Metastasis and Surgery
Many years ago, before I specialised in cancer support, a friend contacted me to say she had discovered a lump in her breast. She lived many miles outside Sydney, but she wanted to come and see me to discuss her health. She had seen her doctor who wanted her to do a mammogram and have a biopsy. She knew of the dangers of both in relation to encouraging metastasis and was terrified. This was the early 1980s and it was difficult to get information as there was no ready internet that we could turn to at the time. In the end, she did have both tests done. Unfortunately, her cancer spread and metastasised to her bowel and she died a short time after.
I have had reason to give a lot of thought to this topic in the years since.
Once someone is diagnosed with a cancerous tumour, their first thought is often to “cut it out” as quickly as possible before parts of it break away and spread elsewhere. This is an understandable reaction, but not accurate and not necessarily a useful one. It could even worsen the problem. There are many reasons for this. In fact, it has been shown, since the late nineteenth century, that it is almost always impossible to cut cancer out and remove it by surgery alone.
Many steps are required and many obstacles must be overcome for cancer cells to escape from a tumour, enter the bloodstream, migrate to a new location, penetrate that tissue and become established. [i]
For one or more isolated cells to break away from a tumour, they first have to break through the connective tissue that surrounds the latter. To travel through the body, the cancer cells have to enter the bloodstream. To do this they have to break through the blood vessel before they can start to circulate. In order to do this, cancer cells must secrete enzymes [ii] that breakdown the basement membrane of the blood vessel wall.
Blood flow through and along blood vessels is rapid and turbulent. This is a ‘rough and tumble’ environment and can damage or break down the floating cancer cells. As well as remaining intact, the cancer cells must also avoid the various components of the immune system, such as the large and powerful white blood cells that travel in the bloodstream and patrol it, looking for unwanted cells and substances.
If they manage to survive that experience, they have to grapple with and dock at a target destination. This is not easy. The cells have to cling to a part of the blood vessel wall, resisting the flow of blood, and then break through it. Even then the cancer cells are not safe. They have to break through the surrounding connective tissue, back out and into the target tissue or organ where they can establish a new home.
Free-floating cancer cells have a short lifespan and this complex and difficult process has to be accomplished rapidly. The chances of success are poor. They can, however; be helped or blocked further by a number of factors. One of the processes that encourage the success of this attempt at metastasising, travelling, to and becoming established at a new site, is surgery. Yes, surgery can actually make metastasis easier for these wayward cancer cells. Cancer surgery can lead to an alternative and easier method of metastasis, making cancer progression more likely.
When a tumour is removed, this almost inevitably disrupts the structure of the tumour and the blood vessels that supply it. This encourages the spread of cancer cells into and through the bloodstream, or to the seeding of these cancer cells into the chest or the abdomen. [iii] [iv],[v]
One study showed that surgery improved survival in the early years, but further monitoring over time led the authors to state ” ..….primary tumour removal may result in sudden acceleration of metastatic process….).
Another study noted that, “… surgery, although reducing tumour mass, and potentially curative, can also augment metastatic development.” [vi]
One of the methods that aid the cancer cells in their efforts to spread, more formally known as Circulating Tumour Cells, is the use of cell-to-cell adhesion molecules such as galectin-3. This is present on the surface of cancer cells and enables cancer cells to stick to each other and to stick to the lining of blood vessels.[vii] This is an essential step in the development of metastatic spread and the establishment of a new tumour. If a circulating tumour cell does not find a new home, it is eventually detected and destroyed by the white blood cells and other immune agents.
Surgery can increase tumour cell adhesion by up to 250% or more [viii]. Fortunately, modified citrus pectin which is readily available as a supplement powder can help to reduce cancer cell adhesion. It does this by binding to the galectin-3 on the surface of the cancer cells, and thus preventing the cancer cells from sticking to each other and forming a cluster, and by preventing the circulating tumour cells from attaching to the lining of the blood vessels. [ix] In other studies, MCP reduced lung metastasis from 93% to 50%.
Studies would seem to suggest a maintenance dose of 5 g or one teaspoon a day on a maintenance diet and 15 g or three teaspoons for a couple of weeks prior to surgery [x].
I wish I had known this all those many years ago when my friend had worried about biopsies and mammograms for her breast lump.
[i] van der Bij GJ, Oosterling SJ, Beelen RH, Meijer S, Coffey JC, van Egmond M. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer Ann Surg. 2009 May;249(5):727-34. doi: 10.1097/SLA.0b013e3181a3ddbd.
[ii] Wagenaar-Miller RA1, Gorden L, Matrisian LM. Matrix metalloproteinases in colorectal cancer: is it worth talking about? Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):119-35.
[iii] Yamaguchi K1, Takagi Y, Aoki S, Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Futamura M, Saji S.Ann Surg. 2000 Jul;232(1):58-65.
[iv] Da Costa ML1, Redmond P, Bouchier-Hayes DJ. The effect of laparotomy and laparoscopy on the establishment of spontaneous tumour metastases. Surgery. 1998 Sep;124(3):516-25.
[v] Shakhar G1, Ben-Eliyahu S.Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol. 2003 Oct;10(8):972-92.
[vi] van der Bij GJ, Oosterling SJ, Beelen RH, Meijer S, Coffey JC, van Egmond M. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer Ann Surg. 2009 May;249(5):727-34. doi: 10.1097/SLA.0b013e3181a3ddbd.
[vii] Yu LG1, Andrews N, Zhao Q, McKean D, Williams JF, Connor LJ, Gerasimenko OV, Hilkens J, Hirabayashi J, Kasai K, Rhodes JM. Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion J Biol Chem. 2007 ;5;282(1):773-81.
[viii] ten Kate M1, Hofland LJ, van Grevenstein WM, van Koetsveld PV, Jeekel J, van Eijck CH. Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium. Int J Cancer. 2004 Dec 20;112(6):943-50.
[ix] Pratima Nangia-Makker, Victor Hogan, Yuichiro Honjo, Sara Baccarini, Larry Tait, Robert Bresalier, Avraham Raz. Inhibition of Human Cancer Cell Growth and Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin. J.Nat.Cancer Inst.2002;94(24):1854–1862,
[x] Guess BW1, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI. Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study. Prostate Cancer Prostatic Dis. 2003;6(4):301-4