Gastrointestinal side effects of somatostatin analogs in neuroendocrine tumors: a focused review.

Neuroendocrine tumors (NETs) are a group of well-differentiated heterogeneous neoplasms characterized by slow progression and distinct clinical and biological behavior. In the majority of patients with NET, first-line treatment is represented by somatostatin analogs (SSAs) that, despite being drugs with high tolerability (even at high doses) and providing to carcinoid symptoms control and anti-proliferative effects, may present some side effects, with potential impact on quality of life and nutritional status. The most frequent side effects are represented by gastrointestinal events in particular alterations in bowel habits (diarrhea and constipation), abdominal pain, exocrine pancreatic insufficiency, and cholelithiasis. Considering the relative rarity of NETs, literature about frequency and standard clinical management of adverse events SSA-related is still lacking and heterogeneous. The aim of this review is to arm gastroenterologists and other physicians treating NET patients with essential knowledge on the side effects of SSAs. By identifying and managing these adverse events early, healthcare professionals can offer optimal care, avert foreseeable complications, and ensure the best outcomes for patients. Without such early recognition, there is a risk of diminishing the patient's quality of life and their ability to sustain treatment over time.

Sarcopenia, biological age and treatment eligibility in patients with cancer.

PURPOSE OF REVIEW: Cancer incidence will dramatically increase, especially among older adults, during the next few decades. This may lead to bankruptcy of the healthcare systems worldwide if the current approach to treatment eligibility is not improved. In fact, current treatment personalization is mostly focusing on the genetic and molecular characteristics of cancer cells, whereas clinical characterization of patients is still dependent on gross variables (i.e. chronological age, BMI, comorbidities, Performance Status and so on). This could have contributed to the poor performance of many anticancer drugs in the real-world setting when compared with the results obtained in prospective, randomized clinical trials. RECENT FINDINGS: The role of chronological age in identifying patients with increased likelihood to respond to therapies has been challenged, pointing to biological age (i.e. accumulated damage to biological systems over the life course, leading to loss of reserve and capacity to respond to challenges) as a robust predictor of outcome encompassing genetic, phenotypic and clinical factors. Sarcopenia has been proposed as a reliable clinical index of biological age, but the complexity of body composition changes occurring during tumour growth appears to preclude its routine use when assessing eligibility in cancer patients. SUMMARY: Integration of sarcopenia measures within scores of allostatic load may further increase the clinical relevance of changes of body composition, highlight its sensitivity to early nutritional intervention leading to mitigation of accelerated ageing, and contribute to wide delivery of precision oncology.

High protein diet in digestive cancers.

PURPOSE OF REVIEW: Recent advances in the nutritional management of patients with digestive cancers suggest that modulation of protein intake may significantly contribute to achieve nutritional and clinical benefits. By reviewing the available evidence, a quantitatively and qualitatively optimal protein intake could be derived. RECENT FINDINGS: High protein diets (i.e., 1-1.5 g/kg body weight/day) appear key to maintain the adequate nutritional status, and may also contribute to achieve clinical benefits. This target appears particularly relevant in patients with digestive cancers at risk or already malnourished, or in older patients. During active cancer treatments, protein intake should be closer to the upper limit of the recommended intake. Also, high protein intake should be maintained beyond the periods of catabolic crisis associated with active treatments. In contrast with general reasoning, animal proteins should represent the majority of the recommended intake. Based on the available evidence, the intake of no specific amino acid can be strongly recommended to enhance anabolic potentials or the immune modulating effects of high protein diets. SUMMARY: High protein intake, mostly based on animal proteins, should be recommended to patients with digestive cancers. However, this target should be translated into clinical prescription after considering the clinical and metabolic needs of the patients. The quest for the optimal protein intake of patients with cancer at different time points of their clinical journey is still open.

Clinical and economic value of oral nutrition supplements in patients with cancer: a position paper from the Survivorship Care and Nutritional Support Working Group of Alliance Against Cancer.

Malnutrition is a common clinical and public health problem that can frequently affect patients in hospital and community settings. In particular, cancer-related malnutrition results from a combination of metabolic dysregulation and anorexia, caused both by the tumor itself and by its treatment. Patients with head-neck cancer, or with gastroesophageal, pancreatic, lung, and colorectal cancer, are particularly at risk of developing malnutrition, with a prevalence varying between 30 and 50% depending on tumor location and anti-cancer treatment complications. Prevention and adequate management of malnutrition is now considered an essential key point of therapeutic pathways of patients with cancer, with the aim to enhance their quality of life, reduce complications, and improve clinical outcomes. Oral nutritional supplements (ONS) are part of the nutritional therapy and represent an effective tool to address cancer-related malnutrition, as supported by growing literature data. However, patients' access to ONS - which is regulated by different national and regional policies in terms of reimbursement - is quite heterogeneous. This narrative review aims to summarize the current knowledge about the role of ONS in terms of cost-effectiveness in the management of actively treated patients with cancer, following surgery and/or radiotherapy/chemotherapy treatment and to present the position on this issue of the Alliance Against Cancer, the Italian National Oncology Network, coming up from a focused virtual roundtable of the Survivorship Care and Nutritional Support Working Group.

Examining guidelines and new evidence in oncology nutrition: a position paper on gaps and opportunities in multimodal approaches to improve patient care.

Malnutrition, muscle loss, and cachexia are prevalent in cancer and remain key challenges in oncology today. These conditions are frequently underrecognized and undertreated and have devastating consequences for patients. Early nutrition screening/assessment and intervention are associated with improved patient outcomes. As a multifaceted disease, cancer requires multimodal care that integrates supportive interventions, specifically nutrition and exercise, to improve nutrient intake, muscle mass, physical functioning, quality of life, and treatment outcomes. An integrated team of healthcare providers that incorporates societies' recommendations into clinical practice can help achieve the best possible outcomes. A multidisciplinary panel of experts in oncology, nutrition, exercise, and medicine participated in a 2-day virtual roundtable in October 2020 to discuss gaps and opportunities in oncology nutrition, alone and in combination with exercise, relative to current evidence and international societies' recommendations. The panel recommended five principles to optimize clinical oncology practice: (1) position oncology nutrition at the center of multidisciplinary care; (2) partner with colleagues and administrators to integrate a nutrition care process into the multidisciplinary cancer care approach; (3) screen all patients for malnutrition risk at diagnosis and regularly throughout treatment; (4) combine exercise and nutrition interventions before (e.g., prehabilitation), during, and after treatment as oncology standard of care to optimize nutrition status and muscle mass; and (5) incorporate a patient-centered approach into multidisciplinary care.

Safety and Tolerability of Targeted Medical Nutrition for Cachexia in Non-Small-Cell Lung Cancer: A Randomized, Double-Blind, Controlled Pilot Trial.

Background: This pilot, double-blind, comparator-controlled trial evaluated the safety and tolerability of an oral targeted medical nutrition (TMN) supplement for the management of cachexia in patients with non-small-cell lung cancer (NSCLC).Methods: Patients receiving first-line chemotherapy for NSCLC with weight loss or low BMI were randomized 1:1 to receive juice-based TMN (∼200 kcal; 10 g whey protein; ≥2.0 g eicosapentaenoic acid/docosahexaenoic acid in fish oil; and 10 µg 25-hydroxy-vitamin D3) or a milk-based isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov: NCT02515032). Primary endpoints included number/type of adverse events and changes in vital signs/laboratory parameters. Secondary endpoints included measures of clinical relevance. Survival was an exploratory endpoint.Results: The TMN group (n = 26; mean 64.4 years) experienced fewer adverse events (64 vs. 87) than the comparator group (n = 29; mean 66.0 years), including fewer cases of neutropenia (0 vs. 4). Compliance was slightly lower in the TMN (58.5%) vs. comparator group (73.6%). There were no statistically significant between-group differences in efficacy endpoints. Fewer (4 vs. 10) patients who received TMN than comparator had died by 1-year post baseline.Conclusions: TMN was well tolerated. Trends for improved clinical outcomes with TMN identified in this study warrant further investigation.

Nutrition Information in Oncology - Extending the Electronic Patient-Record Data Set.

Electronic health records (EHRs) present extensive patient information and may be used as a tool to improve health care. However, the oncology context presents a complex content that increases the difficulties of EHR application. This study aimed at developing openEHR-archetypes representing clinical concepts in cancer nutrition-care, as well as to develop an openEHR-template including the aforementioned archetypes. The study involved the following stages: 1) a thorough literature review, followed by an expert's (nutrition guideline authors) survey, aiming to identify the main statements of published clinical guidelines on nutrition in cancer patients that were not included on the Clinical Knowledge Manager (CKM) repository; 2) modelling of the archetypes using the Ocean Archetype Software and submission to the CKM repository; 3) creating an example template with Template Designer; and 4) automatic conversion of the openEHR-template into a readily usable EHR using VCIntegrator. The clinical concepts (among 17 clinical concepts not yet available in the CKM repository) chosen for further development were: body composition, diet plan, dietary nutrients, dietary supplements, dietary intake assessment, and Malnutrition Screening Tool (MST). So far, four archetypes were accepted for review in the CKM repository and a template was created and converted into an EHR. This study designed new openEHR-archetypes for nutrition management in cancer patients. These archetypes can be included in EHR. Future studies are needed to assess their applicability in other areas and their practical impact on data quality, system interoperability and, ultimately, on clinical practice and research.

A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice.

BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

The determinants of reduced dietary intake in hospitalised colorectal cancer patients.

PURPOSE: Patients with colorectal cancer (CRC) often experience malnutrition and weight loss, largely resulting from reduced dietary intake. The aim of this study was to identify determinants of reduced dietary intake in order to facilitate early recognition of malnutrition and optimise nutritional treatment. METHODS: Data from nutritionDay, an international 1-day survey investigating patient, disease and food profiles, were used. To identify determinants of dietary intake, defined as normal vs. reduced in the last week, univariate and multivariate logistic regressions were performed. RESULTS: Of 1131 hospitalised CRC patients, 54% reported reduced dietary intake. Patient- and disease-related characteristics significantly associated with reduced dietary intake were female gender (odds ratio (OR) 1.38), cancer stage III (OR 1.52) or IV (OR 1.70) vs. I, performance status 2 (OR 1.56), 3 (OR 2.37) or 4 (OR 4.15) vs. 0, duration since hospital admission of ≥ 4 days (OR 4-7 days, 1.91; 8-21 days, 1.97; > 21 days, 1.92) vs. < 4 days, and unintentional weight loss (OR 2.56). Additionally, higher symptom scores of pain, weakness, depression, tiredness and lack of appetite were associated with reduced intake. CONCLUSIONS: Patient- and disease-related determinants for reduced dietary intake were being female, higher cancer stage, worse performance status, duration since hospital admission ≥ 4 days and unintentional weight loss. Furthermore, multiple symptoms were associated with a reduced dietary intake. Future trials should assess whether early recognition of patients at risk of malnutrition and the combination of treating symptoms and dietary advice result in improved intake and treatment-related outcomes.

Assessing pathophysiology of cancer anorexia.

PURPOSE OF REVIEW: Cancer anorexia is a negative prognostic factor and is broadly defined as the loss of the interest in food. However, multiple clinical domains contribute to the phenotype of cancer anorexia. The characterization of the clinical and molecular pathophysiology of cancer anorexia may enhance the efficacy of preventive and therapeutic strategies. RECENT FINDINGS: Clinical trials showed that cancer anorexia should be considered as an umbrella encompassing different signs and symptoms contributing to appetite disruption in cancer patients. Loss of appetite, early satiety, changes in taste and smell are determinants of cancer anorexia, whose presence should be assessed in cancer patients. Interestingly, neuronal correlates of cancer anorexia-related symptoms have been revealed by brain imaging techniques. SUMMARY: The pathophysiology of cancer anorexia is complex and involves different domains influencing eating behavior. Limiting the assessment of cancer anorexia to questions investigating changes in appetite may impede correct identification of the targets to address.

Influence of Transiently Increased Nutritional Risk on a Left Ventricle Myocardial Mass Assessed by Echocardiography.

BACKGROUND/AIM: Metabolic derangements due to increased nutritional risk lead to catabolism and loss of proteins, muscle tissue and eventually mass of parenchymatous organs. The aim of our study was to assess whether transitory nutritional risk after heart surgery influences on the left ventricle myocardial mass (LVMM), assessed by echocardiography. METHODS: Consecutive sample of patients scheduled for cardiovascular rehabilitation, in period 0-3 months after surgery. Nutritional risk screening (NRS) was analyzed using the NRS-2002 tool. RESULTS: Study sample included 330 patients after heart surgery for ischemic 186 (56.4%); valvular 91 (27.6%) and valvular plus ischemic 53 (16.1%) heart disease. Age was 65.5 ± 10.6 (range 23-84) and there were more male patients than female - 240 (72.7%) and 90 (27.3%), respectively. The percentage of unintentional loss of weight was 10.8 ± 3.4%, in range 0-23.81%, whereas NRS-2002 was 4.4 ± 1.1. LVMM was 218.7 ± 65.9 g vs. 252.3 ± 51.7 (p = 0.015); for patients with increased nutritional risk and controls, respectively. There was no significant correlation of LVMM with NRS-2002, while the percentage of unintentional loss of weight displayed only weakly inverse correlation (Rho CC = -0.197; p = 0.007). LVMM also correlated significantly with body mass index (Rho CC = 0.247; p < 0.001) and waist-to-hip ratio (Rho CC = 0.291; p < 0.001). In conclusion, LVMM was found to decrease slightly in the period of increased nutritional risk, following heart surgery. Changes in LVMM are partially consequences of systemic catabolic response, as well as anthropometric changes due to unintentional loss of weight.

Validating Appetite Assessment Tools Among Patients Receiving Hemodialysis.

OBJECTIVE: To test the performance of appetite assessment tools among patients receiving hemodialysis (HD). DESIGN: Cross-sectional. SUBJECTS: Two hundred twenty-one patients receiving HD enrolled in seven dialysis facilities in Northern California. INTERVENTION: We assessed 5 appetite assessment tools (self-assessment of appetite, subjective assessment of appetite, visual analog scale [VAS], Functional Assessment of Anorexia/Cachexia Therapy [FAACT] score, and the Anorexia Questionnaire [AQ]). MAIN OUTCOME MEASURES: Reported food intake, normalized protein catabolic rate, and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake. RESULTS: Fifty-eight (26%) patients reported food intake ≤ 50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All the tools were significantly associated with food intake ≤ 50% (P < .001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake ≤ 50% (C-statistic 0.80 and 0.76). Patients with food intake ≤ 50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; P = .03). Normalized protein catabolic rate was lower among anorexic patients based on the VAS (1.1 ± 0.3 vs 1.2 ± 0.3, P = .03). Ln interleukin-6 correlated inversely with food intake (P = .03), but neither interleukin-6 nor C-reactive protein correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (P = .02), prealbumin (P = .02) and adiponectin concentrations (P = .03). CONCLUSIONS: Alternative appetite assessment tools yielded widely different estimates of the prevalence of anorexia in HD. When considering self-reported food intake as the criterion standard for anorexia, the FAACT score and VAS discriminated patients reasonably well.

Metabolic and nutritional support of critically ill patients: consensus and controversies.

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients.

Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia.

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

Characteristics of NRS-2002 Nutritional Risk Screening in patients hospitalized for secondary cardiovascular prevention and rehabilitation.

OBJECTIVE: The aim of our study was to assess the prevalence and characteristics of nutritional risk in patients scheduled for cardiovascular rehabilitation. BACKGROUND: Knowledge concerning nutritional aspects of cardiovascular diseases is contemporary limited. METHODS: Nutritional risk screening using a standardized Nutritional Risk Screening-2002 (NRS-2002) questionnaire was performed on a cohort of consecutive patients scheduled for rehabilitation 1-6 months after treatment for ischemic, valvular, or combined causes of heart diseases. Baseline weight was available for more than 80% of patients. RESULTS: The study population consisted of 317 patients, aged 23-85 years, with a mean age of 62.5 ± 11.3 years. Male to female share was 253 (79.8%) and 64 (20.2%), respectively. Twenty-eight (8.8%) were treated for myocardial infarction conservatively, 151 (47.6%) by percutaneous coronary interventions, and 145 (45.7%) by surgery. NRS-2002 was 3.56 ± 1.54 in range 0-6. A high correlation was found between the NRS-2002 and percentage weight loss history (rho = 0.813; p <0.001). Significant differences according to increased nutritional risk (NRS-2002 ≥ 3) were found within age groups (p < 0.001), disease etiology (p = 0.002), cardiovascular treatments (p < 0.001), and grades of renal function (p < 0.001). Odds for developing increased nutritional risk (NRS-2002 ≥ 3) were significant for cardiovascular treatments (odds ratio [OR] = 4.35, 95% confidence interval [CI], 2.28-8.30, p < 0.001), age (OR = 3.19, 95% CI, 2.00-5.09, p < 0.001), grade of renal function (OR = 1.91, 95% CI, 1.17-3.09, p = 0.009), diabetes mellitus (OR = 2.37, 95% CI, 1.09-5.16, p = 0.029), and any psychological disturbance (OR = 2.04, 95% CI, 1.06-3.90, p = 0.032). CONCLUSIONS: Pronounced nutritional risk frequently existed among patients at stationary cardiovascular rehabilitation. Nutritional risk was connected with preceding cardiovascular treatments, patient age, and renal function. Further studies concerning nutritional risk and its connections with clinical outcomes might serve as a resourceful perspective to improve outcomes or quality of care for the entities from the cardiovascular diseases continuum.

ESPEN practical guideline: Nutritional support for polymorbid medical inpatients.

BACKGROUND: Disease-related malnutrition in polymorbid medical inpatients is a highly prevalent syndrome associated with significantly increased morbidity, disability, short- and long-term mortality, impaired recovery from illness, and healthcare costs. AIM: As there are uncertainties in applying disease-specific guidelines to patients with multiple conditions, our aim was to provide evidence-based recommendations on nutritional support for the polymorbid patient population hospitalized in medical wards. METHODS: The 2023 update adheres to the standard operating procedures for ESPEN guidelines. We undertook a systematic literature search for 15 clinical questions in three different databases (Medline, Embase and the Cochrane Library), as well as in secondary sources (e.g., published guidelines), until July 12th, 2022. Retrieved abstracts were screened to identify relevant studies that were used to develop recommendations (including SIGN grading), which was followed by submission to Delphi voting. Here, the practical version of the guideline is presented which has been shortened and equipped with flow charts for patients care. RESULTS: 32 recommendations (7× A, 11× B, 10× O and 4× GPP), which encompass different aspects of nutritional support were included from the scientific guideline including indication, route of feeding, energy and protein requirements, micronutrient requirements, disease-specific nutrients, timing, monitoring and procedure of intervention. Here, the practical version of the guideline is presented which has been shortened and equipped with flow charts for patients care. CONCLUSIONS: Recent high-quality trials have provided increasing evidence that nutritional support can reduce morbidity and other complications associated with malnutrition in polymorbid patients. The timely screening of patients for risk of malnutrition at hospital admission followed by individualized nutritional support interventions for at-risk patients should be part of routine clinical care and multimodal treatment in hospitals worldwide. Use of this updated practical guideline offers an evidence-based nutritional approach to polymorbid medical inpatients and may improve their outcomes.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.