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1.  Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods 
Integrative cancer therapies  2011;10(3):240-259.
Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference—namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified.
doi:10.1177/1534735411406539
PMCID: PMC4081504  PMID: 21964510
colon cancer; survival; Chinese herbal medicine; vitamins; propensity score; marginal structural models; chemotherapy; radiotherapy
2.  Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial 
Integrative cancer therapies  2012;12(4):323-335.
Background
Physical activity may provide benefits for breast cancer survivors in part by reducing systemic inflammation. Physical activity behavior change studies are a type of implementation research in which exercise efficacy information is translated into a “real world” setting, allowing determination of whether physical activity changes are sufficient to improve health outcomes. We hypothesized that breast cancer survivors (BCS) who undertook a physical activity behavior change intervention would have less systemic inflammation and improved cardiorespiratory fitness, muscle strength, body composition, fatigue, and sleep as compared with BCS receiving usual care. The goal of this pilot study was to determine the magnitude and direction of intervention effect sizes for inflammatory related serum markers and relevant health outcomes.
Methods
This randomized controlled trial enrolled 28 Stage I, II, or IIIA BCS who were post-primary treatment and were not regular exercisers. These women were assigned to either a 3-month physical activity behavior change intervention group (ING) or usual care group (UCG). Intervention included supervised aerobic (150 weekly minutes, moderate-intensity) and resistance (two sessions per week) exercise that gradually tapered to home-based exercise. At baseline and after 3 months, health outcomes and serum concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, leptin, and adiponectin were measured.
Results
Cardiorespiratory fitness significantly improved in the ING versus UCG (between group difference=3.8 ml/kg/min; d=1.1; P=0.015). Self-reported sleep latency was significantly reduced in the ING versus UCG (between group difference=−0.5; d=−1.2; P=0.02) as was serum leptin (between group difference=−9.0 ng/ml; d=−1.0; P=0.031). Small to medium non-significant negative effect sizes were noted for IL-10 and TNF-alpha and ratios of IL-6:IL-10, IL-8:IL10, and TNF-alpha:IL-10, with non-significant positive effect sizes noted for IL-6 and high molecular weight adiponectin.
Conclusions
Physical activity behavior change interventions in BCS can achieve large effect size changes for several health outcomes. Although effect sizes for inflammatory markers were often small and not significant, changes were in the hypothesized direction for all except IL-6 and IL-10. These preliminary data support larger trials that would more fully examine potential inflammatory changes that accompany physical activity behavior change interventions.
doi:10.1177/1534735412449687
PMCID: PMC3909487  PMID: 22831916
exercise; intervention; oncology; cytokine; inflammation; survivorship
3.  Cancer-Specific Concerns and Physical Activity Among Recently Diagnosed Breast and Prostate Cancer Survivors 
Integrative cancer therapies  2012;12(3):206-212.
Background
Cancer treatment-related side effects may have a negative impact on quality of life among cancer survivors, and may limit participation in physical activity.
Hypothesis
Cancer-specific concerns will be reduced throughout a 10-month diet and exercise intervention among recently-diagnosed cancer survivors. Additionally, participants reporting greater levels of physical activity will also report fewer cancer-specific concerns.
Study Design
This study is an exploratory analysis of 452 recently diagnosed, early stage breast and prostate cancer survivors who participated in the FRESH START diet and exercise trial. Data were collected at baseline and 1-year follow-up via telephone administration of the Functional Assessment of Cancer Therapy (FACT) instrument and the 7-Day Physical Activity Recall.
Results
At baseline, chief concerns among prostate cancer survivors included ability to have an erection (mean score [SD]: 1.0 [1.3]) and urinary frequency (2.5 [1.4]), whereas among breast cancer survivors eminent concerns were not feeling sexually attractive (2.0 [1.3]) and worry about cancer in other members of their family (2.1 [1.3]). At 1 year, there was a significant improvement in cancer-specific concerns on breast cancer specific-concerns (p<0.01), but not on prostate cancer-specific concerns. Physical activity (PA) was generally not related to cancer-specific concerns, though at baseline women who were self-conscious about their dress had higher levels of PA, whereas men reporting issues with incontinence reported lesser increases in PA in response to the intervention.
Conclusion
While cancer survivors have several cancer-specific concerns, these concerns diminish over time, especially among breast cancer survivors. Furthermore, this reduction appears independent of changes in physical activity. Among prostate cancer survivors, incontinence is a significant barrier that hinders benefit from PA interventions. Thus, there is a need either for medical interventions to ameliorate incontinence or for behavioral interventions to address this issue among survivors, especially given the importance of PA for overall health.
doi:10.1177/1534735412449734
PMCID: PMC3764991  PMID: 22879576
breast neoplasms; prostatic neoplasms; physical activity; quality of life
4.  A Randomized Controlled Trial of Mindfulness-Based Stress Reduction for Women With Early-Stage Breast Cancer Receiving Radiotherapy 
Integrative cancer therapies  2013;12(5):404-413.
Purpose
To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA) undergoing radiotherapy.
Methods
Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables.
Results
A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control.
Conclusions
MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.
doi:10.1177/1534735412473640
PMCID: PMC3758444  PMID: 23362338
mindfulness-based stress reduction program; breast cancer; quality of life; psychosocial intervention; radiotherapy; radiation therapy
5.  A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma 
Integrative cancer therapies  2013;13(1):46-53.
Purpose
To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction.
Experimental Design
Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks.
Results
Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug.
Conclusion
Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.
doi:10.1177/1534735413490798
PMCID: PMC3866213  PMID: 23757319
phase I clinical trial; milk thistle; hepatocellular carcinoma; herbal supplement; dietary supplement
6.  Practices, Attitudes, and Beliefs associated with Complementary and Alternative Medicine (CAM) use among Cancer Patients 
Integrative cancer therapies  2012;11(3):10.1177/1534735411433832.
Introduction
The high prevalence of complementary and alternative medicine (CAM) use among cancer patients (40 – 83%) receiving conventional treatment and the complex relationship between the psychosocial factors that may contribute to or result from CAM use requires further understanding. We conducted a descriptive mixed-methods pilot study to understand CAM practices, attitudes and beliefs among cancer patients at the Loma Linda University Medical Center (LLUMC).
Methods
This was the qualitative phase of the study and no hypotheses were set. Twenty-three face-to-face interviews were conducted and thematic coding was used to analyze 22 interview transcriptions. There were fourteen CAM users (64%) and eight non-users (36%).
Findings
The themes present among those who used CAM were: physicians viewed as one aspect of health care options, a holistic view on wellbeing, satisfaction with CAM use, and three key coping methods (confrontive, supportive, and optimistic) to confront cancer. Themes were not independent of each other. Two themes were present among nonusers; nonusers trusted their physician and were more likely to express evasive coping methods.
Discussion
Perceptions and behavioral patterns are complex predictors of CAM use. A better understanding of CAM, medical pluralism, and the perceptions of patients would help health care providers deliver a better quality of care. The promotion of integrative care may help health care providers better identify medical pluralism and would shift focus to patient-centered care.
doi:10.1177/1534735411433832
PMCID: PMC3873860  PMID: 22313741
CAM; medical pluralism; integrative medicine; perceptions among cancer patients; coping methods; thematic coding
7.  Effect of Coenzyme Q10 on Doxorubicin Cytotoxicity in Breast Cancer Cell Cultures 
Integrative cancer therapies  2012;11(3):10.1177/1534735412439749.
Background/hypotheses
Doxorubicin is a standard adjuvant therapy for early-stage breast cancer and it significantly improves disease-free and overall survival. However, 3-20% of breast cancer patients develop chronic cardiomyopathic changes and congestive heart failure due to doxorubicin therapy. Doxorubicin-induced cardiotoxicity is thought to be due to increased generation of reactive oxygen species (ROS) within cardiac myocyte mitochondria. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant that may protect against mitochondrial ROS, and thus prevent doxorubicin-induced cardiotoxicity. Despite the potential benefits of CoQ10 in preventing cardiotoxicity, it is unknown if CoQ10 diminishes the antineoplastic effects of doxorubicin therapy.
Study design
In vitro cell culture experiments.
Methods
Breast cancer cell lines (MDA-MB-468 and BT549) were tested for their ability to uptake exogenous CoQ10 using high performance liquid chromatography (HPLC). Breast cancer cell lines were then treated with doxorubicin and a range of CoQ10 concentrations to determine the effect of CoQ10 on doxorubicin’s cytotoxicity.
Results
This study demonstrated that intracellular and mitochondrial CoQ10 concentrations increased substantially as higher exogenous concentrations are administered to breast cancer cells. CoQ10 had no effect on the ability of doxorubicin to induce apoptosis or inhibit growth or colony formation in both cell lines tested when CoQ10 was applied over a wide dose range, which encompassed typical basal plasma levels as well as plasma levels above those typically achieved by supplemented patients.
Conclusion
The clinical testing of CoQ10 as supplement to prevent doxorubicin induced cardiotoxicity requires confidence that it does not decrease chemotherapy efficacy. These results support the hypothesis that CoQ10 does not alter the antineoplastic properties of doxorubicin. Further in vivo studies, as well as combination chemotherapy studies, would be reassuring before large scale clinical testing of CoQ10 as a cardioprotective drug.
doi:10.1177/1534735412439749
PMCID: PMC3840161  PMID: 22544232
Doxorubicin; Adriamycin; Coenzyme Q10; cytotoxicity; breast cancer; in vitro
8.  The Role of Religion and Spirituality in Psychological Distress Prior to Surgery for Urologic Cancer 
Integrative cancer therapies  2011;11(3):212-220.
The present study examined the associations between religion and spirituality (R/S), presurgical distress, and other psychosocial factors such as engagement coping, avoidant coping, and social support. Participants were 115 men scheduled for surgery for urologic cancer. Before surgery, participants completed scales measuring intrinsic religiosity, organized religious activity, and nonorganized religious activity (IR, ORA, NORA); social support (Medical Outcomes Study Social Support Survey); and distress (Impact of Event Scale [IES], Perceived Stress Scale [PSS], Brief Symptom Inventory-18 [BSI-18], and Profile of Mood States [POMS]). R/S was positively associated with engagement coping. Social support was positively associated with engagement coping and inversely associated with POMS and PSS scores. Engagement coping was positively associated with IES and BSI scores, and avoidant coping was positively associated with all distress measures. R/S moderated the association between engagement coping and IES scores, such that the association between engagement coping and IES was not significant for men with high R/S scores (greater religious belief). R/S moderated the association between social support and distress; the inverse association between social support and PSS and POMS scores was only significant for men who scored high on R/S. This study replicated findings from previous studies suggesting that engagement and avoidant types of coping can lead to increased distress prior to surgery. Although R/S was associated with engagement coping, it was not associated with any of the distress measures. The finding that R/S moderated the associations between engagement coping and distress and social support and distress suggests that the association between R/S, coping style, social support, and adjustment to stressful life situations is not simplistic, and indirect associations should be explored.
doi:10.1177/1534735411416456
PMCID: PMC3746331  PMID: 21964511
oncology; cancer; spirituality; religion; distress; surgery
9.  Feasibility Trial of Electro-acupuncture for Aromatase Inhibitor Related Arthralgia in Breast Cancer Survivors 
Integrative cancer therapies  2009;8(2):123-129.
Background
Arthralgia affects postmenopausal women receiving aromatase inhibitors (AI) for breast cancer. Given the existing evidence for electro-acupuncture (EA) for treatment of osteoarthritis in the general population, this study aims to establish the feasibility of studying EA for treating AI-related arthralgia.
Patients and Methods
Postmenopausal women with stage I-III breast cancer who reported AI-related arthralgia were enrolled in a single arm feasibility trial. EA was provided twice a week for two weeks followed by six weekly treatments. The protocol was based on Chinese medicine diagnosis of “Bi” syndrome with electro-stimulation of needles around the painful joint(s). Pain severity of the modified Brief Pain Inventory was used as the primary outcome. Joint stiffness, Joint interference, and Patient Global Impression of Change (PGIC) were secondary outcomes. Paired-t tests were used for analysis.
Results
Twelve women were enrolled and all provided data for analysis. From baseline to the end of intervention, patients reported reduction in pain severity (5.3 to 1.9), stiffness (6.9 to 2.4), and joint symptom interference (4.7 to 0.8), all P<0.001; 11/12 considered joint symptoms “very much better” based on PGIC. Subjects also reported significant decrease in fatigue (4.4 to 1.9, p=0.005) and anxiety (7.1 to 4.8, p=0.01). No infection or development or worsening of lymphedema was observed.
Conclusion
Preliminary data establishes the feasibility of recruitment and acceptance as well as promising preliminary safety and effectiveness. A randomized controlled trial is warranted to establish the efficacy of EA for AI-related arthralgia in breast cancer survivors.
doi:10.1177/1534735409332903
PMCID: PMC3569528  PMID: 19679620
Acupuncture; breast neoplasm; clinical trial; Aromatase inhibitors/*adverse effects; joint diseases
10.  Prevalence and Correlates of Vitamin and Supplement Usage among Men with a Family History of Prostate Cancer 
Integrative Cancer Therapies  2011;11(2):83-89.
Hypotheses
Men who have a brother with prostate cancer have a two-fold increased risk of being diagnosed with prostate cancer. Strategies employed by these men to reduce prostate cancer risk are not well understood. Preliminary studies have shown that men with a family history of prostate cancer have a high rate of vitamin and supplement usage aimed at the prevention of prostate cancer.
Study Design
We analyzed data from a cross-sectional study of men with familial and hereditary prostate cancer and their unaffected brothers. We interviewed 542 unaffected men who had at least one brother who had been diagnosed with prostate cancer regarding their use of vitamins and supplements, as well as the motivation for use.
Methods
The associations between subject characteristics and vitamin and supplement use were evaluated using an unconditional logistic regression modeling approach.
Results
Overall, 59.2 and 36.5 percent of men reported ever using and currently using, respectively, one or more vitamins or supplements (including multivitamins). One-third of men took a vitamin or supplement that has been targeted for prostate health or cancer prevention, including green tea, magnesium, male hormones, saw palmetto, selenium, soy, vitamins A, C, E and zinc. Increasing age at time of survey was associated with vitamin/supplement use (OR=1.03; 95% CI=1.01–1.0). After adjusting for age at time of survey, being younger than an affected brother was associated with vitamin and supplement use (OR=1.51; 95% CI=1.01–2.25). 25% of men reported obtaining information from books or articles as the most common source of information.
Conclusions
Our findings indicate that men at an increased risk for prostate cancer report a high rate of vitamin and supplement use, including supplements targeted for prostate cancer prevention. Men with a family history of prostate cancer represent a target population for future chemopreventative agents.
doi:10.1177/1534735411413262
PMCID: PMC3213317  PMID: 21821653
Prostate Cancer Chemoprevention; Family History; Complementary and Alternative Medicine
11.  Classification of CAM Use and its Correlates in Early Stage Breast Cancer Patients 
Integrative cancer therapies  2011;10(2):138-147.
Hypothesis
Self-reported use of complementary and alternative medicine (CAM) has been shown to increase following a cancer diagnosis, and breast cancer survivors are the heaviest users among cancer survivors. The aim of this study was to determine whether the prevalence estimate of CAM use varied according to classification of CAM. We used a comprehensive system to classify CAM users and test differences in demographic, lifestyle, quality of life, and cancer characteristics among them.
Study Design and Methods
Participants were 2562 breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study, aged 28-74 years. A structured telephone interview assessed CAM use, questioning about specific CAM practices, and whether use was related to cancer. We examined CAM use in relation to demographics, health behaviors, and quality of life.
Results
Approximately 80% of the women used CAM for general purposes but only 50% reported CAM use for cancer purposes. Visual imagery, spiritual healing, and meditation were the most frequently used practices for cancer purposes. CAM use, defined as consulting a CAM practitioner and regular use, was significantly related to younger age, higher education, increased fruit & vegetable intake, and lower body mass index (p < .05). CAM users who had seen a practitioner were also more likely to report poor physical and mental health than non-CAM users (p < .05). CAM use was not associated with changes in physical and mental health between study baseline and 1-year follow-up.
Conclusion
This study addressed important differences in the classification of CAM use among breast cancer survivors. Future studies need to further test the potential benefits and risks associated with CAM use.
doi:10.1177/1534735410392578
PMCID: PMC3126886  PMID: 21382963
12.  Polarity Therapy for Cancer-Related Fatigue in Patients With Breast Cancer Receiving Radiation Therapy: A Randomized Controlled Pilot Study 
Integrative Cancer Therapies  2011;10(1):27-37.
Background
Cancer-related fatigue (CRF) is the most frequently reported side effect of cancer and its treatment. In previous research, Polarity Therapy (PT), an energy therapy, was shown to reduce CRF in patients receiving radiation. This study reports on a small randomized clinical trial designed to collect preliminary data on the efficacy of PT compared with an active control (massage) and passive control (standard care) for CRF among cancer patients receiving radiation therapy.
Methods
Forty-five women undergoing radiation therapy for breast cancer were randomized to I of 3 weekly treatment conditions. Patients received standard clinical care, 3 modified massages, or 3 PT treatments. CRF and healthrelated quality of life (HRQL) were assessed during baseline and the 3 intervention weeks.
Results
TResults show CRF ratings were reduced after PT. The effect sizes for PT versus modified massage and versus standard care were small when using the primary measure of CRF (Brief Fatigue Inventory) and large when using the secondary measure of CRF (Daily CRF Diaries).The effect size was medium when assessing the benefit of PT on maintaining HRQL compared with standard care with very little difference between the PT and modified massage conditions. Patients’ feedback showed that both the modified massage and PT treatments were deemed useful by radiation patients. Conclusion. The present pilot randomized clinical trial supports previous experimental research showing that PT, a noninvasive and gentle energy therapy, may be effective in controlling CRF. Further confirmatory studies as well as investigations of the possible mechanisms of PT are warranted.
doi:10.1177/1534735410397044
PMCID: PMC3085180  PMID: 21382958
cancer-related fatigue; radiation; Polarity Therapy; massage; quality of life; complementary and integrative medicine
13.  A Mineral-Rich Red Algae Extract Inhibits Polyp Formation and Inflammation in the Gastrointestinal Tract of Mice on a High-Fat Diet 
Integrative cancer therapies  2010;9(1):93-99.
The purpose of this study was to determine whether a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum (Pallas), could be used as a dietary supplement for chemoprevention against colon polyp formation. Sixty C57bl/6 mice were divided into three groups based on diet. One group received a low-fat, rodent chow diet (AIN76A). The second group received a high-fat “Western style” diet (HFWD). The third group was fed the same HFWD with the mineral-rich extract included as a dietary supplement. Mice were maintained on the respective diets for 15 months. Autopsies were performed at the time of death or at the completion of the study. To summarize, the cumulative mortality rate was higher in mice on the HFWD during the 15 month period (55%) than in mice from the low-fat diet or the extract-supplemented high-fat diet groups (20% and 30%, respectively; p<0.05 with respect to both). Autopsies revealed colon polyps in 20% of the animals on the HFWD and none in animals of the other two groups (p<0.05). In addition to the grossly visible polyps, areas of hyperplasia in the colonic mucosa and inflammatory foci throughout the gastrointestinal tract were observed histologically in animals on the high-fat diet. Both were significantly reduced in animals on the low-fat diet and animals on the extract-supplemented HFWD. These data suggest that the mineral-rich algae extract may provide a novel approach to chemoprevention in the colon.
doi:10.1177/1534735409360360
PMCID: PMC2861409  PMID: 20150219
colorectal cancer; chemoprevention; epithelial cell differentiation; extracellular calcium-sensing receptor; mineral-rich red algae extract; Aquamin®
14.  Acupuncture for Dysphagia after Chemoradiation Therapy in Head and Neck Cancer: A Case Series Report* 
Integrative cancer therapies  2010;9(3):284-290.
Background
Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients.
Methods
In this retrospective case series, ten HNC patients were treated with acupuncture for radiation-induced dysphagia and xerostomia. All patients were diagnosed with stage III/IV squamous cell carcinoma. Seven of 10 patients were percutaneous endoscopic gastrostomy (PEG) tube-dependent when they began acupuncture. Manual acupuncture and electroacupuncture were used once a week.
Results
Nine of 10 patients reported various degrees of subjective improvement in swallowing functions, xerostomia, pain and fatigue levels. Six (86%) of 7 PEG tube-dependent patients had their feeding tubes removed after acupuncture, with a median duration of 114 days (range 49–368) post CRT. One typical case is described in detail.
Conclusions
A relatively short PEG tube duration and reduced symptom severity following CRT were observed in these patients. Formal clinical trials are required to determine the causality of our observations.
doi:10.1177/1534735410378856
PMCID: PMC3014053  PMID: 20713374
acupuncture; chemoradiation therapy; radiation therapy; head and neck cancer; dysphagia; percutaneous endoscopic gastrostomy (PEG) tube
15.  Circadian Disruption, Per3, and Human Cytokine Secretion 
Integrative cancer therapies  2009;8(4):329-336.
Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n = 70). Adjusted mean serum cytokine concentrations (IL-6, TNF-alpha, gamma-INF, IL-I ra, IL-I-beta, VEGF) were compared among patients with high and low scores for fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory II), or sleep disruption (Pittsburgh Sleep Quality Index), or among patients with different Per3 clock gene variants. Poor sleep was associated with elevated VEGF, and fatigue-related reduced activity was associated with elevated TNF-alpha concentrations. Participants with the 4/5 or 5/5 Per3 variable tandem repeat sequence had elevated IL-6 concentrations compared to those with the 4/4 genotype. Biological processes linking circadian disruption with cancer remain to be elucidated. Increased inflammatory cytokine secretion may playa role.
doi:10.1177/1534735409352029
PMCID: PMC2959170  PMID: 19926609
circadian rhythm; clock gene; cytokine; inflammation
16.  Nr1d1, an Important Circadian Pathway Regulatory Gene, Is Suppressed By Cigarette Smoke in Murine Lungs 
Integrative cancer therapies  2009;8(4):321-328.
Nuclear receptor subfamily 1, group D member 1 (Nr1d1), also known as Rev-erb-α, belongs to the family of “orphan receptors” and functions as a member of clock gene family. In addition to being an important member of clock circuitry, Nr1d1, also regulates cell proliferation, lipid metabolism, and inflammation and is also touted as a tumor suppressor. Our focus on Nr1d1 was stimulated by data from a genome-wide search for mRNA correlates of cigarette smoke (CS) sensitive—whole smoke (WS) and filtered smoke (FS)—lung transcriptomes in tumor-resistant C57BL6 and tumor-susceptible AJ mice strains. Differential analysis of ~15 000 genes using Affymetrix 430A 2.0 high-density oligonucleotide arrays identified modulation of genes related to circadian pathways by CS in lungs of both mouse strains. Nr1d1 expression was downregulated by both WS and FS irrespective of mouse strain as compared to respective air-breathing controls. WS was more effective than FS on decreasing Nr1d1 expression. The present data suggest that transcriptional regulation of Nr1d1 by CS may affect circadian rhythmicity and thus may play a complementary role in CS-induced lung respiratory tract pathobiology and/or lung tumorigenesis.
doi:10.1177/1534735409352027
PMCID: PMC2837720  PMID: 19926613
Nr1d1; Rev-erb-α; C57BL6 mice strain; AJ mice strain; lungs; cigarette smoke; gene expression profiling; chronobiology
17.  Integrative Tumor Board: a Case Report and Discussion from Dana-Farber Cancer Institute 
Integrative cancer therapies  2009;8(3):235-241.
A 34-year-old female carrying a BRCA1 gene and a significant family history was diagnosed with T1c, N1 breast cancer. The tumor was estrogen receptor, progesterone receptor and HER-2/Neu negative. The patient received dose-dense chemotherapy with Adriamycin and Cytoxan followed by Taxol, and left breast irradiation. Later, a bilateral S-GAP flap reconstruction with right prophylactic mastectomy and left mastectomy were performed. During her treatment, the patient had an integrative medicine consultation and was seen by a team of healthcare providers specializing in integrative therapies including integrative nutrition, therapeutic massage, acupuncture, and yoga. Each modality contributed unique benefit in her care that led to a satisfactory outcome of the patient. A detailed discussion regarding her care from each modality is presented. The case elucidates the need of integrative approaches for cancer patients in a conventional medical setting.
doi:10.1177/1534735409343446
PMCID: PMC2831080  PMID: 19815593
breast cancer; integrative oncology; acupuncture; massage; yoga; nutrition; exercise; case discussion; integrative medical consult; Dana-Farber; complementary therapies; integrative therapies
18.  DISCLOSURE TO PHYSICIANS OF CAM USE BY BREAST CANCER PATIENTS: FINDINGS FROM THE WOMEN’S HEALTHY EATING AND LIVING STUDY 
Integrative cancer therapies  2008;7(3):122-129.
Background
Physician awareness of their patients’ use of complementary and alternative medicine (CAM) is crucial, particularly in the setting of a potentially life-threatening disease such as cancer. The potential for harmful treatment interactions may be greatest when a patient sees a CAM practitioner – perceived as a physician-like authority figure – but does not disclose this to their physician. We therefore investigated the extent of nondisclosure in a large cohort of cancer patients.
Methods
We investigated CAM use in participants of the UCSD Women’s Healthy Eating and Living (WHEL) Study, a multicenter study of the effect of diet and lifestyle on disease-free and overall survival in women ages 18–70 who had completed treatment for invasive breast cancer between 1995 and 2000. Data regarding CAM use and disclosure was collected via a telephone-administered questionnaire in 2003–2004. This questionnaire asked about different CAM modalities including those requiring a “skilled CAM practitioner” (acupuncturist, chiropractor, homeopath, or naturopath) for administration. Demographic data was obtained at the WHEL baseline clinic interview. Modality-specific disclosure rates were determined and a comparison of demographic variables of disclosers versus nondisclosers was conducted using Chi-squared tests for categorical variables, and t-tests for continuous variables.
Results
Of 3088 total WHEL participants, 2527 completed the CAM questionnaire. Of these, 2017 reported using some form of CAM. Of these, 300 received treatment from an acupuncturist, chiropractor, homeopath, or naturopath and also provided information on whether or not they disclosed this care to their conventional physician. The highest disclosure rate was for naturopathy (85%), followed by homeopathy (74%), acupuncture (71%), and chiropractic (47%). Among demographic characteristics, only education (p = 0.047) and study site (p=0.039) were associated with disclosure. College graduates and postgraduates, in particular, were more likely to disclose CAM use to their physicians than those with lesser education.
Conclusion
Overall, we observed moderately high rates of physician disclosure of CAM use for all modalities except chiropractic. Education and study site associations suggest that disclosure may be greater when CAM use is more prevalent and possibly more socially accepted. These findings underscore the importance of open, destigmatized patient-physician communication regarding CAM use.
PMCID: PMC2763208  PMID: 18956493
Breast cancer; CAM; complementary and alternative medicine; acupuncture; naturopathy; chiropractic; health communication; disclosure
19.  Patients’ Interactions With Physicians and Complementary and Alternative Medicine Practitioners: Older Women With Breast Cancer and Self-Managed Health Care 
Integrative cancer therapies  2009;8(1):63-70.
Older patients are more likely than ever to be under the care of both physicians and complementary and alternative medicine (CAM) practitioners, yet there is little research on older patients’ experience of these different relationships. This article addresses older breast cancer patients’ seeking of concurrent care and examines patients’ understandings of interactions with physicians and CAM practitioners. This is a qualitative study of a random, population-based sample of 44 older women with breast cancer who are simultaneously under the care of at least 1 physician and 1 CAM practitioner.
doi:10.1177/1534735408329410
PMCID: PMC2754706  PMID: 19147647
breast cancer; complementary and alternative medicine; patient–practitioner communication; aging; qualitative research
20.  BIOLOGICAL MEDIATORS OF EFFECT OF DIET AND STRESS REDUCTION ON PROSTATE CANCER 
Integrative cancer therapies  2008;7(3):130-138.
Background
The Western diet has been associated with prostate cancer (PC) incidence as well as risk of disease progression after treatment. Conversely, plant-based diets have been associated with decreased risks. A 6-month pilot intervention trial was conducted to determine whether adoption of a plant-based diet, reinforced by stress reduction, could reduce the rate of prostate specific antigen (PSA) rise, a marker of disease progression, in asymptomatic, hormonally untreated patients experiencing consistently rising PSA levels after surgery or radiation.
Methods
A pre-post design was employed in which each patient served as his own control. In the current investigation, we examine: (1) the effect of intervention on potential mediators of disease progression, including body composition and weight-related biomarkers (sex steroid hormones and cytokines), and (2) whether changes in these variables were associated with change in rate of PSA rise. The baseline rate of PSA rise (from the time of post-treatment recurrence to the start of intervention) was ascertained by review of patients’ medical records. Body composition and biomarker assessments were performed at Baseline (prior to intervention), during intervention (3 months), and at the end of intervention (6 months). Changes in body composition and biomarkers were determined and compared with rates of PSA rise over the corresponding time intervals.
Results
Over the course of the intervention period, there was a significant reduction in waist-to-hip ratio (WHR) (p=0.03) and increase in circulating sex hormone binding globulin (SHBG) (p=0.04). The rate of PSA rise decreased when comparing the pre-intervention period (PSA slope=0.059) to the period from 0–3 months (PSA slope=−0.002, p<0.01) and increased slightly, though not significantly, when comparing the period from 0–3 months to the period from 3–6 months (0.029, p=0.43).
Conclusion
These results provide preliminary evidence that adoption of a plant-based diet and stress reduction may result in reduction of central adiposity and improvement of the hormonal milieu in patients with recurrent PC. Changes in the rate of rise in PSA were in the same direction as changes in WHR and opposite those of SHBG, raising the possibility that the effect of the intervention may have been mediated, in part, by these variables.
doi:10.1177/1534735408322849
PMCID: PMC2733349  PMID: 18815144
prostate; prostatic neoplasms; prostate-specific antigen; plant-based diet; stress reduction; sex steroid hormones; cytokines; disease progression

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