For example a risk from melanoma is that it could grow to reach blood vessels, providing a highway to spread to other parts of the body - how then during the process of the excision of a melanoma (pre wider local excision) where doctors cut around the mole but may cut into parts of the skin that have melanoma cells in it, does this not result in cancer cells seeping into the wound and spreading to other parts of the body?
They only remove a tumor if they can cleanly remove the entire tumor and a sufficient margin of non-cancerous cells around it. Otherwise yeah, they risk spreading cancer further.
And also, they usually recommend further treatment like chemotherapy or radiation afterwards to help ensure they got everything.
Not so much risk the cancer spreading further, more so that the risky surgery will have been pointless as the tumour will just grow back if there aren’t well defined healthy margins.
If you don't remove enough, then you risk the tumor growing back where it was.
If you break the tumor and leave pieces behind, you risk them latching on to something else and growing there.
My dad had an emergency appendectomy removed via laparoscopic surgery. The appendix ended up cancerous, and it was incised with healthy margins. However—and this could be the doctors being extra conservative—the oncology team recommended Chemo due to the risk of cells spreading from this surgery and the fact it was performed laparoscopically (less careful about spreading cancer cells).
Best of luck to your dad 🤞 I didn't know you could even get cancer in your appendix until my sister was diagnosed a while back. She's been in the clear for a few years now
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Congratulations! You found the exception to the rule!
Removing prostate tumors has a high risk of side effects. And most of the time it's an extremely slow growing cancer, so its less risky than pretty much any other type - unless you get extremely unlucky like Joe Biden.
Pretty much every other type of cancer they won't remove unless they can remove it all with a clean margin.
This is why cancer treatment is a whole plan. Surgery might be one part, but it's almost always connected with other types of therapy, like chemo as well.
This way you can remove the major tumors and hopefully reduce the amount of chemotherapy that needs to happen. A hard chemo regimen is extremely hard on the body, and if you can reduce it with surgery then the prognosis may improve.
The answer part 1 is "carefully".
The answer part 2 is "all cancer treatments have risks".
Part 2a "yes it does"
Morcellation during hysterectomies
They will take out healthy tissue around the tumor to make sure they get it all.
They will also potentially take out vessels around the tumor like lymph nodes to limit the chance of metastasis.
They will also do chemo which should kill any rogue cells that get out.
It's not necessarily an issue if a few cells get into the bloodstream since not all cancers metastasize easily.
And cancer cells need to ACQUIRE the ability to escape, implant, recruit blood vessels. It’s a stepwise process.
It literally can, you try to not cut directly into tumors, good technique involves removing tissue widely depending on the type of cancer and avoiding violating capsules if present, not cutting into lymph nodes, etc. but risk of seeding is less than risk of having cancer so you still do surgery. 100 cancer cells is better to have than 1 billion cancer cells. Chemo/Radiation target “leftover”cells when surgery is initial treatment. Source: am surgeon.
Great question, I think what you’re trying to ask is do sloughed off cancer cells from surgery have the potential to create metastases or ‘new growths’ by entering the vascular circulation of a wound.
Not all cancer cells are equal within the same colony and have therefore not all cells have the potential to metastasise. Cancer cells in the same colony can have vastly different biologies due to a tumours inherent genomic instability.
Cancer cells need to have several traits to be able to form a new colony including: ability to evade immune system (say a prostate cell in a bone tissue environment would be identified and usually go through programmed cell death by the surrounding tissue/immune system), ability to locally invade and disseminate often through a process called epithelial to mesenchymal transition and also the multipotent potential to actually start growing when it has reached a different tissue site. There are plenty studies investigating the neoplastic potential of injecting a huge cancer cell colony with no cells that have this multipotent ‘stem cell’ versus -just a few hundred cells with ‘stem’ ability. The smaller stem colony reliably produces new proliferating tumours in vivo animal models. This all requires an enormous amount of mutations in the right genes to be able to bypass the bodies fail-safes.
What we probably think happens is that cells come off a tumour regularly , but are destroyed by the body because they don’t belong in that new tissue and don’t present the appropriate ‘im supposed to be here’ markers on their cell surface. However, there is always the incalculable chance that a liberated cluster of cells may hold the potential to form a new colony in a different tissue
TLDR- maybe but probably not. Also, most solid cancers tend to invade via the lymphatic channels rather than vascular.
Does that apply to a fine needle aspiration procedure (for a biopsy), too? How does it not cause a leak of malignant cells into the bloodstream?
Perhaps the treatment of my melanoma would be of help.
The tumour itself was removed with a large margin of healthy tissue to avoid damaging the tumour and at the same operation the sentinel lymph nodes (lymph nodes nearest the tumour site) were biopsied for the presence of cancer cells (negative). The site was repaired with a skin graft.
I had a year of pembrolizumab immunotherapy after the operation (to tackle any shed melanoma cells) with frequent MRI and CT scans looking for growth of masses. Everything was clear and now I'm on long term watching to check for continued absence of of secondary melanoma.
It’s easiest to think of cancer cells not as good/bad, but more like Pokémon accumulating different abilities over time.
One cell may develop a “grow” mutation andand multiply. One of those subsequent cells may add a “break through blood vessels” mutation. Yet another one may add a “seed in different organ” mutation. Without all of those, the cancer may just be a growing lump that never becomes deadly. The body is always looking for early mutated cells to destroy them.
So if you cut out a tumor before it gains an aggressive mutation, it may be cured before it has a chance to spread.
This varies by type of cancer.
I had Stage 1 kidney cancer which was treated surgically by removing the kidney. Whilst the operation was done by keyhole surgery, I have a large scar as they had to remove the kidney whole so that none of the cancerous cells remained.
This also meant that I didn't need any form of radiotherapy or chemotherapy.
Blood vessels are closed off from their surroundings. Things like cancer cells outside them won't just end up inside easily. The tumor is carefully dissected away from the surrounding tissue. Blood vessels are cauterized. Also, most cancers spread through the lymph system, not blood. There is a risk of some cancers "seeding" tissue by shedding some cells that can then start new tumors. This sometimes happens when doing a biopsy with a needle. Luckily, this doesn't happen with most types of cancer.
Most cancer surgery is completed via WIDE AREA EXTRACTION. The idea is that you remove the cancer AND an area around the cancer to guarantee its removal. If the cancer is next to the blood vessels or lymph system there is a good chance it has already spread. This is why early detection is critical.
There are some cancers, like thyroid, where all of the gland/tissue cannot be excised. We have thyroid cells all over our bodies. Suppression therapy is used afterward to be sure the body doesn't activate those leftover cells. For others, chemo &/or radiation are used to get everything (for some kinds of T-cancer, too).
It can, though they try to make a clean removal, sometimes removing a bunch of surrounding healthy tissue to be sure they got it all, since the edges are not necessarily obvious by looking.
But even then, some cancers will have tiny pieces break off into the bloodstream normally, "seeding" your body with cancerous cell clusters - but also releasing hormones that suppress other tumors from forming. But remove the main tumor, you remove the suppression, and all the "seeds" start growing.
That's why surgery is often combined with chemotherapy. Beforehand to shrink the tumor and make it easier to remove cleanly, and afterwards to hopefully kill any remaining cells.
Hi I’m a skin cancer surgeon.
While others have said that surgeons have to cut around it to avoid this risk, the simple truth is (at least for melanoma and non-melanoma skin cancer) that cutting into it is not all that risky.
We cut into them all the time, even during the initial diagnosis steps (biopsy). Many tumors like basal cell skin cancer even often have visible blood vessels in them.
It takes a lot of mutations steps for a cancer cell to gain the ability to spread to other areas, so often the cells won’t be able to if caught early. Also, for most tumors, they usually do so through the lymph system (kind of like the sewers of the body), although some can go through the blood.
But even still, it’s almost always better for the patient to cut it out even if you cut into it rather than allow it to grow.
That said there are a few cancers that we avoid cutting into exactly for the reason you mentioned like testicular cancer. Thankfully for the skin, it’s not that big of a concern.
Thank you so much for this answer.
Even if an incomplete excision is unlikely to cause cells to enter blood or lymph and re-establish at another location as you said, is there a risk of cells being pushed deeper into the skin at the local site? When re-excising from incomplete margins, do you cut deeper too, or just wider?
Not typically! Remember, skin cancers cells are skin cells themselves (just ones that have turned bad), and there are still other cells around them and in the way. You can't just push them in.
As to the margin, we cut more in any direction that we need to! Wider or deeper depending on the which margin is positive. Sometimes only cutting a little bit and sometimes cutting a lot (see my comment to OP below where I explain how Mohs surgery works, which is a specialized approach for exactly this reason).
This is such a helpful explanation thank you! So basically, have I understood correctly that - in the case of a melanoma for example - unless it has already mutated to be able to spread and embed somewhere else, then cutting into surrounding skin during an excision where cancer cells may be present or cutting directly into the mole for a biopsy, wouldn't lead to cancer spreading even if cancer cells seeped into open wound for that period of the biopsy/excision?
Pretty much! The first step is always to biopsy it first which by its nature is a partial sample of the tumor where you do cut into it. You don't typically try to cut it all out with the initial biopsy because if it's not cancer, then you've caused a huge wound for no reason.
Also many skin cancers can even be ulcerated and bleeding at baseline when the patient walks in the door. Especially basal cell carcinoma (which has one of the lowest metastasis [spreading inside] rates of any cancer, close to 1/10,000), and sometimes melanomas (although this admittedly is a bad sign in melanomas).
In fact, the gold standard method of removing high risk skin cancers is through Mohs Surgery (which is my specialty) which is a layer-by-layer approach in which we:
Through this process, the patient may sit there with a partially cut out cancer and an open wound for 1-6 hours until we have completely clear margins. And this has a 99% cure rate for most skin cancers (Basal Cell, Squamous Cell, and even Melanoma).
It's really simply not a concern that we think about. We care a lot about getting it out of course.
It can.
There is a risk with surgery and with biopsies that cancer cells are pushed into parts of tissue that were previously cancer free or into the bloodstream, but the actual impact is very small.
Cancer cells usually cant survive outside the original tumor site and it takes a lot of malignant changes for them to survive in the blood or in different parts of the body. So in theory if surgery led to cells getting into the blood and they survived/spread the cancer was likely already on the verge of metastasizing anyway.
Mice studies have shown that you need to inject about a million cancer cells into blood to cause spread of a solid organ (ie not leukaemia or lymphoma) cancer. In surgery, the number of cells that a surgeon might accidentally shave off into the bloodstream is less than that.
Additionally, the main reason cancer cells are shielded from the body's immune system is because they've released lots of anti inflammatory cytokines or signalling molecules to tell the immune system to stay away from the tumour. But if you extract those cancer cells and dump them somewhere else in the body, they don't have time to secrete all these signalling molecules so quickly, so the immune system can get to them.
So might then ask how cancer can spread normally then. The answer is that cancer cells are released into the circulation all the time. But only a small fraction succeed in seeding themselves elsewhere.
You say, "may cut into the skin that have melanoma cells in it". That is exactly what they must NOT do! Because yes, that would indeed spread cancer.
That is the reason why they need to cut around it, with a margin of safety.
One consideration is that when cancer has spread, the main tumor actually sends out suppressing chemicals to the others. If you remove the big one, the others all start to grow which is why they do the chemo and aggressive treatments.
Since it's just cells in the blood, your body can destroy them, but they do get through, which is why you have follow ups
Have we tried to harness those "suppressing chemicals" to use as a medicine to slow cancer growth?
Yeah that’s why chemotherapy and immunomodulators are big in cancer treatments now and radiation oncology is lowkey becoming a dying field in medicine.
Also, the answer to Ops question is yes it happens and that’s why usually you’re supposed to do chemo and radiation to shrink the tumor first before it gets removed surgically. There’s actually multiple cancers you’re not supposed to rush into surgery for and have to do a debulking process first with chemo and radiation.
Cancer treatment has made a lot of process and now targets the genetics of the cancer itself. That’s why you hear of ppl having HER2 negative breast cancer as the worst because if they’re negative for that HER2 receptor that means the current specific drugs on the market targeting that receptor aren’t gonna work on it (that’s why it’s negative) and those patients have a horrible survival rate and even when they do survive it comes back super easily and fast. Since there’s no receptors to target.
Cancer treatment is a multi front assault.
Surgery to remove tumors is the “basic” attack. A surgeon will do a lot of imaging to see where the tumor is and how big it is. They’ll determine how much healthy tissue around the tumor they can cut because if they leave any bit, the tumor can grow back and they’ll be back at square one (if not worse due to having to recover from surgery).
On top of that, many different types of medication are prescribed to poison the cancer. Things like chemotherapy. Cancer is a very “hungry” type of cell. It will consume lots and lots of nutrients from the blood to fuel its rapid division. This is partly what ends up killing people. The organs around the tumor basically starve and begin to shut down (there’s still a lot of mechanisms that lead to death when it comes to cancer).
Chemotherapy drugs are incredibly toxic to tissue. But, because cancer absorbs so much more nutrients than typical cells, it will absorb more poison than the cells around it. Chemotherapy is basically poisoning yourself as much as you can handle with the hopes that the cancer dies first. This will help to ensure that any cancerous cells that did escape have less success reproducing and forming more tumors.
There’s also radiation. Basically, beams of highly energetic light are blasted in such a way that they will enter your body and destroy the DNA within the cancerous cells. Much like surgical removal, blasting healthy cells around the cancer to ensure the entire tumor is hit is also part of this process.
Combinations of these procedures are used for cancer treatments as well as managing the symptoms from these treatments (surgery obviously has its side effects, chemo is poison so it makes you sicker than hell, and radiation destroys tissue that your body has to work to get rid of and heal from).
There’s also immunotherapy where they basically engineer your own cells to fight the cancer. It’s super cool. They basically take your own immune cells out and teach them to hunt specifically for the cancerous cells and then put them back in your body. It’s sort of a systemic protection from cancer spreading but it’s still pretty new.
Killing cancer is easy. Not killing the person in the process is the hard part
You can never lose a battle with cancer. The best it can do is tie because, if you die, the cancer dies, too.
Tell that to Henrietta Lacks.
Or canine transmissible venereal tumor or devil facial tumour disease.
This a great way to think outside of the norm.
Norm!
I think this comes from xkcd, but a 9mm bullet can kill 100% of cancer cells in a petri dish, does not make it a valid cure.
This is actually a great way of explaining why curing cancer is hard!
Thanks, I'd actually somehow never heard of immunotherapy until just now. That is really cool, and any new cancer treatment is a win.
Presumably chemotherapy needs to be carefully managed then in order to avoid causing any permanent damage that might cause a patient's death even in the event the cancer is treated? Or am I exaggerating the risk?
All cancer treatments are about choosing the lesser devil, so to speak. They will cause permanent damages, especially chemotherapy and radiation, and they will make you die sooner. BUT between cutting your life short by 10 years compared to a healthy person due to chemotherapy and cutting your life short by 30 years due to cancer, it's rather obvious which one to choose.
Worth caveating this with all traditional cancer treatments.
Some of the CAR-T, TCR-T and other immunotherapies are rapidly presenting a more favourable side effect profile.
Autologous therapies tend to typically only present a risk of a rare self-reaction is identified (which can be mitigated by better target selection) or by causing cytokine storm via the high rate of cancer cell death (also a risk with chemo). However, these are expensive and have a rather extended vein to vein time of 30-45 days from cell collection to administration.
Allogeneic therapies either require immunosuppressants, which fits the narrative from your ‘lesser evil’ comment, or can be ‘hidden’ from the immune system such that they are comparable with autologous therapies (at a lower cost, greater availability, and with (typically) healthier starting material.
Good info.
So what you're saying is that now is exactly the time that we should be slashing the funding for cancer research?
I’m assuming (hoping) this is a dig at the current US administration and related policies.
In all honesty investment in the kind of biotech and research organisations who make these kind of treatments possible is in an appalling state.
The whole ATMP (Advanced Therapeutic Medicinal Product) industry is suffering an acute contraction in funding availability following the proverbial boom of the pandemic.
A lot of these products are ~10-20years from concept to commercial product (assuming they succeed as the process of getting to market tends to whittle down candidates), but investment tends to look at 1, 2 or 5 year returns in line with tech startups.
Currently on Opdivo/Yervoy therapy for stage 3C melanoma, and besides some extreme fatigue and muscle weakness (which was cleared via a 5 day steroid dose) this has been a breeze. Immunotherapy is used to target certain mechanisms in the cancer’s growth and progression pathway, and a gene called BRAF is examined for mutations. Depending on the presence of BRAF (I have it and had 10 mutations, for instance) this is more info the docs use to decide which therapy is right for you.
Yeah, they’re very target specific at the moment, relatively few broad spectrum targets.
Glad to hear it’s been relatively tolerable for you though!
I used to work for a company making a TCR-T Cell product and I think you had to have the target TCR variant and be a specific HLA subtype in order for it to work. Even then, because it was clinical trials, and those cost the company ~$1million USD per patient (trials are run at the company’s expense obviously) the initial patient pool tends to be low.
It does, the patients have lab work done, the Oncologists decide on the Drug treatment plan that is known to help with that type of cancer. Then dosing may be like drug X every other week, drug y on alternate weeks etc. Each dose they have lab work done to see how well their body is tolerating it and adjust accordingly. There are General purpose cancer drugs and more targeted drugs that work only on specific types of cells.
I had chemotherapy for leukemia followed by a stem cell transplant. Basically went scorches earth on my bone marrow till it was dead then gave me someone else's stem cells. Those stem cells took up residence in my bone marrow and when they started growing they started to rebuild my donor's immune system in my body. So not only did my doctors replace my faulty blood but they replaced it with blood that doesn't have cancer and can therefore recognize, target and destroy any remnants of my old blood that may try to become cancer again. It's a really crazy idea.
Whoa!
How are you doing now? Hopefully you are healing, recovering, and thriving. ❤️
I'm alive. Plagued by tiredness, depression, and a list of long term effects. Doc mentioned the possibility of testosterone replacement but it's ultimately not up to him. I'm lucky to have the support I do. Not many employers would keep me on at full pay for over a year and accomodate me when I did come back to work. Just gets hard to see the light at the end of the tunnel when you've already been hit by a few freight trains.
Ugh, I’m sorry for your troubles. The emotional complexity of this disease (and its treatments) can be as devastating as the ravenous cancer cells themselves.
I've had cancer, and 2 auxiliary cancers after the main stage 4 went into remission, this is an amazing overview on the topic.
For anyone interested, I also went through a stem cell transplant. This is where the doctors give you so much chemo, specifically targeting your immune system in order to kill it.
They do this after most if not all cancerous cells are gone from previous rounds of chemo. They then implant another healthy person's stem cells into your blood (sometimes it's your own cells previously taken) in order to give you a fresh immune system to fight the cancerous cells off if they grow back. This treatment has its own risks, no immune system, graft Vs host etc but it has helped me and many others recover.
Fun fact, because the immune system is replaced you change blood type to the donor blood type. I used to be O- now I'm O+
Immunotherapy does not involve removing and reintroducing your cells. It involves giving medications which make the cancer cells detectable by the immune system which can then attack the cells and kill them.
One of the ways cancer cells survive is by evading the immune system, especially the T cells. Immunotherapy is designed to counter this.
There are adoptive cell therapies (a type of immunotherapy) like CAR-T and TCR-T therapy where they basically take your own immune system's cells, modify them, and reinfuse them back in. These therapies are very new. CAR-T therapy has been shown to be very successful against some blood cancers.
Radiation treatments are not only found in the beams. I had an ocular melanoma and they treated it with radioactive brachiotherapy. They sewed a radioactive piece of metal to the back of my eye for three days to kill it off.
I know its very stuupid but based on what you said, is there any incidence in the mortality of people with obesite, celiac disease, diabetes ,etc?
Probably. You're poisoning someone to the edge of death, anything that complicates their health probably plays into that game.
It could just be me, it’s 1 am here and my daughter finally went down for the night so I’m exhausted lol. But I have no clue what you’re asking.
What about if a doctor examines a patient with a lump of some sort and squeezes pretty hard on it? Won't that risk a spread?