BreastCancerChoices.org |
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| Scrutinizing the evidence for breast cancer procedures and treatments |
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Take home question to ask yourself: Can you plan your surgery with your doctor in order to avoid trauma to your breast in order to forestall possible spread of cancer cells? |
by Steven Nemeroff ND
Reprinted from Life Extension Magazine December 2009
Cancer Surgery: What You Need to Know Ahead of Time
The cornerstone of treatment for the great majority of cancers is the surgical removal of the primary tumor. The
rationale for this approach is straightforward: if you can get rid of the cancer by simply removing it from the body,
then a cure can likely be achieved. Unfortunately, this approach does not take into account that after surgery the
cancer will frequently metastasize (spread to different organs). Quite often the metastatic recurrence is far more
serious than the original tumor. In fact, for many cancers it is the metastatic recurrence—and not the primary
tumor—that ultimately proves to be fatal.1
In a shocking irony, a growing body of scientific evidence has revealed that cancer surgery can increase the risk of
metastasis.2 This would fly in the face of conventional medical thinking, but the facts are undeniable.
To gain a better understanding of how surgery can increase the risk of metastasis, let’s first discuss the actual
process of cancer metastasis. A complicated sequence of events must occur in order for cancer to spread to
another part of the body.2 Isolated cancer cells that break away from the primary tumor must first breach the
connective tissue immediately surrounding the cancer. Once the cancer cell has broken free of the surrounding
connective tissue, the next step is to enter a blood or lymphatic vessel. This is easier said than done, as entry into a
blood vessel requires the cancer cell to secrete enzymes that degrade the basement membrane of the blood
vessel.3 Entry into a blood vessel is vitally important for the aspiring metastatic cancer cell, since it uses the
bloodstream as a highway for transportation to other vital organs of the body—such as the liver, brain, or lungs—
where it can form a new deadly tumor.
Now that the lone cancer cell has finally entered the bloodstream, its problems have only just begun. Traveling
within the bloodstream can be a hazardous journey for cancer cells. Turbulence from the fast moving blood can
damage and destroy the cancer cell. Furthermore, cancer cells must avoid detection and destruction from white
blood cells circulating in the blood stream.
To complete its voyage, the rogue cancer cell must adhere to the lining of the blood vessel, where it degrades
through and exits the basement membrane of the blood vessel. Its final task is to burrow through the surrounding
connective tissue to arrive at the organ that is its final destination. Now the cancer cell can multiply and form a
growing colony that serves as the foundation for a new metastatic cancer. Time is working against these solitary
cancer cells. This entire sequence of events must happen quickly, since these cells have a limited life span.1
We now see that cancer metastasis is a complicated and difficult process. Fraught with peril, very few free-standing
cancer cells survive this arduous journey.2 The probability of cancer cells surviving this journey and forming new
metastases can be increased by anything that serves to make this process easier.
In a groundbreaking study published in the medical journal Annals of Surgery in 2009, researchers reported that
cancer surgery itself can create an environment in the body that greatly lessens the obstacles to metastasis that
cancers cells must normally face.2
Just as concerning is the revelation that cancer surgery can produce an alternate route of metastasis that
bypasses natural barriers. During cancer surgery, the removal of the tumor almost always disrupts the structural
integrity of the tumor and/or the blood vessels feeding the tumor. This can lead to an unobstructed dispersal of
cancer cells into the bloodstream, or seeding of these cancer cells directly into the chest or abdomen.4-7 This
surgery-induced “alternate route” can greatly simplify the path to metastasis.
To illustrate, a study published in the British Journal of Cancer in 2001 compared the survival of women with breast
cancer who had their tumors removed surgically, to the survival of women with breast cancer who did not have
surgery. As expected, the findings established that surgery substantially improved survival in the early years.
However, further analysis of the data determined that women who had surgery had a spike in their risk of death at
eight years that was not evident in the group who did not have surgery.8 In their interpretation of the results, the
authors of the study stated: “A reasonable hypothesis to explain the observed patterns of the hazard functions [risk
of cancer death] is to assume that…primary tumor removal may result in sudden acceleration of metastatic
process…”
Another group of researchers commenting on a study examining the surgical treatment of colon cancer were far
bolder in their conclusions: “This finding strongly supports that surgery alters the natural course of the disease by
elongating life expectancy in the greater part of the patient population, but also by simultaneously shortening
survival in a smaller subset of patients. Thus, both experimental and clinical evidence support that surgery,
although greatly reducing tumor mass and potentially curative, paradoxically can also augment metastasis
development.”2
Given these disturbing findings, what can individuals undergoing surgery for their cancers do to protect themselves
against an increased risk of metastasis? A worthwhile strategy would be to examine all of the mechanisms by
which surgery promotes metastasis, and then create a comprehensive plan that counteracts each and every one of
these mechanisms.
WHAT YOU NEED TO KNOW: CANCER SURGERY
• Surgical removal of cancer typically provides the best chance of disease-free survival.
• A growing body of evidence suggests that cancer surgery itself may increase the risk of metastasis (spread to
other areas) via numerous mechanisms including: increasing cancer cell adhesion, suppressing immune
function, promoting angiogenesis, and stimulating inflammation.
• Since metastatic disease is often deadlier than the original tumor, it is important to utilize preventive strategies
to prevent cancer metastasis.
• Steps to help prevent cancer metastasis include: combating cancer cell adhesion, supporting immune health,
heightening immune surveillance, inhibiting angiogenesis, minimizing inflammation, and choosing surgeons and
anesthesiologists who utilize advanced techniques that may reduce metastatic risk.
• Certain nutrients, drugs, types of anesthesia, and surgical techniques are associated with reduced risk of
metastasis.
Surgery Increases Cancer Cell Adhesion
One mechanism by which surgery increases the risk of metastasis is by enhancing cancer cell adhesion.9 Cancer
cells that have broken away from the primary tumor utilize adhesion to boost their ability to form metastases in
distant organs. These cancer cells must be able to clump together and form colonies that can expand and grow. It
is unlikely that a single cancer cell will form a metastatic tumor, just as one person is unlikely to form a thriving
community. Cancer cells use adhesion molecules—such as galectin-3—to facilitate their ability to clump together.
Present on the surface of cancer cells, these molecules act like velcro by allowing free-standing cancer cells to
adhere to each other.10 Cancer cells circulating in the bloodstream also make use of galectin-3 surface adhesion
molecules to latch onto the lining of blood vessels.11 The adherence of circulating tumor cells (CTC) to the blood
vessel walls is an essential step for the process of metastasis.
Just like a person sliding down an icy hill has no hope of stopping if they cannot grab onto something, a cancer cell
that cannot adhere to the blood vessel wall will just continue to wander through the blood stream incapable of
forming metastases. Unable to latch onto the wall of the blood vessel, these circulating tumor cells become like
“ships without a port” and are unable to dock. Eventually, white blood cells circulating in the bloodstream will target
and destroy the CTC. If the CTC successfully bind to the blood vessel wall and burrow their way through the
basement membrane, they will then utilize galectin-3 adhesion molecules to adhere to the organ to form a new
metastatic cancer.10
Combating Cancer Cell Adhesion
Regrettably, research has shown that cancer surgery increases tumor cell adhesion. In one experiment that
mimicked surgical conditions, scientists reported that the binding of cancer cells to the blood vessel walls was
increased by 250%, compared to cancer cells not exposed to surgical conditions.12 Therefore, it is critically
important for the person undergoing cancer surgery to take measures that can help to neutralize the surgery-
induced increase in cancer cell adhesion.
Modified Citrus Pectin
Fortunately, a natural supplement called modified citrus pectin (MCP) can do just that. Citrus pectin—a type of
dietary fiber—is not absorbed from the intestine. However, modified citrus pectin has been altered so that it can be
absorbed into the blood and exert its anti-cancer effects. The mechanism by which modified citrus pectin inhibits
cancer cell adhesion is by binding to galectin-3 adhesion molecules on the surface of cancer cells, thereby
preventing cancer cells from sticking together and forming a cluster.13 Modified citrus pectin can also inhibit
circulating tumor cells from latching onto the lining of blood vessels. This was demonstrated by an experiment in
which modified citrus pectin blocked the adhesion of galectin-3 to the lining of blood vessels by an astounding
95%. Modified citrus pectin also substantially decreased the adhesion of breast cancer cells to the blood vessel
walls.13
Impressive research has documented the power of modified citrus pectin to directly inhibit cancer metastasis. In a
study published in the Journal of the National Cancer Institute, modified citrus pectin was administered to rats that
were injected with prostate cancer cells, while rats not receiving modified citrus pectin served as the control group.
Lung metastasis was noted in 93% of the control group, whereas only 50% of the modified citrus pectin group
experienced lung metastasis. Even more noteworthy was the finding that the modified citrus pectin group had an
89% reduction in the size of the metastatic colonies, compared to the control group.14 In a similar experiment,
mice injected with melanoma cancer cells that were fed modified citrus pectin experienced a greater than 90%
reduction in lung metastasis compared to the control group.15
After these exciting findings in animal research, modified citrus pectin was then put to the test in men with prostate
cancer. In this trial, 10 men with recurrent prostate cancer received modified citrus pectin (14.4 g per day). After one
year, a considerable improvement in cancer progression was noted, as determined by a reduction of the rate at
which the prostate-specific antigen (PSA) level increased.16 This was followed by a study in which 49 men with
prostate cancer of various types were given modified citrus pectin for a four-week cycle. After two cycles of treatment
with modified citrus pectin, 22% of the men experienced a stabilization of their disease or improved quality of life;
12% had stable disease for more than 24 weeks. The authors of the study concluded that “MCP (modified citrus
pectin) seems to have positive impacts especially regarding clinical benefit and life quality for patients with far
advanced solid tumor.”17
Please remember that these prostate cancer study subjects already suffered from advanced disease. It would
appear more logical if these patients had initiated modified citrus pectin supplementation before surgical
procedures to prevent metastatic colonies from being established, as was done in the successful laboratory
studies.
Tagamet (cimetidine) and Cell Adhesion
In addition to modified citrus pectin, a well-known over-the-counter medication can also play a pivotal role in
reducing cancer cell adhesion. Cimetidine—commonly known as Tagamet®—is a drug historically used to
alleviate heartburn. A growing body of scientific evidence has revealed that cimetidine also possesses potent anti-
cancer activity. Cimetidine inhibits cancer cell adhesion by blocking the expression of an adhesive molecule—
called E-selectin—on the surface of cells lining blood vessels.15 Cancers cells latch onto E-selectin in order to
adhere to the lining of blood vessels.18 By preventing the expression of E-selectin, cimetidine significantly limits
the ability of cancer cell adherence to the blood vessel walls. This effect is analogous to removing the velcro from
the blood vessels walls that would normally enable circulating tumor cells to bind.
Cimetidine’s potent anti-cancer effects were clearly displayed in a report published in the British Journal of Cancer
in 2002. In this study, 64 colon cancer patients received chemotherapy with or without cimetidine (800 mg per day)
for one year. The 10-year survival for the cimetidine group was almost 90%. This is in stark contrast to the control
group, which had a 10-year survival of only 49.8%. Remarkably, for those patients with a more aggressive form of
colon cancer, the 10-year survival was 85% in those treated with cimetidine compared to a dismal 23% in the
control group.19 The authors of the study concluded, “Taken together, these results suggested a mechanism
underlying the beneficial effect of cimetidine on colorectal cancer patients, presumably by blocking the expression
of E-selectin on vascular endothelial [lining of blood vessels] cells and inhibiting the adhesion of cancer cells.”
These findings were supported by another study with colorectal cancer patients wherein cimetidine given for just
seven days at the time of surgery increased three-year survival from 59% to 93%!20
This data provides a compelling case for cancer patients, at least five days prior to surgery, to ingest at least 14
grams of modified citrus pectin and 800 mg of cimetidine daily. This combination regimen may be followed for a
year or longer to reduce metastatic risk.
Preventing Surgery-Induced Immune Suppression
The essential role the immune system plays in combating cancer cannot be overstated. Although there are many
aspects of the immune system that come into play when fighting cancer, the role of the natural killer cell
predominates. Natural killer (NK) cells are a type of white blood cell tasked with seeking out and destroying cancer
cells. Research has shown that NK cells can spontaneously recognize and kill a variety of cancer cells.21
Natural Killer Cell (NK) Activity and Cancer
To illustrate the importance of NK cell activity in fighting cancer, a study published in the journal Breast Cancer
Research and Treatment examined NK cell activity in women shortly after surgery for breast cancer. The
researchers reported that low levels of NK cell activity were associated with an increased risk of death from breast
cancer.22 In fact, reduced NK cell activity was a better predictor of survival than the actual stage of the cancer. In
another alarming study, individuals with reduced NK cell activity before surgery for colon cancer had a 350%
increased risk of metastasis during the following 31 months!23
The likelihood of surgery-induced metastasis requires the immune system to be highly active and vigilant in
seeking out and destroying renegade cancer cells during the perioperative period (the time immediately before and
after surgery). Tragically, numerous studies have documented that cancer surgery results in a substantial reduction
in NK cell activity.6,7,24,25 In an investigation having ominous implications, NK cell activity in women having
surgery for breast cancer was reduced by over 50% on the first day after surgery.24 In light of this mounting
evidence, a group of researchers stated: “We therefore believe that shortly after surgery, even transitory immune
dysfunction might permit neoplasms [cancer] to enter the next stage of development and eventually form sizable
metastases.”7
The surgical procedure itself reduces NK activity. This NK cell-impairing effect that occurs immediately after surgery
could not happen at a worse possible time. NK cell activity falters when it is most needed to fight metastasis. The
surgery-induced increased risk of metastasis combined with a reduction in NK cell activity can have disastrous
consequences for the person undergoing cancer surgery. With that said, the perioperative period presents a
window of opportunity to actively strengthen immune function by enhancing NK cell activity. Fortunately, numerous
nutraceutical, pharmaceutical, and medical interventions known to enhance NK cell activity are available to the
person undergoing cancer surgery.
PSK Increases NK Cell Activity
One prominent natural supplement that can increase NK cell activity is PSK, (protein-bound polysaccharide K) a
specially prepared extract from the mushroom Coriolus versicolor. PSK has been shown to enhance NK cell activity
in multiple studies.26-29 PSK’s ability to enhance NK cell activity helps to explain why it has been shown to
dramatically improve survival in cancer patients. For example, 225 patients with lung cancer received radiation
therapy with or without PSK (3 grams per day). For those with more advanced Stage 3 cancers, more than three
times as many individuals taking PSK were alive after five years (26%), compared to those not taking PSK (8%).
PSK more than doubled five-year survival in those individuals with less advanced Stage 1 or 2 disease (39% vs.
17%).30
A group of colon cancer patients were randomized to receive chemotherapy alone or chemotherapy plus PSK,
which was taken for two years. The group receiving PSK had an exceptional 10-year survival of 82%. Sadly, the
group receiving chemotherapy alone had a 10-year survival of only 51%.31 In a similar trial reported in the British
Journal of Cancer in 2004, colon cancer patients received chemotherapy alone or combined with PSK (3 grams per
day) for two years. In the group with a more dangerous Stage 3 colon cancer, the five-year survival was 75% in the
PSK group. This compared to a five-year survival of only 46% in the group receiving chemotherapy alone.32
Research has confirmed that PSK also improves survival in cancers of the breast, stomach, esophagus, and
uterus.33-36
Nutraceuticals, Herbals and Pharmaceuticals that Increase NK Cell Activity
Other nutraceuticals that have been documented to increase NK cell activity are garlic, glutamine, IP6 (inositol
hexaphosphate), AHCC (active hexose correlated compound), and lactoferrin.37-41 One experiment in mice with
breast cancer found that glutamine supplementation resulted in a 40% decrease in tumor growth paired with a 2.5-
fold increase in NK cell activity.40
Scientists in Germany explored the effects of mistletoe extract on NK cell activity in 62 patients undergoing surgery
for colon cancer. The participants were randomized to receive an intravenous infusion of mistletoe extract
immediately before they were given general anesthesia, or were given general anesthesia alone. Measurements of
NK cell activity were taken before and 24 hours after surgery. As expected, the group that did not receive mistletoe
experienced a 44% reduction in NK cell activity 24 hours after surgery. Interestingly, the scientists reported that the
group receiving mistletoe did not experience a significant decrease in NK cell activity after surgery. They went on to
conclude that “perioperative infusion of mistletoe extracts can prevent a suppression of NK cell activity in cancer
patients.”42
Pharmaceuticals used to increase NK cell activity include interferon-alpha and granulocyte-macrophage colony-
stimulating factor. These drugs were shown to prevent surgery-induced immune suppression when given
perioperatively.43,44 Another immune boosting drug to consider in the perioperative setting may be interleukin-2.45
At least five days prior to surgery, it would appear logical to institute a natural killer (NK) cell-enhancing program
involving nutrients like PSK, lactoferrin, glutamine, and others. Drugs such as interleukin-2 and granulocyte-
macrophage colony-stimulating factor are approved in the United States, but health insurance does not usually
cover them for the perioperative purposes suggested here. To receive a free copy of the latest dosing
recommendations for these nutrients and drugs, call 1-800-841-5433 or log on to our Cancer Surgery Special
Report.
Heightening Immune Surveillance with Cancer Vaccines
An enlightened medical approach to cancer treatment involves the use of cancer vaccines. The concept is the
same as using vaccines for infectious diseases, except that tumor vaccines target cancer cells instead of a virus.
Another distinguishing feature of tumor vaccines is that while viral vaccines are created from a generic virus, tumor
vaccines are autologous, that is, they are produced from a person’s own cancer cells removed during surgery. This
is a critical distinction since there can be considerable genetic differences between cancers. This highly
individualized cancer vaccine greatly amplifies the ability of the immune system to identify and target any residual
cancer cells present in the body. Cancer vaccines provide the immune system with the specific identifying markers
of the cancer that can then be used to mount a successful attack against metastatic cancer cells.
Autologous cancer vaccines have been studied extensively, with the most encouraging results noted in
randomized, controlled clinical trials including more than 1,300 colorectal cancer patients in which tumor vaccines
were given after surgery. These trials reported reduced recurrence rates and improved survival.46 Unlike
chemotherapy, which can cause severe side effects and toxicity, cancer vaccines are a gentle therapy with proven
long-term safety.47
In a landmark study reported in 2003, 567 individuals with colon cancer were randomized to receive surgery alone,
or surgery combined with vaccines derived from their own cancer cells. The median survival for the cancer vaccine
group was over 7 years, compared to the median survival of 4.5 years for the group receiving surgery alone. The
five-year survival was 66.5% in the cancer vaccine group, which dwarfed the 45.6% five-year survival for the group
receiving surgery alone.48 This glaring difference in five-year survival clearly displays the power of individually-
tailored cancer vaccines to greatly focus a person’s own immunity to target and attack residual metastatic cancer
cells.
Cancer Surgery, Angiogenesis, and Metastasis
Cancers employ a clever strategy in their quest to grow and thrive within the body. Angiogenesis is the process by
which new blood vessels are formed from pre-existing blood vessels. The formation of new blood vessels is a
normal and necessary process for childhood growth and development, as well as for wound healing. Unfortunately,
cancers hijack this otherwise normal process in order to increase blood supply to the tumor. The formation of new
blood vessels supplying the tumor is an absolute requirement for successful metastasis since tumors cannot
grow beyond the size of a pinhead (i.e., 1-2mm) without expanding their blood supply.49,50
Anti-angiogenic Factors
It might be surprising to learn that the presence of the primary tumor serves to inhibit the growth of metastatic
cancer elsewhere in the body. The primary tumor produces anti-angiogenic factors which restrict the growth of
metastases.51-54 These anti-angiogenic factors inhibit the formation of new blood vessels to potential sites of
metastasis. Regrettably, the surgical removal of the primary cancer also results in the removal of these anti-
angiogenic factors, and the growth of metastasis is no longer inhibited. With these restrictions lifted, it is now
easier for small sites of metastatic cancer to attract new blood vessels that promote their growth.55 Indeed, these
concerns were voiced by researchers who declared that “… removal of the primary tumor might eliminate a
safeguard against angiogenesis and thus awaken dormant micrometastasis [small sites of metastatic cancer].”7
As if the loss of angiogenic inhibition by the primary tumor were not enough of a problem, it turns out the surgery
causes another angiogenic predicament. After surgery, levels of factors that increase angiogenesis—also known
as vascular endothelial growth factor (VEGF)—are significantly elevated. This can result in an increased formation
of new blood vessels supplying areas of metastatic cancer. A group of scientists summarized this research quite
well when they asserted that “after surgery, the angiogenic balance of pro- and antiangiogenic factors is shifted in
favor of angiogenesis to facilitate wound healing. Especially levels of vascular endothelial growth factor (VEGF) are
persistently elevated. This may not only benefit tumor recurrence and the formation of metastatic disease, but also
result in activation of dormant micrometastases.”2
Nutrients that Inhibit VEGF
Given the metastatic cancer’s need for an expanding blood supply, inhibition of angiogenesis would certainly be an
integral part of a comprehensive strategy to combat surgery-induced metastasis. To that end, various nutrients
have been shown to inhibit VEGF. These include soy isoflavones (genistein), silibinin (a component of milk thistle),
chrysin, epigallocatechin gallate (EGCG) from green tea, and curcumin.56-62
In one experiment, EGCG—the active constituent of green tea—was administered to mice with stomach cancer.
The results demonstrated that EGCG reduced the tumor mass by 60%, while also reducing the concentration of
blood vessels feeding the tumor by 38%. Remarkably, EGCG decreased the expression of VEGF in cancer cells by
an astounding 80%! The authors of the study concluded “EGCG inhibits the growth of gastric cancer by reducing
VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.”
56
In the evaluation of the research pertaining to curcumin’s anti-angiogenic effects, researchers at Emory University
School of Medicine noted that “Curcumin is a direct inhibitor of angiogenesis and also downregulates various
proangiogenic proteins like vascular endothelial growth factor…” Additionally, the scientists remarked, “Cell
adhesion molecules are upregulated in active angiogenesis and curcumin can block this effect, adding further
dimensions to curcumin’s antiangiogenic effect.” In conclusion, they commented that “Curcumin’s effect on the
overall process of angiogenesis compounds its enormous potential as an antiangiogenic drug.”44
Five days prior to surgery, the patient may consider supplementing with standardized green tea extract, curcumin,
soy genistein extract and other nutrients that suppress VEGF and thus may help protect against angiogenesis. To
receive a free copy of the latest dosing recommendations for these nutrients, call 1-800-841-5433 or log on to the
Life Extension Foundation’s Cancer Surgery Special Report: http://www.lef.org/featured-articles/Cancer-Surgery-
Special-Report.htm
The Choice of Surgical Anesthesia Can Influence Metastasis
The conventional medical approach to surgical anesthesia has been the use of general anesthesia during surgery,
followed by intravenous morphine after surgery for pain control. The conventional approach, however, may not be
the optimal approach for preventing surgery-induced metastasis. The use of morphine directly after surgery poses
significant problems. At a time when immune function is already suppressed, morphine further weakens the
immune system by diminishing NK cell activity.63
Surgical anesthesia has also been shown to weaken NK cell activity.64 One study found that morphine increased
angiogenesis and stimulated the growth of breast cancer in mice. The researchers concluded: “These results
indicate that clinical use of morphine could potentially be harmful in patients with angiogenesis-dependent
cancers.”65
Regional Anesthesia and Pain Control
Given the inherent problems associated with the use of morphine and anesthesia, researchers have explored
other approaches to surgical anesthesia and pain control. One novel approach is the use of conventional general
anesthesia combined with regional anesthesia, which refers to anesthesia that only affects a specific part of the
body. The benefits achieved with this approach are two-fold: the use of regional anesthesia reduces the amount of
general anesthesia required during surgery, as well as decreasing the amount of morphine needed after surgery
for pain control.55
This elegant approach to surgical anesthesia and pain control has been validated in scientific studies. In one
experiment, cancerous mice received surgery with general anesthesia alone or combined with regional
anesthesia. The scientists reported that the addition of regional anesthesia to general anesthesia “markedly
attenuates the promotion of metastasis by surgery.” Regional anesthesia reduced 70% of the metastasis-
promoting effects of surgery caused by general anesthesia alone.66
Doctors at Pennsylvania State University College of Medicine compared NK cell activity in patients receiving general
or regional anesthesia for abdominal surgery. NK cell activity dropped substantially in the general anesthesia
group, while NK cell activity was preserved at pre-operative levels in the group that received regional anesthesia.67
Building upon these encouraging findings, researchers then explored if regional anesthesia can affect metastasis
in women undergoing surgery for breast cancer. In a pioneering study, 50 women having breast cancer surgery
with general anesthesia combined with regional anesthesia were compared to 79 women who received general
anesthesia during their breast cancer surgery followed by morphine for pain control. The type of regional
anesthesia used is called a paravertebral block, which involves the injection of a local anesthetic around the spinal
nerves between the vertebral bones of the spine. After a follow-up period of nearly three years, dramatic differences
were noted between the two groups. Only 6% of patients who received regional anesthesia experienced a
recurrence, compared to a 24% risk of metastatic recurrence in the group that did not receive regional anesthesia.
Stated differently, women who received regional and general anesthesia had a 75% decreased risk for metastatic
cancer. These findings led researchers to proclaim that regional anesthesia for breast cancer surgery “markedly
reduces the risk of recurrence or metastasis during the initial years following surgery.”55
Surgeons at Duke University Medical Center compared regional anesthesia alone to general anesthesia in women
having surgery for breast cancer. The surgeons reported that while 39% of the general anesthesia group required
medication for nausea and vomiting, only 20% of the regional anesthesia group needed this medication. Narcotic
medication was needed for pain control after surgery in 98% of the general anesthesia group, compared to only
25% of the regional anesthesia group. And 96% of the women receiving regional anesthesia had returned home
within a day after surgery, compared with 76% of the women who received general anesthesia. The surgeons
concluded that regional anesthesia “can be used to perform major operations for breast cancer with minimal
complications… Most importantly, by reducing nausea, vomiting, and surgical pain, paravertebral block [regional
anesthesia] markedly improves the quality of operative recovery for patients who are treated for breast cancer and
therefore provides the patient with the choice to return home as early as desired after surgery.”68
The results of these studies have vast implications for those undergoing cancer surgery, as a group of researchers
enthusiastically announced: “As regional techniques [anesthesia]… are easy to implement, inexpensive, and do
not pose a threat greater than general anesthesia, it would be easy for anesthesiologists to implement them, thus
reducing the risk of disease recurrence and metastasis.”55
Finally, those requiring morphine for pain control after surgery can consider asking their doctor for a medication
called tramadol instead. Unlike morphine, tramadol does not suppress immune function.69 On the contrary,
tramadol has been shown to stimulate NK cell activity. In one experiment, tramadol blocked the formation of lung
metastasis induced by surgery in rats. Tramadol also prevented the surgery-induced suppression of NK cell activity.
70
Less Invasive Surgery Reduces Risk of Metastasis
Surgery places an enormous physical stress upon the body. There is considerable scientific evidence supporting
that surgeries that are less invasive—and therefore less traumatic—pose less risk of metastasis, compared to
more invasive and traumatic surgery. Laparoscopic surgery is one type of minimally invasive surgery, in which
operations in the abdomen, pelvis, and other regions are performed through small incisions, as compared to the
much larger incisions needed in traditional “open” surgeries.
A study published in the prestigious medical journal The Lancet compared laparoscopic to open surgery to remove
part of the colon (colectomy) in patients with colon cancer. In contrast to the group receiving traditional open
surgery, the laparoscopic surgery group had a 61% decreased risk of cancer recurrence coupled with a 62%
decreased risk of death from colon cancer. The surgeons concluded that laparoscopic colectomy is more effective
than open colectomy for treatment of colon cancer as assessed by tumor recurrence and cancer-related survival.71
A long-term follow-up of these patients (median time 95 months) reported a 56% decreased risk of death from
colon cancer for laparoscopic surgery as compared to traditional open surgery.72 Another comparison of
laparoscopic surgery to open surgery for colon cancer reported a five-year survival rate of 64.1% for the
laparoscopic group, and a five-year survival rate of 58.5% for the group receiving open surgery.73
Minimally invasive surgery has produced substantial improvements in survival for those with lung cancer. Video-
assisted thoracoscopic surgery (VATS), a minimally invasive surgery, was compared to traditional open surgery for
removing lung tumors (lobectomy). The five-year survival from lung cancer was 97% in the VATS group. This greatly
contrasts the 79% five-year survival in the open surgery group.74
Commenting on the use of minimally invasive surgery for lung cancer, surgeons at Cedars-Sinai Medical Center
stated that minimally invasive surgery for lung cancer “… can be performed safely with proven advantages over
conventional thoracotomy [chest surgery] for lobectomy: smaller incisions, decreased postoperative pain,
…decreased blood loss, better preservation of pulmonary function, and earlier return to normal activities… the
evidence in the literature is mounting that VATS may offer reduced rates of complications and better survival.”75
Administering Chemo and Radiation Therapies Prior to Surgery
Doctors at the University of North Carolina School of Medicine studied the use of combined radiation and
chemotherapy prior to surgery for individuals with esophageal cancer. Twenty-six patients received surgery alone,
while 30 patients received radiation and chemotherapy followed by surgery. The group receiving combined
treatment had a five-year survival of 39%, while the group treated with surgery alone experienced a five-year survival
of only 16%.99
A study published in the New England Journal of Medicine in 2006 compared treatment with surgery alone to
treatment with chemotherapy—given both directly before and after surgery—in patients with stomach or
esophageal cancer. The five-year survival for the group receiving surgery and chemotherapy was 36%, compared to
a five-year survival of 23% in the group receiving surgery alone.100
Research also supports the use of chemotherapy and radiation therapy during the critical perioperative period. In
one study, 544 patients with stomach cancer received combined chemotherapy and radiation therapy shortly after
surgery. Survival comparisons were made with a similar group of 446 patients with stomach cancer treated with
surgery alone. Postoperative chemotherapy and radiation led to a dramatic improvement in survival. The group
treated with surgery alone had a median survival of only 62.6 months, compared to a median survival of 95.3
months in the group receiving postoperative radiation and chemotherapy.101 A similar study also demonstrated
improved survival with the use of postoperative radiation and chemotherapy compared to surgery alone.102
Inflammation and Metastasis
Cancer surgery causes an increased production of inflammatory chemicals, such as interleukin-1 and interleukin-
6.76-78 These chemicals are known to increase the activity of cyclooxygenase-2 (COX-2). A highly potent
inflammatory enzyme, COX-2 plays a pivotal role in promoting cancer growth and metastasis.
This was evident in an article appearing in the journal Cancer Research that found levels of COX-2 in pancreatic
cancer cells to be 60 times greater than in normal pancreatic cells.79 Levels of COX-2 were 150 times higher in
cancer cells from individuals with head and neck cancers compared to normal tissue from healthy volunteers.80
COX-2 fuels cancer growth by stimulating the formation of new blood vessels feeding the tumor.81,82 COX-2
increases cancer cell adhesion to the blood vessel walls,83 and also enhances the ability of cancer cells to
metastasize. Experiments in mice revealed that colon cancer cells expressing high levels of COX-2 metastasized
freely to the liver, while colon cancer cells expressing low levels of COX-2 did not metastasize to the liver.83
The adverse influence of COX-2 on the growth and progression of cancer was clearly revealed in a study published
in the journal Clinical Cancer Research in 2004. Two hundred eighty-eight individuals undergoing surgery for colon
cancer had their tumors examined for the presence of COX-2. The findings were alarming—when other factors
were controlled for, the group whose cancers tested positive for the presence of COX-2 had a 311% greater risk of
death compared to the group whose cancers did not express COX-2.84 A subsequent study in lung cancer patients
found that those with high tumor levels of COX-2 had a median survival of only 15 months, whereas those with low
tumor levels of COX-2 had a median survival of 40 months.85
Given these findings, researchers began investigating the anti-cancer effects of COX-2 inhibitor drugs. Although
initially used for inflammatory conditions, such as arthritis, COX-2 inhibitor drugs have been shown to possess
powerful anti-cancer activity. For example, 134 patients with advanced lung cancer were treated with chemotherapy
alone or combined with Celebrex® (a COX-2 inhibitor). For those individuals with cancers expressing higher
amounts of COX-2, treatment with Celebrex® dramatically prolonged survival.86 Treatment with Celebrex® also
slowed cancer progression in men with recurrent prostate cancer.87
Perhaps the most impressive display of the anti-metastatic effects of COX-2 inhibitor drugs was presented at the
annual conference of the American Society of Clinical Oncology in 2008. In this study, the incidence of bone
metastases in breast cancer patients who had taken a COX-2 inhibitor for at least six months following the
diagnosis of breast cancer was compared to the incidence of bone metastases in breast cancer patients who had
not taken a COX-2 inhibitor. Remarkably, those who were treated with a COX-2 inhibitor were almost 80% less
likely to develop bone metastases than those who were not treated with a COX-2 inhibitor drug.88
Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are COX inhibitors. The
widespread use of NSAIDs for pain and arthritis has created an ideal environment in which to examine if these
drugs can prevent cancer. Large-scale studies have documented a substantial reduction in cancer risk with the
use of NSAIDs. A comprehensive review of the scientific literature (91 published studies) reported that the long-
term use of NSAIDs (primarily aspirin) produced risk reductions of 63% for colon cancer, 39% for breast cancer,
36% for lung cancer, 39% for prostate cancer, 73% for esophageal cancer, 62% for stomach cancer, and 47% for
ovarian cancer. “This review provides compelling… evidence that regular intake of NSAIDs that… block COX-2
protects against the development of many types of cancer,” the authors concluded.89
A number of nutritional and herbal supplements are known to inhibit COX-2. These include curcumin, resveratrol,
vitamin E, soy isoflavones (genistein), green tea (EGCG), quercetin, fish oil, garlic, feverfew, and silymarin (milk
thistle).58,90-97
Scientists at Memorial Sloan-Kettering Cancer Center in New York created an experimentally-induced increase in
COX-2 activity in human breast cells, which was completely prevented by resveratrol. Resveratol blocked the
production of COX-2 within the cell, as well as blocking COX-2 enzyme activity.98
Conclusion
A group of noted experts in the field of surgery-induced metastasis stated that cancer treatment “…necessitates the
surgical excision of the primary tumor in order to relieve the patient of the major tumor burden, which is the main
source of mutating and metastasizing cells. However, along with its obvious benefits, the surgical procedure has
been suggested to involve serious hazards as it releases tumor cells into the circulation or lymphatics, promotes
the secretion of angiogenic and growth factors, and induces suppression of CMI [immune function]. These
consequences synergistically facilitate the establishment of new metastases and the development of preexisting
micrometastases. As cancer-related death is most commonly the result of metastatic disease, it is crucial to
minimize this facilitation.”55
Remarking further, they commented that “Taken together, it is evident that the perioperative period harbors many
risks; however, it is also the ideal time for battling MRD [small numbers of cancer cells remaining after surgery] to
reduce recurrence and future metastases.” Thus, these scientists believe “…it is essential to employ preventative
interventions during this critical time.” Additionally, they urge that, “Ideally, each problematic aspect of surgery
should be treated when oncological patients undergo resection [surgery] in order to minimize recurrence and
metastatic spread.”55
Armed with the knowledge discussed in this article, the person with cancer can reap all the benefits that cancer
surgery offers, while simultaneously avoiding the metastatic perils imposed by this procedure.
As this article was going to press, a dedicated team of clinical oncologists and researchers are preparing a
meticulous report on the optimal doses of nutrients and drugs that a cancer patient should consider during the pre-
and post-operative period. You can obtain a free copy of this report by logging on to our Cancer Surgery Special
Report — http://www.lef.org/featured-articles/Cancer-Surgery-Special-Report.htm — or calling 1-800-841-5433.
If you have any question on the scientific content of this article, please call a Life Extension® Health Advisor at 1-
866-864-3027.
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Reprinted from Life Extension Magazine December 2009
Cancer Surgery: What You Need to Know Ahead of Time
The cornerstone of treatment for the great majority of cancers is the surgical removal of the primary tumor. The
rationale for this approach is straightforward: if you can get rid of the cancer by simply removing it from the body,
then a cure can likely be achieved. Unfortunately, this approach does not take into account that after surgery the
cancer will frequently metastasize (spread to different organs). Quite often the metastatic recurrence is far more
serious than the original tumor. In fact, for many cancers it is the metastatic recurrence—and not the primary
tumor—that ultimately proves to be fatal.1
In a shocking irony, a growing body of scientific evidence has revealed that cancer surgery can increase the risk of
metastasis.2 This would fly in the face of conventional medical thinking, but the facts are undeniable.
To gain a better understanding of how surgery can increase the risk of metastasis, let’s first discuss the actual
process of cancer metastasis. A complicated sequence of events must occur in order for cancer to spread to
another part of the body.2 Isolated cancer cells that break away from the primary tumor must first breach the
connective tissue immediately surrounding the cancer. Once the cancer cell has broken free of the surrounding
connective tissue, the next step is to enter a blood or lymphatic vessel. This is easier said than done, as entry into a
blood vessel requires the cancer cell to secrete enzymes that degrade the basement membrane of the blood
vessel.3 Entry into a blood vessel is vitally important for the aspiring metastatic cancer cell, since it uses the
bloodstream as a highway for transportation to other vital organs of the body—such as the liver, brain, or lungs—
where it can form a new deadly tumor.
Now that the lone cancer cell has finally entered the bloodstream, its problems have only just begun. Traveling
within the bloodstream can be a hazardous journey for cancer cells. Turbulence from the fast moving blood can
damage and destroy the cancer cell. Furthermore, cancer cells must avoid detection and destruction from white
blood cells circulating in the blood stream.
To complete its voyage, the rogue cancer cell must adhere to the lining of the blood vessel, where it degrades
through and exits the basement membrane of the blood vessel. Its final task is to burrow through the surrounding
connective tissue to arrive at the organ that is its final destination. Now the cancer cell can multiply and form a
growing colony that serves as the foundation for a new metastatic cancer. Time is working against these solitary
cancer cells. This entire sequence of events must happen quickly, since these cells have a limited life span.1
We now see that cancer metastasis is a complicated and difficult process. Fraught with peril, very few free-standing
cancer cells survive this arduous journey.2 The probability of cancer cells surviving this journey and forming new
metastases can be increased by anything that serves to make this process easier.
In a groundbreaking study published in the medical journal Annals of Surgery in 2009, researchers reported that
cancer surgery itself can create an environment in the body that greatly lessens the obstacles to metastasis that
cancers cells must normally face.2
Just as concerning is the revelation that cancer surgery can produce an alternate route of metastasis that
bypasses natural barriers. During cancer surgery, the removal of the tumor almost always disrupts the structural
integrity of the tumor and/or the blood vessels feeding the tumor. This can lead to an unobstructed dispersal of
cancer cells into the bloodstream, or seeding of these cancer cells directly into the chest or abdomen.4-7 This
surgery-induced “alternate route” can greatly simplify the path to metastasis.
To illustrate, a study published in the British Journal of Cancer in 2001 compared the survival of women with breast
cancer who had their tumors removed surgically, to the survival of women with breast cancer who did not have
surgery. As expected, the findings established that surgery substantially improved survival in the early years.
However, further analysis of the data determined that women who had surgery had a spike in their risk of death at
eight years that was not evident in the group who did not have surgery.8 In their interpretation of the results, the
authors of the study stated: “A reasonable hypothesis to explain the observed patterns of the hazard functions [risk
of cancer death] is to assume that…primary tumor removal may result in sudden acceleration of metastatic
process…”
Another group of researchers commenting on a study examining the surgical treatment of colon cancer were far
bolder in their conclusions: “This finding strongly supports that surgery alters the natural course of the disease by
elongating life expectancy in the greater part of the patient population, but also by simultaneously shortening
survival in a smaller subset of patients. Thus, both experimental and clinical evidence support that surgery,
although greatly reducing tumor mass and potentially curative, paradoxically can also augment metastasis
development.”2
Given these disturbing findings, what can individuals undergoing surgery for their cancers do to protect themselves
against an increased risk of metastasis? A worthwhile strategy would be to examine all of the mechanisms by
which surgery promotes metastasis, and then create a comprehensive plan that counteracts each and every one of
these mechanisms.
WHAT YOU NEED TO KNOW: CANCER SURGERY
• Surgical removal of cancer typically provides the best chance of disease-free survival.
• A growing body of evidence suggests that cancer surgery itself may increase the risk of metastasis (spread to
other areas) via numerous mechanisms including: increasing cancer cell adhesion, suppressing immune
function, promoting angiogenesis, and stimulating inflammation.
• Since metastatic disease is often deadlier than the original tumor, it is important to utilize preventive strategies
to prevent cancer metastasis.
• Steps to help prevent cancer metastasis include: combating cancer cell adhesion, supporting immune health,
heightening immune surveillance, inhibiting angiogenesis, minimizing inflammation, and choosing surgeons and
anesthesiologists who utilize advanced techniques that may reduce metastatic risk.
• Certain nutrients, drugs, types of anesthesia, and surgical techniques are associated with reduced risk of
metastasis.
Surgery Increases Cancer Cell Adhesion
One mechanism by which surgery increases the risk of metastasis is by enhancing cancer cell adhesion.9 Cancer
cells that have broken away from the primary tumor utilize adhesion to boost their ability to form metastases in
distant organs. These cancer cells must be able to clump together and form colonies that can expand and grow. It
is unlikely that a single cancer cell will form a metastatic tumor, just as one person is unlikely to form a thriving
community. Cancer cells use adhesion molecules—such as galectin-3—to facilitate their ability to clump together.
Present on the surface of cancer cells, these molecules act like velcro by allowing free-standing cancer cells to
adhere to each other.10 Cancer cells circulating in the bloodstream also make use of galectin-3 surface adhesion
molecules to latch onto the lining of blood vessels.11 The adherence of circulating tumor cells (CTC) to the blood
vessel walls is an essential step for the process of metastasis.
Just like a person sliding down an icy hill has no hope of stopping if they cannot grab onto something, a cancer cell
that cannot adhere to the blood vessel wall will just continue to wander through the blood stream incapable of
forming metastases. Unable to latch onto the wall of the blood vessel, these circulating tumor cells become like
“ships without a port” and are unable to dock. Eventually, white blood cells circulating in the bloodstream will target
and destroy the CTC. If the CTC successfully bind to the blood vessel wall and burrow their way through the
basement membrane, they will then utilize galectin-3 adhesion molecules to adhere to the organ to form a new
metastatic cancer.10
Combating Cancer Cell Adhesion
Regrettably, research has shown that cancer surgery increases tumor cell adhesion. In one experiment that
mimicked surgical conditions, scientists reported that the binding of cancer cells to the blood vessel walls was
increased by 250%, compared to cancer cells not exposed to surgical conditions.12 Therefore, it is critically
important for the person undergoing cancer surgery to take measures that can help to neutralize the surgery-
induced increase in cancer cell adhesion.
Modified Citrus Pectin
Fortunately, a natural supplement called modified citrus pectin (MCP) can do just that. Citrus pectin—a type of
dietary fiber—is not absorbed from the intestine. However, modified citrus pectin has been altered so that it can be
absorbed into the blood and exert its anti-cancer effects. The mechanism by which modified citrus pectin inhibits
cancer cell adhesion is by binding to galectin-3 adhesion molecules on the surface of cancer cells, thereby
preventing cancer cells from sticking together and forming a cluster.13 Modified citrus pectin can also inhibit
circulating tumor cells from latching onto the lining of blood vessels. This was demonstrated by an experiment in
which modified citrus pectin blocked the adhesion of galectin-3 to the lining of blood vessels by an astounding
95%. Modified citrus pectin also substantially decreased the adhesion of breast cancer cells to the blood vessel
walls.13
Impressive research has documented the power of modified citrus pectin to directly inhibit cancer metastasis. In a
study published in the Journal of the National Cancer Institute, modified citrus pectin was administered to rats that
were injected with prostate cancer cells, while rats not receiving modified citrus pectin served as the control group.
Lung metastasis was noted in 93% of the control group, whereas only 50% of the modified citrus pectin group
experienced lung metastasis. Even more noteworthy was the finding that the modified citrus pectin group had an
89% reduction in the size of the metastatic colonies, compared to the control group.14 In a similar experiment,
mice injected with melanoma cancer cells that were fed modified citrus pectin experienced a greater than 90%
reduction in lung metastasis compared to the control group.15
After these exciting findings in animal research, modified citrus pectin was then put to the test in men with prostate
cancer. In this trial, 10 men with recurrent prostate cancer received modified citrus pectin (14.4 g per day). After one
year, a considerable improvement in cancer progression was noted, as determined by a reduction of the rate at
which the prostate-specific antigen (PSA) level increased.16 This was followed by a study in which 49 men with
prostate cancer of various types were given modified citrus pectin for a four-week cycle. After two cycles of treatment
with modified citrus pectin, 22% of the men experienced a stabilization of their disease or improved quality of life;
12% had stable disease for more than 24 weeks. The authors of the study concluded that “MCP (modified citrus
pectin) seems to have positive impacts especially regarding clinical benefit and life quality for patients with far
advanced solid tumor.”17
Please remember that these prostate cancer study subjects already suffered from advanced disease. It would
appear more logical if these patients had initiated modified citrus pectin supplementation before surgical
procedures to prevent metastatic colonies from being established, as was done in the successful laboratory
studies.
Tagamet (cimetidine) and Cell Adhesion
In addition to modified citrus pectin, a well-known over-the-counter medication can also play a pivotal role in
reducing cancer cell adhesion. Cimetidine—commonly known as Tagamet®—is a drug historically used to
alleviate heartburn. A growing body of scientific evidence has revealed that cimetidine also possesses potent anti-
cancer activity. Cimetidine inhibits cancer cell adhesion by blocking the expression of an adhesive molecule—
called E-selectin—on the surface of cells lining blood vessels.15 Cancers cells latch onto E-selectin in order to
adhere to the lining of blood vessels.18 By preventing the expression of E-selectin, cimetidine significantly limits
the ability of cancer cell adherence to the blood vessel walls. This effect is analogous to removing the velcro from
the blood vessels walls that would normally enable circulating tumor cells to bind.
Cimetidine’s potent anti-cancer effects were clearly displayed in a report published in the British Journal of Cancer
in 2002. In this study, 64 colon cancer patients received chemotherapy with or without cimetidine (800 mg per day)
for one year. The 10-year survival for the cimetidine group was almost 90%. This is in stark contrast to the control
group, which had a 10-year survival of only 49.8%. Remarkably, for those patients with a more aggressive form of
colon cancer, the 10-year survival was 85% in those treated with cimetidine compared to a dismal 23% in the
control group.19 The authors of the study concluded, “Taken together, these results suggested a mechanism
underlying the beneficial effect of cimetidine on colorectal cancer patients, presumably by blocking the expression
of E-selectin on vascular endothelial [lining of blood vessels] cells and inhibiting the adhesion of cancer cells.”
These findings were supported by another study with colorectal cancer patients wherein cimetidine given for just
seven days at the time of surgery increased three-year survival from 59% to 93%!20
This data provides a compelling case for cancer patients, at least five days prior to surgery, to ingest at least 14
grams of modified citrus pectin and 800 mg of cimetidine daily. This combination regimen may be followed for a
year or longer to reduce metastatic risk.
Preventing Surgery-Induced Immune Suppression
The essential role the immune system plays in combating cancer cannot be overstated. Although there are many
aspects of the immune system that come into play when fighting cancer, the role of the natural killer cell
predominates. Natural killer (NK) cells are a type of white blood cell tasked with seeking out and destroying cancer
cells. Research has shown that NK cells can spontaneously recognize and kill a variety of cancer cells.21
Natural Killer Cell (NK) Activity and Cancer
To illustrate the importance of NK cell activity in fighting cancer, a study published in the journal Breast Cancer
Research and Treatment examined NK cell activity in women shortly after surgery for breast cancer. The
researchers reported that low levels of NK cell activity were associated with an increased risk of death from breast
cancer.22 In fact, reduced NK cell activity was a better predictor of survival than the actual stage of the cancer. In
another alarming study, individuals with reduced NK cell activity before surgery for colon cancer had a 350%
increased risk of metastasis during the following 31 months!23
The likelihood of surgery-induced metastasis requires the immune system to be highly active and vigilant in
seeking out and destroying renegade cancer cells during the perioperative period (the time immediately before and
after surgery). Tragically, numerous studies have documented that cancer surgery results in a substantial reduction
in NK cell activity.6,7,24,25 In an investigation having ominous implications, NK cell activity in women having
surgery for breast cancer was reduced by over 50% on the first day after surgery.24 In light of this mounting
evidence, a group of researchers stated: “We therefore believe that shortly after surgery, even transitory immune
dysfunction might permit neoplasms [cancer] to enter the next stage of development and eventually form sizable
metastases.”7
The surgical procedure itself reduces NK activity. This NK cell-impairing effect that occurs immediately after surgery
could not happen at a worse possible time. NK cell activity falters when it is most needed to fight metastasis. The
surgery-induced increased risk of metastasis combined with a reduction in NK cell activity can have disastrous
consequences for the person undergoing cancer surgery. With that said, the perioperative period presents a
window of opportunity to actively strengthen immune function by enhancing NK cell activity. Fortunately, numerous
nutraceutical, pharmaceutical, and medical interventions known to enhance NK cell activity are available to the
person undergoing cancer surgery.
PSK Increases NK Cell Activity
One prominent natural supplement that can increase NK cell activity is PSK, (protein-bound polysaccharide K) a
specially prepared extract from the mushroom Coriolus versicolor. PSK has been shown to enhance NK cell activity
in multiple studies.26-29 PSK’s ability to enhance NK cell activity helps to explain why it has been shown to
dramatically improve survival in cancer patients. For example, 225 patients with lung cancer received radiation
therapy with or without PSK (3 grams per day). For those with more advanced Stage 3 cancers, more than three
times as many individuals taking PSK were alive after five years (26%), compared to those not taking PSK (8%).
PSK more than doubled five-year survival in those individuals with less advanced Stage 1 or 2 disease (39% vs.
17%).30
A group of colon cancer patients were randomized to receive chemotherapy alone or chemotherapy plus PSK,
which was taken for two years. The group receiving PSK had an exceptional 10-year survival of 82%. Sadly, the
group receiving chemotherapy alone had a 10-year survival of only 51%.31 In a similar trial reported in the British
Journal of Cancer in 2004, colon cancer patients received chemotherapy alone or combined with PSK (3 grams per
day) for two years. In the group with a more dangerous Stage 3 colon cancer, the five-year survival was 75% in the
PSK group. This compared to a five-year survival of only 46% in the group receiving chemotherapy alone.32
Research has confirmed that PSK also improves survival in cancers of the breast, stomach, esophagus, and
uterus.33-36
Nutraceuticals, Herbals and Pharmaceuticals that Increase NK Cell Activity
Other nutraceuticals that have been documented to increase NK cell activity are garlic, glutamine, IP6 (inositol
hexaphosphate), AHCC (active hexose correlated compound), and lactoferrin.37-41 One experiment in mice with
breast cancer found that glutamine supplementation resulted in a 40% decrease in tumor growth paired with a 2.5-
fold increase in NK cell activity.40
Scientists in Germany explored the effects of mistletoe extract on NK cell activity in 62 patients undergoing surgery
for colon cancer. The participants were randomized to receive an intravenous infusion of mistletoe extract
immediately before they were given general anesthesia, or were given general anesthesia alone. Measurements of
NK cell activity were taken before and 24 hours after surgery. As expected, the group that did not receive mistletoe
experienced a 44% reduction in NK cell activity 24 hours after surgery. Interestingly, the scientists reported that the
group receiving mistletoe did not experience a significant decrease in NK cell activity after surgery. They went on to
conclude that “perioperative infusion of mistletoe extracts can prevent a suppression of NK cell activity in cancer
patients.”42
Pharmaceuticals used to increase NK cell activity include interferon-alpha and granulocyte-macrophage colony-
stimulating factor. These drugs were shown to prevent surgery-induced immune suppression when given
perioperatively.43,44 Another immune boosting drug to consider in the perioperative setting may be interleukin-2.45
At least five days prior to surgery, it would appear logical to institute a natural killer (NK) cell-enhancing program
involving nutrients like PSK, lactoferrin, glutamine, and others. Drugs such as interleukin-2 and granulocyte-
macrophage colony-stimulating factor are approved in the United States, but health insurance does not usually
cover them for the perioperative purposes suggested here. To receive a free copy of the latest dosing
recommendations for these nutrients and drugs, call 1-800-841-5433 or log on to our Cancer Surgery Special
Report.
Heightening Immune Surveillance with Cancer Vaccines
An enlightened medical approach to cancer treatment involves the use of cancer vaccines. The concept is the
same as using vaccines for infectious diseases, except that tumor vaccines target cancer cells instead of a virus.
Another distinguishing feature of tumor vaccines is that while viral vaccines are created from a generic virus, tumor
vaccines are autologous, that is, they are produced from a person’s own cancer cells removed during surgery. This
is a critical distinction since there can be considerable genetic differences between cancers. This highly
individualized cancer vaccine greatly amplifies the ability of the immune system to identify and target any residual
cancer cells present in the body. Cancer vaccines provide the immune system with the specific identifying markers
of the cancer that can then be used to mount a successful attack against metastatic cancer cells.
Autologous cancer vaccines have been studied extensively, with the most encouraging results noted in
randomized, controlled clinical trials including more than 1,300 colorectal cancer patients in which tumor vaccines
were given after surgery. These trials reported reduced recurrence rates and improved survival.46 Unlike
chemotherapy, which can cause severe side effects and toxicity, cancer vaccines are a gentle therapy with proven
long-term safety.47
In a landmark study reported in 2003, 567 individuals with colon cancer were randomized to receive surgery alone,
or surgery combined with vaccines derived from their own cancer cells. The median survival for the cancer vaccine
group was over 7 years, compared to the median survival of 4.5 years for the group receiving surgery alone. The
five-year survival was 66.5% in the cancer vaccine group, which dwarfed the 45.6% five-year survival for the group
receiving surgery alone.48 This glaring difference in five-year survival clearly displays the power of individually-
tailored cancer vaccines to greatly focus a person’s own immunity to target and attack residual metastatic cancer
cells.
Cancer Surgery, Angiogenesis, and Metastasis
Cancers employ a clever strategy in their quest to grow and thrive within the body. Angiogenesis is the process by
which new blood vessels are formed from pre-existing blood vessels. The formation of new blood vessels is a
normal and necessary process for childhood growth and development, as well as for wound healing. Unfortunately,
cancers hijack this otherwise normal process in order to increase blood supply to the tumor. The formation of new
blood vessels supplying the tumor is an absolute requirement for successful metastasis since tumors cannot
grow beyond the size of a pinhead (i.e., 1-2mm) without expanding their blood supply.49,50
Anti-angiogenic Factors
It might be surprising to learn that the presence of the primary tumor serves to inhibit the growth of metastatic
cancer elsewhere in the body. The primary tumor produces anti-angiogenic factors which restrict the growth of
metastases.51-54 These anti-angiogenic factors inhibit the formation of new blood vessels to potential sites of
metastasis. Regrettably, the surgical removal of the primary cancer also results in the removal of these anti-
angiogenic factors, and the growth of metastasis is no longer inhibited. With these restrictions lifted, it is now
easier for small sites of metastatic cancer to attract new blood vessels that promote their growth.55 Indeed, these
concerns were voiced by researchers who declared that “… removal of the primary tumor might eliminate a
safeguard against angiogenesis and thus awaken dormant micrometastasis [small sites of metastatic cancer].”7
As if the loss of angiogenic inhibition by the primary tumor were not enough of a problem, it turns out the surgery
causes another angiogenic predicament. After surgery, levels of factors that increase angiogenesis—also known
as vascular endothelial growth factor (VEGF)—are significantly elevated. This can result in an increased formation
of new blood vessels supplying areas of metastatic cancer. A group of scientists summarized this research quite
well when they asserted that “after surgery, the angiogenic balance of pro- and antiangiogenic factors is shifted in
favor of angiogenesis to facilitate wound healing. Especially levels of vascular endothelial growth factor (VEGF) are
persistently elevated. This may not only benefit tumor recurrence and the formation of metastatic disease, but also
result in activation of dormant micrometastases.”2
Nutrients that Inhibit VEGF
Given the metastatic cancer’s need for an expanding blood supply, inhibition of angiogenesis would certainly be an
integral part of a comprehensive strategy to combat surgery-induced metastasis. To that end, various nutrients
have been shown to inhibit VEGF. These include soy isoflavones (genistein), silibinin (a component of milk thistle),
chrysin, epigallocatechin gallate (EGCG) from green tea, and curcumin.56-62
In one experiment, EGCG—the active constituent of green tea—was administered to mice with stomach cancer.
The results demonstrated that EGCG reduced the tumor mass by 60%, while also reducing the concentration of
blood vessels feeding the tumor by 38%. Remarkably, EGCG decreased the expression of VEGF in cancer cells by
an astounding 80%! The authors of the study concluded “EGCG inhibits the growth of gastric cancer by reducing
VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.”
56
In the evaluation of the research pertaining to curcumin’s anti-angiogenic effects, researchers at Emory University
School of Medicine noted that “Curcumin is a direct inhibitor of angiogenesis and also downregulates various
proangiogenic proteins like vascular endothelial growth factor…” Additionally, the scientists remarked, “Cell
adhesion molecules are upregulated in active angiogenesis and curcumin can block this effect, adding further
dimensions to curcumin’s antiangiogenic effect.” In conclusion, they commented that “Curcumin’s effect on the
overall process of angiogenesis compounds its enormous potential as an antiangiogenic drug.”44
Five days prior to surgery, the patient may consider supplementing with standardized green tea extract, curcumin,
soy genistein extract and other nutrients that suppress VEGF and thus may help protect against angiogenesis. To
receive a free copy of the latest dosing recommendations for these nutrients, call 1-800-841-5433 or log on to the
Life Extension Foundation’s Cancer Surgery Special Report: http://www.lef.org/featured-articles/Cancer-Surgery-
Special-Report.htm
The Choice of Surgical Anesthesia Can Influence Metastasis
The conventional medical approach to surgical anesthesia has been the use of general anesthesia during surgery,
followed by intravenous morphine after surgery for pain control. The conventional approach, however, may not be
the optimal approach for preventing surgery-induced metastasis. The use of morphine directly after surgery poses
significant problems. At a time when immune function is already suppressed, morphine further weakens the
immune system by diminishing NK cell activity.63
Surgical anesthesia has also been shown to weaken NK cell activity.64 One study found that morphine increased
angiogenesis and stimulated the growth of breast cancer in mice. The researchers concluded: “These results
indicate that clinical use of morphine could potentially be harmful in patients with angiogenesis-dependent
cancers.”65
Regional Anesthesia and Pain Control
Given the inherent problems associated with the use of morphine and anesthesia, researchers have explored
other approaches to surgical anesthesia and pain control. One novel approach is the use of conventional general
anesthesia combined with regional anesthesia, which refers to anesthesia that only affects a specific part of the
body. The benefits achieved with this approach are two-fold: the use of regional anesthesia reduces the amount of
general anesthesia required during surgery, as well as decreasing the amount of morphine needed after surgery
for pain control.55
This elegant approach to surgical anesthesia and pain control has been validated in scientific studies. In one
experiment, cancerous mice received surgery with general anesthesia alone or combined with regional
anesthesia. The scientists reported that the addition of regional anesthesia to general anesthesia “markedly
attenuates the promotion of metastasis by surgery.” Regional anesthesia reduced 70% of the metastasis-
promoting effects of surgery caused by general anesthesia alone.66
Doctors at Pennsylvania State University College of Medicine compared NK cell activity in patients receiving general
or regional anesthesia for abdominal surgery. NK cell activity dropped substantially in the general anesthesia
group, while NK cell activity was preserved at pre-operative levels in the group that received regional anesthesia.67
Building upon these encouraging findings, researchers then explored if regional anesthesia can affect metastasis
in women undergoing surgery for breast cancer. In a pioneering study, 50 women having breast cancer surgery
with general anesthesia combined with regional anesthesia were compared to 79 women who received general
anesthesia during their breast cancer surgery followed by morphine for pain control. The type of regional
anesthesia used is called a paravertebral block, which involves the injection of a local anesthetic around the spinal
nerves between the vertebral bones of the spine. After a follow-up period of nearly three years, dramatic differences
were noted between the two groups. Only 6% of patients who received regional anesthesia experienced a
recurrence, compared to a 24% risk of metastatic recurrence in the group that did not receive regional anesthesia.
Stated differently, women who received regional and general anesthesia had a 75% decreased risk for metastatic
cancer. These findings led researchers to proclaim that regional anesthesia for breast cancer surgery “markedly
reduces the risk of recurrence or metastasis during the initial years following surgery.”55
Surgeons at Duke University Medical Center compared regional anesthesia alone to general anesthesia in women
having surgery for breast cancer. The surgeons reported that while 39% of the general anesthesia group required
medication for nausea and vomiting, only 20% of the regional anesthesia group needed this medication. Narcotic
medication was needed for pain control after surgery in 98% of the general anesthesia group, compared to only
25% of the regional anesthesia group. And 96% of the women receiving regional anesthesia had returned home
within a day after surgery, compared with 76% of the women who received general anesthesia. The surgeons
concluded that regional anesthesia “can be used to perform major operations for breast cancer with minimal
complications… Most importantly, by reducing nausea, vomiting, and surgical pain, paravertebral block [regional
anesthesia] markedly improves the quality of operative recovery for patients who are treated for breast cancer and
therefore provides the patient with the choice to return home as early as desired after surgery.”68
The results of these studies have vast implications for those undergoing cancer surgery, as a group of researchers
enthusiastically announced: “As regional techniques [anesthesia]… are easy to implement, inexpensive, and do
not pose a threat greater than general anesthesia, it would be easy for anesthesiologists to implement them, thus
reducing the risk of disease recurrence and metastasis.”55
Finally, those requiring morphine for pain control after surgery can consider asking their doctor for a medication
called tramadol instead. Unlike morphine, tramadol does not suppress immune function.69 On the contrary,
tramadol has been shown to stimulate NK cell activity. In one experiment, tramadol blocked the formation of lung
metastasis induced by surgery in rats. Tramadol also prevented the surgery-induced suppression of NK cell activity.
70
Less Invasive Surgery Reduces Risk of Metastasis
Surgery places an enormous physical stress upon the body. There is considerable scientific evidence supporting
that surgeries that are less invasive—and therefore less traumatic—pose less risk of metastasis, compared to
more invasive and traumatic surgery. Laparoscopic surgery is one type of minimally invasive surgery, in which
operations in the abdomen, pelvis, and other regions are performed through small incisions, as compared to the
much larger incisions needed in traditional “open” surgeries.
A study published in the prestigious medical journal The Lancet compared laparoscopic to open surgery to remove
part of the colon (colectomy) in patients with colon cancer. In contrast to the group receiving traditional open
surgery, the laparoscopic surgery group had a 61% decreased risk of cancer recurrence coupled with a 62%
decreased risk of death from colon cancer. The surgeons concluded that laparoscopic colectomy is more effective
than open colectomy for treatment of colon cancer as assessed by tumor recurrence and cancer-related survival.71
A long-term follow-up of these patients (median time 95 months) reported a 56% decreased risk of death from
colon cancer for laparoscopic surgery as compared to traditional open surgery.72 Another comparison of
laparoscopic surgery to open surgery for colon cancer reported a five-year survival rate of 64.1% for the
laparoscopic group, and a five-year survival rate of 58.5% for the group receiving open surgery.73
Minimally invasive surgery has produced substantial improvements in survival for those with lung cancer. Video-
assisted thoracoscopic surgery (VATS), a minimally invasive surgery, was compared to traditional open surgery for
removing lung tumors (lobectomy). The five-year survival from lung cancer was 97% in the VATS group. This greatly
contrasts the 79% five-year survival in the open surgery group.74
Commenting on the use of minimally invasive surgery for lung cancer, surgeons at Cedars-Sinai Medical Center
stated that minimally invasive surgery for lung cancer “… can be performed safely with proven advantages over
conventional thoracotomy [chest surgery] for lobectomy: smaller incisions, decreased postoperative pain,
…decreased blood loss, better preservation of pulmonary function, and earlier return to normal activities… the
evidence in the literature is mounting that VATS may offer reduced rates of complications and better survival.”75
Administering Chemo and Radiation Therapies Prior to Surgery
Doctors at the University of North Carolina School of Medicine studied the use of combined radiation and
chemotherapy prior to surgery for individuals with esophageal cancer. Twenty-six patients received surgery alone,
while 30 patients received radiation and chemotherapy followed by surgery. The group receiving combined
treatment had a five-year survival of 39%, while the group treated with surgery alone experienced a five-year survival
of only 16%.99
A study published in the New England Journal of Medicine in 2006 compared treatment with surgery alone to
treatment with chemotherapy—given both directly before and after surgery—in patients with stomach or
esophageal cancer. The five-year survival for the group receiving surgery and chemotherapy was 36%, compared to
a five-year survival of 23% in the group receiving surgery alone.100
Research also supports the use of chemotherapy and radiation therapy during the critical perioperative period. In
one study, 544 patients with stomach cancer received combined chemotherapy and radiation therapy shortly after
surgery. Survival comparisons were made with a similar group of 446 patients with stomach cancer treated with
surgery alone. Postoperative chemotherapy and radiation led to a dramatic improvement in survival. The group
treated with surgery alone had a median survival of only 62.6 months, compared to a median survival of 95.3
months in the group receiving postoperative radiation and chemotherapy.101 A similar study also demonstrated
improved survival with the use of postoperative radiation and chemotherapy compared to surgery alone.102
Inflammation and Metastasis
Cancer surgery causes an increased production of inflammatory chemicals, such as interleukin-1 and interleukin-
6.76-78 These chemicals are known to increase the activity of cyclooxygenase-2 (COX-2). A highly potent
inflammatory enzyme, COX-2 plays a pivotal role in promoting cancer growth and metastasis.
This was evident in an article appearing in the journal Cancer Research that found levels of COX-2 in pancreatic
cancer cells to be 60 times greater than in normal pancreatic cells.79 Levels of COX-2 were 150 times higher in
cancer cells from individuals with head and neck cancers compared to normal tissue from healthy volunteers.80
COX-2 fuels cancer growth by stimulating the formation of new blood vessels feeding the tumor.81,82 COX-2
increases cancer cell adhesion to the blood vessel walls,83 and also enhances the ability of cancer cells to
metastasize. Experiments in mice revealed that colon cancer cells expressing high levels of COX-2 metastasized
freely to the liver, while colon cancer cells expressing low levels of COX-2 did not metastasize to the liver.83
The adverse influence of COX-2 on the growth and progression of cancer was clearly revealed in a study published
in the journal Clinical Cancer Research in 2004. Two hundred eighty-eight individuals undergoing surgery for colon
cancer had their tumors examined for the presence of COX-2. The findings were alarming—when other factors
were controlled for, the group whose cancers tested positive for the presence of COX-2 had a 311% greater risk of
death compared to the group whose cancers did not express COX-2.84 A subsequent study in lung cancer patients
found that those with high tumor levels of COX-2 had a median survival of only 15 months, whereas those with low
tumor levels of COX-2 had a median survival of 40 months.85
Given these findings, researchers began investigating the anti-cancer effects of COX-2 inhibitor drugs. Although
initially used for inflammatory conditions, such as arthritis, COX-2 inhibitor drugs have been shown to possess
powerful anti-cancer activity. For example, 134 patients with advanced lung cancer were treated with chemotherapy
alone or combined with Celebrex® (a COX-2 inhibitor). For those individuals with cancers expressing higher
amounts of COX-2, treatment with Celebrex® dramatically prolonged survival.86 Treatment with Celebrex® also
slowed cancer progression in men with recurrent prostate cancer.87
Perhaps the most impressive display of the anti-metastatic effects of COX-2 inhibitor drugs was presented at the
annual conference of the American Society of Clinical Oncology in 2008. In this study, the incidence of bone
metastases in breast cancer patients who had taken a COX-2 inhibitor for at least six months following the
diagnosis of breast cancer was compared to the incidence of bone metastases in breast cancer patients who had
not taken a COX-2 inhibitor. Remarkably, those who were treated with a COX-2 inhibitor were almost 80% less
likely to develop bone metastases than those who were not treated with a COX-2 inhibitor drug.88
Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are COX inhibitors. The
widespread use of NSAIDs for pain and arthritis has created an ideal environment in which to examine if these
drugs can prevent cancer. Large-scale studies have documented a substantial reduction in cancer risk with the
use of NSAIDs. A comprehensive review of the scientific literature (91 published studies) reported that the long-
term use of NSAIDs (primarily aspirin) produced risk reductions of 63% for colon cancer, 39% for breast cancer,
36% for lung cancer, 39% for prostate cancer, 73% for esophageal cancer, 62% for stomach cancer, and 47% for
ovarian cancer. “This review provides compelling… evidence that regular intake of NSAIDs that… block COX-2
protects against the development of many types of cancer,” the authors concluded.89
A number of nutritional and herbal supplements are known to inhibit COX-2. These include curcumin, resveratrol,
vitamin E, soy isoflavones (genistein), green tea (EGCG), quercetin, fish oil, garlic, feverfew, and silymarin (milk
thistle).58,90-97
Scientists at Memorial Sloan-Kettering Cancer Center in New York created an experimentally-induced increase in
COX-2 activity in human breast cells, which was completely prevented by resveratrol. Resveratol blocked the
production of COX-2 within the cell, as well as blocking COX-2 enzyme activity.98
Conclusion
A group of noted experts in the field of surgery-induced metastasis stated that cancer treatment “…necessitates the
surgical excision of the primary tumor in order to relieve the patient of the major tumor burden, which is the main
source of mutating and metastasizing cells. However, along with its obvious benefits, the surgical procedure has
been suggested to involve serious hazards as it releases tumor cells into the circulation or lymphatics, promotes
the secretion of angiogenic and growth factors, and induces suppression of CMI [immune function]. These
consequences synergistically facilitate the establishment of new metastases and the development of preexisting
micrometastases. As cancer-related death is most commonly the result of metastatic disease, it is crucial to
minimize this facilitation.”55
Remarking further, they commented that “Taken together, it is evident that the perioperative period harbors many
risks; however, it is also the ideal time for battling MRD [small numbers of cancer cells remaining after surgery] to
reduce recurrence and future metastases.” Thus, these scientists believe “…it is essential to employ preventative
interventions during this critical time.” Additionally, they urge that, “Ideally, each problematic aspect of surgery
should be treated when oncological patients undergo resection [surgery] in order to minimize recurrence and
metastatic spread.”55
Armed with the knowledge discussed in this article, the person with cancer can reap all the benefits that cancer
surgery offers, while simultaneously avoiding the metastatic perils imposed by this procedure.
As this article was going to press, a dedicated team of clinical oncologists and researchers are preparing a
meticulous report on the optimal doses of nutrients and drugs that a cancer patient should consider during the pre-
and post-operative period. You can obtain a free copy of this report by logging on to our Cancer Surgery Special
Report — http://www.lef.org/featured-articles/Cancer-Surgery-Special-Report.htm — or calling 1-800-841-5433.
If you have any question on the scientific content of this article, please call a Life Extension® Health Advisor at 1-
866-864-3027.
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