Surgery side-effects and solutions.

Surgery side-effects and solutions.

On this page:
Part 1: Surgery side-effects – how to reduce risk and severity
Part 2: Surgery can spread cancer – how to reduce your risk


Part 1: Surgery side-effects – how to reduce risk and severity

Possible risks and side-effects associated with surgical procedures include:

  • Risk of metastasis (cancer spreading)
  • Fluid or blood build up under the skin
  • Mild or severe bleeding – may require a transfusion
  • Infection at the incision site
  • Numbness and tingling which may be permanent
  • Lymphedema  swelling in arms or legs
  • Damage to other organs
  • Pain
  • Urinary Incontinence
  • Impotence
  • Heart problems
  • Breathing problems
  • Pneumonia 
  • Blood clots
  • Serious allergy to drugs (rare)
  • Nerve damage (rare)
  • Atrial fibrillation after surgery increases risk of heart attacks, strokes
  • Death (rare)

Sources: Mayo Clinic, Science Daily / University of Toronto, NHS, American Cancer Society


Solutions

Your medical team will prescribe pharmaceutical drugs to deal with some of the side-effects of surgery, but these come with their own risks. However, there are many other evidence-based solutions you can use to reduce side-effects, make your treatment work better and safer, and significantly improve your chances of survival. These solutions (most of them natural) are listed below – along with scientific studies showing their benefits.

INTERVENTIONPROVEN BENEFIT
PREHABILITATION Quit smoking Reduce alcohol intake Engage in rigorous physical exercise Engage in inspiratory muscle training Eat a healthy nutritious diet Engage in mind-body practicesPrehabilitation prepares individuals to ‘weather the storm’ of their operation and to avoid or overcome complications by preparing themselves physically and mentally beforehand. 
POST SURGERY PAIN MANAGEMENT Accupuncture Biofeedback Cannabis Cesium Chloride Chiropractic Care Hypnotherapy Low Dose Naltrexone Massage Methadone Progressive Muscle Relaxation Pulsed Electromagnetic Field (PEMF) Therapy Reiki Reflexology Herbs Turmeric White Willow Bark California Poppy Corydalis Red Pepper Noni Root Kava / Kava LactonesReduces or eliminates pain
WOUND HEALING (Naturally) Aloe Vera Calendula officinalis  (an annual herb)Helps with wound healing
BRUISING / SWELLING / INFLAMMATION (Naturally) Bromelain (pineapple stem) Quercetin (plant flavanoid derived from fruits) Arnica montana (an herb) Curcumin Reduces bruising and swelling
INFECTION PREVENTION Honey (natural product) Berberex (a patented formulation) Prevents infections
HEALING YOUR GUT Eat a diverse range of foods Eat lots of fibre Include Probiotics Eat Prebiotic foodsImproves overall health.

Here is scientific evidence supporting the efficacy of all the solutions listed above.

Please note: a. All scientific studies appear with a coloured background like this. b. Only sample studies are cited for each of the following solutions, but there may be many more available on PubMed and elsewhere. c. Many of the following solutions have multiple benefits in addition to those shown below.

1. PREHABILITATION

“Prehabilitation” is any interventions given between the time of diagnosis and the start of cancer treatment. According to a report in the American Journal of Physical Medicine & Rehabilitation, prehabilitation is aimed at reducing complications from treatments and improving physical and mental health outcomes. Here are some scientifically validated actions: 

Quit smoking
Quit smoking

A review of data from over 20,000 patients who underwent cancer surgery found that smoking status significantly negatively affected all postoperative outcomes.

Reduce alcohol intake
Reduce Alcohol intake

This Review article found that reducing consumption to within recommended limits (14 units per week) reduces incidence of postoperative complications.

Engage in rigorous physical exercise
Engage in Rigorous Physical Exercise

One study involving 125 patients scheduled for major surgery. 62 patients who underwent a supervised rigurous exercise training program had 51% fewer postoperative complications as compared with the control group of 63 patients who did normal exercises.

Engage in inspiratory muscle training
Engage in Inspiratory muscle training

This study found that preoperative inspiratory muscle training (a form of resistance training for the respiratory muscles) demonstrated reductions in postoperative pulmonary complications in surgical populations.

Eat a healthy nutritious diet
Eat a healthy nutritious diet Malnourished patients are at increased risk of post-operative complications, such as reduced wound healing, increased infection rates, and skin breakdown.

This study says pre-operative energy reserves, such as lean body mass, are required to support the body’s response to the stress of surgery. Surgical patients with low reserve, including malnourished, frail and sarcopaenic (muscle-depleted) patients, are vulnerable, with diminished capacity to respond to the added demands of a surgical insult.

Consume lots of fruit, vegetables, and water

This Livestrong.com articles reports: The Leukemia and Lymphoma Society says the best way to fill your bank prior to surgery is to eat 3-5 servings of fruits and vegetables every day, eat mostly whole grain (brown rice, quinoa) and include a protein at every meal. They also recommend you make water your go-to beverage and aim to drink 64 to 80 ounces each day.

Avoid fried foods, excess fat, and sugar The Leukemia and Lymphoma Society adds: Avoid fried foods. Excess fat and sugar contain empty calories that do not provide the body with any nutrients. Too many empty calories and not enough nutritious food may have an effect on the immune system.

Engage in mind-body exercises
Engage in Mind-Body Practices Yoga.

This study looked at the effects of yoga on wound healing and other outcomes following surgery. Sixty-nine stage II and III breast cancer patients took part in a yoga program, while a control group of patients undertook supportive therapy and exercise. The results suggest a significant decrease in the duration of hospital stay, days of drain retention and days for suture removal in the yoga group as compared to the controls. There was also a significant decrease in plasma TNF alpha levels [high levels lead to inflammation and pain] following surgery in the yoga group, as compared to the controls.

Meditation.

This study says: In the present investigation, meditation reduced all subjects’ pain intensity and unpleasantness ratings with decreases ranging from 11 to 70% and from 20 to 93%, respectively.

Guided Imagery has been shown to reduce blood loss during surgery, reduce opioid use after it, and many post-surgery patients leave the hospital sooner. Guided Imagery lowers anxiety and pain, according to Stanford Health Care.

This is from the American Psychological Association website: During guided imagery, patients think about what is happening to their bodies, and how their bodies should respond in order to be healthy. For example, in a classic study, psychologist Henry Bennett and colleagues gave three groups of spinal surgery patients three different sets of instructions before their operations. Patients in the control group learned only about some aspects of the surgery. Patients in the relaxation group also learned strategies for succumbing to and emerging from anesthesia. Patients in a third, “blood shunting” group not only learned these strategies, but were also taught the importance of not losing too much blood during the operation, and imagined that “the blood will move away” from the injury during surgery, but will return to the area after surgery. After all of the operations were completed, the researchers found that the patients who imagined the blood moving away from their injuries during surgery, but returning after surgery, lost only about half as much blood as patients who were not given these guided imagery instructions.

See PREHABILITATION


2. POST-SURGERY PAIN MANAGEMENT

Acupuncture
Acupuncture The technique of inserting thin needles through the skin at specific points on the body to control pain and other symptoms. It is a type of complementary and alternative medicine. See Acupuncture page

Biofeedback
Biofeedback is a technique you can use to learn to control your body’s functions, such as your heart rate. With biofeedback, you’re connected to electrical sensors that help you receive information (feedback) about your body (bio). This feedback helps you focus on making subtle changes in your body, such as relaxing certain muscles, to achieve the results you want, such as reducing pain. See Biofeedback page

Cannabis
Cannabis According to the National Cancer Institute, when cancer pain is severe and persistent, it is often resistant to treatment with opioids. Two studies examined the effects of oral delta-9-THC on cancer pain. The first, a double-blind, placebo-controlled study involving ten patients, measured both pain intensity and pain relief. It was reported that 15 mg and 20 mg doses of the cannabinoid delta-9-THC were associated with substantial analgesic effects, with antiemetic effects and appetite stimulation. See Cannabis  page

Cesium Chloride
Cesium Chloride Cesium chloride not only kills cancer cells, but it immediately stops the metastasis of the cancer, can shrink tumor masses within weeks, and almost always stops the pain of cancer within 12 to 36 hours. See Cesium Chloride page

Chiropractic Care
Chiropractic Care Cancer and its treatments often cause stress on the musculoskeletal system. Some cancer patients experience peripheral neuropathy, aches and pains in the neck and/or back, muscle tension, headaches or difficulty walking. Chiropractic care may help to reduce stress and increase mobility, flexibility, strength and function. See Chiropractic Care page

Hypnotherapy
Hypnotherapy Hypnosis has been suggested to be a useful adjunct for pain reduction in cancer patients and can significantly reduce cancer-related pain, antiemetic use, nausea and emesis (vomiting) during medical procedures, as well as anxiety related to all of the mentioned symptoms occurring in cancer patients. See Hypnotherapy page

Low Dose Naltrexone
Low dose Naltrexone

Evidence suggests that naltrexone, when used in low dose (1.75-4.5mg), shows inhibitory properties at the opioid receptors enabling the body to increase the production of endogenous opioids (endorphins) along with upregulating the immune system, according to this Study.

See Low dose Naltrexone page

Massage
Massage Massage treatment is the manipulation of muscles and soft tissue through kneading, rubbing, pressing, etc. Studies have shown that a massage will decrease stress, anxiety, depression, pain, and fatigue. Therefore, it is very beneficial in any cancer protocol. The connection among physical well-being, touch, and relaxation is very strong and can enhance the body’s own abilities to heal. See Massage page

Methadone
Methadone

This 2017 study says: Methadone has beneficial characteristics as an analgesic against cancer pain, including high bioavailability, multiple receptor affinities, and lack of active metabolites that might induce adverse side effects.

Progressive Muscle Relaxation
Progressive Muscle Relaxation Progressive Muscle Relaxation (PMR) therapy involves sequential tensing and relaxation of major skeletal muscle groups and aims to reduce feelings of tension, to lower perceived stress, and to induce relaxation. Reports of patients who participated in PMR training following cancer treatment indicate that they experienced reduced state anxiety, pain, and symptoms of depression, as well as improvements in sleep parameters and overall quality of life. See Progressive Muscle Relaxation page

Pulsed Electromagnetic Field therapy
Pulsed Electromagnetic Field (PEMF) therapy
Pulsed Electromagnetic Field (PEMF) therapy is a safe, and non-invasive way to reduce pain and inflammation. It can be used to supplement and enhance currently existing healthcare modalities. The PEMF apparatus includes various devices including full body mats, localized pad applicators, and pinpointed probe or “spot” applicators. See Pulsed Electromagnetic Field (PEMF) therapy page

Reiki
Reiki Reiki is a natural non-invasive therapy that promotes healing through stress reduction, relaxation and balancing of your energy systems. Reiki helps the muscles and tissues relax resulting in an increase in the blood flow to the treated area. This helps to reduce stress and pain and quickens the healing process. See Reiki page

Reflexology
Reflexology Reflexology is a therapy involving the physical application of pressure to the feet with the premise that massaging certain zones positively affects other areas of the body. A small study funded by the National Cancer Institute found that the ancient therapy may be an effective way to deal with cancer-related pain. See Reflexology page

Herbs
Herbs Turmeric White Willow Bark California Poppy Corydalis Red Pepper Noni Root Kava / Kava Lactone


3. WOUND HEALING

Aloe Vera
Aloe Vera

This study says: In terms of quality and speed of wound healing, Aloe vera is much more effective and less costly compared to the currently available alternative treatments.

Calendula Officinalis
Calendula officinalis  (an annual herb)

This study says the antibacterial activity of C.officinalis prevents secondary infections of wounds…Therefore, the C. officinalis extracts act in a positive form on the inflammatory and proliferative phases of the healing process of cutaneous wounds.


4. BRUISING / SWELLING / INFLAMMATION

Bromelain
Bromelain (pineapple stem)

According to this review article, Bromelain supplementation before and after surgery has been shown to reduce swelling, bruising, healing time, and pain…Presurgical administration of bromelain can accelerate visible signs of healing.

Quercetin
Quercetin (plant flavanoid derived from fruits)

This study says Quercetin has important biological activities related to the improvement of the wound healing process. 

Arnica montana
Arnica montana (an herb)

This study says: Cumulative evidence suggests that both Arnica in gel formulation and in homeopathic dilutions are more effective than placebo in treating several inflammatory conditions, in pain management and postoperative settings. Its clinical efficacy in these fields and its high tolerability make it a potential therapeutic alternative target to non-steroidal anti-inflammatory drugs…

Curcumin
Curcumin

This study says: In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe.it is quite apparent that curcumin has tremendous potential for prevention and therapy of various cancers.


5. INFECTION PREVENTION

Honey
Honey (natural product)

Infection still poses a serious threat to postoperative surgical wound care and are a leading cause for postoperative illness and death, says this study. This study says: Manuka honey has been widely researched and its antibacterial potential is renowned worldwide. The potency of honeys, such as Tualang honey, against microorganisms suggests its potential to be used as an alternative therapeutic agent in certain medical conditions, particularly wound infection. This study says: The antimicrobial and anti-inflammatory activity of honey and its ability to accelerate wound healing make it an attractive option in surgical wound care…The healing process of the surgical wound and its final aesthetic result could be improved by using honey dressing.

Berberex
Berberex (a patented formulation)

This study says BerbereX® appears to be a potent agent that positively affects cosmetic healing while protecting the wound from bacterial-affected wound infection…As such, it may serve as a candidate for routine post-operative incision site care.

According to the manufacturers website: BerbereX® Wound Cleanser will help to decolonize infected wounds. In antimicrobial tests, BerbereX® Wound Cleanser showed efficacy against standard and highly virulent strains of antibiotic-resistant bacteria such as Methicillin Resistant Staphylococcus Aureus (MRSA), Vancomycin Resistant Enterococcus (VRE), Group B Streptococcus (B-Strep) and E. Coli. BerbereX® is simple to use, requires no significant changes in current wound care protocols, and has no known side effects.


6. HEAL YOUR GUT

Your body has trillions of bacteria, viruses and fungi known collectively as the microbiome. While some bacteria are harmful, others are extremely important for your health. The human gut flora (microbiome) contains a total of about 100,000,000,000,000 organisms.

This review of 9 clinical trials found: Eight of nine trials showed a benefit with regards to infectious complications in patients who were treated with synbiotics or probiotics. Eight of nine also found beneficial effect on the gut flora. The review says there might be a relationship between the gut flora and the development of postoperative complications.

There are many ways to improve your gut microbiome, including:

Eat a diverse range of foods
Eat a diverse range of foods

The more diverse the diet, the more diverse the microbiome and the more adaptable it will be to disruptions, says this study.

Eat lots of fibre

Eat lots of Fiber.

Dietary fibers can be considered key ancestral compounds that preserve gut ecology and host physiology, says this study

According to the British Nutrition Foundation, fibre rich foods include:

  • Wholegrain breakfast cereals, wholewheat pasta, wholegrain bread and oats, barley and rye
  • Fruit such as berries, pears,  melon and oranges
  • Vegetables such as broccoli, carrots and sweetcorn
  • Peas, beans and pulses
  • Nuts and seeds
  • Potatoes with skin

Include Probiotics
Include Probiotics Probiotics are live bacteria or yeasts found in fermented foods that, when consumed, take up residence in the gut and improve health. 

Fermented foods include Yogurt (study), Sauerkraut (study), Kefir (study), Kombucha (study), Tempeh, Miso, Pickles, Natto and some types of cheese.

Eat prebiotic foods: 

Prebiotics are a type of fiber that stimulates the growth of healthy bacteria. Food sources include Oats (study), Apples (study), garlic, onions, leeks, asparagus, bananas, flaxseeds and wheat bran. This study says: Prebiotics play an important role in human health. They naturally exist in different dietary food products, including asparagus, sugar beet, garlic, chicory, onion, Jerusalem artichoke, wheat, honey, banana, barley, tomato, rye, soybean, human’s and cow’s milk, peas, beans, etc., and recently, seaweeds and microalgae.


Major surgery is like running a marathon—and both require training

Source: BMJ The impact of surgery leads to significant homeostatic disturbance. The surgical stress response is characterised by catabolism and increased oxygen demand. The extent and duration of the stress response is proportionate to the magnitude of surgery and the associated risk of developing postoperative complications. Patients who experience postoperative complications within 30 days of surgery have a reduced long term survival rate. Even in the absence of complications there is a 20-40% reduction in postoperative physical function and a significant deterioration in quality of life after major surgery.


Are we doing too much in oncology backwards?

Writing in The Journal of Hematology Oncology Pharmacy, Julie Silva MD says: One cancer survivor wrote a blog that included this question in the title: Are we doing too much in oncology backwards? In his blog post he said, “I was reviewing my blood work after my recent stem cell transplant and noticed that my hemoglobin and red blood cells had dropped 47% from my normal health to their lowest values two weeks after my transplant. I then checked what altitude a 50% drop in oxygen would correspond to. A 50% drop in oxygen represents an altitude of over 19,000 feet. Mt. Everest south base camp is 16,700 feet.” The survivor continued, “It would be irresponsible to send someone to Mt. Everest base camp without training them first, but it is common practice in oncology to physically challenge patients in a similar manner without training them for the difficulty to come. Instead, we nurse patients through the treatment challenge, cheer them when they are finished, then send them off to physical therapy to address injuries.” Then, in bold and italics for emphasis, he admonished, “This is not a success story, this is poor survivorship planning.”


Part 2: Surgery can spread cancer – how to reduce your risk

Surgery and Biopsy induced Metastasis

Biopsies and surgery can promote metastasis in a number of ways, including neoplasm seeding.

Neoplasm Seeding
The unintentional release of cancer cells from a tumor by a biopsy needle or surgical instrument, which then spread to other parts of the body resulting in new tumor formation.


Surgery
This 2017 Study published by the American Association for Cancer Research says: Both experimental and clinical evidence lend support to the idea that surgery which is intended to be a curative option to remove and reduce tumor mass, can paradoxically also augment development of metastases. If one can address those factors in the peri-operative period…might become a unique window to control residual malignant cells.

Biopsies
This published review says: Many a times to obtain sufficient amount of sample during needle biopsy for diagnosis the tumor may need to be penetrated several times. This repeated puncturing and manipulation inside the tumor mass with needle may seed tumor cells into the needle track and also may spill the cancerous cells directly in to the circulation.
See more at Neoplasm Seeding


Surgery causes metastasis by:

Promoting Angiogenesis (formation of new blood vessels)
Causing Inflammation
Damaging your Immune System

The following can also have an effect on surgery outcome:
Timing of Surgery
Less Invasive Surgery
Choice of Surgical Anaesthesia
Choice of post-surgery Analgesic drugs (pain killers)
All these can be addressed using the products and strategies listed below.

Note: These are backed by studies which are published further down the page.

SUPPLEMENTSPROVEN BENEFIT
EGCG (green tea)Inhibits angiogenesis (new blood vessels)
CurcuminInhibits angiogenesis (new blood vessels)
Genistein (food supplement)Inhibits angiogenesis (new blood vessels)
Silymarin (extract of milk thistle seeds)Inhibits angiogenesis (new blood vessels)
CannabisInhibits angiogenesis (new blood vessels)
AspirinCOX-2 Inhibitors (reduces inflammation)
ResveratrolCOX-2 Inhibitors (reduces inflammation)
Genistein (food supplement)COX-2 Inhibitors (reduces inflammation)
ECGC (Green Tea)COX-2 Inhibitors (reduces inflammation)
CurcuminCOX-2 Inhibitors (reduces inflammation)
Quercetin (a plant pigment)COX-2 Inhibitors (reduces inflammation)
Fish oilCOX-2 Inhibitors (reduces inflammation)
GarlicCOX-2 Inhibitors (reduces inflammation)
Feverfew (plant extract)COX-2 Inhibitors (reduces inflammation)
Silymarin (extract of milk thistle seeds)COX-2 Inhibitors (reduces inflammation)
Sodium Butyrate (sodium salt of butyric acid)COX-2 Inhibitors (reduces inflammation)
PSK (medicinal mushroom extracts)Immune Booster (enhances NK cell activity)
IP-6 ( a vitamin-like substance)Immune Booster (enhances NK cell activity)
AHCC (fermented mushroom extract)Immune Booster (enhances NK cell activity)
CurcuminImmune Booster (enhances NK cell activity)
MistletoeImmune Booster (enhances NK cell activity)
Aged Garlic Extract (AGE)Immune Booster (enhances NK cell activity)
Lactoferrin (protein found in milk)Immune Booster (enhances NK cell activity)
Useful StrategiesProven benefit
The Luteal PhaseThe optimal time for breast cancer surgery
LaparoscopyLess invasive surgery – may reduce metastasis
Video-assisted Thoracic Surgery (VATS) lobectomyLess invasive surgery – may reduce metastasis
General or Locoregional anaesthesia?Locoregional anaesthesia may be better
Morphine, Tramadol, or CBD?Tramadol or CBD may be better option
  

Here is scientific evidence supporting the efficacy of all the items listed above.

Angiogenesis

Angiogenesis is the formation of new blood vessels Angiogenesis plays a critical role in the growth of cancer because solid tumors need a blood supply if they are to grow beyond a few millimeters in size. Tumors can actually cause this blood supply to form by giving off chemical signals that stimulate angiogenesis. – National Cancer Institute.

This study says it is known that after surgery a sharp spike in angiogenesis stimulators and growth factors occurs to aid in wound healing. Thus, it is not surprising that tumour angiogenesis and proliferation result after surgery to remove a primary tumour. Therefore, a likely trigger for kick-starting the growth of micro-metastases, could be the act of surgery itself… It suggests that surgery could be responsible for accelerating the clinical appearance of metastatic disease.

The following can inhibit angiogenesis

EGCG (green tea)
This study says:  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.
This study says: These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer,

Curcumin
This study says: In summary, our present study indicates that curcumin is a potent inhibitor of angiogenesis…Given the importance of angiogenesis and tumour neovascularisation in cancer progression, our data also suggest that the anticancer effects of curcumin may also involve direct effects on local microvascular populations.

This study says: According to our study, curcumin inhibits tumor growth, tumor angiogenesis and induces apoptosis of endothelial cells, and suppresses HIF-1 mediated VEGF production and VEGF mediated signaling pathways.

Genistein
This study says: These observations support the hypothesis that genistein may inhibit prostate tumor angiogenesis…

NOTE:  This study states: In this model, a bivalent effect of genistein was demonstrated on sprouting angiogenesis, with angiogenic stimulation at low concentrations (0.001–1 µM) and inhibition at higher ones (25–100 µM).

Silymarin (SM)
This study says:
This study was designed to evaluate the anti-angiogenic effect of silymarin (SM) and its major pure component silibinin (SB), and also thalidomide (TH). Conclusion. SM/SB has a strong anti-angiogenesis effect on the colon cancer cell line, and this might provide an alternative treatment option for anticancer treatment.

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.

Cannabis
According to the National Cancer Institute  Cannabinoids, also known as phytocannabinoids, are chemicals in Cannabis that cause drug-like effects in the body, including the central nervous system and the immune system. Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis.

A study published in the Journal Molecular Cancer showed that THC reduced tumour growth and tumour numbers. They determined that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis and impair tumour angiogenesis .
See Cannabinoids page


Inflammation

Cancer surgery increases the production of inflammatory chemicals, such as interleukin-1 and interleukin-6. These increase the activity of COX-2 – a highly potent inflammatory enzyme involved in promoting cancer growth and metastasis.

This study says: Elevated expression of COX-2 is a common characteristic of many human carcinomas. COX-2 plays an important role in tumorigenesis as mediating the progression and metastasis of tumors, such as nasopharyngeal carcinoma, hepatocellular carcinoma, lung cancer and melanoma. The differential expression of COX-2 highly correlates to the progression of malignant melanoma and severely impairs the survival of patients.

This study says: (COX-2)…is associated with inflammatory diseases and carcinogenesis, which is suspected to promote angiogenesis and tissue invasion of tumors and resistance to apoptosis. Meanwhile, COX-2 contributes to immune evasion and resistance to cancer immunotherapy….

COX-2 Inhibitors:

Aspirin (See also: Pycnogenol – Aspirin alternative at https://cancerireland.ie/aspirin/

Resveratrol
This study says: …the results of the present study clearly show that resveratrol suppressed the synthesis of PGE2 by inhibiting COX-2 enzyme activity.  https://cancerireland.ie/resveratrol-and-mske/

Genistein (Soy isoflavones)
This study says: We found in this study that genistein in combination with EPA and DHA [both are fatty acids ] affected the expression of COX-2…

Green tea (EGCG)
This study concluded: In conclusion, these data suggest that inhibition of COX-2 is a mechanism for the anti-proliferative effect of green tea and emphasizes the role that dietary factors have as anti-cancer agents… Green tea and its derived compounds such as EGCG offer several advantages as putative anticancer agents; the foremost being that they are non-toxic to normal cells, produce few side effects, and are widely available.

Curcumin
This study says: Curcumin markedly inhibited the mRNA and protein expression of COX-2, but not COX-1…Therefore, curcumin may be superior to commonly used NSAIDs, which have anti-inflammatory and chemopreventive effects. Moreover, our study demonstrates for the first time that curcumin does not alter the expression of COX-1, so additional benefits may be gained by this agent over NSAIDs. In conclusion, our study suggests that curcumin should be considered as a possible safe and nontoxic chemopreventive agent for colorectal cancer in humans.
https://cancerireland.ie/curcumin/

Quercetin
This study says: These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers.

Fish oil
This study says: …fish oils contain the natural COX inhibitor EPA, which inhibits both COX-1 and COX-2 activity… In a medical environment in which messages molded by pharmaceutical interests stress the ‘need’ for NSAIDs, prescribers should consider the NSAID-sparing effects, the lack of serious side effects and the positive health benefits of fish oil. Importantly, recipients should be informed that there is a ‘mainstream’ evidence base for such a recommendation…

Garlic
This study says: In this study we report on the effectiveness of diallyl sulphides (DAS), which are derivatives of garlic, as potent COX-2 inhibitors.

This study says: Ajoene, a garlic-derived natural product that interfaces with the COX-2 enzyme, has anti-cancer activities

Feverfew
This study says: Feverfew appears to be an inhibitor of prostaglandin synthesis, leukotrienes (LT) and expression of pro-inflammatory cytokines…Further studies revealed that it inhibits inflammatory mediators including activity and expression of cyclo-oxygenase (COX) specifically COX-2, which also enhances cancer stem-like cells’ characteristics such as higher colony formation efficiency and over expression of stemness-associated genes

Silymarin (milk thistle)
This study says: Silymarin treatment significantly inhibited the expression of COX-2, thereby maintaining increased levels of free arachidonic acid in the cells, which might have resulted in the suppression of carcinogenesis. In conclusion, we found that the chemoprevention of liver cancer by silymarin might be due to its strong hypolipidemic activity.

This study says: Numerous studies have shown that silymarin suppresses COX-2 expression…Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-‚, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules).

This study says: Recent studies have reported that silymarin and its constituents including silibinin inhibit prostate-specific antigen (PSA) levels regulated by both serum and androgen, causing strong inhibition of human prostate carcinoma LNCaP cell growth… Preclinical results have also shown that silymarin and silibinin cause synergistic effects on cancer cell growth inhibition and apoptotic death by various chemotherapeutic agents, suggesting that these agents should be evaluated in more clinical trials along with other chemotherapeutic agents. In this regard, clinical studies have shown that silymarin treatment in combination with chemotherapeutic agents reduces the toxicity associated with chemotherapy. Silymarin treatment has also shown favorable results in clinical trials in prostate cancer patients and has been suggested as an integral part of a nutraceutical program tailored for cancer management.

Sodium Butyrate
This study says Sodium Butyrate inhibits growth and metastasis in colorectal cancer cells.

Sodium butyrate (NaB) is a short-chain fatty acid which is produced by bacterial fermentation of nondigestible dietary fiber and has been reported to exert anti-tumor effects in many tumors including colorectal cancer (CRC).

Sodium Butyrate and Artemisinin
This study says: The oral intake of artemisinin and its analogs and butyric acid is safe. The artemisinin-butyrate combination may work well, particularly for colon cancer where butyrate concentrations can be raised by simple oral probiotic intake of butyric acidproducing Lactobacilli.

See Artemisinin


Immune System 

Natural killer (NK) cells are part of a healthy immune system, which is critical to overcoming cancer. They can detect and kill many types of cancer cells but numerous studies tell us that surgery reduces their numbers dramatically.

For example, this study looked at 43 patients with operable breast cancer before and after surgery and found that NK cell activity decreased by over 50 per cent on the first day after surgery and did not return to preoperative levels by day 7.

This study says NK cells play an important role in preventing metastasis.

PSK enhances NK activity
Studies have shown that the natural supplement PSK can enhance NK cell activity. For example, this study analyzed the efficacy of Krestin (PSK) in 225 patients with non-small cell lung cancer (NSCLC). The 5-year survival rates of patients with stages I-II and stage III disease were 39% and 26%, respectively, while the non-administered responder group were only 17% and 8%.
See PSK page

IP6 (inositol hexaphosphate) enhances NK activity
See IP6 page

AHCC (active hexose correlated compound) enhances NK activity
See AHCC page

Curcumin enhances NK activity
This study says angiogenesis, the formation of new blood vessels from host vasculature, is critical for tumor growth and metastases. Curcumin is a direct inhibitor of angiogenesis. Curcumin affects the overall process of angiogenesis by downregulating VEGF, bFGF, and COX-2; inhibiting cell motility, cellular adhesion molecules, endothelial cell migration, invasion, and extracellular proteolysis. It also has antiproliferative and proapoptotic effects on tumor cells. See Curcumin page

Mistletoe enhances NK activity
In this study 62 colorectal cancer patients undergoing open tumour surgery were randomly assigned to either mistletoe infusion or no additional therapy.

NK cell activity differed significantly between the therapy groups 24 h after surgery. NK cell activity of patients treated with mistletoe extract only decreased by 7.9% 24 hours after surgery while control patients saw a 44.4% decrease after 24 hours.

According to these study results, perioperative infusion of mistletoe extracts offers an effective and safe protection against surgery-induced suppression of NK cell activity in colorectal cancer patients.
See Mistletoe page

Aged Garlic Extract (AGE) enhances NK activity
This study says: In this series of in vitro and in vivo studies, we showed that both AGE and PSK could stimulate cell mediated immunity, i.e. activate NK cells and cytotoxic T cells, and subsequently suppress tumor cell growth. PSK, which is prescribed for cancer patients in Japan, is used to enhance the survival of gastric and colon cancer patients and the disease-free period of small cell lung cancer patients when used in combination with chemotherapy agents. The anti-cancer mechanism(s) of PSK appears to be modulation of host immune responsiveness, such as restoration of depressed late phase reaction, enhancement of natural killer cell activity and macrophage functions, augmentation of cytotoxic cell induction, and antagonistic action against humoral immunosuppresive factors produced by a cancer patient

This study says:
The study’s subjects were patients with inoperable colorectal, liver, or pancreatic cancer.In a randomized double-blind trial, AGE was administered to one group and a placebo was administered to another for 6 mo… consisted of 42 patients with liver cancer, 7 patients with pancreatic cancer, and 1 patient with colon cancer…both the number of NK cells and the NK cell activity increased significantly in the AGE group. No adverse effect was observed in either group.

Lactoferrin enhances NK activity
This study says: We report that lactoferrin has a significant effect on natural killer (NK) cell cytotoxicity against haematopoietic and breast epithelial cell lines. Furthermore, we have demonstrated that the increase in NK cell cytotoxicity induced by lactoferrin is only observed at low concentrations of lactoferrin; at high concentrations, lactoferrin decreased NK cell activity.

We have also demonstrated that lactoferrin inhibits epithelial cell proliferation by blocking the cell cycle progression.

This study says: In vitro treatment with Naturin, a new Chinese medical herb, significantly restored lymphocyte proliferation and NK cell activity that were suppressed in cancer patients (Shen et al., 1996). In vivo, Naturin was reported to have significantly improved symptoms of cancer patients including leukemia and lung cancers (Mori et al., 1988).

Cancer Vaccines
Cancer vaccines are produced from a person’s own cancer cells removed during surgery. They are a form of immunotherapy that can help educate the immune system about what cancer cells (including metastatic cancer cells). “look like” so that it can recognize and eliminate them.

This study involved 335 patients with malignant tumors of digestive tract who were treated with autologous [patient’s own] tumor cell vaccine and NDV [Newcastle disease virus] vaccine. After NDV* vaccine immunotherapy, the number of NK cell increased and immune function improved. The study concluded: The autologous tumor cell vaccine and NDV vaccine can prolong the patients’ life.

This study says: In this chapter, we have summarized a number of clinical trials performed in various cancers with focus on the clinical outcome of vaccination therapy. We have also attempted to draw objective inferences from the published data that may influence the clinical effectiveness of vaccination approaches against cancer. Collectively the data indicate that vaccine therapy is safe, and no significant autoimmune reactions are observed even on long term follow-up. The design of clinical trials have not yet been optimized, but meaningful clinical effects have been seen in B-cell malignancies, lung, prostate, colorectal cancer, and melanoma.

This study review found: The most encouraging results were noted in randomised controlled phase II/III trials including over 1300 colorectal carcinoma patients with minimal residual disease. A statistically significantly improved disease-free or overall survival was shown either in all vaccinated or in sub-groups of patients. Promising results were also reported in pancreatic and hepatocellular carcinoma.

In another large randomised study including 567 stage I–IV colorectal carcinoma patients, autologous tumour cells mixed with NDV as an adjuvant was used for vaccination after surgery and compared to surgery alone. A significant prolongation of overall survival duration was seen in the vaccine group. Patients mounting a DTH response to the vaccine survived significantly longer. Six of the 25 patients (24%) with stage IV disease had complete or partial responses in the vaccine group.

In hepatocellular carcinoma (HCC) a tumour-cell-based vaccine combined with adjuvant cytokines significantly improved overall and disease-free survival compared to resection alone. Recurrences were less frequent in patients mounting a DTH response. In a few other studies, immune responses were associated with regression of metastasis or prolongation of disease-free survival.

Nearly a thousand patients with GI malignancies have been enrolled in nine phase II/III randomised controlled vaccination trials. All trials, with the exception of one, showed a statistically significantly improved progression-free or overall survival, either in all vaccinated or in sub-groups of patients. Most of these patients, nearly 700, were vaccinated with autologous tumour cells after surgery. A statistically significantly longer disease-free survival for stage II colon cancer patients was demonstrated using BCG as an adjuvant. Furthermore, autologous tumour cell-based vaccines with NDV or cytokine adjuvants showed a statistically significant overall survival benefit for patients with stages I–IV CRC, as well as stages I–III hepatocellular carcinoma.

At least a week before surgery, it seems a good idea to start a natural killer (NK) cell-enhancing program involving nutrients like PSK, Lactoferrin, etc.


Timing of Surgery

This study says: An intriguing controversy regarding the surgical treatment of breast cancer patients in the last two decades was initiated following a publication by Hrushesky et al. who reported that the timing of surgery for the resection of breast cancer tumors within the menstrual cycle influences disease recurrence and patient survival rates. Since then, several independent groups have corroborated these surprising findings, suggesting that the optimal time for the resection is the early luteal phase*. This phenomenon was independent of estrogen receptor status and more prominent in node-positive women.

[ *The luteal phase: The time between ovulation and before the start of menstruation]

Less Invasive Surgery

Surgery causes huge physical stress to the body, suppressing immunity and increasing the risk of metastasis. Studies show that less invasive surgery such as Laparoscopy and Video-assisted Thoracic Surgery (VATS) lobectomy may be a better option.

Laparoscopy
This study compared Laparoscopy (LAC) to open Colectomy (OC) in 219 patients with Colon cancer. It states: In summary, our results show that LAC should be preferred to OC in patients with colon cancer because it reduces perioperative morbidity, shortens hospital stay, and prolongs cancer-related survival. This latter benefit was mainly due to differences in the subset of patients with stage III tumours, in whom LAC was also associated with lower tumour recurrence and longer overall survival.

This follow-up study of the patients over a 95 month period states: The striking finding of our trial was a higher probability of the cancer-related survival in the LAC group and that LAC was independently associated with a reduced risk of tumor relapse and death from a cancer-related cause when compared with the OC. Interestingly, these differences between the LAC and OC groups were only due to the patients with advanced nonmetastatic cancer (stage III). Conclusions: LAC is more effective than OC in the treatment of colon cancer.

Video-assisted Thoracic Surgery (VATS) lobectomy
This study looked at 204 video-assisted thoracic surgery lobectomies. Results… the 5-year survival rate of pathologic stage I lung cancers after video-assisted thoracic surgery was 97.0%, whereas that after open thoracotomy was 78.5% Conclusions. Pulmonary function and prognosis were far better after video-assisted thoracic surgery lobectomy than after open thoracotomy.It is believed that metastases occur most frequently during the perioperative period, when injury and repair are most prominent and stress can elaborate various humoral substances that potentiate the growth of carcinomas. Thus, Lewis proposed that minimally invasive surgical procedures with the small incisions required for VATS could account for improved long-term survival after a VATS lobectomy.


Choice of Surgical Anaesthesia 

Many laboratory studies have suggested that tumor metastasis after cancer surgery may be impacted by surgical anaesthesia techniques.

General or Locoregional anaesthesia?
This study says: Anaesthesia technique could differentially affect cancer recurrence in oncologic patients undergoing surgery, due to immunosuppression, stimulation of angiogenesis, and dissemination of residual cancer cells… Thus, NK cell function seems to be better preserved by locoregional anaesthesia; in addition, the possibility of metastatic disease is significantly limited.

Moreover, the combined use of locoregional anaesthesia with general anaesthesia reduces the amount of general anesthetic required, as well as degree of immunosuppression.

Locoregional analgesia provides better pain control, eliminating the need for opioids in the postoperative period and resulting in negative effects on immune function and tumor growth; it also reduces the release of endogenous opioids.

This study review found: Immunosuppression caused by anesthetic agents should not be ignored, as there are potential ways to circumvent it. One such method is the addition of regional anaesthesia and analgesia to general anaesthesia. This approach reduces the amount of general anaesthesia required during surgery, as well as the quantities of postoperative opioid analgesia, which is itself known to be immunosuppressive… . A retrospective study investigating the effects of regional anaesthesia and analgesia in women who underwent surgery for the resection of breast cancer confirmed our prediction with respect to cancer recurrence. In this study the medical records of 129 patients undergoing mastectomy and axillary clearance were examined. Fifty patients had surgery with paravertebral anaesthesia combined with general anaesthesia, and 79 patients had general anaesthesia combined with postoperative morphine analgesia…after a follow-up period of 24 months only 6% of the regional anaesthesia group showed recurrence, whereas 18% of the general anaesthesia and morphine analgesia group showed recurrence. At 36 months, the difference between the groups increased to 6% vs. 23%, respectively.

This study says: A retrospective analysis of 145 consecutive patients undergoing 156 breast cancer operations using paravertebral block and 100 patients undergoing general anaesthesia during a 2-year period was performed. Conclusions: Paravertebral block can be used to perform major operations for breast cancer with minimal complications and a low rate of conversion to general anaesthesia. Paravertebral block markedly improves the quality of recovery after breast cancer surgery and provides the patient with the option of ambulatory discharge.

A review of our early experience revealed that this regional anesthetic technique enables effective anaesthesia for operative procedures of the breast and axilla, reduces postoperative nausea and vomiting, and provides prolonged postoperative sensory block that minimizes narcotic requirements.

Post-surgery Analgesic

Acute and chronic opioid administration is known to have inhibitory effects on natural killer cell activity according to this study.

This study review advises: …physicians should always try to prescribe postoperative analgesia that is minimally immunosuppressive (e.g., avoid chronic systemic administration of morphine), especially following oncological surgeries. The use of pharmacological interventions perioperatively such as the intervention mentioned above employing a βblocker and a COX2 inhibitor should be considered, as they are feasible and can easily be implemented.

Morphine or Tramadol (or CBD)?
Doctors and cancer care teams may prescribe  opioids such as Morphine or Tramadol for patients having increasing or severe pain from their cancer or their treatment. 

The effects of these drugs on your immune system – and consequently your risk of metastasis / recurrence – is an important consideration.

CBD
This study says: …using CBD for chronic pain in patients using opioids has a significant effect on reducing opioid intake, reducing pain and improving QoL [quality of life]. CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patients who are currently using opioids for pain management.

Morphine or Tramadol
This 2019 study found: Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. Conclusions. After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality.

This study concluded: In conclusion, morphine, fentanyl and tramadol showed comparable analgesic activity in postoperative patients. The immunosuppression of morphine, at least partly, through NF-κB pathway, made it unfavorable for postoperative analgesia. Fentanyl had a different effect on the immune response as seen in vitro and in vivo studies. Tramadol demonstrated immune enhancement both in vitro and in vivo. Therefore, tramadol and fentanyl may be preferred to morphine for the treatment of postoperative pain from the immunological point of view.

This study says: This study compared the effects on immune responses of morphine and of the atypical opioid analgesic, tramadol, given for postoperative pain to gynecological cancer patients. Tramadol and morphine showed comparable analgesic activity; however, tramadol, in contrast to morphine, induced an improvement of postoperative immunosuppression and, therefore, may be preferred to morphine for the treatment of postoperative pain.

In this study says: …evidence exists in the literature suggesting that low NK activity during the peri-operative period can be associated with higher incidence of cancer relapse and mortality in humans. This seems to be particularly true for some breast, neck, lung and colorectal cancers for which the presence of low NK activity is predictive of a poor prognosis…On the basis of the data reported in the present study…and considering the immune profile of tramadol in man in the post-operative period (Sacerdote et al., 2000), we hypothesize that the use of tramadol in the treatment of perioperative pain in cancer patients might be particularly beneficial.

Patients requiring morphine for post-surgery pain control may consider asking their doctor about prescribing Tramadol instead to preserve immunity and thereby decrease the chances of metastasis.

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