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Effects of a high-protein, increased-fibre, dry diet supplemented with omega-3 fatty acids on quality of life in dogs undergoing chemotherapy
Abstract
Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double‐blinded, multicenter clinical trial to investigate a high‐protein, increased‐fibre diet supplemented with omega‐3 fatty acids, for dogs with cancer undergoing standard‐of‐care chemotherapy. Client‐owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non‐resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet ( n = 24) or control diet ( n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C‐reactive protein and monocyte chemoattractant protein‐1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for ‘frequency of signs of illness’ ( P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted.
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Chemotherapy is a commonly integrated treatment option within human and animal oncology regimes. Limited research has investigated pet owners’ treatment decision-making in animals diagnosed with malignant neoplasia. Dog and cat owners were asked to complete an online questionnaire to elucidate factors which are key to the decision making process. Seventy-eight respondents completed the questionnaire in full. Fifty-eight percent of pet owners would not elect to treat pets with chemotherapy due to the negative impact of the associated side effects. Seventy-two percent of respondents over estimated pet survival time post chemotherapy, indicating a general perception that it would lead to remission or a cure. Vomiting was considered an acceptable side effect but inappetence, weight loss and depression were considered unacceptable. Owners did expect animals’ to be less active, sleep more and play less, but common side effects were not rated as acceptable despite the potential benefits of chemotherapy. Based on the results, veterinary teams involved with oncology consultations should establish if clients have prior experience of cancer treatments and their expectations of survival time. Quality of life assessments should also be implemented during initial oncology consultations and conducted regularly during chemotherapy courses to inform client decision making and to safe guard animal welfare.
Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy. Previous reports showed that suppression of nuclear factor-κB, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. In this review, we have collected the available clinical data on the therapeutic role of omega-3 FAs against breast cancer, colorectal cancer, leukemia, gastric cancer, pancreatic cancer, esophageal cancer, prostate cancer, lung cancer, head and neck cancer, as well as cancer cachexia. We also discussed the chemistry, dietary source, and bioavailability of omega-3 FAs, and the potential molecular mechanisms of anticancer and adverse effects.
Objective:
To develop a quality of life (QOL) survey for use in a canine cancer chemotherapy setting, validate the instrument's utility, identify key questions that facilitate client and clinician communication regarding decisions in patient care, and use human and veterinary QOL literature to develop a comprehensive yet simple proxy survey instrument.
Design:
Survey.
Animals:
29 canine chemotherapy patients.
Procedures:
Patients were evaluated by both owners and veterinarians at the time of initial visit to the clinic and at 3 and 6 weeks after the initiation of chemotherapy. This survey consisted of a longitudinal evaluation of QOL with 6 components addressing the animal's QOL retrospectively, before onset of cancer; changes in the animal's QOL since manifestation of disease; changes in the animal's QOL with regard to treatment response; owner's QOL and its impact on priorities in decision making; clinician's impression of the owner's priorities and QOL; and clinician's impression of the dog's QOL.
Results:
Multiple regression analysis indicated 3 significant predictors of canine cancer patient QOL to be play behaviors, signs of illness, and canine happiness as perceived by owners.
Conclusions and clinical relevance:
The QOL instrument was easy to use and enhanced client perception of patient care and clinician concern. Owners enjoyed the opportunity to complete the survey. Since questions regarding play behaviors, clinical signs of disease, and canine happiness were significant indicators of changes in QOL, these should be included in future studies. Quality of life assessment may facilitate treatment decisions and assessment of canine patients undergoing chemotherapy.
To collect information on the cause of death and longevity of dogs owned by members of the numerically largest breed clubs of 169 UK Kennel Club-recognised breeds.
A cross-sectional study was carried out. Approximately 58,363 questionnaires were sent out to breed club members in 2004 (nine clubs failed to report the exact number of questionnaires sent out). Owners reported age at death and cause(s) of death for all dogs that had died within the previous 10 years.
A total of 13,741 questionnaires (24% response rate) containing information on 15,881 deaths were included in the analysis. Breed-specific response rates ranged from 64·7 to 4·5%. The median age at death was 11 years and 3 months (minimum=2 months, maximum=23 years and 5 months) and it varied by breed. The most common causes of death were cancer (n=4282, 27%), "old age" (n=2830, 18%) and cardiac conditions (n=1770, 11%). Clinical
This survey shows breed differences in lifespan and causes of death, and the results support previous evidence that smaller breeds tend to have longer lifespan compared with larger breeds. Although many of the breeds in the study may not be representative of the general pedigree dog population in the UK, the results do contribute to the limited information currently available.
Five ileal-cannulated adult dogs were utilized in a 5 x 5 Latin square design to determine the effects of fructan type and concentration on nutrient digestibility, stool metabolite concentrations, and fecal microbiota. Five diets were evaluated that contained cellulose alone or with inulin or short-chain fructooligosaccharides (scFOS) each at 0.2 or 0.4% of the diet. Dogs were fed 175 g of their assigned diet twice daily. Chromic oxide served as a digestibility marker. Nutrient digestibility; ileal and fecal pH and ammonia concentrations; ileal IgA concentrations; and fecal short- and branched-chain fatty acid concentrations, microbiota, and concentrations of phenol, indole, and biogenic amines were measured. No differences were observed in ileal pH or ammonia or fecal concentrations of indole or valerate. Ileal DM, OM, and CP digestibility coefficients; total tract DM and OM digestibility coefficients; and fecal concentrations of phenylethylamine increased linearly (P < 0.05), and fecal concentrations of phenol decreased linearly (P < 0.05) with inulin supplementation. Fecal concentrations of acetate, propionate, and total short-chain fatty acids decreased quadratically (P < 0.05) with inulin supplementation. Ileal DM, OM, and CP digestibility coefficients increased linearly (P < 0.05), and fecal phenol concentration decreased linearly (P < 0.05) with scFOS supplementation. Total tract DM and OM digestibility coefficients as well as fecal butyrate and isobutyrate concentrations increased quadratically (P < 0.05) with scFOS supplementation. Although a greater level of inclusion is needed to modify gut microbiota populations, low-level inclusion of inulin or scFOS is effective in modifying key nutritional outcomes in the dog.
Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago. How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo.
To describe the relative importance of pets' quality versus quantity of life among owners of dogs with heart disease.
Prospective questionnaire-based clinical study.
Owners of 201 dogs with heart disease.
Owners each completed a questionnaire that was designed to ascertain the relative importance of quality versus quantity of life for their pet and to assess the owners' willingness to trade survival time for quality of life, if that were possible. Analyses were performed to evaluate factors associated with owner willingness to trade time for quality of life.
Most owners (170/197 [86%]) were willing to trade survival time for quality of life for their heart disease-affected dogs; of those owners, 88 (52%) were willing to trade 6 months. Owners were highly concerned with detection of perceived pet suffering and their pet's ability to interact with them. Owners whose pets had respiratory difficulty or fainting episodes and were treated on an outpatient basis had a greater willingness to trade survival time than owners of dogs that were treated on an emergency basis. Among owners willing to trade time for quality of life, younger owners and those whose pets had fainting episodes were willing to trade the most amount of time.
Results indicated that quality of life is highly important to owners of dogs with heart disease. Owners' priorities partly depend on owner age and the pet's clinical circumstances; ongoing client-veterinarian communication is important to optimize treatment success as perceived by owners.
In humans, multiple cytokines have been linked to the development of lymphoma, and are relevant biomarkers for response to chemotherapy and prognosis. In contrast, only a few circulating cytokines have been studied in dogs with lymphoma. We prospectively enrolled thirty-one dogs newly diagnosed with multicentric lymphoma. Immunophenotype was determined by flow cytometry in all dogs, separating them into 2 subgroups: B cell lymphoma (n = 21) and T cell lymphoma (n = 10). Nineteen healthy dogs were enrolled in the control group. Circulating cytokine concentrations were measured using a commercial canine multiplex magnetic bead-based assay which included Interleukin-2 (IL-2), IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), Tumor Necrosis Factor-α (TNF-α), Interferon γ (IFN-γ), IFN-γ induced Protein-10 (IP-10), Keratinocyte Chemoattractant-like (KC-like), and Monocyte Chemoattractant Protein-1 (MCP-1). The serum levels of each cytokine were first compared between the lymphoma and control groups, and then between the B cell lymphoma, T cell lymphoma, and control groups. There was no significant difference between the lymphoma and healthy control groups regarding sex, age and weight. MCP-1, IL-6, and IL-10 were significantly higher in dogs with lymphoma compared to healthy dogs (p < 0.01, p = 0.01 and p = 0.03, respectively). MCP-1 and IL-10 were significantly higher in the B cell lymphoma group than in the healthy group (p = 0.01, p = 0.01, respectively). MCP-1 and IL-6 levels were significantly higher in the T cell lymphoma group than in the healthy group (p = 0.02, p < 0.01, respectively). IL-6 was significantly higher in the T cell lymphoma group than in the B cell lymphoma group (p = 0.03). Significant differences among the groups were found for IL-15 and KC-like, but they were affected by age and/or sex. There were no significant differences in serum IL-2, IL-7, IL-8, IL-18, GM-CSF, TNF-α, IFN-γ, and IP-10 between any of the groups. Significant differences in red blood cell, white blood cell, neutrophil, lymphocyte and monocyte counts were also found between the different groups of dogs. Our data showed different serum cytokine and peripheral blood cell profiles between dogs with lymphoma and healthy dogs, and between dogs with B cell and T cell lymphoma. Further study is necessary to investigate the role of these cytokines in lymphoma pathogenesis, response to treatment, and prognosis, and the influence of age, sex and blood cell counts on their expression.
Objectives:
To investigate owner attitudes and dietary practices following cancer diagnosis in a dog.
Methods:
A retrospective cross-sectional survey of 75 dog owners presenting with their dogs to a tertiary referral oncology service through a demographic questionnaire and in-person or telephone interviews regarding the dog's nutrition.
Results:
Conventional diets (71%) were most commonly fed as a single diet to canine cancer patients followed by homemade cooked (7%) and homemade raw (4%). Several owners (18%) provided combinations of these diets. Owners reported some distrust towards conventional diets (51%). Appetite loss occurred in 35% of dogs and diet changes reported for 25% of dogs in the study involved exclusion of a conventional (63%) and/or inclusion of a homemade (54%) component. 90% of owners noted the diet change was associated with the cancer diagnosis. Supplements were given by 39% of owners. 85% of owners highly valued veterinary nutritional advice.
Clinical relevance:
Following a cancer diagnosis, dog owners appear to change their approach to managing their dog's nutrition. Given the value owners place on veterinary nutritional advice, veterinarians have a key role in guiding nutritional management of the canine cancer patient.
BACKGROUND
Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. This double-blind, randomized study was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease free interval and survival time for dogs treated for lymphoblastic lymphoma with doxorubicin chemotherapy.METHODS
Thirty-two dogs with lymphoma were randomized to receive one of two diets supplemented with menhaden fish oil and arginine (experimental diet) or an otherwise identical diet supplemented with soybean oil (control diet). Diets were fed before and after remission was attained with up to five dosages of doxorubicin. Parameters examined included blood concentrations of glucose, lactic acid, and insulin in response to glucose and diet tolerance tests; alpha-1 acid glycoprotein; tumor necrosis factor; interleukin-6; body weight; amino acid profiles; resting energy expenditure; disease free interval (DFI); survival time (ST); and clinical performance scores.RESULTSDogs fed the experimental diet had significantly (P < 0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) compared with controls. Higher serum levels of C22:6 and C20:5 were associated with lesser (P < 0.05) plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22:6 levels were significantly (P < 0.05) associated with longer DFI and ST for dogs with Stage III lymphoma fed the experimental diet.CONCLUSIONS
Fatty acids of the n-3 series normalize elevated blood lactic acid in a dose-dependent manner, resulting in an increase in DFI and ST for dogs with lymphoma. Cancer 2000;88:1916–28. © 2000 American Cancer Society.
Objectives Careful assessment of the nutritional needs of cats and dogs must be taken into consideration in order to maintain optimum health, be part of a treatment regimen for a diseased state, or to maximize the quality of life in all animals. The goal of these World Small Animal Veterinary Association (WSAVA) Guidelines is that a nutritional assessment and specific nutritional recommendation is made for every patient on every visit. This will become known as the 5th Vital Assessment (5VA), following the four vital assessments of temperature, pulse, respiration and pain that are already addressed on each patient interaction.
Evaluation of nutritional status A brief screening evaluation of nutritional status can be routinely and seamlessly performed during the history-taking and physical examination of every patient. Nutrition-related risk factors that can be easily identified from the history and physical examination include age (growing or old), suboptimal body condition score (overweight or thin), muscle loss, atypical or homemade diet, medical conditions or changes in appetite. An extended evaluation would follow if one or more risk factors is identified on screening. These guidelines provide criteria with which to evaluate the animal and the diet, as well as key feeding and environmental factors. In addition, recommendations for interpretation, analysis and action are included so that a plan for optimizing the animal's nutritional status can be instituted.
Team approach Client compliance with nutritional recommendations requires input from the veterinarian, veterinary technicians/nurses and hospital staff. A team approach to continuous nutritional education, implementation of appropriate protocols, and focused client communication, utilizing these WSAVA Nutritional Assessment Guidelines, is key to reaching this 5VA goal.
Eighty-three cutaneous mast cell tumors in the dog were classified morphologically into three grades. The neoplasms were excised surgically, and the dogs were followed for 1500 days. Comparison of morphologic grade of tumor with survival time revealed significant differences among the three groups (p less than 0.00010). Comparison of sex and age (above and below ten years) with morphologic grade of tumor revealed no significant differences.
Cancer-caused cachexia has been reported to be caused in part by an increase in energy expenditure, and diets with nutrient profiles containing 30-50% nonprotein calories as fat instead of carbohydrate may exacerbate this state of inefficient energy utilization.
Indirect calorimetry was performed on 22 dogs with high-grade lymphoblastic lymphoma that were randomized into a blind study and fed isocaloric amounts of a high-fat diet (Diet A) or a high-carbohydrate diet (Diet B) before and after remission was attained with up to five doses of doxorubicin chemotherapy (30 mg/m2 intravenously). Indirect calorimetry was also performed on 30 normal dogs for comparison.
During the initial evaluation period, the resting energy expenditure (REE/kg0.75, P < 0.05) and respiratory quotient (RQ, P < 0.05) were significantly lower than in the controls. Six weeks after the start of the study, the REE/kg0.75 and oxygen consumption (VO2/kg0.75) were significantly (P < 0.05) lower in both groups of dogs with lymphoma compared with the controls. The RQ determined 6 weeks after the start of the study for the dogs fed Diet A was significantly (P < 0.05) lower compared with that in the controls evaluated at the same time. When the two groups of dogs with lymphoma were compared with each other, there was no significant difference in any of the outcomes. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group fed Diet A after the third evaluation period compared with the second evaluation. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group given Diet B at the fourth evaluation period compared with the fifth.
These data suggest that energy expenditure of dogs with lymphoma decreases transiently in response to chemotherapy and remission, but these values are less than those determined in normal dogs and not altered significantly by diet.
A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.
Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. This double-blind, randomized study was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease free interval and survival time for dogs treated for lymphoblastic lymphoma with doxorubicin chemotherapy.
Thirty-two dogs with lymphoma were randomized to receive one of two diets supplemented with menhaden fish oil and arginine (experimental diet) or an otherwise identical diet supplemented with soybean oil (control diet). Diets were fed before and after remission was attained with up to five dosages of doxorubicin. Parameters examined included blood concentrations of glucose, lactic acid, and insulin in response to glucose and diet tolerance tests; alpha-1 acid glycoprotein; tumor necrosis factor; interleukin-6; body weight; amino acid profiles; resting energy expenditure; disease free interval (DFI); survival time (ST); and clinical performance scores.
Dogs fed the experimental diet had significantly (P < 0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) compared with controls. Higher serum levels of C22:6 and C20:5 were associated with lesser (P < 0.05) plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22:6 levels were significantly (P < 0.05) associated with longer DFI and ST for dogs with Stage III lymphoma fed the experimental diet.
Fatty acids of the n-3 series normalize elevated blood lactic acid in a dose-dependent manner, resulting in an increase in DFI and ST for dogs with lymphoma.
The final necropsy diagnoses, obtained between 1985 and 1999, were compared among 1,206 golden retrievers, boxers, German shepherd dogs, Labrador retrievers, and rottweilers. A significantly larger proportion of boxers and golden retrievers died of neoplastic disease than the other three breeds. The ages at death were not significantly different among golden retrievers, German shepherd dogs, and Labrador retrievers. However, rottweilers and boxers died at a younger age from both neoplastic and nonneoplastic diseases. Although boxers were already known to be at a higher risk for neoplasia, a similar index of suspicion for neoplasia should now be used for golden retrievers.
In this experiment, three concentrations (0.3, 0.6, and 0.9% of diet, as-fed basis) of two fructans, oligofructose (OF) and inulin, were tested against a 0% supplemental fructan control. Seven ileal-cannulated adult female dogs were fed a meat-based, kibbled diet and assigned to treatments in a 7 x 7 Latin square design. Dietary supplementation of fructans had no effect on nutrient intakes or ileal digestibilities. Total-tract digestibilities of DM, OM, and CP decreased (P < 0.05) as a result of dietary OF and inulin supplementation. Dogs fed the control diet had a DM total-tract digestibility of 83.0%. The percentages of fecal DM for dogs fed the control and 0.3, 0.6, and 0.9% OF were 36.6, 33.3, 32.8, and 31.7%, respectively. When compared with the control, OF (P < 0.01) and inulin (P < 0.01) supplementation increased fecal ammonia concentrations. Higher fecal short-chain fatty acid (SCFA; P < 0.10) and isovalerate concentrations (P < 0.01) were noted for dogs fed both fructans. Total fecal SCFA for dogs fed the control diet and 0.3, 0.6, and 0.9% OF were 406.4, 529.9, 538.3, and 568.8 micromol/g of feces (DM basis), respectively. Dogs fed 0.3, 0.6, and 0.9% inulin had total fecal SCFA of 472.2, 468.8, and 471.5 micromol/g of feces (DM basis), respectively. Linear increases were observed in putrescine (P < 0.11), cadaverine (P < 0.07), spermidine (P < 0.12), and total amines (P < 0.05) in feces of dogs fed OF. Lower fecal phenol (P < 0.08) and total phenol (P < 0.04) concentrations occurred in dogs fed inulin, along with a linear decrease (P < 0.08) in total phenols with OF supplementation. Total fecal phenols for dogs fed the control, 0.3, 0.6, and 0.9% inulin were 3.03, 1.86, 1.97, and 2.23 micromol/g of feces (DM basis), respectively. Low-level dietary inclusion of inulin and OF positively affected indices known to be associated with gut health of the dog without seriously compromising nutrient digestibility or stool quality. Overall, the 0.9% OF treatment resulted in the best responses, including no adverse effect on nutrient intakes, ileal digestibilities, or stool quality, as well as increased fecal SCFA and decreased fecal phenols. The biological responses due to inulin were more variable.
Criteria for designation of clinical substage in canine lymphoma: a survey of veterinary oncologists
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Veterinary cooperative oncology group -common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1
Veterinary cooperative oncology group -common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or
biological antineoplastic therapy in dogs and cats v1.1. Vet Comp
Oncol. 2016;14:417-446.