Metastasis [3]

Metastasis [3]

The development of remote haematogenous metastases is the most dangerous manifestation of a tumour’s progression. However, despite extensive studies of metastases in different tissues and organs, the reasons why and how cancer cells enter the bloodstream and why metastases spread via the lymphatic or circulatory systems are still not fully understood.

Why does a cancer cell feel the need to travel? What motivates it to do so? How does it choose its next home? Even in the second half of the 19th century James Paget observed that different tumours chose a variety of different tissues and organs in which to metastasise. We know this as the seed and soil theory. Not unlike in nature – radishes that are sown in sandy dunes probably won’t grow. Moreover, as it turn out, over the course of a day roughly 4×106 cancer cells are circulated per one gram of tumour mass. Thankfully, the vast majority of these cells are destroyed. It’s also been observed that connective tissue tumours and gliomas travel alone, whereas melanomas and carcinomas mostly travel in groups (tumour emboli which can be seen under a microscope). In short, there are lots of interesting facts, but very few answers.

Haematogenous dissemination

For cancer cells to enter the bloodstream from their primary location they have to be able to penetrate an anatomical barrier – the basal membranes of the walls of the capillaries, which can be found under the layer of endothelial cells that line the interior surface of blood vessels. We now know that tumours are capable of stimulating the development of new blood vessels in their direction. This is called angiogenesis. Therefore, at least some of the cancer cells which enter the bloodstream do so via these newly formed blood vessels. That said, unlike common blood vessels, the ones created by tumours are much more fragile. The second way cancer cells enter the bloodstream is via blood vessels created by the tumour itself (angiogenesis).

Once they’ve entered the bloodstream, the cancer cells are met with a hostile environment causing many to perish before they’ve really even begun to migrate. On the other hand, tumour cell emboli, or groups of cancer cells, can get stuck in narrower blood vessels. Among the body’s weak points are the tiny blood vessels of the lungs, the large pulmonary capillary (the smallest blood vessels) systems, which deliver blood to other organs, the portal vein system, which delivers blood from the capillaries of abdominal cavity to the liver, and the small calibre blood vessels in bones. This weak point theory explains why certain tumours metastasise in the lungs, liver and bones.

It has been observed that certain tumours prefer specific places to metastasise. For example, prostate cancer most often metastasises in the bones, lung cancer in the liver, brain, adrenal glands and the skin, while breast cancer often metastasises in the bones, lungs, liver, pleura and peritoneum. Colon and pancreatic cancers often metastasise in the liver and peritoneum, but thyroid and kidney tumours most often choose the bones and lungs.

The treatment of haematogenous metastases is complex. If the metastases are few in number and it’s possible to remove the sources of dissemination surgically or by targeted radiation, then this chosen method of treatment will definitely be followed by a course of drug therapy. Currently, a number of local methods to eradicate metastases are available in Latvia – surgery, radiation, stereotactic radiosurgery and invasive methods of radiology, which block blood flow to the tumour. Therefore, there are possibilities and many of them can significantly prolong life, even for years. However, if an organ is riddled with metastases, which can’t be surgically removed or treated individually with radiation, then systemic drug treatment will be prescribed to shrink the mass of the tumour, to stabilise the process for as long as possible and to alleviate painful symptoms. The conundrum of how to treat an initially metastatic tumour is still up for discussion. In some cases it’s possible to effectively reduce or even completely eradicate distant locations of metastases with systemic therapy, yet the primary tumour remains like a dormant volcano that can eject newly cloned cancer cells at any moment. The current conservative school of thought is not to remove the primary location of a metastatic tumour as it will not significantly affect life expectancy. However, cases do differ from one another. If systemic therapy has been very effective, then it’s worth considering the complete eradication of the primary source of metastases, either surgically or with radiation. If this is not done, then it’s only a matter of time before the illness returns and it’s possible that the drugs that were used previously will no longer be effective.

Metastasis in natural cavities

            This is called implantation metastasis. The malignant cells of tumours in the chest, abdomen or pelvic cavity can, if they grow through the serous membranes (which cover the exterior of organs), slough off individually or in small groups and migrate further throughout the abdomen, chest, pelvic cavity, pleurae or the pericardial cavity. These migrating cell colonies are often either free-floating or found attached to the peritoneum, fascia and mesentery. This type of dissemination is most often observed with stomach and ovarian tumours. It’s also believed that implantation metastasis could be the reason why tumours spread to the pelvic lymph nodes, the aorta and below the diaphragm.

The most common locations for metastases

Every tumour has its favourite places to metastasise. I’ll list the main ones. It’s important to know this, so you can recognise the symptoms of these damaged organs chosen by the tumour. Tumours can also metastasise in less likely tissues and organs, but the main locations for metastases include:

  • Pancreatic cancer – liver, lungs, peritoneum;
  • Uterine cancer – bones, liver, lungs, peritoneum, vagina;
  • Breast cancer – bones, liver, brain, lungs;
  • Stomach cancer – liver, lungs, peritoneum;
  • Melanoma – bones, brains, liver, lungs, skin, muscles;
  • Kidney cancer – adrenal glands, bones, brains, liver, lungs;
  • Ovarian cancer – lungs, liver, peritoneum;
  • Lung cancer – adrenal glands, bones, brains, liver, other lung;
  • Prostate cancer – adrenal glands, bones, liver, lungs;
  • Colon cancer – liver, lungs, peritoneum;
  • Rectal cancer – liver, lungs, peritoneum;
  • Bladder cancer – bones, liver, lungs;
  • Thyroid cancer – bones, liver, lungs.

Symptoms of metastases

Metastases are often asymptomatic. However, once the first symptoms manifest themselves, their intensity will depend upon the location of the metastasis and the extent of the damage. The most common complaints, depending on the location of the metastases, are pain or abnormal fractures in the case of bone metastases. Symptoms of brain metastases include headaches, cramps and dizziness. Jaundice, pain in the right side or a heavy feeling in the chest can indicate liver damage, while shortness of breath or a persistent cough can be a sign of lung metastases. Of all the available examination methods, PET/CT (positron emission tomography) scans, which are available at two locations in Latvia, are the most precise way of measuring the spread and extent of metastases. Although a common method for monitoring disease progression in Latvia, tumour markers are not enough to decide on a course of therapy. The presence of metastases must be confirmed, ideally by examining a sample under a microscope. The tissues of the metastases could differ from those in the primary tumour, which would require a different treatment strategy.

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