Conceptualizing an Integrative Multiple Myeloma Care: The Role of Nutrition, Supplements, and Complementary Modalities.

Multiple Myeloma (MM) is the second most prevalent hematologic malignancy, and its incidence has been increasing enormously in recent years. The prognosis of MM has changed radically with the introduction of new drugs that have improved life expectancy; recurrences are a common occurrence during the course of the disease and are characterized by an increase in refractory to treatment. Moreover, MM patients are challenged by quality of life-related concerns while limited conventional therapy may be offered. This includes bone pain and dialysis due to the complications of acute renal failure. We, therefore, believe that it is very important to add new treatment modalities, including supplements, nutritional modifications, acupuncture, and mind-body therapies, with the goal of improving treatment tolerance, effectiveness, and patients' quality of life. Moreover, many patients use some of these supplements on their own, in the hope of reducing the side effects, so it is even more important to know their action and potential. The purpose of this review is to illustrate all these strategies potentially available to enrich our approach to this, to date, incurable disease.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer: A multicenter retrospective observational comparative study.

BACKGROUND: Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy (CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electro-hyperthermia (mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer. AIM: To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer. METHODS: This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer (stage III and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128 (59%) of them were treated with CHT (no-mEHT) and 89 (41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT. RESULTS: Median patients' age was 67 years (range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group (20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses (45% vs 24%, P = 0.0018) and a lower number of progressions (4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions. CONCLUSION: mEHT seems safe and has beneficial effects on survival and tumor response of stage III-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

Integrative Hematology: State of the Art.

Blood cancers are a group of diseases with thus far frequently poor prognosis. Although many new drugs, including target therapies, have been developed in recent years, there is still a need to expand our therapeutic armamentarium to better deal with these diseases. Integrative hematology was conceived as a discipline that enriches the patient's therapeutic possibilities with the use of supplements, vitamins and a nutritional approach aiming at improving the response to therapies and the clinical outcome. We will analyze the substances that have proved most useful in preclinical and clinical studies in some of the most frequent blood diseases or in those where these studies are more numerous; the importance of the nutritional approach and the role of the intestinal microbiota will also be emphasized.

A Systematic Review of Systematic Reviews and a Pooled Meta-Analysis on Complementary and Integrative Medicine for Improving Cancer-Related Fatigue.

PURPOSE: Evidence supporting complementary and integrative medicine (CIM) for improving cancer-related fatigue (CRF) is still fragmented. This study therefore critically appraised all the systematic reviews (SRs) regarding the effectiveness of CIM in mitigating CRF in adults. METHODS: A systematic review of SRs and a meta-analysis were conducted in 4 databases. The effect sizes of the included SRs were quantitatively pooled (standardized mean difference [SMD]; 95% CI) using a random-effects model. Heterogeneity was tested by using χ2 (Q) tests and I² statistics. FINDINGS: Twenty-two SRs met the inclusion criteria, and results from 20 SRs underwent meta-analysis. The pooled significant estimate of fatigue reduction was as follows: SMD, -0.50; 95% CI, -0.67 to -0.32; P < 0.001. The subgroup analysis based on the type of CIM intervention revealed that the approach showing higher effects in reducing fatigue thus far is acupuncture: SMD, -0.99; 95% CI = -1.37 to -0.62, P < 0.001; I2 = 84%. CIM therapies showed a significant reduction of fatigue in patients with breast cancer: SMD, -0.46; 95% CI, -0.69 to -0.23; P < 0.001; I2 = 82%. IMPLICATIONS: CIM interventions showed effectiveness in reducing CRF. Subgroup analysis suggested some potential influencing, such as tumor type and specific CIM therapy factors, that require in-depth assessment in future research. Study protocol registration: PROSPERO CRD42020194254.

Resources for Human Health from the Plant Kingdom: The Potential Role of the Flavonoid Apigenin in Cancer Counteraction.

Apigenin is one of the most widespread flavonoids in the plant kingdom. For centuries, apigenin-containing plant preparations have been used in traditional medicines to treat diseases that have an inflammatory and/or degenerative component. In the 1980s, apigenin was proposed to interfere with the process of carcinogenesis. Since then, more and more evidence has demonstrated its anticancer efficacy, both in vitro and in vivo. Apigenin has been shown to target signaling pathways involved in the development and progression of cancer, such as PI3K/Akt/mTOR, MAPK/ERK, JAK/STAT, NF-κB, and Wnt/ß-catenin pathways, and to modulate different hallmarks of cancer, such as cell proliferation, metastasis, apoptosis, invasion, and cell migration. Furthermore, apigenin modulates PD1/PD-L1 expression in cancer/T killer cells and regulates the percentage of T killer and T regulatory cells. Recently, apigenin has been studied for its synergic and additive effects when combined with chemotherapy, minimizing the side effects. Unfortunately, its low bioavailability and high permeability limit its therapeutic applications. Based on micro- and nanoformulations that enhance the physical stability and drug-loading capacity of apigenin and increase the bioavailability of apigenin, novel drug-delivery systems have been investigated to improve its solubility.

Complementary and Integrative Approaches to Cancer: A Pilot Survey of Attitudes and Habits among Cancer Patients in Italy.

Background: Cancer patients are among the main consumers of traditional, complementary, integrative, and alternative medicine (TCIM) such as natural products (herbals, integrators, etc.) and mind and body practices (yoga, acupuncture, etc.). Methods: A questionnaire on TCIM was submitted to 415 Italian cancer patients. The questionnaire consisted of three sections: (i) biographical and clinical information; (ii) use of natural substances; and (iii) use of mind-body practices. Results: 406 patients completed the questionnaire. The prevalence of TCIM use was 72.3%. Of them, 75.6% started to use TCIM after a tumor diagnosis. The main reasons for using TCIM were to mitigate side effects (65.0%), to regain physical and mental balance (35.9%), to relieve pain (18.3%), and to improve the efficacy of cancer therapy (16.0%). 44.7% of patients taking natural products used them during conventional therapies (chemotherapy, radiotherapy, etc.), and in 67.5% of cases without consulting a doctor. As a consequence, only about 50% of patients taking natural substances used these compounds appropriately, and the most common errors were related with the purpose of reducing the side effects of the therapy (52.3%) and for boosting immune system (32.1%). Conclusions: There is an impelling need to provide patients with scientifically validated information to raise awareness about the benefits and risks of using TCIM.

The Combination of AHCC and ETAS Decreases Migration of Colorectal Cancer Cells, and Reduces the Expression of LGR5 and Notch1 Genes in Cancer Stem Cells: A Novel Potential Approach for Integrative Medicine.

The AHCC standardized extract of cultured Lentinula edodes mycelia, and the standardized extract of Asparagus officinalis stem, trademarked as ETAS, are well known supplements with immunomodulatory and anticancer potential. Several reports have described their therapeutic effects, including antioxidant and anticancer activity and improvement of immune response. In this study we aimed at investigating the effects of a combination of AHCC and ETAS on colorectal cancer cells and biopsies from healthy donors to assess the possible use in patients with colorectal cancer. Our results showed that the combination of AHCC and ETAS was synergistic in inducing a significant decrease in cancer cell growth, compared with single agents. Moreover, the combined treatment induced a significant increase in apoptosis, sparing colonocytes from healthy donors, and was able to induce a strong reduction in migration potential, accompanied by a significant modulation of proteins involved in invasiveness. Finally, combined treatment was able to significantly downregulate LGR5 and Notch1 in SW620 cancer stem cell (CSC) colonospheres. Overall, these findings support the potential therapeutic benefits of the AHCC and ETAS combinatorial treatment for patients with colorectal cancer.

Association of Polygenic Risk Score and Bacterial Toxins at Screening Colonoscopy with Colorectal Cancer Progression: A Multicenter Case-Control Study.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and its incidence is correlated with infections, chronic inflammation, diet, and genetic factors. An emerging aspect is that microbial dysbiosis and chronic infections triggered by certain bacteria can be risk factors for tumor progression. Recent data suggest that certain bacterial toxins implicated in DNA attack or in proliferation, replication, and death can be risk factors for insurgence and progression of CRC. In this study, we recruited more than 300 biopsy specimens from people undergoing colonoscopy, and we analyzed to determine whether a correlation exists between the presence of bacterial genes coding for toxins possibly involved in CRC onset and progression and the different stages of CRC. We also analyzed to determine whether CRC-predisposing genetic factors could contribute to bacterial toxins response. Our results showed that CIF toxin is associated with polyps or adenomas, whereas pks+ seems to be a predisposing factor for CRC. Toxins from Escherichia coli as a whole have a higher incidence rate in adenocarcinoma patients compared to controls, whereas Bacteroides fragilis toxin does not seem to be associated with pre-cancerous nor with cancerous lesions. These results have been obtained irrespectively of the presence of CRC-risk loci.

Enhancing Palliative Care With Mindful Touch: Impact of a Manual and Movement Therapy Training Program in an International Multidisciplinary Integrative Oncology Setting.

CONTEXT: Manual and movement therapies (MMTs) play a central role in the integrative oncology setting, significantly improving patients' quality of life (QOL). Despite research supporting the effectiveness and safety of these modalities, most oncology health care providers (HCPs) lack any MMT training. OBJECTIVES: In this study, we examine the impact of an MMT-based integrative oncology training program with the participation of an international and multidisciplinary group of oncology HCPs. The feasibility of implementing these skills in palliative cancer care is examined. METHODS: A three-day evidence-based hands-on teaching program was designed to train oncology HCPs working in supportive cancer care MMT modalities from traditional Chinese and anthroposophic medicine. Prequalitative and postqualitative assessments of the trainees' narratives were analyzed using ATLAS.Ti software (Scientific Software Development GmbH, Berlin, Germany) for systematic coding. RESULTS: The training program was attended by 30 participants from Israel (15), Germany (7), Italy (6), Turkey (1), and Cyprus (1). The group included 13 nurses, 10 physicians, 6 complementary/integrative HCPs, and 1 psycho-oncologist. The pretraining expectations that were met at post-training included gaining knowledge and practical QOL-oriented skills, which could be implemented in the palliative and supportive care setting. A significant change in the attitude of trainees to touch therapy was also identified, with respondents seeing MMTs promoting patient-centered palliative care, including nonverbal communication. CONCLUSION: An MMT training program for oncology HCPs for QOL-related indications is both feasible and likely to be implemented in palliative and supportive cancer care. Nonspecific effects of MMTs were also recognized for their ability to facilitate patient-centered care.

Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation.

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.

Bioactive Immunomodulatory Compounds: A Novel Combinatorial Strategy for Integrated Medicine in Oncology? BAIC Exposure in Cancer Cells.

The Standardized Cultured Extract of Lentinula edodes Mycelia (also known as Active Hexose Correlated Compound, AHCC) and Wasabia japonica (Wasabi) are natural nutritional supplements known for their immunomodulatory and anticancer potential. The aim of this study was to evaluate the combinatorial effect of the bioactive immunomodulatory compound (BAIC), obtained by combining Wasabi and AHCC, on human breast (MCF-7) and pancreatic (Panc02) adenocarcinoma cell lines. Data obtained revealed that BAIC determines a striking decline in cancer cell growth at minimal concentrations compared with the use of Wasabi and AHCC as single agents. A significant increase in the G0/G1 subpopulation together with a marked augmentation in the percentage of apoptotic cells was demonstrated by flow cytometry, together with a significant upregulation in the expression of genes associated to the apoptotic cascade in both cell lines. The inhibitory role BAIC plays in mammospheres formation from MCF-7-derived cancer stem cells was shown with a marked reduction in size and number. Interestingly, when BAIC was exposed to monocytic cells, no cytotoxic effects were observed. A monocytes-to-macrophages differentiation was rather observed with the concomitant acquisition of an anti-inflammatory phenotype. Taken together, our findings suggest that BAIC could be used as a potential integration of standard chemotherapy treatments because of the improved inhibitory activity on cancer cell proliferation and reduced potential adverse effects.

Accreditation Standard Guideline Initiative for Tai Chi and Qigong Instructors and Training Institutions.

Evidence of the health and wellbeing benefits of Tai Chi and Qigong (TQ) have emerged in the past two decades, but TQ is underutilized in modern health care in Western countries due to lack of promotion and the availability of professionally qualified TQ instructors. To date, there are no government regulations for TQ instructors or for training institutions in China and Western countries, even though TQ is considered to be a part of Traditional Chinese medicine that has the potential to manage many chronic diseases. Based on an integrative health care approach, the accreditation standard guideline initiative for TQ instructors and training institutions was developed in collaboration with health professionals, integrative medicine academics, Tai Chi and Qigong master instructors and consumers including public safety officers from several countries, such as Australia, Canada, China, Germany, Italy, Korea, Sweden and USA. In this paper, the rationale for organizing the Medical Tai Chi and Qigong Association (MTQA) is discussed and the accreditation standard guideline for TQ instructors and training institutions developed by the committee members of MTQA is presented. The MTQA acknowledges that the proposed guidelines are broad, so that the diversity of TQ instructors and training institutions can be integrated with recognition that these guidelines can be developed with further refinement. Additionally, these guidelines face challenges in understanding the complexity of TQ associated with different principles, philosophies and schools of thought. Nonetheless, these guidelines represent a necessary first step as primary resource to serve and guide health care professionals and consumers, as well as the TQ community.

Integrated Cancer Treatment in the Course of Metastatic Pancreatic Cancer: Complete Resolution in 2 Cases.

Pancreatic cancer (PC) has a very low average survival, but its prognosis is further reduced in the case of metastatic spread. Medical therapy in these cases is the only applicable methodology in the international guidelines. During anticancer treatments, common side effects are nausea, vomiting, arthralgia, neuropathy, and alopecia as well as a myelosuppressive effect. The toxicity of various drugs not only affects the quality of life of the patient, but often its severity requires a reduction in if not the termination of drug administration. Scientific studies have shown that a combined use of chemotherapy and certain natural substances, in the form of standardized extracts, can lead to an enhancement of the action of the chemotherapy. Here, we describe 2 cases of metastatic PC. The first case concerns the integrated treatment of a patient with cancer of the pancreas tail with metastatic involvement ab initio of peripancreatic lymph nodes and liver parenchyma, with numerous secondary lesions greater than 9.5 cm. The second case concerns the integrated treatment of a patient with cancer of the pancreatic body with metastatic involvement of the liver parenchyma, with a small secondary lesion. In both cases, an integrated cancer treatment approach, combining chemotherapy with natural remedies, extracts, and hyperthermia, induced a notable remission of primary and metastatic lesions.

Refugees in Conflict: Creating a Bridge Between Traditional and Conventional Health Belief Models.

The recent wave of migration from Middle Eastern countries to Europe presents significant challenges to the European health profession. These include the inevitable communication gap created by differences in health care beliefs between European oncologists, health care practitioners, and refugee patients. This article presents the conclusions of a workshop attended by a group of clinicians and researchers affiliated with the Middle East Cancer Consortium, as well as four European-based health-related organizations. Workshop participants included leading clinicians and medical educators from the field of integrative medicine and supportive cancer care from Italy, Germany, Turkey, Israel, Palestine, Iran, Lebanon, Jordan, Egypt, and Sudan. The workshop illustrated the need for creating a dialogue between European health care professionals and the refugee population in order to overcome the communication barriers to create healing process. The affinity for complementary and traditional medicine (CTM) among many refugee populations was also addressed, directing participants to the mediating role that integrative medicine serves between CTM and conventional medicine health belief models. This is especially relevant to the use of herbal medicine among oncology patients, for whom an open and nonjudgmental (yet evidence-based) dialogue is of utmost importance. The workshop concluded with a recommendation for the creation of a comprehensive health care model, to include bio-psycho-social and cultural-spiritual elements, addressing both acute and chronic medical conditions. These models need to be codesigned by European and Middle Eastern clinicians and researchers, internalizing a culturally sensitive approach and ethical commitment to the refugee population, as well as indigenous groups originating from Middle Eastern and north African countries. IMPLICATIONS FOR PRACTICE: European oncologists face a communication gap with refugee patients who have recently immigrated from Middle Eastern and northern African countries, with their different health belief models and affinity for traditional and herbal medicine. A culturally sensitive approach to care will foster doctor-refugee communication, through the integration of evidence-based medicine within a nonjudgmental, bio-psycho-social-cultural-spiritual agenda, addressing patients' expectation within a supportive and palliative care context. Integrative physicians, who are conventional doctors trained in traditional/complementary medicine, can mediate between conventional and traditional/herbal paradigms of care, facilitating doctor-patient communication through education and by providing clinical consultations within conventional oncology centers.