Anorexia In Cancer Research Articles

Growth differentiation factor 15 (GDF15) elevation in children with newly diagnosed cancer.

Growth differentiation factor 15 (GDF15), an inflammatory marker and mediator of adult cancer cachexia, remains largely unexplored in children. GDF15 increases nausea, vomiting, and anorexia in cancer and contributes to malnutrition, with the potential to be a cachexia therapeutic target. No studies have examined GDF15 in children with newly diagnosed cancer. Our pilot study compares GDF15 in children with newly diagnosed cancer to age- and sex-matched controls and correlates levels with anthropometric measurements and quality of life (QOL). Children with newly diagnosed cancer aged 2-21 years were enrolled with serum GDF15 ELISA, anthropometric measures [height, weight, and mid-upper arm circumference (MUAC)], and QOL assessments (using PedsQL™ Core and Gastrointestinal Modules), which were collected at baseline and repeated 3 months later. Serum GDF15 levels were obtained from age- and sex-matched controls for comparison. A total of 57 participants enrolled (N=30, cancer group; N=27, control group) with a median age of 8.8 years (IQR 5.6-15.9 years). The participants were primarily male (54.4%), white (82.5%), and non-Hispanic (82.5%). Cancer diagnoses included acute lymphoblastic leukemia (N=8), lymphoma (N=8), neuroblastoma (N=5), soft tissue tumors (N=4), acute myeloid leukemia (N=2), and single participants with brain, kidney, and bone tumors. Baseline GDF15 was higher in the cancer cohort compared to the control cohort (median=614.6pg/mL and 320.5pg/mL, respectively; p<0.001). When examining participants with evaluable baseline and 3-month follow-up GDF15 levels (N=18), GDF15 was not statistically different (median=657.1pg/mL and 675.3pg/mL, respectively; p=0.702). A total of 13 of the 30 participants and 21 caregivers completed the PedsQL™ Core and Gastrointestinal symptom modules. QOL scores did not differ significantly at 3-month follow-up compared to baseline, but diarrhea worsened (p=0.017). Median participant response for diarrhea at baseline was 92.9 (IQR=92.9-96.4; N=13), which was significantly better than the follow-up (median=78.6; IQR= 71.4-92.9; p=0.017). There were no correlations between change in height, weight, or MUAC and change in GDF15 levels (p=0.351, 0.920, and 0.269 respectively). GDF15 was elevated in children with cancer at diagnosis compared to controls but did not correlate with anthropometric measurements or QOL. This pilot study will inform future prospective studies to better describe the natural history of GDF15 and its role in cachexia and as a potential therapeutic target.

Evaluation of Anorexia in Cancer and Its Association with Autonomic Nervous System Activity Assessed by Heart Rate Variability

Alterations in the central nervous system in cancer patients are pivotal in determining appetite dysregulation and body weight loss (BWL). Autonomic nervous system activity was tested by measuring heart rate variability (HRV) in cancer patients presenting with anorexia. We considered inpatients with different types of cancer and investigated anorexia using their FAACT scores. HRV was evaluated by a three-channel Holter ECG. The domains of low frequencies (LF, sympathetic activity) and high frequencies (HF, parasympathetic activity) were calculated. Also, SDNN (autonomic activity) and RMSSD (parasympathetic activity) were assessed. We enrolled 56 patients with cancer and 23 controls. In cancer patients, RMSSD and SDNN were lower than in controls (p &lt; 0.001 and p = 0.009). Sympathetic activity (LF nu) was lower in cancer patients than in controls (p = 0.023), including sympathovagal balance (LF/HF nu ratio) (p = 0.025). RMSSD was reduced in anorexic (p &lt; 0.001) and non-anorexic (p = 0.003) cancer patients compared to controls. The SDNN was lower in anorexic cancer patients than in non-anorexic cancer patients (p = 0.025), and it was lower in anorexic cancer patients than in controls (p = 0.001). LF nu was lower in anorexic cancer patients than in controls (p = 0.015), as was LF/HF (p = 0.031). SDNN was negatively correlated with BWL in the cancer group (rho = −0.40; p = 0.007). Our data support the hypothesis that autonomic nervous system dysregulation exists in patients with cancer presenting with anorexia, with implications for its diagnosis and treatment.

Kampo medicine bukuryoingohangekobokuto and ninjin'yoeitoyoeito as supportive care for management of anorexia and tightness of the esophagus in advanced esophageal cancer: A case report

• Kampo medicine can be used as supportive care for management of anorexia and tightness of the esophagus in advanced esophageal cancer. • Bukuryoingohangekobokuto improves the symptoms of tightness of the esophagus in advanced esophageal cancer. • Ninjin'yoeitoyoeito improves anorexia in advanced esophageal cancer.

Herbal medicines for anorexia in lung cancer: A protocol for systematic review and meta-analysis.

Introduction:Lung cancer is the leading cause of cancer-related death worldwide. Anorexia is the most common cause of malnutrition in lung cancer patients as well as an independent prognostic factor for cancer survival. This review will deal with the clinical evidence of herbal medicine use for reducing anorexia in lung cancer patients.Methods and analysis:Fourteen electronic databases will be searched from inception until October 2020. We will include randomized controlled trials (RCTs) assessing herbal medicines for anorexia in lung cancer patients. Interventions of any herbal medicines will be included. The methodological qualities of the included RCTs will be assessed via the Cochrane Collaboration tool for assessing the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument will be used to evaluate the confidence in the cumulative evidence.Ethics and dissemination:This systematic literature review does not require an ethics review. This review will be published in a peer-reviewed journal and disseminated electronically and in print. The review will be updated to inform and guide healthcare practices.Registration number:reviewregistry1038.

Cachexia and anorexia in cancer; a systematic review

The treatment strategy for cancer cachexia is based on the cachexia stage of the cancer and its phenotypes, therefore interventions and expected outcomes vary. In order for the patient to get the most out of the treatment, it should be done based on the mechanism of intervention and the quality of life of patients should be addressed, including aspects of rehabilitation and reduction of the patient’s suffering using a multidisciplinary team. Given the importance of the subject, the present study aims to investigate cachexia and anorexia in cancer. From the electronic databases, PubMed, Cochrane Library, Embase, Web of Sciences have been used to perform a systematic literature until 2020. Therefore, a software program (Endnote X8) has been utilized for managing electronic titles. Searches were performed with mesh terms. This review recommended that clinicians establish an interaction between cancer anorexia-cachexia syndrome (CACS) treatments and chronic pain treatments and choose the best treatment option.

Cannabinoids Dramatically Improve Symptoms of Refractory Gastroparesis

Introduction: Cannabinoids, primarily delta—9—tetrahydrocannabinol (THC) and cannabidiol (CBD), are increasingly used for medicinal purposes. Dronabinol, a THC analogue, is used for nausea, vomiting and anorexia in HIV and cancer. Medical marijuana in New York is permitted to treat neuropathy with severe nausea. Gastroparesis is a neuromuscular disorder that causes many difficult—to—treat symptoms. Neuropathy plays a large role in its pathogenesis. We showed that cannabinoids significantly improve symptoms in patients with refractory gastroparesis. Methods: The effects of cannabinoids on gastroparesis symptoms were assessed in 24 patients. All patients' symptoms were refractory to standard therapies for gastroparesis including dietary modification, medications (prokinetics, antiemetics, neuromodulators), endoscopic therapy, and some patients had gastric stimulators. Patients were prescribed either Dronabinol, medical cannabis, or both for symptom management. Patients who received both treatments were prescribed them sequentially (Dronabinol then marijuana) if Dronabinol did not adequately relieve symptoms. Medical marijuana was taken via vaporized inhalation or sublingual drops and prescribed as needed at varying THC: CBD ratios. Dosage of Dronabinol ranged from 2—10mg twice daily to four times daily. All patients completed a ‘Gastroparesis Cardinal Symptom Index’ (GCSI), a validated symptom index for gastroparesis, before and after treatment. Results: Six patients were prescribed Dronabinol, ten were prescribed marijuana and eight were prescribed Dronabinol then marijuana. Baseline patient characteristics were collected (Table 1). Paired sample T—tests were performed and statistically significant improvement in GCSI total symptom composite score was seen in patients who received either cannabinoid treatment (mean score difference of 14.097, CI 11.487—16.707; p—value < 0.001). Patients prescribed marijuana experienced statistically significant improvement in every symptom subgroup, while the Dronabinol group experienced statistically significant improvement in all symptom subgroups except ‘bloating/distention’ (Table 2, Figure 1).1203_A Figure 1. Patient baseline characteristicsConclusion: Our study shows that cannabinoids significantly improve symptoms of gastroparesis, which is a notoriously difficult condition to manage. Therapeutic options for gastroparesis are limited, so cannabinoids can play an important role in the treatment of the condition, especially in patients with refractory symptoms.1203_B Figure 2. Paired sample T—tests and differences of the mean for composite symptom score and symptom subgroup scores before and after cannabinoid treatment [abbreviations: SD = Standard Deviation; SER = Standard Error of Mean]1203_C Figure 3. Comparison of composite symptom score and symptom subgroup scores before and after cannabinoid treatment (either marijuana or Dronabinol), marijuana treatment alone, and Dronabinol treatment alone

Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer.

The true incidence of anorexia secondary to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and cancer is not well classified owing to the fact that there is a lack of standardized definitions and recent clinical data in these settings. Dronabinol, or Δ-9-tetrahydrocannabinol, is a synthetic molecule that closely mimics the action of Cannabis sativa L., a naturally occurring compound activated in the central nervous system by cannabinoid receptors. Dronabinol exerts its effects by directly acting on the vomiting and appetite control centers in the brain, which in turn increases appetite and prevents vomiting. In the USA, dronabinol is currently available in two dosage formulations – oral capsule and oral solution. While the oral capsule was initially approved by the US Food and Drug Administration in 1985, the recent approval of the oral solution in 2016 presents an “easy-to-swallow” alternative for patients using or intending to use dronabinol. Dronabinol is indicated in adult patients with HIV/AIDS for the treatment of anorexia and weight loss. However, there is no approved indication in the setting of cancer-related anorexia and weight loss. This review aims at presenting available data on the use of oral dronabinol in the management of anorexia and weight loss in HIV/AIDS and cancer, as well as characterizing and highlighting the pharmacotherapeutic considerations of the newest formulation of dronabinol.

Systematic review and meta-analysis of cannabinoids in palliative medicine.

We provide a systematic review and meta‐analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]: 0.2 95% confidence interval [CI]: [−0.66, 1.06] P = 0.65), appetite (SMD: 0.81 95% CI: [−1.14, 2.75]; P = 0.42), nausea/vomiting (SMD: 0.21 [−0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [−0.01, 0.16]; P = 0.07), or sleep problems (SMD: −0.09 95% CI: [−0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [−0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [−0.02; 0.08]; P = 0.23) or poor mental health (RD: −0.01 [−0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer‐associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.

Cannabinoids in Pain Management and Palliative Medicine.

There are conflicting interpretations of the evidence regarding the efficacy, tolerability, and safety of cannabinoids in pain management and palliative medicine. We conducted a systematic review (SR) of systematic reviews of randomized controlled trials (RCT) and prospective long-term observational studies of the use of cannabinoids in pain management and palliative medicine. Pertinent publications from January 2009 to January 2017 were retrieved by a selective search in the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and Medline. The methodological quality of the SRs was assessed with the AMSTAR instrument, and the clinical relevance of quantitative data syntheses was assessed according to the standards of the Cochrane Collaboration. Of the 750 publications identified, 11 SRs met the inclusion criteria; 3 of them were of high and 8 of moderate methodological quality. 2 prospective long-term observational studies with medical cannabis and 1 with tetrahydrocannabinol/cannabidiol spray (THC/CBD spray) were also analyzed. There is limited evidence for a benefit of THC/CBD spray in the treatment of neuropathic pain. There is inadequate evidence for any benefit of cannabinoids (dronabinol, nabilone, medical cannabis, or THC/CBD spray) to treat cancer pain, pain of rheumatic or gastrointestinal origin, or anorexia in cancer or AIDS. Treatment with cannabis-based medicines is associated with central nervous and psychiatric side effects. The public perception of the efficacy, tolerability, and safety of cannabis-based medicines in pain management and palliative medicine conflicts with the findings of systematic reviews and prospective observational studies conducted according to the standards of evidence-based medicine.

The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

1386O - Cancer cachexia (CAX), anorexia and muscle wasting (sarcopenia) assessment in non-small cell lung cancer (NSCLC): an observational study in 531 patients

1386O - Cancer cachexia (CAX), anorexia and muscle wasting (sarcopenia) assessment in non-small cell lung cancer (NSCLC): an observational study in 531 patients

Cancer anorexia: hypothalamic activity and its association with inflammation and appetite‐regulating peptides in lung cancer

BackgroundEnergy homeostasis is mediated by the hypothalamus, whose inflammation‐induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non‐anorexic (NA) cancer patients, and in controls (C).MethodsLung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)‐1, IL‐6, tumour necrosis factor (TNF)‐α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used.ResultsThirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all‐time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0–T1 than NA (−8.5% vs. −6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL‐1 and ghrelin (P < 0.001).ConclusionsHypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake.

Pathophysiology of anorexia in the cancer cachexia syndrome.

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

A mixed-methods qualitative research study to develop a complex intervention for weight loss and anorexia in advanced cancer: The Family Approach to Weight and Eating

Background: Worldwide, most people with incurable cancer experience weight loss and anorexia. These symptoms can distress patients and their family caregivers. Interventions that take account of the relationship between patient and family caregiver may improve outcomes for both members of this dyad. Aim: To report an example of process for the development of a complex intervention, the Family Approach to Weight and Eating. Design: A mixed-methods process informed by the Medical Research Council’s guidelines for developing a complex intervention was used to develop a psychosocial intervention for patients with incurable cancer and weight loss or poor appetite and their family caregivers and then to test for its feasibility, acceptability and perceived benefit. Setting: South of England in 2010/2011. Participants: A purposive sample of patient–family caregiver dyads under the care of a specialist community palliative care team. Patient participants had incurable cancer and were cachectic or at risk of cachexia. Results: The patient–family caregiver dyads comprised seven female and nine male patients (age range 41–84 years) and their carers. The emergent form of the Family Approach to Weight and Eating was found to aid family talk about food, feelings and reciprocity, without adverse consequences. Of the dyads, 15 reported benefits of the Family Approach to Weight and Eating. Three patient participants spoke of the approach evoking sadness and three carers of guilt. Conclusion: The Family Approach to Weight and Eating should now be tested in a pilot trial and the effect on emotional health outcomes in patients and their family caregivers evaluated.

Effect of Sipjeondaebo-tang on cancer-induced anorexia and cachexia in CT-26 tumor-bearing mice.

Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

A Phase II Study of an Herbal Decoction That Includes Astragali Radix for Cancer-Associated Anorexia in Patients With Advanced Cancer

Anorexia and cancer cachexia produce significant loss of adipose tissue and muscle mass and eventually reduce survival in cancer patients. This phase II study was conducted to assess the efficacy and the safety of an herbal decoction with Astragali radix in patients with anorexia in advanced cancer. All patients with histologic evidence of an incurable malignancy had a weight loss of at least 5% during the preceding 6 months and a patient-estimated severe anorexia.The herbal decoction was administered 30 minutes after meals, three times a day for 3 weeks.The score of appetite, body weight, the cytokines, IL-1beta, IL-6, TNF-alpha, and anthropometric measurements were assessed. For the assessment of anorexia, a visual analog scale (VAS: 0 mm = no anorexia, 100 mm = maximal anorexia) was used. Eleven patients were recruited from January, 2007 to January, 2009. The mean age was 59.8 years old. The change in anorexia from baseline with the herbal decoction was significantly different and anorexia was improved (anorexia VAS score, 60 mm vs. 40 mm, p = 0.008). The mean value of the maximal body weight was 55.6 kg and differed significantly from the 54.6 kg at baseline (p = 0.009). Changes in cytokine levels and anthropometric measurements from baseline to the 3rd week were not significant. All toxicities were manageable. Appetite and body weight were improved with the herbal decoction. This herbal decoction shows some potential for management of cancer-related anorexia.

Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer

Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.

Anorexia in cancer: role of feeding-regulatory peptides

Anorexia is one of the most common symptoms in advanced cancer and is a frequent cause of discomfort for cancer patients and their families. The pathogenesis of cancer anorexia is multi-factorial and involves most of the hypothalamic neuronal signalling pathways modulating energy homeostasis. It is considered to be the result of a failure of usual appetite and satiety signals. Loss of appetite can arise from decreased taste and smell of food, as well as from dysfunctional hypothalamic signalling pathways and cytokine production. Cytokines in particular, appear to play a key role in energy balance through persistent activation of the melanocortin system and inhibition of the neuropeptide Y pathway. The imbalance between anorexigenic and orexigenic peptides leads to suppression of appetite, and increased satiety and satiation associated with marked weight loss and decline in physical performance. High levels of serotonin also appear to contribute to these effects and recent findings implicate corticotropin-releasing factor in the pathogenesis of cancer anorexia as well. Despite significant advances in our understanding of the regulation of food intake and energy expenditure, few effective therapies are available. A better appreciation of the molecular and neuronal mechanisms that control body weight homeostasis may lead to the development of new therapies for improving the survival and quality of life of these patients.

Food intake and nutritional status in patients with newly detected gastric or colorectal cancer

The study of malnutrition and anorexia in cancer patients is hampered by a lack of practicable definitions for each entity. We therefore conceived definitions that would be practicable and would define malnourished and well-nourished cancer patients, and anorectic and non-anorectic patients. Nutritional assessment was performed using a Nutritional Index that considers serum albumin, total lymphocyte count and percentage ideal body weight. Malnutrition was considered present if nutritional index values were below the mean value of a previously investigated healthy, normal control group. Food intake was considered relative to usual food intake, while anorexia was defined to be present if actual total energy intake was 80% or less of usual intake. Employing the above definitions we prospectively studied 46 consecutive patients with gastric or colorectal cancer, admitted for surgical treatment of their malignancies. In this study malnutrition occurred as often in gastric cancer patients as in colorectal cancer patients. Anorexia occurred more frequently in gastric cancer patients than in colorectal cancer patients. The anorexia in gastric cancer appeared to be caused by many factors. Metabolic disorders seemed to play a major role in the development of malnutrition in colorectal cancer. The proposed definitions separated groups well, appeared practicable, but need further evaluation in larger patient groups. These definitions may allow further study of the pathogenesis of malnutrition in cancer patients.

Plasma tryptophan and anorexia in human cancer

A correlation between anorexia and brain levels of serotonin and trytophan (TRP) has been reported in tumor-bearing animals. In the present investigation 45 patients with various types of cancer and 13 control subjects were studied. Prior to the study the patients had received no antineoplastic therapy and were unaware of the malignancy of their disease. Feeding behavior was investigated by means of a questionnaire in which the presence of anorexia (A), aversion to meat (MA), taste (TA) or smell (SA) alterations, nausea and/or vomiting (NV) and early satiety (ES) was assessed. Plasma levels of free TRP, the other neutral amino acids (NAA), albumin and non-esterified fatty acids (NEFA) were assayed. Plasma-free TRP was significantly increased in anorectic cancer patients. The free TRP/competing NAA ratio, which might better predict brain TRP levels, was significantly higher in patients with A, MA, TA, SA, NV and ES than in controls or in non-anorectic (NA) cancer patients. These findings seem to confirm that free TRP may play an important role in human cancer anorexia.