Surgery for cancer recovery and survival

Surgery is one of the oldest and most important treatments for cancer. Its main aim is to remove cancer from the body, either completely when the disease is localised, or as much as possible when reducing the tumour burden may help other treatments work more effectively. Surgery may also be used to diagnose cancer, determine its stage, relieve symptoms, prevent complications, or restore function after treatment. For many solid tumours, especially when cancer is found early, surgery can offer the strongest chance of long-term control or cure. However, its role depends on many factors, including cancer type, tumour location, stage, general health, and whether additional treatments such as chemotherapy, radiotherapy, immunotherapy, targeted therapy, or hormonal therapy are needed before or after the operation.

Get the latest on surgery from the National Cancer Institute

Note: This article is aimed at bringing balance to the debate about Surgery use in cancer treatment. I’m not trying to dissuade you from having this treatment as it might be of some help, depending on your situation. I’m simply providing unbiased, independent information that you might otherwise not be made aware of, but which may be helpful to you.

Quick Summary
Research shows that Surgery:

• can extend survival in certain cases
• can result in long-term remission in some instances
• is not automatically beneficial for all patients
• can result in serious complications
• may be responsible for causing metastasis
• can be supported by adding Complementary therapies

What are the dangers of surgery?

Possible complications for any surgical procedure 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)
• Death (rare)

Atrial fibrillation after surgery increases risk of heart attacks, strokes
An irregular heartbeat following surgery known as post-operative atrial fibrillation (POAF) often is dismissed as a transient phenomenon. But a study has found that POAF can significantly increase the risk of heart attack or stroke during the first 12 months after surgery.

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

Do Biopsies cause metastasis?

Biopsies can promote metastasis via 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.

This study identified 663 patients with biopsy-proven invasive breast cancer who underwent sentinel lymph node dissection. Patients were divided into 3 groups based on type of biopsy: fine-needle aspiration (FNA), large-gauge needle core, and excisional.

Results: Of the 676 cancers, 126 were biopsied by fine-needle aspiration, 227 by large-gauge needle core biopsy, and 323 by excisional biopsy before sentinel lymph node dissection…the incidence of sentinel node metastases was higher in patients whose cancer was diagnosed by fine-needle aspiration or large-gauge needle core biopsy than by excision.

Conclusions: Manipulation of an intact tumor by fine-needle aspiration or large-gauge needle core biopsy is associated with an increase in the incidence of sentinel node metastases, perhaps due in part to the mechanical disruption of the tumor by the needle.

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.

Does Surgery cause metastasis?

Surgery can promote metastasis in a number of ways, including:

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
Invasiveness of 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 (backed by studies which are published further down the page)

But first, here are some supporting studies:

This study says: Given that evidence is continuously accumulating to support the hypothesis that surgery is a facilitator of the metastatic process, it is critical to consider the alarming clinical notion that surgery is a double-edged sword—it is necessary and life-saving; yet, has deleterious long-term impacts, potentially increasing the risk of metastases. We believe that surgery is indeed a major risk factor for the spread, establishment, and growth of malignancy…We believe that the integration of etodolac and propranolol into the preoperative setting of oncological surgery will improve postoperative well-being and decrease long-term recurrence rates in patients with breast, colon, and other types of cancer.

Study: 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.

Study: We have shown indirect but compelling evidence that there is dormancy in breast cancer and that surgery to remove the primary tumor does occasionally break dormancy.

Study: Primary tumor removal, usually considered intrinsically beneficial, can perturb metastatic homeostasis, and for some patients results in the acceleration of metastatic cancer.

Study: The role of breast tumour removal is different from the role of surgery by itself. Our findings suggest that the major effect of reconstructive surgery is microscopic metastasis acceleration, while breast tumour surgical removal (either primary or IBTR or CBC) involves both tumour homeostasis interruption and microscopic metastasis growth acceleration.

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.

An article published on the UKs number one cancer website canceractive.com includes the following important points:

• Research has also shown that tumours actually produce chemicals that stop vascular growth to these dormant cancer cells lying in other parts of the body. In other words the cancer cells need a blood supply in order to grow into a tumour but the main primary tumour actually stops rivals forming. Remove the primary and the others can come out to play.
• Major surgery will produce a large growth hormone response. (This is one reason why I believe strongly that people with cancer should not touch one drop of mass market cows´ dairy. Because of the way the cows are kept, it increases blood levels of IGF-1, a growth hormone).

How can I reduce risk of metastasis during surgery?

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

Cancer Surgery and 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.
Go to curcumin page

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

Surgery and 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%.

AHCC (active hexose correlated compound) enhances NK activity
AHCC is a natural immune-modulating compound derived from specially-cultured medicinal mushroom which has been clinically shown to strengthen the body’s immune system.

In this study of 269 patients with liver cancers, 113 received AHCC orally after undergoing curative surgery. This group had a significantly longer no recurrence period …and an increased overall survival rate when compared to the control group.

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 (randomized phase III trial) 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 hours 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]

Get treated in a high-volume centre

This 2017 study Is the Distance Worth It? Patients With Rectal Cancer Traveling to High-Volume Centers Experience Improved Outcomes which included 18,605 patients says:

“…this is the first study to examine the complex relationship among travel burden, volume, and outcomes among patients with rectal cancer. This study found that patients traveling to high volume centers had superior short-term outcomes including increased odds of lymph node yield and neoadjuvant chemoradiation receipt and lower odds of 30- and 90-day mortality. In addition, we found that patients who traveled to a high-volume center had improved 5-year survival compared with those who were resected at a local low-volume center.

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.

See also:
Surgery Side Effects and solutions
Vital questions to ask your doctor about surgery
Cancer Treatment Options for Recovery and Survival

Three studies by cancer researcher D.J. Benjamin who argues that surgery does not improve survival because cancer is a systemic disease.
The efficacy of surgical treatment of cancer
The efficacy of surgical treatment of breast cancer
The efficacy of surgical treatment of cancer – 20 years later

Last updated January 2026