Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study.

BACKGROUND & AIMS: The benefits of immunonutrition in patients with head and neck cancer (HNC), especially for those undergoing definitive concurrent chemoradiation (CCRT), remain unclear. We evaluated the benefits of immunonutrition regarding the prevention of severe oral mucositis. Secondary objectives included assessments of other treatment-related toxicities, changes of nutritional and inflammatory marker levels, treatment tolerance, and survival. METHODS: In total, 110 patients with HNC undergoing definitive CCRT including 3-week cycles of cisplatin were enrolled in our double-blind phase II study. Patients were randomly assigned to receive an immunonutrient formula containing omega-3-fatty acids, arginine, dietary nucleotides, and soluble fiber (n = 55) or an isocaloric isonitrogenous control (n = 55). All patients received the assigned product 5 consecutive days before each chemotherapy session. The proportion of patients with severe oral mucositis was compared between the immunonutrients and control groups. RESULTS: The rates of nasopharyngeal cancer (NPC) were 67% and 51% in the immunonutrients and control groups, respectively. All patients had 100% compliance to the assigned product. There was no difference of the proportion of patients with grade 3-4 oral mucositis between the two groups (62% vs. 67%, p = 0.690). At the time of analyses, survival tended to be better in the immunonutrients group. The 3-year progression-free survival rates were 69% (95% confidence interval [CI] = 55%-80%) and 44% (95% CI = 30%-57%) in the immunonutrients and control groups, respectively (p = 0.056), whereas the 3-year overall survival rates in these groups were 69% (95% CI = 54%-80%) and 50% (95% CI = 36%-66%; p = 0.065), respectively. In subgroup analyses according to the primary tumor location, the survival benefits were apparently maintained in patients with NPC. CONCLUSIONS: Although our study did not demonstrate a reduced risk of severe oral mucositis, we found that immunonutrition might improve survival. Larger studies are needed to determine the optimal dose and schedule of immunonutrition to prevent oral mucositis. In addition, randomized phase III trials evaluating the survival benefits of immunonutrition in patients with cancer are required, and NPC might be a primary malignancy of interest. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05101889.

Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial.

Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1-Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (p = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (p = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2-Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12-0.92) and relapse/death (HR, 0.37; 95% CI, 0.15-0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (Pinteraction = 0.02 for death, Pinteraction = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1.

Postoperative complication rate and survival of patients with gastric cancer undergoing immunonutrition: A retrospective study.

OBJECTIVES: This study aimed to evaluate the effect of preoperative immunonutrition on the rate of postoperative complication and survival of patients with gastric cancer. METHODS: A retrospective cohort was formed after data collection of patients hospitalized with gastric cancer. Postoperative complications classified according to the Clavien-Dindo classification system, length of hospital stay, readmissions, and rates of survival at 6 mo, 1 y, and 5 y were analyzed. A χ2 or Fisher's exact test, Student or Mann-Whitney t test, and Kaplan-Meier and Cox regressions were used in the statistical analysis. RESULTS: A total of 164 patients were included in the study, with 56 patients assigned to the immunonutrition group and 108 to the conventional group. There were no significant differences in postoperative complications between the immunonutrition and conventional groups (51.8% versus 58.3%; P = 0.423). The most frequent complications were fistula and surgical wound infection. Length of hospital stay did not differ between the groups (median of 7.0 d: P = 0.615) and the presence of readmissions did not differ either (12.5% versus 15.7%; P = 0.648). In the multivariate Cox regression, in a pooled model for group, age, sex, body mass index, Charlson comorbidity index, staging, neoadjuvant chemotherapy, and type of surgery, there was a significant difference in survival rates at 6 mo (P = 0.011), 1 y (P = 0.006), and 5 y (P < 0.001). CONCLUSIONS: Preoperative immunonutrition in patients with gastric cancer did not reduce postoperative complications or length of hospital stay. More studies are needed to confirm the benefit of immunonutriton supplementation for overall survival when associated with other protective factors.

Association of Inadequate Caloric Supplementation with 30-Day Mortality in Critically Ill Postoperative Patients with High Modified NUTRIC Score.

Modified NUTRIC (mNUTRIC) score is a useful assessment tool to determine the risk of malnutrition in patients on mechanical ventilation (MV). We identified associations between postoperative calorie adequacy, 30-day mortality, and surgical outcomes in patients with high mNUTRIC scores. Medical records of 272 patients in the intensive care unit who required MV support for >24 h after emergency gastro-intestinal (GI) surgery between January 2007 and December 2017 were reviewed. Calorie adequacy in percentage (Calorie intake in 5 days ÷ Calorie requirement for 5 days × 100) was assessed in patients with high (5⁻9) and low (0⁻4) mNUTRIC scores. In the high mNUTRIC score group, patients with inadequate calorie supplementation (calorie adequacy <70%) had higher 30-day mortality than those with adequate supplementation (31.5% vs. 11.1%; p = 0.010); this was not observed in patients with low mNUTRIC scores. This result was also confirmed through Kaplan⁻Meier survival curve (p = 0.022). Inadequate calorie supplementation in the high mNUTRIC score group was not associated with Intra-abdominal infection (p = 1.000), pulmonary complication (p = 0.695), wound complication (p = 0.407), postoperative leakage (p = 1.000), or infections (p = 0.847). Inadequate calorie supplementation after GI surgery was associated with higher 30-day mortality in patients with high mNUTRIC scores. Therefore, adequate calorie supplementation could contribute to improved survival of critically ill postoperative patients with high risk of malnutrition.

Alterações gastrintestinais de pacientes críticos em uso de norepinefrina e terapia nutricional enteral / Gastrointestinal disorders of critical patients in use of norepinephrine and enteral nutrition therapy / Trastornos gastrointestinales de los pacientes críticos en el uso de la norepinefrina y la terapia nutricional enteral

A terapia nutricional em pacientes críticos com uso de vasoconstrictores é um desafio na prática clínica, tanto pelas alterações hemodinâmicas comuns da alimentação, quanto pelas mudanças na perfusão esplâncnica provocada por estas drogas. O objetivo do presente estudo foi avaliar as principais alterações gastrointestinais de pacientes críticos em uso de noradrenalina (norepinefrina) e terapia nutricional. Estudo retrospectivo realizado em uma Unidade de Terapia Intensiva (UTI) de emergências traumáticas da cidade de Salvador. Foram analisados pacientes em uso de terapia nutricional enteral e noradrenalina por no mínimo 48 horas. Os pontos de corte para dose de noradrenalina foram menor e igual que 0,3mcg/kg/min e maior que 0,3mcg/kg/min. Foram avaliados resíduo gástrico elevado, distensão abdominal, vômito e diarréia. Trinta e cinco pacientes foram estudados, sendo a maioria do sexo masculino (83%) com idade média de 37,3 mais ou menos 18,1 anos. O diagnóstico clínico mais frequente foi o traumatismo cranioencefálico (68,6%). A terapia nutricional precoce ocorreu em 91% dos casos e o tempo médio de uso da noradrenalina foi de 7,9 mais ou menos 5,6 dias. Os sintomas de intolerância mais frequentes foram distensão abdominal e resíduo gástrico elevado, ambos com frequência de 42,9%. Apenas nove pacientes (25,7%) tiveram suspensão provisória da terapia nutricional por alterações gastrointestinais, sendo resíduo gástrico elevado o motivo mais frequente. O tempo de uso da noradrenalina na concentração menor ou igual 0,3mcg/kg/min foi maior entre pacientes que apresentaram distensão abdominal comparado com aqueles que não tiveram esse sintoma (p < 0,05). Concluindo-se, a terapia nutricional enteral precoce foi possível nos pacientes que utilizaram noradrenalina em dose menos ou igual 0,3mcg/kg/min por tempo prolongado sem grandes prejuízos.

Nutritional support in critical patients with the use of vasoconstrictors is a challenge in clinical practice, both by hemodynamic common food, as by changes in splanchnic perfusion caused by these drugs. The aim of this study was to assess the main gastrointestinal disorders in critically ill patients using noradrenaline (norepinephrine) and nutritional therapy. Retrospective study on an Intensive Care Unit (ICU) of traumatic emergencies in the city of Salvador. We analyzed patients on enteral nutrition therapy and norepinephrine for at least 48 hours. The cutoff points for the dose of norepinephrine were smaller and less than 0.3 mcg/kg/min and greater than 0.3 mcg/kg/min. We evaluated high gastric residuals, abdominal distension, vomiting and diarrhea. Thirty-five patients were studied, most were male (83%) with mean age of 37.3 plus or minus 18.1 years. The most common clinical diagnosis was head injury (68.6%). Nutritional therapy occurred early in 91% of cases and mean duration of use of norepinephrine was 7.9 plus or minus 5.6 days. The most common symptoms of intolerance were abdominal distension and elevated gastric residuals, both with frequency of 42.9%. Only nine patients (25.7%) had temporary suspension of nutrition therapy for gastrointestinal disorders, and high gastric residue the most frequent reason. The time of use of noradrenaline in the concentration less than or equal to 0.3 mcg/kg/min was higher among patients who had abdominal distension compared with those without this symptom (p < 0.05). Concluding, nutritional therapy Early enteral possible in patients using norepinephrine dose less or equal to 0.3 mcg/kg/min for a prolonged period without large losses.

El soporte nutricional en pacientes críticos con el uso de vasoconstrictores es un desafío en la práctica clínica, tanto por los alimentos comunes hemodinámicos, como por los cambios en la perfusión esplácnica causados por estas drogas. El objetivo de este estudio fue evaluar los principales trastornos gastrointestinales en pacientes críticamente enfermos con la noradrenalina (norepinefrina) y la terapia nutricional. Estudio retrospectivo de una Unidad de Cuidados Intensivos (UCI) de las emergencias traumáticas en la ciudad de Salvador. Se analizaron los pacientes en terapia de nutrición enteral y la noradrenalina durante al menos 48 horas. Los puntos de corte para la dosis de noradrenalina eran más pequeños y menos del 0,3 mcg/kg/min y mayor de 0,3 mcg/kg/min. Se evaluó alta residuos gástricos, distensión abdominal, vómitos y diarrea. Treinta y cinco pacientes fueron estudiados, la mayoría eran hombres (83%) con edad media de 37,3 más o menos 18,1 años. El diagnóstico clínico más frecuente fue la lesión en la cabeza (68,6%). La terapia temprana nutricional se produjo en el 91% de los casos y el tiempo promedio de uso de norepinefrina fue de 7,9 más o menos 5,6 días. Los síntomas más comunes de la intolerancia fueron distensión abdominal y aumento de residuos gástricos, ambos con una frecuencia del 42,9%. Sólo nueve pacientes (25,7%) tenían una suspensión temporal de la terapia nutricional para los trastornos gastrointestinales, y los residuos de alta gástrico la causa más frecuente. El tiempo de uso de la noradrenalina en la concentración menor o igual a 0,3 mcg/kg/min fue mayor entre los pacientes que habían distensión abdominal en comparación con aquellos sin este síntoma (p < 0,05). En conclusión, la terapia nutricional Los primeros posibles enteral en pacientes que utilizan dosis de noradrenalina menor o igual a 0,3 mcg/kg/min durante un período prolongado sin grandes pérdidas.