An unanswered NET cancer question

I’ve been writing about NET cancer for nearly 25 months. But yesterday someone asked in a search that brought them here, “How does neuroendocrine cancer kill you?” And that question brought me up short because while I have written about Jane’s death, I have not written about the biology involved in death from NET cancer.

NET cancer can kill in a variety of ways…

While I can already tell this is going to be a difficult piece to write–my hands are already shaking–I am going to try to answer the question as clearly as I can. But the subject is a complex one because NET cancer is a complex disease.

NET cancer more complex than others

That complexity starts with an understanding of how it is different from other cancers that involve tumors. A normal cancerous tumor, for the most part, takes up space and consumes resources the body would normally use elsewhere. Because a NET cancer tumor sometimes secretes hormones, it gets involved with the body’s chemistry in ways other tumors generally do not.

Some pancreatic NET cancer patients have to set their alarm…

In my wife’s case, her tumors were secreting the hormone serotonin. Serotonin is involved with a whole host of things, including depression when you have too little of it. But while lots of research has been done on finding ways to increase serotonin levels for depressed patients, too much of it can be deadly as well.

Impact of too much serotonin

And that was the problem Jane faced. Her tumors were all producing additional quantities of serotonin above and beyond what her body was normally producing–or had any need for. Serotonin helps regulate things like appetite, sleep, temperature regulation, cardiovascular function, muscle contraction and the levels of other endocrines. In essence, the excess serotonin Jane was dealing with messed up her body chemistry in very serious ways. And the larger and more numerous those tumors became the more serious her physical problems became.

NET cancers can form anywhere in the body.

These issues initially included low blood pressure, persistent insomnia, headaches, loss of appetite, and frequent diarrhea. While we generally think of low blood pressure as a good thing, low blood pressure can be just as fatal as high blood pressure.

NET cancer and the heart

By the time Jane’s NET cancer was diagnosed the tumors in her liver had been shooting raw serotonin up through the valves in the right side of her heart for some time. Normally, serotonin in the blood stream is metabolized in the liver, but when it is produced there that action does not happen. And serotonin is what is called a “hot” chemical. That means it is very damaging to any tissue it comes in contact with.

…the heart surgery would buy us the time to do the liver treatments…

What sent us to her primary care doctor that spring was a built up of fluid in her legs that interfered with her ability to walk or climb stairs. That excess fluid turned out to be the blood the valves in her heart were now too weak to propel to the lungs and that was now falling back into the blood vessels from the legs. Eventually, the volume of regurgitated blood would begin to fill her abdomen as well.

Serotonin and digestion

Without the heart surgery that replaced those valves Jane would have died of heart failure caused by the excess serotonin her NET cancer tumors were creating. But that was not what killed her–nor was it the only thing the NET cancer was causing that had potentially fatal consequences.

…the carcinoid attack put her in a coma for 30 hours.

Serotonin also regulates digestion. With too little serotonin, we get constipation. With too much of the hormone, we get diarrhea. And with way too much serotonin that diarrhea becomes increasingly uncontrollable. Uncontrolled diarrhea, in turn, leads to dehydration unless we find other avenues to get fluids into the body. And if that diarrhea get so bad that intravenous fluids can’t make up the deficit, then dehydration leads inevitably to death. Jane’s diarrhea was at close to that level when she died, but it was not the dehydration that killed her–though it easily could have been.

NET cancer and appetite

But serotonin also regulates whether we are hungry or not. That, in combination with the regurgitated blood that was filling her abdomen, made it increasingly difficult for Jane to eat even small amounts of food. She finished every day with a significant caloric imbalance: she was literally starving to death. And food contains more than calories. She was being shorted on vitamins and minerals as well. Even taking supplements did little good because the speed at which she digested her food was so great that her intestines did not have time to absorb the nourishment that was passing through.

Jane’s liver was in a pretty damaged state…

One of the critical things she was missing as a result was albumin. It is the stuff that helps keep the fluids inside the individual cells and keeps the cell walls from breaking down. Any pin prick caused Jane to leak cell fluid onto her clothes and bedding. The same process was likely going on in her internal organs. The failure of any major organ is generally fatal.

NET cancer and the liver

And Jane’s liver was in a pretty damaged state by the time she was diagnosed. She had three tumors in her liver–the largest being nearly three centimeters in length. Those tumors had already caused so much damage that she was rejected for a Phase III trial of a drug that has since been approved for use on NET cancers. If her heart problem had not been so critical, we would likely have tried liver ablation therapy to kill those tumors first. Either that or a liver transplant–or perhaps both–were things we were discussing as next treatment steps shortly before her death.

…she was literally starving to death.

But what ultimately killed Jane was a carcinoid attack triggered, we now think, by her attempts to do the physical therapy required to recover from the heart surgery. A carcinoid attack often happens to NET cancer patients following during or following any type of surgery. Suddenly the body is flooded with whatever hormone or peptide the tumors produce. In the case of serotonin, respiration and blood pressure collapse, reducing the patient’s blood oxygen level to unsustainable levels, and the patient lapses into a coma. Without intervention, the patient dies.

Carcinoid attacks

For this reason, NET cancer patients undergoing surgery receive massive doses of octreotide before and after surgery. Octreotide blocks the receptors on the tumors and, essentially, blocks the release of excess serotonin. But Jane’s tumors were bigger and more advanced than a normal NET cancer patient. She suffered her first carcinoid attack shortly after she first started doing physical therapy following the heart surgery. She was doing so well with that we were only waiting for a bed in the step-down unit to move her out of intensive care. But the night nurse discovered her pulse oxygen levels had dropped into the mid-to-high 80s.

Serotonin also regulates digestion.

Jane recovered from that and began physical therapy again. This time the carcinoid attack put her in a coma for 30 hours. Octreotide brought her back, but she was now much weaker than she had been. And the third attack left her weaker still. It was not until after the fourth attack that we made the connection between her physical therapy and the attacks–and by then it was too late. Jane died the next day. We think the tumors in her liver and elsewhere were ramping up because of the body’s call for hormones to rebuild muscle in physical therapy. Whether that is true or not cannot be determined for certain because there is only the one case to work from.

Jane’s NET cancer death

In any event, the proximate cause of Jane’s death was the depressed respiration and blood pressure caused by the carcinoid attack. But the heart valve issue, the dehydration, the starvation and the chemical imbalances that creates, or the liver damage the tumors created could have killed her just as easily had her doctors not intervened.

…serotonin is what is called a “hot” chemical.

We all believed–including Jane–that my wife could win her battle with NET cancer–that the heart surgery would buy us the time to do the liver treatments and that would buy us enough time to remove the primary tumors in her intestines and that would buy us enough time to find a cure.

NET cancer knowledge

It didn’t happen that way. We knew too little and what we did not know proved to be too much. And while we have made great strides in our knowledge over the 25 months since Jane’s death, there is still a great deal more we need to learn to prevent even the deaths caused by serotonin producing NET cancers.

…low blood pressure can be just as fatal as high blood pressure.

That is equally true of the myriad other forms of NET cancer. NET cancers can form anywhere in the body. They can, at least theoretically, produce any of hormones or peptides the body produces. They form in the brain, in the bone, in the pancreas, in the lung–anywhere. And if they are producing a hormone or a peptide they will get involved in body chemistry in many different ways with many different effects–most of them not good.

Pancreatic NET cancers

For example, everyone knows what happens when the pancreas does not create enough insulin: diabetes causes high blood sugar because there is not enough insulin to move the sugars the blood transports into the cells of muscle and other tissue. It can result in heart problems and blindness and circulation issues. But if a NET cancer causes an overproduction of insulin, that can have equally bad consequences–starting with the effects of very low blood sugar. And insulin is not the only thing a pancreatic NET cancer can create. Some pancreatic NET cancer patients have to set their alarm to wake them up a couple of times a night to get something to eat to avoid lapsing into a coma while they sleep.

…a NET cancer tumor sometimes secretes hormones…

Apple founder Steve Jobs suffered from pancreatic NET cancer. We do not know what his tumor was over-producing, but his liver was damaged enough by the metastases that he underwent a liver transplant at one point. Without that transplant, liver failure would have killed him. But half a dozen other things could have as well–just as was the case with Jane.

We need more NET cancer research

In short, NET cancer can kill in a variety of ways, depending on the hormone or peptide produced and the effects of a gradually building overdose of that hormone or peptide on the other parts of the body. And if that NET cancer has metastasized to the liver, those impacts can be even greater and, sometimes, stranger–at least from a layperson’s point of view.

…my hands are already shaking…

What we continue to need is far more research than we can do with the small sums of money available. If you can do anything to help we need you to contribute.