergic pathways to produce analgesia.[1–4]
While acetaminophen shares the analgesic and antipyretic properties of other COX inhibitors such as aspirin and the non-steroidal anti-inflammatory drugs (NSAIDs), it does not possess significant anti-inflammatory properties. Unlike aspirin, acetaminophen does not inhibit thromboxane and, as a result, does not alter platelet aggregation.[1–4]
Recent studies have suggested that acetaminophen may work through additional mechanisms, including modulation of the body's endogenous cannabinoid system. One of the metabolites of acetaminophen (N-arachidonoylphenolamine or AM404) inhibits the uptake of anandamide, increasing concentrations of endogenous cannabinoids. These substances can both modulate serotonergic descending pain pathways and lower body temperature. Other investigators have suggested that acetaminophen produces direct inhibition of N-methyl-D-aspartate (NMDA) receptors, blocking substance P-dependent synthesis of nitric oxide through the L-arginine-nitric oxide pathway and reducing nociception. These proposed mechanisms are not likely exclusive; in fact, they may all be components of an interwoven series of responses to acetaminophen administration.[1–4]
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From cid.oxfordjournals:
Acetaminophen has very little anti-inflammatory effect, if any......
From a structural standpoint, it is challenging to envision how acetaminophen would inhibit the COX site of COX because it lacks a carboxylic acid moiety for interaction with arginine 120 (figure 1). However, other simple, nonacidic compounds such as resveratrol are also known to inhibit both COX-1 and COX-2 [52, 53] (figure 1). Their mechanism of inhibition is currently unknown, and it is unclear whether they inhibit the COX or peroxidase active sites of the enzyme. The early work of Flower and Vane [6] established the possibility that acetaminophen exerted its action through inhibition of COX. Moreover, their work provided a mechanistic rationale as to why acetaminophen would possess part of the complement of therapeutic activities possessed by NSAIDs (analgesia and antipyresis) but lack anti-inflammatory and anticoagulatory activity. That is, that acetaminophen exerts its effect on a subtype of COX located in the brain. The finding of 2 forms of COX confirmed the notion of COX subtypes, but further investigation of COX-2 failed to find it to be significantly inhibited by acetaminophen [54].
Recently, our laboratory identified a way to induce murine J774.2 cells to produce a COX activity that was more sensitive to acetaminophen inhibition than is COX-1 or COX-2. Ironically, the inducer of this activity was diclofenac, a potent inhibitor of COX-1 and COX-2. The remainder of this review summarizes those studies.
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Solfeo - You don't have to sign the consent for lymph node dissection. It's your body, your risk for lymphedema, your right to refuse. I had a lumpectomy but a good friend of mine had a bmx. shortly after I had surgery and our mutual surgeon was FINE with doing SNB only for both of us. We both subsequently had radiation to the nodes. This may be still "under study" but it's hardly revolutionary.
As to the pre/intra-operative toradol - best to get that in writing prior to surgery.
Good luck with everything!
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Solfeo, when's your surgery? Please, never do something without your surgeon/doc knowing. Want to discuss it , but working through a family problem. Be here more this weekend. PLEASE, read Forget's first study and Retsk's study. Once you read them you will understand the significance of the pre-incision Toradol injection. Honest, as studies go, the aren't that hard to wade through.
Loverly, thanks, for the Tylenol description of how it DOESN"T play into the cascade that the NSAIDS do. Very helpful
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Interesting info regarding opiods:
http://www.uchospitals.edu/news/2012/20120321-opioid.html0 -
ok ladies I have surgery next week I am going to ask for a thoracic epidural and non opiod pain control is there anything else I should ask or request for?
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Toradol pre-incision
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[Did a thread that incorporates all the info below suitable to be taken to your doc].
https://community.breastcancer.org/forum/73/topics/843381?page=1#post_4691605
TORADOL/KETOROLAC
Dear Doctor, I request that you consider the use of Toradol pre-incision for my upcoming surgery. Below are the relevant studies.
The amount and timing recommended by Dr.Patrice Forget is 20 mg pre-incision in patients under 60 kg, and 30 mg in patients over 60 kg.
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There has been ongoing research that is looking at the specific use of Torodal/ketorolac in the perioperative(preincision) phase of breast surgery. The initial study was from Belgium. This study is known as the Forget study published in 2010. A particular isolated group of patients that had an unusually low rate of breast cancer recurrence. All had the same breast surgeon and one of two anesthesiologist. The anesthesiologists had a common approach to drugs used for surgery. Toradol was identified as the common drug given intraoperative.
This link is to an article about the Dr. Forget study, 2010. Patient cohort 327.
http://www.medscape.com/viewarticle/723293
Dr. Forget' s study. This is benchmark original research.
http://www.ncbi.nlm.nih.gov/pubmed/20435950
Dr. Forget' s study 2014. Follow up retrospective study of the 2010 retrospective study. Patient cohort 720.
http://bja.oxfordjournals.org/content/early/2014/01/23/bja.aet464.full.pdf
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Dr. Retsky' s study is a broader based analysis of Dr. Forget' s
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831877/
Curr Med Chem. 2013 Nov; 20(33): 4163–4176.
Published online 2013 Nov. doi: 10.2174/09298673113209990250
Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review
Michael Retsky,1,2,*Romano Demicheli,3William J.M Hrushesky,4Patrice Forget,5Marc De Kock,5Isaac Gukas,6Rick A Rogers,1Michael Baum,7Vikas Sukhatme,8 and Jayant S Vaidya7
Quotes and graphs from Dr. Retsky's study.
"Using Computer Simulation to Analyze Bimodal Relapse Pattern
Based on computer simulation, to explain the 10 month peak we postulated that induction of angiogenesis at the time of surgery provoked sudden exits from dormant avascular phases to active growth and then to detection. That mode is quite sharp and most often seen among premenopausal patients with axillary lymph node involvement (N+). We suggested the remainder of relapses within the first 40 or so months to be surgery-induced growth of previously dormant single malignant cells. We proposed that the broad late peak relapses result from steady stochastic progressions from single dormant malignant cells to avascular micro-metastases and then on to growing deposits with no apparent synchronization to the time of surgery.
Most Important Finding – Early Relapses are the Result of Something that Happens at Surgery
The most important finding of this early work is that something happens at or about the time of surgery to accelerate or induce metastatic activity that results in early relapses. These early relapses comprise over half of all relapses. Surgery-induced angiogenesis of dormant avascular micrometastases and surgery-induced activity of single malignant cells are implicated. Late relapses are apparently not accelerated by surgery but the shallow peak at 5 years occurs as a result of shedding from primary ceasing after primary removal. We have been vigilantly looking for new data with which we can learn more about surgery-induced tumor activity and that perhaps will also lead to improved outcomes. As we describe here, there has been an important development."
Forget et al. [40] data from Universite catholique de Louvain in Brussels, Belgium. Relapse hazard is shown for mastectomy patients given ketorolac or not. Data are smoothed as indicated for fig. fig.11.
Forget et al. data were updated September 2011 and shown in hazard form but not smoothed as in fig. fig.7.7. Patient data are presented in the table. Patients included in this figure were less than 80 years of age, tumor less than 9 cm diameter and disease free survival greater than 2 months. It can be seen that relapses in months 9 -18 accounted for the major difference between ketorolac and non-ketorolac patients.
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Very often the excuse to not use Toradol is because of concern about postop bleeding. Here are links and abstracts related to studies re: Toradol and postop bleeding.
http://www.ncbi.nlm.nih.gov/pubmed/24572864
2014 Mar;133(3):741-55. doi: 10.1097/01.prs.0000438459.60474.b5.Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.
Gobble RM1, Hoang HL, Kachniarz B, Orgill DP.
Abstract:
BACKGROUND:
Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use.
METHODS:
Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups.
RESULTS:
Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids.
CONCLUSIONS:
This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications.
CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
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The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.
http://www.ncbi.nlm.nih.gov/pubmed/11214049
Plast Reconstr Surg. 2001 Feb;107(2):352-5.
Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.
Sharma S1, Chang DW, Koutz C, Evans GR, Robb GL, Langstein HN, Kroll SS.
Abstract:
Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.
///////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////This study states a three fold increase in hematoma formation after a reduction mammoplasty. if you evaluate the numbers sited in the study, they are small in actual occurrence, but when the phrase "three fold increase" is used in the conclusion of the actual study and then repeated in the abstract, the implication is the numbers are ominous. Another way the authors of the study describe the risk is a 1:16 ratio. When the risk of recurrence is balanced against the hematoma risk, the reduction in recurrence should be weighted in favor of disease free survival(opinion)http://www.ncbi.nlm.nih.gov/pubmed/22434401
Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty.
Abstract:
PURPOSE:
We conducted a retrospective review following concerns involving a suspected increase in the requirement for surgical re-exploration for hematoma evacuation when ketorolac was administered perioperatively in patients undergoing reduction mammoplasty.
METHODS:
Following ethics approval, a retrospective chart review was conducted of all patients who underwent reduction mammoplasty at our two institutions from the time ketorolac became available in 2004 until surgeons requested its use discontinued in 2007. The data we collected included patient demographics, ketorolac administration, requirement for surgical re-exploration, documented hematoma formation not requiring surgical re-exploration, and excessive bleeding in the perioperative period. Three hundred and seventy-nine patient records were reviewed; 127 of the patients received a single intravenous dose of ketorolac (15 or 30 mg), and 252 of the patients did not receive ketorolac.
RESULTS:
Patients who received ketorolac were at an increased risk of requiring surgical re-exploration for hematoma evacuation (relative risk [RR] = 3.6; 95% confidence interval [CI], 1.4 to 9.6) and hematoma formation not requiring re-exploration (RR = 2.2; 95% CI, 1.3 to 3.6).
CONCLUSIONS:
A single perioperative intravenous dose of ketorolac was associated with a greater than three-fold increase in the likelihood of requirement for surgical hematoma evacuation. Our data suggest that it may be prudent to consider carefully whether the potential risks associated with the use of ketorolac outweigh the potential benefits of using ketorolac in patients undergoing reduction mammoplasty.
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thank you for consideration of this information.
----------------------------------------------------------------------Nov 23, 2015 10:26AM - edited Nov 23, 2015 11:47AM by sas-schatzi
Geewhiz, Falls sent me a copy of a letter she wrote to her old doc. I asked that she revise it and post here. I would then erase the old doc letter from page 1 or pg 2. Time is short. Just in case Falls doesn't see your post, I'm reposting part of it. It's really well done
Written by Falleaves November 2015
Summarizing the papers I have read, inhaled anesthetics and opioids should be avoided because of their immunosuppressive effects. Opioids have also been implicated in increasing angiogenesis. Total intravenous anesthesia (TIVA) with propofol (which may reduce postoperative nausea) seems to suppress the inflammatory response to surgery. COX-2 inhibitors and NSAIDS, in particular preoperative ketorolac, could also reduce recurrence due to their anti-inflammatory properties, and their reduction of the need for opioids. Paravertebral nerve block (frequently with propofol) may be particularly valuable in reducing inflammatory cascades and preserving immune function, and reducing recurrence. It also provides better pain control than general anesthesia, reducing the need for opioids post surgery. Local anesthetics such as lidocaine and bupivicaine have been shown to cause apoptosis in breast cancer cells, and liposomal bupivacaine can provide good postsurgical analgesia and reduce the need for opioids. Preoperative gabapentin and pregabalin are effective in reducing postoperative pain and opioid use, and is preventive for chronic post surgical pain.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615712/
Interestingly, many of the anesthetic choices that appear most likely to reduce recurrence, are also better for overall patient well-being. You may be familiar with enhanced recovery pathways. Johns Hopkins has developed an ERP for colorectal patients: "The goals of the perioperative anesthesiology pathway were achieving superior analgesia, minimizing postoperative nausea and vomiting, facilitating patient recovery, and preserving perioperative immune function...The perioperative anesthetic regimen was tailored to meet the goal of perioperative immune function (in an attempt to decrease surgical site infection and decrease cancer recurrence), in part by minimizing perioperative opioid use." http://www.ncbi.nlm.nih.gov/pubmed/26404073 The Mayo Clinic has created an ERP for breast reconstruction operations, as well. This includes preoperative analgesics and preventive nausea treatment, NSAIDS, liposomal bupivacaine, reduction in opioids post surgery, and resumption of eating and walking soon after surgery. http://newsnetwork.mayoclinic.org/discussion/new-approach-to-breast-reconstruction-surgery-reduces-opioid-painkiller-use-hospital-stays/
It is my thought that if you are talking about a wide range of drugs and techniques that have ALL been tested, approved, and are in wide use, it is wise to favor those that do not promote the growth of cancer. Clearly anesthetics need to be tailored to each patient, but the impact on cancer recurrence should be a factor in the equation. It would be beneficial for breast cancer patients if an enhanced recovery pathway could be developed for them, with particular attention to use of drugs and techniques to reduce the chance of recurrence.
You are a very busy person, and I realize anesthesia is not your area, but as the director of the Breast Center you are in a position to influence every aspect of care. I am linking some of the best studies I have found, and hope that you will share them with your anesthesiologists.
Paravertebral block/Propofol
"Can anesthestic technique for primary breast cancer surgery affect recurrence or metastasis?""Efficacy and safety of paravertebral blocks in breast surgery: a meta-analysis of randomized controlled trials."
http://www.ncbi.nlm.nih.gov/pubmed/20947592"Anesthesia technique may reduce breast cancer recurrence, death."
http://www.sciencedaily.com/releases/2013/10/131015191057.htm"Thoracic paravertebral regional anesthesia improves analgesia after breast cancer surgery: a controlled randomized multicentre clinical trial"
http://www.ncbi.nlm.nih.gov/pubmed/25480319Ketorolac
"Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery."
http://www.ncbi.nlm.nih.gov/pubmed/24464611/"Reduction of Breast Cancer Relapse with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831877/Local Anesthesia
"Local anesthetics induce apoptosis in breast cancer cells"
http://www.ncbi.nlm.nih.gov/pubmed/24247230
"Evolving Role of Local Anesthestics in Managing Postsurgical Analgesia."
http://www.ncbi.nlm.nih.gov/pubmed/25866297Gabapentin and Pregabalin
"The Prevention of Chronic Postsurgical Pain Using Gabapentin and Pregabalin: A Combined Systemic Review and Meta-Analysis"
http://www.ncbi.nlm.nih.gov/pubmed/22415535Review articles on Anesthesia and Cancer
"The effects of anesthesia on tumor progression"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601457/#b58"Are we causing the recurrence-impact of perioperative period on long-term cancer prognosis: Review of currrent evidence and practice"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009631/0 -
thank you so much! Have you all noticed your anetheologist giving a hard time about this? I wonder if I should show it to my surgeon or plastic surgeon I have an appt with my plastic surgeon Friday but won't see my surgeon until surgery although they don't make the decision for pain control do they? Ugh so confusing and I just want to do everything right and all I can to live
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Steph I'm not done yet. Trying to put it together so, you can copy off and have the exact studies to put under their noses
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Steph okay done......read and let me know what you think.?
123 and Falleaves need your help. What do you think?
This pretty well pulls together the research about Toradol. I purposefully put in the studies re: bleeding to counter the immediate reaction of docs re: bleeding risk.
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Love it!
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Steph what did your anestheologist say?
123 the lead statement is pretty "in your face". LOL quite inflammatory. My thought being is it challenges the docs to make a decision on the value of the current literature and not just what has been accepted from a previous time.
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wow this is great thanks for all the great information and all the studies I have not talked to my anesthesiologist will not until right before surgery makes me very uncofortable I wonder if I should send this to my surgeon after reading these studies how can I not absolutely request this I feel like I need it to give me my best chance at survival
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thank you for the time and effort you put into this. Wish I had the info when I had MX sx....oh well. I am happy my friend ,who is having MX next week, now has the articles to give to her surgeon0 -
Sometimes "In your face" is exactly what some physicians need
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ok made an appointment to discuss this with my surgeon thank you so much for all the hel
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This is an amazing thread. Meeting with BS tomorrow to discuss my upcoming BMX on 9/22. Will certainly bring this up. Any idea if Sloan Kettering is doing anything with this? I guess I'll find out and report back. Thanks for all of this. Fingers crossed.
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rainy, it's an unknown about SK. You are new here. Welcome
To be able to read Forget's and Retsky's studies and the companion article to Forget;s study, can't see you accomplishing that in one night. I'm an old nurse. A real pain in the ass. Learned early that too many medical professionals didn't keep up beyond school. But at SK , I'd be surprised that they weren't acutely aware of these studies. ..Good Luck rainey Hugs----------let us know what happens sassy
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Thanks, Sas-schatzi. I actually did get through the Retsky study this afternoon. It took a while, and I didn't try to understand absolutely everything, but I think I have enough to talk about it and sound moderately intelligent. (I liked the history and the references to Thomas Kuhn though I doubt this will help my case.) I read through this entire thread carefully, clicking on various links, and certainly am convinced that ketorolac and the paravertebral block are worth doing. I had surgery about 20 years ago and absolutely hated the opium based drugs in my system so will also try to be convincing on that point.
I'd like to think that the folks at SK are on top of this. They are very wedded to their protocols and don't like to be questioned. It may help that the BS is Italian, and a number of these studies are European in origin. I will not meet the anesthesiologist until the day of surgery so feel I need to raise the issue now with the surgeon.
Off to click more links. Will report back. Thanks for compiling this great resource.
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yes I am going to try to read through these studies before my appt thurs hard when you have a 1 year old demanding your full attention all day! I get it but need to study it more so I don't look like an idiot lol I have spent sooooooo many nights. Researching my cancer that I promised myself not anymore but this is worth looking into
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I don't have the answer to those questions, Solfeo, but am glad you have a cooperative surgeon (at least in regard to the SNB). I suspect Sassy will be along soon with some insights - I hope so, at any rate!0
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Rainey , Don't you love the way Retsky writes? I edited my last post to you LOL, that was one glass of wine to much
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Solfeo, Toradol is the drug. It's the only NSAID that is used intraoperatively. Until the further research is done, consider asking for Toradol to be used unless it's contraindicated. I'll bring back Retsky's words
Quotes from Retsky's study
Using Computer Simulation to Analyze Bimodal Relapse Pattern
Based on computer simulation, to explain the 10 month peak we postulated that induction of angiogenesis at the time of surgery provoked sudden exits from dormant avascular phases to active growth and then to detection. That mode is quite sharp and most often seen among premenopausal patients with axillary lymph node involvement (N+). We suggested the remainder of relapses within the first 40 or so months to be surgery-induced growth of previously dormant single malignant cells. We proposed that the broad late peak relapses result from steady stochastic progressions from single dormant malignant cells to avascular micro-metastases and then on to growing deposits with no apparent synchronization to the time of surgery.
Most Important Finding – Early Relapses are the Result of Something that Happens at Surgery
The most important finding of this early work is that something happens at or about the time of surgery to accelerate or induce metastatic activity that results in early relapses. These early relapses comprise over half of all relapses. Surgery-induced angiogenesis of dormant avascular micrometastases and surgery-induced activity of single malignant cells are implicated. Late relapses are apparently not accelerated by surgery but the shallow peak at 5 years occurs as a result of shedding from primary ceasing after primary removal. We have been vigilantly looking for new data with which we can learn more about surgery-induced tumor activity and that perhaps will also lead to improved outcomes. As we describe here, there has been an important development.
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