Gary Deng

Integrative Oncology: Complementary Therapies for Pain, Anxiety, and Mood Disturbance

Many people with cancer experience pain, anxiety, and mood disturbance. Conventional treatments do not always satisfactorily relieve these symptoms, and some patients may not be able to tolerate their side effects. Complementary therapies such as acupuncture, mind‐body techniques, massage, and other methods can help relieve symptoms and improve physical and mental well‐being. Self‐hypnosis and relaxation techniques help reduce procedural pain. Acupuncture is well documented to relieve chronic cancer pain. Massage and meditation improve anxiety and other symptoms of distress. Many dietary supplements contain biologically active constituents with effects on mood. However, not all complementary therapies are appropriate or useful, and even helpful complementary modalities may not be optimal under some circumstances. Situations when precaution is indicated include acute onset of symptoms and severe symptoms, which require immediate mainstream intervention. Dietary supplements are associated with serious negative consequences under some circumstances. The authors summarize the research on these modalities and discuss the rationale, expectation, and necessary precautions involved with combining complementary therapies and mainstream care. Practical clinical issues are addressed.

Randomized, Controlled Trial of Acupuncture for the Treatment of Hot Flashes in Breast Cancer Patients

PURPOSE To determine the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer. PATIENTS AND METHODS Seventy-two women with breast cancer experiencing three or more hot flashes per day were randomly assigned to receive either true or sham acupuncture. Interventions were given twice weekly for 4 consecutive weeks. Hot flash frequency was evaluated at baseline, at 6 weeks, and at 6 months after initiation of treatment. Patients initially randomly assigned to the sham group were crossed over to true acupuncture starting at week 7. RESULTS The mean number of hot flashes per day was reduced from 8.7 (standard deviation [SD], 3.9) to 6.2 (SD, 4.2) in the true acupuncture group and from 10.0 (SD, 6.1) to 7.6 (SD, 5.7) in the sham group. True acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but the difference did not reach statistical significance (95% CI, -0.7 to 2.4; P = .3). When participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes was seen. This reduction in hot flash frequency persisted for up to 6 months after the completion of treatment. CONCLUSION Hot flash frequency in breast cancer patients was reduced following acupuncture. However, when compared with sham acupuncture, the reduction by the acupuncture regimen as provided in the current study did not reach statistical significance. We cannot exclude the possibility that a longer and more intense acupuncture intervention could produce a larger reduction of these symptoms.

Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer

BACKGROUND The majority of breast cancer patients use complementary and/or integrative therapies during and beyond cancer treatment to manage symptoms, prevent toxicities, and improve quality of life. Practice guidelines are needed to inform clinicians and patients about safe and effective therapies. METHODS Following the Institute of Medicines guideline development process, a systematic review identified randomized controlled trials testing the use of integrative therapies for supportive care in patients receiving breast cancer treatment. Trials were included if the majority of participants had breast cancer and/or breast cancer patient results were reported separately, and outcomes were clinically relevant. Recommendations were organized by outcome and graded based upon a modified version of the US Preventive Services Task Force grading system. RESULTS The search (January 1, 1990-December 31, 2013) identified 4900 articles, of which 203 were eligible for analysis. Meditation, yoga, and relaxation with imagery are recommended for routine use for common conditions, including anxiety and mood disorders (Grade A). Stress management, yoga, massage, music therapy, energy conservation, and meditation are recommended for stress reduction, anxiety, depression, fatigue, and quality of life (Grade B). Many interventions (n = 32) had weaker evidence of benefit (Grade C). Some interventions (n = 7) were deemed unlikely to provide any benefit (Grade D). Notably, only one intervention, acetyl-l-carnitine for the prevention of taxane-induced neuropathy, was identified as likely harmful (Grade H) as it was found to increase neuropathy. The majority of intervention/modality combinations (n = 138) did not have sufficient evidence to form specific recommendations (Grade I). CONCLUSIONS Specific integrative therapies can be recommended as evidence-based supportive care options during breast cancer treatment. Most integrative therapies require further investigation via well-designed controlled trials with meaningful outcomes.

Functional magnetic resonance imaging (fMRI) changes and saliva production associated with acupuncture at LI-2 acupuncture point: a randomized controlled study

BackgroundClinical studies suggest that acupuncture can stimulate saliva production and reduce xerostomia (dry mouth). We were interested in exploring the neuronal substrates involved in such responses.MethodsIn a randomized, sham acupuncture controlled, subject blinded trial, twenty healthy volunteers received true and sham acupuncture in random order. Cortical regions that were activated or deactivated during the interventions were evaluated by functional magnetic resonance imaging (fMRI). Saliva production was also measured.ResultsUnilateral manual acupuncture stimulation at LI-2, a point commonly used in clinical practice to treat xerostomia, was associated with bilateral activation of the insula and adjacent operculum. Sham acupuncture at an adjacent site induced neither activation nor deactivation. True acupuncture induced more saliva production than sham acupuncture.ConclusionAcupuncture at LI-2 was associated with neuronal activations absent during sham acupuncture stimulation. Neuroimaging signal changes appear correlated to saliva production.

Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment

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Evaluation of widely consumed botanicals as immunological adjuvants.

BACKGROUND Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects. METHODS Groups of 5-10 mice were immunized with globo H-KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast beta-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH. RESULTS Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast beta-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3-KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast beta-glucan and Astragalus extracts. While extraction with ethanol concentrated the active ingredients in Astragalus, it had no impact on Coriolus where the 90% ethanol precipitate and solute were equally active. CONCLUSIONS Some, but not all, botanicals purported to be immune stimulants had adjuvant activity in our model. PSK and Astragalus were surprisingly active and are being further fractionated to identify the most active adjuvant components.

Randomized controlled trial of a special acupuncture technique for pain after thoracotomy

OBJECTIVE We sought to determine whether an acupuncture technique specially developed for a surgical oncology population (intervention) reduces pain or analgesic use after thoracotomy compared with a sham acupuncture technique (control). METHODS One hundred sixty-two patients with cancer undergoing thoracotomy were randomized to group A (preoperative implantation of small intradermal needles that were retained for 4 weeks) or group B (preoperative placement of sham needles at the same schedule). The numeric rating scale of pain and total opioid use was evaluated during the in-patient stay, and the Brief Pain Inventory and Medication Quantification Scale were evaluated after discharge up to 3 months after the operation. RESULTS The principal analysis, a comparison of Brief Pain Inventory pain intensity scores at the 30-day follow-up, showed no significant difference between the intervention and control groups. Pain scores were marginally higher in the intervention group (0.05; 95% confidence interval, 0.74 to -0.64; P = .9). There were also no statistically significant differences between groups for secondary end points, including chronic pain assessments at 60 and 90 days, in-patient pain, and medication use in the hospital and after discharge. CONCLUSION A special acupuncture technique, as provided in this study, did not reduce pain or use of pain medication after thoracotomy more than a sham technique.

The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.

Using the framework of corporate culture in “mergers” to support the development of a cultural basis for integrative medicine – guidance for building an integrative medicine department or service

Background An increasing number of clinics offer complementary or integrative medicine services; however, clear guidance about how complementary medicine could be successfully and efficiently integrated into conventional health care settings is still lacking. Combining conventional and complementary medicine into integrative medicine can be regarded as a kind of merger. In a merger, two or more organizations − usually companies − are combined into one in order to strengthen the companies financially and strategically. The corporate culture of both merger partners has an important influence on the integration. Purpose The aim of this project was to transfer the concept of corporate culture in mergers to the merging of two medical systems. Methods A two-step approach (literature analyses and expert consensus procedure) was used to develop practical guidance for the development of a cultural basis for integrative medicine, based on the framework of corporate culture in “mergers,” which could be used to build an integrative medicine department or integrative medicine service. Results Results include recommendations for general strategic dimensions (definition of the medical model, motivation for integration, clarification of the available resources, development of the integration team, and development of a communication strategy), and recommendations to overcome cultural differences (the clinic environment, the professional language, the professional image, and the implementation of evidence-based medicine). Conclusion The framework of mergers in corporate culture provides an understanding of the difficulties involved in integrative medicine projects. The specific recommendations provide a good basis for more efficient implementation.

Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology

Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159-62. ©2016 AACR.