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Cancer Surgery

Preventing Surgery-Induced Immune Suppression

The immune system is essential in combating cancer. Natural killer (NK) cells are a type of white blood cell which seeks out and destroys cancer cells. Research has shown that NK cells can spontaneously recognize and kill a variety of cancer cells (Herberman 1981).

In a study examining NK cell activity in women shortly after surgery for breast cancer, it was reported that low levels of NK cell activity were associated with an increased risk of death from breast cancer (Mccoy 2000). In fact, reduced NK cell activity was a better predictor of survival than the actual stage of the cancer itself. In another study, colon cancer patients with a reduced NK cell activity before surgery had a 350% increased risk of metastasis during the following 31 months (Koda 1997).

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, during, and after surgery). Numerous studies have documented that cancer surgery results in a substantial reduction in NK cell activity (Da Costa 1998; Shakhar 2003; McCulloch 1993; Rosenne 2007). In an investigation, NK cell activity in women having surgery for breast cancer was reduced by over 50% on the first day after surgery (McCulloch 1993). A group of researchers stated that “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” (Shakhar 2003).

The surgical procedure itself reduces NK activity. In other words, NK cell activity becomes impaired when it is most needed to fight metastasis. With that said, the perioperative period presents a window of opportunity to actively strengthen immune function by enhancing NK cell activity. Fortunately, numerous nutraceutical (e.g., dietary supplements, herbal products), pharmaceutical, and medical interventions known to enhance NK cell activity are available to the person undergoing cancer surgery.

One prominent natural supplement that can increase NK cell activity is an enzymatically modified rice bran extract. This specialized rice bran extract has been termed a “biological response modifier” because of its ability to enhance several aspects of immune function (Ghoneum 2011). Studies show that enzymatically modified rice bran extract activates natural killer cells, T cells, macrophages, and monocytes (Ghoneum 2011; Ghoneum 2004). This specialized compound can increase the ability of paclitaxel to kill both metastatic and non-metastatic breast cancer cells. In fact, one study found that enzymatically modified rice bran extract increased by more than 100-fold the suceptiabilty of breast cancer cells to paclitaxel. The extract worked in synergy with paclitaxel in this study, causing DNA damage, enhancing apoptosis, and inhibiting proliferation of metastatic breast cancer cells (Ghoneum 2014). A similar laboratory study showed that the specially modified rice bran extract increased the ability of the chemotherapeutic agent daunorubicin to kill breast cancer cells (Gollapudi 2008). Another preclinical model showed that enzymatically modified rice bran extract promoted apoptosis in leukemia cells (Ghoneum 2003).

Enzymatically modified rice bran extract has also been shown to complement conventional treatment of liver cancer. In a randomized, blinded, controlled clinical trial involving 68 liver cancer patients, enzymatically modified rice bran extract was shown to improve the efficacy of common treatment approaches including chemoembolization, ethanol injection, cryoablation, and radiofrequency ablation (collectively termed “interventional therapy”). Thirty-eight subjects underwent interventional therapy and received 1 g of the rice bran extract daily for three years, while 30 underwent interventional therapy only. Compared with interventional therapy alone, enzymatically modified rice bran extract in combination with interventional therapy led to reduced rates of disease recurrence (31% vs. 46%), improved survival rate after two years (6% vs. 35%), and a significant reduction in tumor volume (Bang 2010). Moreover, adverse side effects were more common in the group of subjects who only underwent interventional therapy.

Other nutraceuticals that have been documented to increase NK cell activity are garlic, glutamine, IP6 (inositol hexaphosphate), and lactoferrin (Ishikawa 2006; Baten 1989; Kuhara 2006; Klimberg 1996; Matsui 2002). 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 (Klimberg 1996).

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 either an intravenous infusion of mistletoe extract immediately before general anesthesia or general anesthesia alone. Measurements of NK cell activity were taken before and 24 hours after surgery. The group receiving anesthesia alone experienced a 44% reduction in NK cell activity 24 hours after surgery. 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” (Schink 2007).

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 (Mels 2001; Bhandarkar 2007). Another immune boosting drug to consider in the perioperative setting is interleukin-2 (Brivio 2002).

Tinospora cordifolia (T. cordifolia), long associated with adaptogenic and disease preventive activity, has been used in the traditional Indian Ayurvedic System of medicine to increase immune response against diseases (eg, malaria), infection, and liver toxicity, and reduce immune response in cases of inflammation, allergies, arthritis, fever, and diabetes (Thawani 2006; Sharma 2012; Upadhyay 2010; Wadood 1992; Sharma 2010).

In a human trial of 30 patients undergoing surgical intervention for malignant obstructive jaundice, pretreatment with oral T. cordifolia (16 mg/kg/day) prevented septicemia (a life-threatening infection of the blood), normalized debris removal and killing capacity of the immune system’s white blood cells, and resulted in a postoperative survival rate of 92.4% in the treatment group versus 40% in the control group. Researchers concluded that strengthening of the immune system by extracts of T. cordifolia may be responsible for considerable improvement in post-surgical outcome (Rege 1993).

In a laboratory study, a novel extract of T. cordifolia was found to powerfully activate different types of lymphocytes, which are important immune factors. The researchers found that it increased NK cell activity by 331%, T-cell activity by 102%, and B-cell activity by 39%, all of which demonstrate increased immune activity. These observations prompted the study authors to categorize T. cordifolia as “exhibiting unique immune stimulating properties” (Nair 2004).

Heightening Immune Surveillance with Cancer Vaccines

Using vaccines for cancer 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 they are autologous, that is, they are produced from a person’s own cancer cells and 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 (Mosolits 2005). Unlike chemotherapy, which can cause severe side effects and toxicity, cancer vaccines are a gentle therapy with proven long-term safety (Choudhury 2006).

In a landmark study reported in 2003, 567 individuals with colon cancer were randomized to receive either 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 (66.5% 5-year survival rate) compared to 4.5 years (45.6% 5-year survival rate) for the group receiving surgery alone (Liang 2003). This difference in five-year survival rates 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.