Exam 2 - NUTR 416
o What are the 10 key recommendations for cancer prevention
1. Be a healthy weight 2. Be physically active 3. Eat wholegrains, fruits, vegetables and beans 4. Limit "fast foods" 5. Limit red and processed meats 6. Limit sugar sweetened drinks 7. Limit alcohol consumption 8. Don't rely on supplements 9. Breastfeed your baby 10. Follow recommendations after diagnosis
How many human genes are there and what do they encode?
20,000-25,000 genes that encode for proteins
Vertical transmission
3. Verticle transmission mother fetus/infant • can occur during pregnant, delivery, breastfeeding • with antiretroviral therapy, transmission rate <1%
o Approximately what fraction of cancers are thought to be preventable (diet/PA related, tobacco related)?
30-50% of cancers are estimated to be preventable through healthy lifestyle choices, avoiding exposure to carcinogens, pollution
What is ApoE? With what chronic diseases are ApoE polymorphisms associated -- relationship to each polymorphism type?
APOE • Main apolipoprotein of the chylomicron • Necessary for binding o liver cells for removal of triglycerides, cholesterol, etc, from circulation • Main cholesterol carrier of the brain 3 main gene polymorphisms • ApoE3 (most common ~64% have 2 copies of this fom0 • ApoE2 (may be protective) • ApoE4 (linked to higher TC and LDL-C, atherosclerosis, Alzheimer's disease, dementia)
o What is the AICR?
American Institute for Cancer Research - cancer charity that fosters research on the relationship of nutrition, PA and weight loss to prevent recurrence of cancer
describe the example of sulforaphane (presented in class) in the context of nutrigenomics.
Antioxidant and detoxifying effects of sulforophane: SF activates phase 2 enzymes through the transctiption factor, NF-E2 p45-related factor-3 (Nrf2) • Nrf2 sequestered by KEAP-1; sulforaphane cause s KEAP-1 to relsease Nrf2 which translocates to nucleus and binds to antioxidant response elements (AREs) in gene promoter regions These variable and unknowns mean supplements may not yield expected sulfrophane Glucosinolates are lost in cooking Glucosinolates are lost during transport and storage Broccoli cultivars vary in sulfraphane yield - no way to know amount in available product Broccoli also contains epithiospecifier protein (ESP) which inhibits myrosinase
What is gene expression
Appearance of a phenotype od a characteristic or effect attributed to a particular gene Process by which the instructions in our DNA are converted into a functional product such as a protein (through transcription and translation)
o Breastfeeding: Evidence for decreased risk of what type of cancer?
Breast cancer
Main testing and monitoring parameters for HIV
CD4 count • Most important indicator of immune function • Used as predictor of disease progression and monitored for response to ART • Goal with ART: >500 clls/ul HIV RNA monitoring (vital load) • Goal with ART: undetectable levels Drug resistance testing • In 2016, 10-17% of transmitted HIV drug resistant • Genotyping recommended for all prior to ART initiation
o There may be variations in response to diet intervention and supplementation among the genotypes. What was observed in the study whose results we looked at in class (Corella 2011)?
CHD risk with E3 and E4 in comparison with E2 showed significance with a high saturated fat diet CHD risk with E2 showed significance with a high saturated fat diet compared to E3 but E4 did not
which factors are associated with which cancers and what is the direction of the relationship
Cancer • Incidence in general: decline • Men: decline • Women: incline Esophagus (adenocarcinoma) • Increases risk: alcohol and body fatness Stomach • Increases risk: high salt intake, alcohol, body fatness Pancreas • Increases risk: Body fatness, height Liver • Increases risk: alcohol and body fatness • Decreases risk: coffee • Men: increasing • women: increase Colorectum • Increases risk: processed meat, red meat, alcohol, body fatness height • Decreased risk: whole grains, dietary fiber, fish, calcium, physical activity • Men: decreasing • Women: decrease Breast • Increases risk: alcohol, body weight, height • Women: increase Endometrium • Increases risk: glycemic load, body fatness, height • Decreases risk: Coffee, physical activity Prostate • Increases risk: body fatness, height • Men: increasing Bladder • Increases risk: arsenic • Men: increasing Challenges to studying diet/PA and cancer prevention • Factors intertwine and influence each other, genetics also plays a role
o AIDS-defining conditions and opportunistic infections
Candidiasis of bronchi, trachea, or lungs Candidiasis, esophageal Cervical cancer, invasive Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis intestinal (greater than 1 month's duration) Cryptomegalovirus disease (other than liver, spleen or nodes) Cryptomegalovirus retinitis, (with loss of vision) Encephalopathy, HIV-related Herpes simplex: chronic ulcer (greater than 1 month's duration) or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal (greater than 1 month's duration Kaposi's sarcoma Lymphoma, Burkitt's (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymptoma, primary, of brain Mycobacterium avoim complex or M. kansasii, disseminated or extrapulmonary Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, ther species or unidentified species, disseminated or extrapulmonary Pneumocystis jerovicii pneumonia (previously P. carinii) Pneumonia recurrent Progressive multifocal leukocephalopathy Salmonelle septicemia, recurrent Toxoplasmosis of brain Wasting syndrome due to HIV Oral candidiasis Non-Hodgkins lymphoma in the oral cavity Kaposi's sarcoma - malignanyt vascular proliferation that can appear in several parts of body • Adverse nutritional effects associated w. KS of GI tract - pain, diarrhea, N/V, weight oss, diarrhea, malabsorption
o Cancer survivors: What is the main recommendation?
Check with your health professional what is right for you • All cancer survivors receive nutritional care and guidance on physical activity from trained professionals • Unless other wised advices, and if you can, all cancer survivors are advised to follow the cancer prevention recommendations as at as possible after the acute stage of treatment
o How does this change role of nutrition in HIV from primary focus prior to antiretroviral drugs?
Clinical challenges confronting patients w/ HIV have shifted form AIDS-related illnesses to chronic diseases such as coronary artery disease, chronic lung disease, and chronic anemia. With the growing burgen of HIV-related heart, lung and blood (HLB) disease, the National Heart, Lung, and Blood Institute (NHLBI) recognizes it must stimulate and support HIV-related HLB research
o Regarding the supplementation issue (again) - note that the rate of supplement use is high among cancer survivors - 64-81% -- with 14-32% starting supplementation after dx (ACS 2012). So when IS supplementation appropriate or not appropriate?
Currently, there are no recommendations supporting supplement use with cancer patients or cancer survivors Supplements of antioxidants can protect cancer cells from oxidative stress, potentially giving them a growth advantage Recommendations are to consume the Recommended Daily Allowances by eating a variety of foods and following food dietary practices
Basic structure of DNA
DNA is a sequence of bases with a sugar phosphate background
o He also shared data from recent publications showing the association between EPA, DHA intake and disease- free survival with CRC and survival after breast cancer. What did the results show? How is adherence to healthy dietary patterns or adherence to a Western diet associated with cancer mortality in cancer survivors (meta-analysis by Schwedhelm)? What about association of alcohol with mortality and recurrence in the same meta-analysis? So how would you apply all of this information in real life? What does it mean?
EPA, DHA intake and disease free survival w/ CRC and survival after breast cancer • EPA and DHA intake shows increased risk of survival Western diet vs healthy diet • Western diet pattern increases cancer mortality in cancer survivors Alcohol w/ mortality in cancer survivors • Increases mortality and increases recurrence How would you apply all of this info in real life/what does it mean?
o What is the relationship between fish, EPA, DHA intake and advanced prostate cancer (cohort data) and in adjuvant cancer treatment - experimental data? Cool stuff!
EPA, DHA, and together - no reduction risk
o Alcoholic drinks: Alcohol intake has been associated with risk of what cancer types?
Esophagus, oral cavity and pharynx, liver, esophagus, stomach, colorectal, breast
what was found in the internet-based Food4Me intervention study among individuals shown to be at high risk (APOE risk) vs. at low risk (APOE non-risk) based on their ApoE genotype? What about FTO? In Food4Me?
Food4Me trial • People at risk E4+ changed their dietary intake of total fat or SFA at 6 months compared to baseline FTO • FTO risk carriers lost more weight than controls regardless of intervention level
where is DNA found
Found in the nucleus of cells
o How do you interpret results (reviewed in class) from the studies by Sun and Xiang (examples of nutrigenetics)? What might this mean for effectiveness of the DASH diet?
Genetic variants of the B2-AR affect salt sensitivity, plasma renin activity, and BP • Systolic blood pressure (SBP), plasma renin activity (PRA), serum aldosterone (ALDO) and 24-h urinary potassium (UK) responses to control diet (open bars) and DASH-sodium diet (closed bars) by B2 adrenergic receptor genotype e status at B2-AR A46G (adenine in place of guanine at nucleotide 46 - results in arginine replacing glycine at amino acid 16) o Note: The AA genotype is more common among black individuals - this may help explain greater responsiveness to DASH-sodium intervention
o Physical activity: What are the two goals for physical activity? Which cancers have an inverse relationship with physical activity and which cancer has the strongest inverse relationship with physical activity?
Goals: be at least moderately physically active (150 minutes a week) and limit sedentary habits • Colorectal, breast, endometrial • Strongest inverse relationship: colon cancer
What does the viral genome look like - DNA or RNA?
HIV is a retrovirus that uses CD4 mlcl on surface of CD4+ T helper cells (immune system cells - acquired immunity) and "coreceptors" usually chemokine receptor CCR5 - to gain entry HIV enzymes are injected into the host cell along with RNA, which is copied to make DNA via reverse transcriptase... vital DNA integrated via vital integrase into host cell's DNA where it can remain latent and undetected by the immune system New DNA is copied to make viral RNA which is then translated to make HIV proteins and form immature HIV particles Proteases cleave the large proteins into final form which makes a mature, infectious new copy of the virus Results in lysis/death of T helper cell
surgery
Head and neck: possible impaired chewing, swallowing Gastrointestinal • Esophageal: affected portion of esophagus removed, stomach reattached to remaining esophagus o Jejunal tube feeding usually required short-term o Pt eventually advanced to regular diet • Stomach (gastric) o Gastrectomy ... partial or total o Dumping syndrome is a possible side effect o Other potential nutrient deficiencies? • Colon o Partial or total colectomy may cause fluid, electrolyte losses o Colostomy • Pancreas o If >70% removed/resected, insulin injections required o If >90% removed, malabsorption occurs, pancreatic enzyme replacement needed
Why are there pairs?
Homologous chromosomes are chromosome pairs that are inherited from each parent
o Diet rich in whole grains, vegetables, fruit, and beans: Risk of which cancer is inversely associated with intake of whole grains and foods containing dietary fiber?
It is important to note the emphasis on foods as RCTs of fiber supplement intervention have not proven effective. • Colorectal inversely associated w/ consuming dietary fiber and whole grains
o Metabolic side effects linked to some ARV drugs
Lipohypertrophy: lipid accumulation in • Dorsocervical (buffalo hump) • Abdomen • Breasts Lipoatrophy: fat loss in • Face • Buttocks • Extremities Concimitatnt metabolic complications • Insulin resistance • Dyslipidemia • Osteopenia • Gastrointestinal effects: N/V/D, oral pain • CVD risk
o Limit consumption of "fast foods" and other processed foods high in fat, starches or sugars: What is the main point of including this recommendation?
Main point of limiting these foods helps control calorie intake and maintaining a healthy weight • Increases risk for endometrium
most common cancers for men
Men • 1. Prostate • 2. Lung and bronchus • 3. Colon and rectum
In which cancers are we seeing a decline in death rates in men? In women?
Men: lung and bronchus, prostate, colon and rectum, stomach, leukemia, Women: lung and bronchus, breast, colon and rectum, stomach
What is DNA
Molecule that contains the genetic code of organisms
o Pregnant women w/ HIV
More women getting HIV but in 2017 80% covered
o What is the Continuous Update Project? What kinds of information do you find in the CUP?
Ongoing program to analyze cancer research Info: trends, prevention, risk factors, treatment
o Which dietary and physical activity components have evidence linking them to prevention of which specific cancer types, noting body fatness, alcohol are linked to a number of cancers?
Physical activity decreases risk • Colorectal, breast, endometrial Body fatness • Decreases risk (in young adulthood and adulthood) premenopausal breast cancer • Decreases risk in young adulthood - postmenopausal breast cancer • Increases risk: mouth, esophagus, stomach, pancreas, gallbladder, lung, colorectal, ovary, endometrium, pancreas Alcohol • Decreases risk: kidney • Increases risk: mouth, esophagus, liver, colorectal, breast (pre and post)
o Do not use supplements for cancer prevention: Why no dietary supplements for cancer prevention? What is the potential danger of making an assumption about a single component in food and taking it as a supplement instead?
Potential drug interaction, a dietary supplement is a product intended for ingestion that contains a dietary ingredient intended to achieve levels of consumption of micronutrients that is what is usually achievable through diet alone
o Why is it important to have recommendations for this group (consider what is happening with current 5-year survival rates, personal goals of cancer survivors)?
Prolong survival rates Increase quality of life Maintain healthy lifestyles
o Limit consumption of red and processed meat: What is included in red and processed meat and what is the recommended limit? Which cancers are associated with red and processed meat intake?
Red meat: mammalian muscle meat: beef, pork lamb, veal, mutton, horse and goat Processed meat: meat that has been transformed through salting, curing, fermentation, smoking or other processes to enhance flavor Recommended limit: no more than 3 portions per week = 350 to 500 grams or 12 - 18 oz Cancers associated w/ intake: colorectum
o Do lifestyle risk factors play the same role across all cancer types?
Relevance differs by cancer type Some factors clearly play a role across many cancer types - body fatness, alcohol
o Specific interactions w/ other drugs, dietary supplements, foods, nutrients
St. John's wort decreases efficteness of proteste inhibitors and NNRTs (both classes metabolized by CYP3A4) • Increase indoles in broccoli, cauliflower, cruciferous vegetables; heterocyclic aminses in charbroiled meats, chronic ethanol consumption, St. John's wort (increase CyP3A4 in liver and SI • Decrease in SI by components in grapefruit juice or by acute ethanol consumption resulting in decreased clearance and increased effect • Increase by dithiolthiones and isothiocyanates in cruciferous vegetables; liminoids in citrus, ortanosulfur compounds in allium family, curcumin (in turmeric) • Overall activity of enzyme systems decreases with deficiencies in protein, iron, vitamin C, tocopherol, retinol, other nutrients and increase on high protein diet
o Limit consumption of sugar sweetened drinks: What does this include? What are alternatives? What is the main point of including this recommendation?
Sugar sweetened drinks: drinks sweetened by adding free sugars (sucrose, high fructose corn syrup, honey, syrup, fruit juices, fruit juice concentrate). Drinks such as sodas, sports drinks, energy drinks Alternatives: sugar free, sweetened w/ artificial sweeteners Main point: drink more water, don't overconsume sugar Associated w/ weight gain not really cancer specifically
o Absolutely be familiar with the supplement issue (Dr. Whelan also emphasized this, too) - why is food better (based on what is known so far)?
Synergy - various vitamins, minerals, and other phytochemicals in these whole goods act in synergy
How does DNA make proteins
Transcription is the process of copying a sequence of DNA into mRNA whereas translation involves translating the code carried by mRNA into a sequence of AA to make a protein
o Define basic elements of the AJCC TNM staging system and how this plays into defining cancer as stages 0-4.
Tumor: Tumor extent • TX: primary tumor cannot be evaluated • TO: No evidence of primary tumor • Tis: Tumor in situ - early tumor that has not invaded surrounding tissue • T1-4: Size and/or extent of primary tumor o T1: tumor invading submucosa o T2: Tumor invading the muscularis propia o T3:Tumor penetrating the muscularis propria and arriving at wall of other organ o T4: Tumor invading other organs or structures T4a: tumor directly invading visceral peritoneum T4b: tumor directly invading or adhering to other organs or structures Nodes: has cancer spread to regional lymph nodes and, if so, what is the extent of the spread? • NX: regional lymph nodes cannot be evaluated • N0: No regional lymph node involvement • N1-3: Involvement of regional lymph nodes: Numbers correspond to number/extent of spread Metastases: Has the cancer metastasized? • M0: No distant metastases • M1: Distant mestastases
o What do we know from the examples of Dr. Whelan's research with turmeric and curcumin? Chinese goldthread and berberine?
Turmeric and curcumin • The herbal extract is more powerful than the phytonutrient in the extract
four main points from the oncology evidence-based nutrition practice guidelines (2017).
Validity of malnutrition screening and nutrition assessment tools Association among nutritional status and morbidity and mortality outcomes Effect of medical nutrition therapy (MNT) on patients undergoing chemotherapy (CT) and radiation therapy (RT) Cancer cachexia and the effect of dietary supplements and medical food supplements (MFS) containing fish oil (specifically EPA) on body weight and lean body mass)
o What are the nutrition and PA recommendations from WCRF/AICR and ACS for cancer survivors?
WCRF • Be a healthy weight • Be hphysically active • Eat a diet rich in whole grains, vegetables, fruit and beans • Limit consumption of fast foods (high in fat, starches, or sugars) • Limit consumption of red and processed meat • Limit consumption of sugar sweetened beverages • Limit consumption of alcohol • Do not use supplements for cancer prevention • Breast feed AICR • Be a healthy weight • Be physically active • Eat a diet rich in whole grains, vegetables, fruit and beans • Limit consumption of fast foods (high in fat, starches, or sugars) • Limit consumption of red and processed meat • Limit consumption of sugar sweetened beverages • Limit consumption of alcohol • Do not use supplements for cancer prevention • Breast feed ACS • Stay away from tobacco • Stay safe in the sun • Maintain healthy weight • Be physically active (at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity • Limit sedentary time • Eat healthy diet, focus on plant food • Limit processed meat and red meat • Eat a least 2.5 cups of fruits and veggies each day
o Breastfeeding w/ HIV?
WHO • Mothers w/ HIV need lifelong ART or ARV prophylaxis interventions to reduce HIV transmission through breastfeeding according to WHO recommendations o Should breastfeed for at least 12 months and may continue breastfeeding up to 24 months or longer while being supported for ART Mothers/ HIV should exclusively breastfeed their infants for first 6 months introducing complementary foods thereafter and continue appropriate complementary foods thereafter and continue breastfeeding. BF should only stop once a nutritionally adequate and safe diet without breastmilk can be provided CDC - recommends that women infected with HIV do NOT breastfeed
o Is the isolated component more effective or the whole herbal extract (analogy to isolated component from food compared to a whole food)? Think syngergistic effects!
Whole herbal extract is more effective Foods are more effective than purified nutrients
most common cancers for women
Women • 1. Breast • 2. Lung and Bronchus • 3. Colon and rectum
o What is the WCRF and what is their focus?
World Cancer Research Fund International - analyze global research on diet, nutrition, physical activity and cancer and make public healthy and policy recommendations
o What combination of drugs is typically included
two NRTIs plus one INSTI is first choice; alternatives replace the INSTI with a protease inhibitor or NNRTI or a different INSTI - attempting to target HIV at more than one critical point o Focus areas: efficacy, simplification of regimens and reducing side effects to promote adherence and slow growth of drug resistance
How many chromosomes
23 pairs (22 autosomes and 1 sex)
Where does cancer fall in rankings of causes of US mortality?
2nd
o Do ART drugs cure HIV infection
: treats but does not cure
o Which genotype (polymorphism) is most common?
ApoE3
what are some of the typical side effects and nutrition intervention strategies that may be employed to address them?
NV Dysgeusia Xerostomia Diarrhea, malabsorption, dehydration Mucositis Neutropenia Anorexia
3 stages of HIV infection
o 3 stages of HIV infection 1. Acute infection • during this time, large amounts of the virus are being produced in your body "worst flu ever" 2. Clinical latency • during this stage of the disease, HIV reproduces at very low levels, although it is still active • during this period, you may not have symptoms. w/ proper HIV treatment, people may live w/ clinical latency for several decades 3. AIDS • As your CD4 cells fall below 200 cells/mm3, you are considered to have progressed to AIDS o Without treatment, people typically survive 3 years if untreated? • Clinical latency lasts an average of 10 years but some progress faster • At AIDS stage when CD4 cells are below 200 cells/mm3, people survive 3 years
• Gene variations (SNPs) - what are these - in individual genes, but what do we know about chronic disease?Polygenic!
o A single nucleotide polymorphism (SNP) is a normal variation in a gene in which one nucleotide is replaced by another which can alter function of the encoded protein.
o What are the key recommendations from the ACS (who is this?) 2012 Cancer Prevention Guidelines?
o ACS = American Cancer Society Achieve and maintain a healthy weight throughout life Adopt a physically active lifestyle Consume a healthy diet, with an emphasis on plant foods If you drink alcoholic beverages, limit consumption
What is ART?
o ART: antiretroviral therapy
• What is cancer? How does it begin
o Accumulation of mutations within a single cell can lead to cancer development
Acute HIV
o Acute HIV infection When: 2 - 4 weeks What: large amounts of the virus are being produced in your body • "worst flu ever" • Symptoms: fever, weight loss, malaise, headache, neuropathy, lymphandenopathy, rash, nausea vomiting. Sores, thrush, myalgia, spleen and liver enlargement Enough for HIV infection diagnosis? No, need antibody.antigen combination Does HIV AIDS at this point? No period of a decade or so before developing AIDS, longer if with treatment
Risks/benefits of ART
o Benefits Optimize immune function, reduce morbidity, prolong life and QoL Suppress viral load and minimize risk of transmission o Risks Downsides to less than perfect compliance • Can result in viral mutations o Less ability to treat later o More virulent form of HIV-1 massed on to others o One case-by-case basis may be deferred due to psychological factors
• What is a CSO"?
o Board certified specialist in oncology nutrition
Who are cancer survivors? What are the three phases of survivorship (including above)?
o Cancer survivor: anyone who has been diagnosed with cancer from the time of diagnosis until death o 3 phases diagnosis, treatment, and recovery long-term disease-free survival or stabilized cancer recurrence or living with advanced disease
• Chemotherapy
o Chemotherapy: chemicals used in primary, adjuvant tx Primary mechanism: cell cycle impairment • Common chemotherapeutic drugs (antineoplastic agents): o Alkylating agents: cisplatin, cyclophosphamide o Antimetabolites: mercaptopurine, azathioprine o Plant alkaloids: vincristine (from vinca, paclitaxel (from Pacific yew), docetaxel Adverse effects • Myelosuppression: neutropenia, thrombocytopenia, anemia • Fatigue, N/V, diarrhea and malabsorption appetite loss • Mucositis, painful swallowing, altered taste and smell • Xerostomia, dysphagia • Alopecia
• Why is it not often as simple as modifying the diet according to detection of a single genotype?
o Chronic diseases are polygenic and highly affected by lifestyle factors
• What types/classes of antiretroviral drugs are on the market to treat HIV?
o Classes of antiretroviral drugs Reverse transcriptase inhibitors Protease inhibitors Entry inhibitors • Fusion inhibitor • CCR5 (co-receptor) antagonist Integrase inhibitor Post attachment inhibitor Combination drugs
Diagnostic testing for HIV
o Diagnosis testing Dried blood/oral fluid samples • Test for antibodies against HIV in blood or serum ... cannot detect early. Detects in ~99% individuals infected >12 week. False positives possible, • Follow up: if possible, generally rechecked and then verified by Western blot (detects HIV antibodies) confirmed HIV Blood/serum: • Antibody.antigen combination immunoassay to detect: HIV-1 Ab, HIV-2 Ab, HIV-1 p24 (recommended initial diagnostic test) • Follow up: if positive, immunoassay to differentiate HIV-1 from HIV-2. o If negative/indeterminate HIV-1 nucleic acid test (NAT) to confirm acute infection
How many genes does HIV have?
o HIV genome that contains 9 genes that code 15 vital proteins
• How is HIV transmitted?
o How is HIV transmitted? Via sharing blood or body fluids • 1. Unprotected sex • 2. Blood and blood products: needle sharing, needle stick injury, contaminated equipment o blood transfusions a rare cause in developed countries due to careful screening of donor blood since early days of the epidemic
What is HIV
o Human Immunodefciency Virus
• Cancer diagnosis: What are techniques used in cancer dx?
o Imaging: MRI, CT, xray, ultrasound, mammograms, endoscopy, etc o Biopsy: Sample of tumor to determine tissue type, primary site, potential for recurrence, extent of disease o Biochemical tests (blood, urine) to detect tumor biomarkers such as PSA o Mammogram results with normal fatty breast tissue
what are some of the typical side effects and nutrition intervention strategies that may be employed to address them?
o N/V Chemo: usually at 24 hours and lasting up to a week (emetogenic potential) Radiation, effect varies by site: TBI (100%), head (10-30%) abdomen varies Narcostics (morphine, codeine) to minimize pain Odors can trigger • Cook w. microwave or open windows • Minimize frying • Leave whole food are cooking • Eat, cold, dry foods • Ask family/friends to avoid perfume Delayed gastric emptying ... smell frequent meals may help Avoid friend, greasy, favorite foods when nauseous Beverages for hydration: Gatorade, boost (formerly resource) breeze, ensure clear, no-acidic fruit juices and nectars Anti-emetic medications 30-45 minutes before meals • 5-HT3 receptor antgonists: granisetron, ondansetron, dolasetron, polonsetron • corticosteroids: short-term in combination with other anti-emetics • cannabinoids: dronabinol (marinol) nabolone (cesamet) non-pharmacological approaches o Dysgeusia Causes: tumor, chemotx, irradiation Increases perception of sweet, sour, salty tastes • Avoid sweet foods, i.e sweet nutritional supplements • Try yogurt, juice-based drinks, or sweetened supplements Metallic taste often with cisplatin - metals (ans, utensils) red meats not tolerated • Plastic utensils • Protein foods: cheese, cottage cheese, peanut butter, poultry soy-based meat substitutes Hypogeusia, ageusia • Add spices, marinades, flavorings to foods o Xerostomia Causes: radiation to head and neck, chemotherapy, dehydration, some medications Moist foods, liquids tolerated best No dry foods Artificial saliva Oral lubricants: gels, lozenges, mouthwashes Sour candies, sugar-free gum may increase saliva o Diarrhea, malabsorption, dehydration Cause: chemotherapy Antidiarrheal agents: lomotil, loperamide (Imodium) Small amounts of fluid throughout day to prevent dehydration o Mucositis: Cause: chemotx, radiation, GVHD: painful inflammation, ulceration of mucous membranes in GI tract, risk of oral infections • Good oral hygiene prevents infection • Small, frequent, bland meals without dry or crusty foods, raw fruits and vegetables • Soft or liquid non-acidic foods • Chilled foods, fluids (popsicles frozen yogurt, etc) • Salt water rinses or "magic mouthwash" • Avoid very salty or sugary foods • Avoid hot foods • Avoid acidic foods, carbonated sodas, alcohol, tobacco • Maintain hydration o Neutropenia ... emphasize safe, well-cooked foods o Anorexia Causes: cytokines and hormones, depression, therapy side effects, food aversions, side effects of medications, fatigue Most common in GI cancers, head and neck cancers, lung cancer Small, frequent, nutrient dense meals High kcal, high protein nutrition supplements may be helpful Physical activity Pharmaceutical assistance for anorexia,: megestrol acetate (Megace) corticosteroids
Neutrogenomics
o Neutrogenomics refers to the application of genomics in nutrition research, enabling associations to be made between specific nutrients and genetic factors the way in which good or food ingredients influence gene expression... nutrigenomics should facilitate greater understanding of how nutrition affects metabolic pathways and how this process goes awry in diet-related diseases
• How might this relate to cancer cachexia? How does the tumor (at a very basic level) contribute to cachexia?
o New evidence suggests that maintenance of a minimum of adipose tissue may be of benefit for long-term survival o In mice study - mice who progressively lost most of adipose tissue increased tumor number by 2.5x o When adipose tissue was maintained within a normal range, tumor number did not increase o Patients with cancer-related cachexia experienced prolonged survival with nutritional intervention and this improved outcome was significantly correlated with increased body fat o Body fat is lost more rapidly than skeletal muscle in cancer patients suffering form cachexia and the level of whole body fat significantly predicts survival, whereas lean tissue does not necessarily
Nutrigenetics
o Nutrigenetics - embodies the science of identifying and characterizing gene variants associated with differential responses to nutrients, and relating this variation to disease states"
Nutritional genomics
o Nutritional genomics: Study of how different foods can interact with particular genes to modify the risk of diseases such as type 2 diabetes, obesity, heart disease and some cancers
What is P24
o P24 is a component of the HIV particle capsid
• How do the genome/epigenome contribute to cancer development (think in terms of the cell cycle, p53, for example)? (see transcript from prerecorded cancer presentation
o P53 is guardian of the genome and tumor suppressor acting to prevent cancer if P53 is damaged or mutated then cancer can result
HIV statistics
o People currently infected w/ HIV: 36.9 million o New cases each year: 1.8 million o Deaths/year: 940,000 people o Prevalence changing over time: decreasing by 18% Why: The Initiative targeted resoures to 48 highest burden counties where over 50% of new diagnoses occur Who is most affected: Africa (eastern and southern)
• Are there potential benefits to the consumer with regard to nutritional genomics practice? • Consider the state of DTC testing - what has been happening there?
o Potential benefits Increased focus on a healthy diet and lifestyle Motivate positive behavior change Increased awareness of risk of certain conditions Improved health and quality of life Focus on prevention Decreased morbidity and premature mortality Reduced health care costs Identify subgroups who might be particularly responsive or resistant to environmental (dietary) intervention Better understanding of the mechanisms involved in disease susceptibility
• Are there risk/harms to the consumer with regard to nutritional genomics practice? • Consider the state of DTC testing - what has been happening there?
o Potential risks Tests may mislead consumers by making unsound and ambiguous predictions about health risks Test results frequently include recommendations for the purchase of expensive personalized dietary supplements Risk predictions differed among companies Risk predictions differed within a single report from one company Attention drawn away from other modifiable risk factors Misleading claims based on insufficient research Dilution or contraindication of public health messages Confidentiality not guaranteed Discrimination potential - life insurance, LTC insurance, etc o MCT testing currently provides little info that can meaningfully inform personalized lifestyle change and it is unclear how consumers in general will respond to personalized genomic testing
Radiation therapy
o Radiation therapy Linear accelerator: administers external radiation therapy, in which radiation is delivered to cancer inside the body or on the surface of the skin • External radiation therapy: o Imaging used to specifically target the tumor o Painless treatment for a few minutes daily over several weeks o Side effects depend on area targeted Internal radiation therapy a radioactive substance is sealed inside a smell implant such as a capsule or needle. The implant is placed directly into the tumor or into a body cavity Mechanism: destruction of DNA cell death Adverse effects • Head and neck o Sore mouth and throat o Dysphagia: impaired swallowing o Mucositis: inflammation of mucous membranes o Xerostomia (dry mouth) o Altered taste and smell o Severe dental and gum disease • Thorax o Esophagitis w/ dysphagia, esophageal stricture • Abdomen o N/V diarrhea o Radiation-induced enteritis, gastritis Malabsorption May lead to ulceration, obstruction, bowel resection, SBS
• According to the CDC (as of 2014), when should individuals begin antiretroviral therapy?
o When to begin antiretrovital therapy Adults and adolescents: <500 CD4 cells/mm3 Children: <5: all Pregnant women: al People coinfected w/TB and HIV: ALL People coinfected w/ HIV and Hep B: All w. chronic severe liver disease Serodiscordant couples: all
What are nutritional goals (including Dr. Whelan's #6 and #7), issues, and appropriate interventions during active treatment and recovery?
o prevent/resolve nutritional deficiencies o achieve/maintain healthy weight (including adipose tissue) o reserve lean body mass o minimize nutritionally-related side effects of the treatment o maximize quality of life o don't allow the cancer to progress by working with standard therapies o maximize survival of the patient
What kinds of criteria are included in these screening tools?
• Adult oncology patients should be screened using malnutrition screening tool validated in the setting in which the tool is intended for use (rating: strong, imperative) o In patient Malnutrition screening tool (MST) • Unintended weight loss? o If yes, how much? • Have you been eating poorly b/c decreased appetite Malnutrition screening tool for cancer patients (MSTC) • Intake change • Weight loss • ECOG performance • BMI Malnutrition universal screening tool (MUST) • BMI • Unplanned weight loss in past 3-6 months • Acutely ill and there has been or in likely to ne no nutritional intake for >5 days o Outpatient MST • RDNs should use an assessment tool validated in the setting in which the tool is intended for use as part of the complete nutrition assessment (rating strong, imperative) o Patient generated-subjective global assessment (PG-SGA) Weight (current, last month. 6 months ago) Food intake Symptoms Activities and function Disease Metabolic demand physical o Subjective global assessment (SGA
Why is malnutrition screening important in oncology patients - think about potential impacts of malnutrition
• Cachexia - harder to see in overweight and obese patients • 50% of cancer patients are at risk of malnutrition
o Be a healthy weight: Which cancers are associated with body fatness, particularly adult body fatness?
• Decreases risk (in young adulthood and adulthood) premenopausal breast cancer • Decreases risk in young adulthood - postmenopausal breast cancer • Increases risk: mouth, esophagus, stomach, pancreas, gallbladder, lung, colorectal, ovary, endometrium, pancreas
What do we know about FTO genotype and relationship to obesity as well as apparent responsiveness to weight loss interventions? What are clinical implications if any? Do you think knowing FTO genotype would be helpful in individualizing weight loss interventions or are we still lacking sufficient evidence to modify approach?
• FTO (fat mass and obesity-associated) gene o Expressed in hypothalamus; associated w/ food intake regulation o Variants linked to obesity TT- lower risk TA-intermediate risk AA-higher risk o AA genotype Higher food/energy intake: ~125-280 kcals/d Lower hunger/satiety response after eating Higher BMI (~0.35 kg/m2 per allele) Highest tertile fat/lowest tertile carbohydrate associated w. higher obesity risk in those with high risk FTO alley • Data suggests adults homozygous for the FTO obesity risk allele (AA) may lose more weight in response to diet and lifestyle interventions • Clinical application of this information remains unclear
What kind of outcomes have "early and intensive MNT" improved in oncology patients undergoing CT and RT
• Higher energy and protein intake • Weight gain/weight and LBM preservation • Enhanced quality of life • Reduced hospital admissions and LOS • Better appetite • Better treatment tolerance
Consider examples from the ATBC study -- what did we learn from that experiment? How is it reflected in the WCRF matrix?
• Higher incidence of cancer in group supplemented w/ beta- carotene especially in lung • WCRF matrix also says that it increases risk
What are the five morbidity/mortality outcomes for which there is strong evidence of association with poor nutritional status?
• Higher rates of hospital admissions and readmissions • Greater LOS • Lower Quality of life • Mortality • Lower tolerance of radiation therapy and chemotherapy treatments
Does alcohol play a potential role in oral cancer and breast cancer as explored in the two case study presentations
• Increases risk for development and breast cancer recurrence
What is the combined role of alcohol and smoking (based on Million Women study data)? We also see this in the oral cancer case. How does the risk (think Million Women study and relationship for every 10 g of alcohol intake) relate to the recommendation for limiting daily intake (amount)?
• Smoking and alcohol increases risk o Smoking severely increases risk • Drink as little as possible
Also consider what was observed in the SELECT study with vitamin E supplementation for prostate cancer prevention. What is the lesson learned/the take home message here?
• Vitamin E supplementation increase risk of prostate cancer diagnosis
What does the evidence analysis show and what is recommended regarding dietary supplements or MFS containing EPA
• Weight preservation or weight gain • LBM preservation or gain
