Chinese Medicine for Colorectal Cancer

Full title: “Chinese Medicine Oncology & Immunology: Colorectal Cancer, A Case Study”

ABSTRACT

This case study on colorectal cancer (CRC) demonstrates how Chinese medicine (CM) and other integrative therapies can help ameliorate symptoms of the disease and of the side effects of conventional treatment; an illustrative example of a 68-year-old female patient with an advanced diagnosis focusing on the use of acupuncture, Chinese herbs, functional medicine, dietary and lifestyle adjustments as well as chemotherapy and her decision to discontinue the drug approach moving forward. This case celebrates the individual choices that patients have when facing complex diseases and the importance of having a robust integrative medical team supporting one’s healing journey.

INTRODUCTION

CRC is the third most frequently diagnosed malignancy worldwide.^1,2 Most CRC develops from abnormal polyp growth on the lining of the colon. Polyps are common. Most are benign and asymptotic and therefore only diagnosed upon colonoscopy, which is recommended at 10-year intervals.³ Fewer than 5% of polyps develop into cancer after 7-10 years.⁴ Risk factors for CRC include inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s, as well as low fiber diets high in animal protein, fat and refined carbohydrates. Diagnostic tests include colonoscopic biopsy, computerized tomography (CT) scan and genetic testing.⁵ Functional medicine stool testing may show elevated inflammatory markers indicating a need for further diagnostic testing.⁶ CRC is staged according to the degree of penetration into the epithelium, lymph node involvement and absence or presence of metastasis. Western biomedical treatment may include surgery, chemotherapy and radiation.⁵

Biomedical Introduction

Cancer is fundamentally dysregulation of cellular development. The abnormal processes that underlie the initiation, promotion, and progression of carcinogenesis are essentially the same as those required by individual development and species evolution. Genetic mutation, tissue proliferation, and cell migration are “essential features of embryo development, inflammation and wound healing, tissue renewal, stress response, and placental function in pregnancy.”⁷ The risk of cancer is a tradeoff for the adaptability that has allowed us to evolve and develop as complex multicellular organisms.

A connection was first noted between cancer and inflammation by Rudolf Virchow in 1863.⁸ Inflammation can lead to angiogenesis, the growth of new blood vessels. While beneficial for injury, such as a sprained ankle, when hijacked inflammation can promote cancer growth and metastasis which “depend on angiogenesis and lymphangiogenesis triggered by chemical signals from tumor cells in a phase of rapid growth… Angiogenesis is stimulated when tumor tissues require nutrients and oxygen.”⁹ Further, the process of inflammation can be co-opted by a tumor’s “persistent extravasation of fibrin and fibronectin and continuous generation of extracellular matrix.”⁹

Cancer biology is shifting from a ‘cell centric’ view to place the tumor microenvironment (TME), the network comprising of the cancer cells and surrounding stromal cells (fibroblasts, vascular cells, and inflammatory immune cells) as the center stage of tumorigenesis.¹⁰ Key to TME are the intercellular mediator signaling molecules, cytokines, chemicals which move between immune cells and modulate cellular activities. Cytokines relevant to cancer include Tumor Necrosis Factor (TNF), Interleukins (IL), and Chemokines.^8,11,12

When fecal Calprotectin, an inflammatory biomarker, is elevated, it suggests that neutrophils have migrated across inflamed mucosa and into the gut lumen.¹³ Elevated fecal Calprotectin may indicate infection, history of IBD, chronic NSAID use, polyps or CRC and merits further diagnostic testing.^6,13

Chinese Medicine Introduction

Although the research on acupuncture and CRC is focused on postoperative support, CM has a history spanning millennia in treating various cancers. The character for tumor (liu) was recorded in the oracle bone script of the Shang dynasty circa 16th century BCE, and in the Rites of Zhou, physicians treating ulcers and tumors (yang yi) were already a distinct medical specialty alongside dietitians, internists, and veterinarians.¹⁴

Li Peiwen in Management of Cancer with Chinese Medicine describes that “Damp-Heat, Fire toxins and stagnation are the manifestations of colorectal cancer,” and that “Spleen deficiency, Kidney depletion and insufficiency of vital qi are the root.” Li et al.¹⁴ describe further that external causes such as cold and/or dietary irregularities and extremes can damage the Spleen and Stomach functions, generating damp-heat, which leads to heat toxin in the Large Intestine. Internal factors also contribute, such as congenital weakness of the Spleen and Stomach, constitutional deficiency, overexertion or insufficiency of Liver and Kidneys, and emotional anxiety or depression, which cause Liver qi stagnation.¹⁴

Treatment wise, the practice of CM stems from a whole person perspective recognizing the biopsychosocial influences on health as outlined in Su Wen chapter 77 (the 5 failings and 4 virtues of medical practice).¹⁵ Therefore, treatments will always be personalized to person, time, and place even for the same patient during the course of treatment. However, a general treatment principle in CM oncology is to assist the zheng qi while expelling the pathogen (fu zheng qu xie).¹⁶

CASE DESCRIPTION

Case History

A retired 66-year-old female noticed loss in weight and muscle tone in addition to digestive issues of gas, bloating and loose stools in the Spring of 2020. She consulted a functional medicine doctor who ordered a stool test in May of 2021 revealing gastrointestinal (GI) inflammation, dysbiosis and infection. By Spring of 2021, she continued losing weight and began experiencing rectal bleeding and left leg lymphedema.

The patient’s past medical history includes anterior cruciate ligament reconstruction surgery in her left knee at age 37 and a work-related lumbar injury at approximately age 40. Her diet since her late teenage years consisted of vegan raw foods including juicing, followed by macrobiotic foods in her late twenties and a Mediterranean diet in her thirties. After her lumbar injury in 1993, she added animal products, focusing on the Weston A. Price diet consisting of pastured bone broth, pastured meats, fermented foods, good fats, and plenty of vegetables. Currently she is eating a whole food, plant-based vegan diet with no refined oils, sugar or salt, focusing on anti-angiogenic foods based on the teachings of Dr. Joel Furhman and Dr. William Li. Throughout her life, she has used enemas and colonics and has favored a natural lifestyle.

Diagnostic Assessment

In June 2021 a CT scan and colonoscopy revealed a large mass in the patient’s sigmoid colon. In July she was diagnosed with stage IV CRC. The oncologist recommended against surgery as there was already metastasis to the bone, liver and lungs. A primary tumor biopsy was taken but it was too small for genomic testing, in the absence of which the patient did a Guardant 360 blood test.¹⁷This showed high blood levels of only Tp53 and APC CRC metastatic genes. The presence of these mutations is indicative of the CRC origin. These mutations support continued growth of and invasion by cancer cells. These are only some of the genomics and pathways involved in the pathogenesis of CRC.^18,19

Upon her initial visit on July 8, 2021, the patient’s tongue had a medium white coat throughout with a few horizontal cracks extending from the Stomach and Spleen region to the Kidney / UB region and overall appeared to be dry. The tongue body was pale with raw edges with teeth marks. “Cancer circles” were present throughout the tongue with nodules at the root of the tongue. By March 2022, at the time of submission of this paper, her tongue was less swollen, edges no longer raw and no teeth marks. Also, the tongue appears moister where it had been dry upon the initial visit. The coating had become a thin white coat from a medium white coat at the initial visit. The cracks remain and the tongue body is still pale and slightly swollen.

Our group intake was done via telemedicine in the spring of 2022. Pulse descriptions were provided by Dr. Erlene Chiang from her in-person visits with the patient as follows: On her initial visit, July 8, 2021, the left cun / Heart pulse was normal, guan Liver bowstring slippery, and left chi Kidney weak. Her right side cun Lung was slightly rapid and slightly weak, guan Spleen / Stomach slippery, and chi right Kidney slightly rapid and weak. On March 4, 2022, at the time of the submission of this paper, the patient’s pulses were all slightly fast and weak on both wrists and in all three positions.

The patient received “gold standard” care for stage IV metastatic CRC: FOLFIRI + Avastin (Folinic Acid [Folic Acid], 5-Flourouracil, Irinotecan + Bevacizumab), a combined chemotherapy and monoclonal antibody treatment, every 2 weeks from August 18, 2021 to January 22, 2022. This regimen was prescribed to block cancer DNA replication and prevent metastasis by adding genomic targeted therapy against Vascular Endothelial Growth Factor (VEGF) which promotes angiogenesis. The patient also started several integrative therapies to support her health and help with chemotherapy side effects. After 5 months of chemotherapy, the patient repeated labs and Guardant 360. Carcinoembryonic Antigen (CEA), a biomarker for colorectal metastasis, and levels of TP53 and APC were greatly diminished. A month after those tests, the patient had another CEA blood test, and CEA levels were again rising. She is currently not taking any prescription medications and has no known allergies.

The CM diagnosis is phlegm-damp heat toxin and blood stasis and Liver qi stagnation with an underlying constitutional qi and blood deficiency, and weakened zheng qi. The metastasis is accounted for by phlegm-damp heat toxin spreading to different body systems. Heat toxin manifests in her urine with a darker color and unusual smell. Her tendency to feel cold combined with many years of raw vegan food during her menstrual years created Spleen yang deficiency. Extreme cold stagnation can then generate heat and systemic inflammation. Liver qi stagnation throughout her life is demonstrated by persistent activity without much rest. Qi stagnation and blood stasis can be further observed in her left leg lymphedema. Past feelings of anger and judgment may have contributed to Liver qi stagnation causing overall qi reflux. Patient affirmed that she has very high standards for herself and enjoyed her career. She thrived by using her analytical and critical thinking skills.

TREATMENT

Acupuncture

With the CM diagnosis in mind, acupuncture points in each session have been customized according to the patient’s presentation at the time of each treatment. The example treatment below, recent to writing this case study, involves the main pool of acupuncture points common to many of the ongoing acupuncture treatments. The patient has been receiving acupuncture twice weekly since July 2021.

The patient’s initial visit was on July 8, 2021. From the first appointment through August 10, 2021, she received acupuncture and herbal medicine with no chemotherapy. From August 11, 2021 through Dec 22, 2021, she received chemotherapy treatments of FOLFOX, FOLFIRI every other week while concurrently receiving weekly acupuncture.

Acupuncture often consists of a front and back treatment using single-use, sterile needles size 0.34 x 30mm, retained for approximately 20 minutes on each side. Smokeless moxa was applied during the front treatment broadly for 3-4 minutes to the needled abdomen points and at the needled points on the legs, focusing on St 36 (zu san li) for 3-4 minutes bilaterally. Table 1 shows the points used.

Table 1. Acupuncture Points in a Recent Treatment

Table 2 organizes the acupuncture points in relation to treatment principles. Acupuncture points chosen serve multiple functions individually and paired. For example, LI 4 (he gu) and Liv 3 (tai chong) each have functions appropriate to the patient’s treatment, and combined they form a mini-strategy called the “Four Gates.” Many points straddle multiple treatment principles. For the purposes of this paper, the chart below illustrates a broad and simplified picture of the relevance of the points.

Table 2. Acupuncture Points According to Diagnosis and Treatment Principles

Chinese Herbal Medicine

In the Qing period text, the Golden Mirror, intestinal abscess (chang yong) appears to reference the Han period Golden Cabinet, which differentiates 2 presentations: a heat pattern of ruptured abscess, unresolved toxin with periodic pus and blood in the stool, and a cold pattern of a formed abscess with cold in the bowls, abdominal pain, and chronic dryness throughout the body, skin, and nails due to fluids damage by the abscess.^20,21 Both sources suggest the same formulas Da Huang Mu Dan Tang (DHMDT) (da huang, mu dan, tao ren, meng xiao, gua lou ren) for the former and Yi Yi Fu Zi Bai Jiang San (YYFZBJS) (yi yi ren, fu zi, bai jiang cao) for the latter.²⁰

A literature search was performed on PubMed and EBSCOHost for “Chinese herbal medicine AND colorectal cancer” and 16 papers were selected and reviewed with a focus on Chinese herbal formulas currently being used and researched for CRC and studies on the genomic targets of single herbs.^22-38 Literature search results are shown in supplementary tables, and genomic and signal pathway targets for CRC in Diagrams 1 and 2 below. In the papers reviewed, the following formulas were researched: Zou Jin Wan, Ge Gen Qin Lian Tang, Xiao Ai Jie Du Tang, and 3 variations of Jian Pi Tang. In these formulas and with other single herbs, the following had actions on TP53 and APC mutations, from the patient’s Guardant 360 genomic tests, (as well as other genomic targets for CRC): ban zhi lian, chuan xin lian, hu zhang, huang qi, da huang, and dan shen.^22-38 Ku shen also targets the CEA cancer biomarker.³⁷ These 7 herbs were incorporated into the treatment formulas.

Based on the CM diagnosis, a 2-formula approach was decided. Formula 1 is Li’s¹⁴ prescription for CRC presenting as phlegm-damp heat toxin with blood stasis: Bai Tou Weng Tang modified (BTWTJJ) which includes the classic YYFZBJS, with rou gui substituted for fu zi and the addition of the 7 genomic herbs. Formula 2 addresses blood stasis and Liver qi stagnation with Qing Dynasty physician Wang Qing Ren’s formula Dian Kuang Meng Xing Tang modified (DKMXTJJ) with Zou Jin Wan, and mu xiang substituted for mu tong. The treatment plan is to administer PO, six 500 mg capsules of each formula daily, DKMXTJJ in the morning and BTWTJJ in the evening, taken for 2 months, and followed by a review.

Table 3. Bai Tou Weng Tang Jia Jian (BTWTJJ)

Diagram 1. BTWTJJ CRC Targets Pathways

Table 4. Dian Kuang Meng Xing Tang Jia Jian (DKMXTJJ)

Diagram 2. DKMXTJJ CRC Targets Pathways

Functional Medicine

A stool sample was collected from the patient in May 2021, revealing GI inflammation, dysbiosis, and infection. Based on these findings, a strategy was developed to eliminate the infection, reduce inflammation, and restore the microbiome.

A healthy microbiome regulates the intestinal immune system and protects against pathogens.³⁸ GI pathogens increase the risk of cancer by producing toxins and inducing an inflammatory response. The stool test showed the presence of Klebsiella pneumoniae, known to produce the toxin colibactin, which causes genetic mutations that can lead to CRC.³⁹ Under some conditions, commensal bacteria may also increase the risk of cancer. The patient has an overgrowth of Fusobacterium and Bacteroides species. The species Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis are known to promote CRC.^40,41 To restore the microbiome, this overgrowth should be addressed.

The test also revealed low levels of small chain fatty acids (SCFAs) in the stool. SCFAs come from insoluble fiber and are broken down by bacteria in the gut and are the primary source of energy for colon cells, making their presence important for recovery from CRC.⁴²

Bile acids also play an important role in maintaining the microbiome. They are bactericidal, and evidence suggests that they facilitate recovery from dysbiosis.⁴³ The stool test indicated a high number of phospholipids in the stool and an abdominal CT scan showed her gallbladder was distended, both indicating that the gallbladder would benefit from support.

The functional medicine treatment strategy is outlined in Table 5. Treatment will be done in 2 phases, first eliminating the infection and overgrowth of commensal bacteria and second supporting the restoration of the microbiome through gallbladder support, SCFAs, and probiotics, with each phase lasting 2 months. Results are pending for an H. pylori test and an organic acids test (Organix through Genova Labs). H. pylori is often present in CRC patients⁴⁴ and the organic acids test will indicate liver detoxification pathways functions and oxidative stress levels, which will further inform the patient’s individualized supplement protocols.

Table 5. Functional Medicine Herbal and Supplement Protocols

Diet

In CM, food and herbal medicine are of the same source (yao shi tong yuan) and should be mutually supportive.⁴⁵ Research confirms that a low-insulin provoking and anti-inflammatory diet benefits survival in CRC.^46,47

To support deficient qi and blood and to gently expel the excesses, a regenerative, clearing diet of nutritive, easy to digest, bland foods is advised.⁴⁸ CM recommends avoiding raw foods, so while the patient enjoys berries, she may balance the temperature by eating them with warm porridge and adding ginger.

Eat 3-4 cooked meals a day, in smaller portions, rather than 2 meals a day. Bland foods counteract rising and warming yang qi. Spicy and greasy foods should be avoided. Excess meat should be avoided to emphasize clearing.⁴⁸

Eating a medley of warm, cooked foods is vital. Soups or porridges with the key foods supported by biomedical research and CM foods in Table 6 cleanse and nourish the zheng qi while transforming phlegm and accumulation. Isoflavone-containing legumes and soybeans may help deter the production of CEA.⁴⁹ The most digestible form of legumes, including soy, is as sprouted seeds, which may be eaten daily.⁴⁸ Additionally, celery hearts and spinach as sources of luteolin, and green tea as a source of epigallocataechin gallate are helpful.⁵⁰

Table 6.

Phlegm Transforming Foods. Generally Chosen for Neutral or Cool to only Slightly Warm Nature, and Combined Functions.⁴⁸

Lifestyle

A balanced lifestyle supports health and longevity. Ways to quiet the mind in relaxation, encouraging dominance of the parasympathetic nervous system are recommended for at least an hour per day, aiming for 3 times a day.

Walking in nature, dancing, and looking at art can rest the brain. Science suggests that unhooking from an active mind increases anti-inflammatory activity.⁵¹ Sound therapies shown to help relaxation and foster parasympathetic mode to enhance healing include listening to traditional Chinese music, music in the tonality of gong or jue, and binaural beats⁵¹, which is proposed as a brain entrainment method with many potential therapeutic benefits.⁵² Both theta wave and alpha wave listening are shown to aid in meditation and decrease anxiety.^52,53 Daily biofeedback may be helpful, such as heart rate variability (HRV) biofeedback from the Heart Math Institute’s tools.^54,55

Exercise

The patient is retired and has a healthy lifestyle and diet with adequate rest. Previous to treatment with Chinese medicine, her main form of exercise was walking which had been recently limited by abdominal pain and severe lymphedema in her left leg. After the initiation of chemotherapy and acupuncture treatments, the lymphedema, abdominal pain and hip pain all diminished, her energy improved and she was able to hike 3 times a week from 4-6 miles each time. She was introduced to Qi Gong practice through Chinese medicine.

Qi gong improves quality of life for patients in recovery from cancer.⁵¹ In CM theory, Baduanjin qi gong exercise can help dredge meridians, qi, blood, regulate organ functions, strengthen the body, and improve one’s sleep, stress and metabolism. This exercise can impact one’s body and energy flow while improving essential health. At least 8 exercises focus differently on physical areas and meridians.⁵⁶ Randomized clinical trials by Lu et al.⁵⁶ concluded that Baduanjin qi gong could relieve cancer-related fatigue for CRC patients having undergone chemotherapy.

Although tai ji has not been studied as much as qi gong, it is shown to have a meditative benefit of increasing survival outcomes.⁵⁷ Tai ji exercise has been shown to improve fatigue and sleep quality.⁵⁸ Upper extremity movements and expanding the thoracic and respiratory muscles improves cardiorespiratory fitness, with slow breathing improving the cardiorespiratory system. Activating the lungs can increase the defense in the immune system and the body.

Outcomes and Prognosis

As the patient has chosen to discontinue chemotherapy, our current goals of care are to stabilize the cancer, reduce inflammation and angiogenesis, minimize metastasis, rebuild her strength and zheng qi and strengthen her immune system with a focus on resolving toxin and transforming phlegm. Additionally, we aim to promote good quality of life (QOL) and longevity via natural methods of diet, exercise and adequate rest, supplements, acupuncture and herbal medicine. The patient is encouraged to continue with low or no radiation scans such as ultrasound and labs for TP53, APC and CEA to regularly monitor the ongoing status of the primary tumor and metastases. We will continue tracking her progress additionally with CM diagnostic methods and functional medicine tests.

Over the course of 8 months of treatment with acupuncture and herbal medicine from her initial visit in July 2021 until the submission of this paper in March 2022, the patient’s QOL improvement can be measured by an overall decrease in pain from a 5 to 6 out of 10 to a 2 to 3 out of 10 (using a numerical pain rating scale). Her sleep continues to be at times disrupted by abdominal pain where the tumor is present. Her appetite is good but digestion continues to be affected by gas and her bowel movements regularly contain undigested food, are irregular, loose and dry with yellowish mucus sometimes accompanied by blood. Upon a final editing of this paper in September 2022, the patient reports that her QOL continues to improve.

DISCUSSION & CONCLUSION

In conclusion, this case study shows how a truly integrative approach can support healing through different lenses, including both traditional and modern. Cancer is a complex process involving diverse aspects of physiology and of body, mind and spirit. The patient had been seen by the lead author, Dr. Erlene Chiang for 8 months prior to writing this paper, upon which her case received a comprehensive review, analysis and recommendations for future treatment by Dr Chiang’s graduate students studying Chinese medical immunology and oncology. By approaching this case with thorough methodology that respects the time-tested integrity of CM and at the same time bridges it with innovative diagnostic methods such as genomic and microbiome testing, it is possible to hold a space of healing potential that is broader and deeper than any of the separate modalities on their own.

Erlene Chiang, DAOM, LAc has been practicing Traditional Chinese Medicine since 1985. Her service and experience in the field of oncology includes the following: President, American Cancer Society, California Chinese Unit; Vice President, American Cancer Society; California Chinese Unit, Senior Administrative Director. She grew up in a family of famous physicians of Chinese medicine and is a third generation TCM doctor. Mentored by her father, she possesses a deeply re­fined talent for TCM diagnosis, oncology focused treatment strategies, with specific emphasis on Chinese herbal formulas.

Co-Authors

Co-authors were graduate students with professor Dr. Erlene Chiang at the American College of Traditional Chinese Medicine in San Francisco and completed their doctoral program in April 2022.

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Main Author: Dr. Erlene Chiang
Co-authors: Jasmine Oberste, Hoang Tran, Ana Paula Duarte, Denise Visconte, Ana Hortillosa, Cherie Martyn, Daniel Metzger, Amy Sparrow, Shinae Yun, Jiyoon Kim, Ivan Castillo
Institution: Doctoral Program, American College of Traditional Chinese Medicine at CIIS, San Francisco, USA