Feeding strategies in pediatric cancer patients with gastrointestinal mucositis: a multicenter prospective observational study and international survey.

INTRODUCTION: Currently, there is no adequate prevention or treatment for both oral and gastrointestinal mucositis induced by chemotherapy and/or radiotherapy. Supportive care of symptoms plays a primary role during mucositis in the pediatric clinical setting. We aimed to get insight in the currently used feeding strategies in clinical practice in pediatric cancer patients with chemotherapy-induced mucositis. METHODS: A prospective observational study was performed to identify feeding strategies after chemotherapy courses causing mucositis in almost all patients at the University Medical Center Groningen (UMCG), the Academic Medical Center Amsterdam (AMC), and the Princess Maxima Center Utrecht (PMC). Consecutive patients, aged 0-18 years, either diagnosed with B cell non-Hodgkin lymphoma (B-NHL) or scheduled for autologous stem cell transplantation (SCT) between April 2015 and September 2016 were included in this study. In addition to the observational study in the Netherlands, an international online questionnaire was conducted for pediatric oncology centers. RESULTS: A total of 13 patients were included, after 21 chemotherapy courses. No nutritional support was administered after 23.8% courses, tube feeding after 19.0% of the courses, TPN in 19.0% of courses, and 38.1% received a combination of tube feeding and TPN. The international survey revealed that 63.2% of the centers administered tube feeding as first choice, 31.6% administered only TPN as first choice, and one center administered a combination as first choice. CONCLUSIONS: There is a variability in feeding strategies in the clinical practice both in the Netherlands as well as worldwide. This study is a basis for future studies in this important clinical field to develop clinical trials comparing tube feeding and TPN both in adult and pediatric patients.

Effect of Conjugated Linoleic Acid-enriched Butter After 24 hours of Intestinal Mucositis Induction.

Mucositis is the most common side effect due to chemotherapy or radiotherapy. It refers to the inflammation of intestinal mucous membranes, and it is associated with complications such as diarrhea, weight loss, and increased intestinal permeability (IP). This study was designed to evaluate the effect of diet containing conjugated linoleic acid (CLA)-enriched butter on intestinal damage and inflammatory response after 24 h of 5-fluorouracil (5-FU)-induced mucositis. Mice were divided into four groups: CTL; CLA; 5-FU, and CLA 5-FU, and they were fed for 31 days. On the 30th experimental day, mucositis was induced by unique injection of 300 mg/kg of 5-FU. After 24 h (31st experimental day), IP was evaluated; ileum and fecal material were collected to determine cytokine level and myeloperoxidase (MPO) activity and secretory immunoglobulin A (sIgA). The 5-FU group showed an increase in IP and MPO activity (CTL vs. 5-FU: P < 0.05). Additionally, increased levels of IP and MPO were observed in CLA 5-FU group compared to those in the test groups (P < 0.05). Animals in the CLA 5-FU group showed reduced concentrations of sIgA (CTL vs. CLA 5-FU: P < 0.05). CLA-enriched butter exacerbating the 5-FU-induced intestinal damage. Safety concerns regarding the use of CLA require further investigation.

Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model.

BACKGROUND AND AIMS: Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. METHODS: Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation. RESULTS: Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (P<0.001). Those mice in 5-FU groups had significantly higher proinflammatory cytokine levels (TNF-α: 234.80 vs. 29.10, P<0.001, IL-6: 25.13 vs. 7.43, P<0.001, IFN-γ: 22.07 vs. 17.06, P = 0.137). A repairing of damage in jejunal villi was observed following probiotics administration. We also found TNF-α, IL-1ß and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1ß: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (P<0.05). No bacterial translocation was found in this study. CONCLUSIONS: In conclusion, our results show that oral administration of probiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in the future.

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

Elemental diet moderates 5-fluorouracil-induced gastrointestinal mucositis through mucus barrier alteration.

PURPOSE: There are reports that elemental diet (ED) ameliorates oral mucositis caused by antineoplastic chemotherapy. Although this effectiveness may be partly due to high nutrient absorption, the effects of chemotherapy on mucosal defense mechanisms remain unclear. We investigated the effects of oral supplementation with ED on mucin in 5-fluorouracil (5-FU)-induced intestinal mucositis. METHODS: 5-FU was administered to rats orally once daily, and ED was supplied orally twice daily for 5 days. The severity of mucositis was assessed by length, dry tissue weight, and villus height of the intestinal tract. Using anti-mucin monoclonal antibody, we compared the immunoreactivity in the gastrointestinal (GI) tract and mucin content by histological and biochemical examinations. RESULTS: Oral supplementation with ED reduced histological damage and loss of length, dry tissue weight, and villus height induced by 5-FU administration. ED markedly altered PGM34 antibody immunoreactivity and mucin contents in the small intestine of rats with 5-FU-induced mucositis. CONCLUSIONS: ED may possibly be more effective for the prevention of antineoplastic chemotherapy-induced mucositis through the activation of GI mucus cells.

Uso de la glutamina en la nutricion parenteral total de pacientes sometidos a trasplante de médula ósea / Use of glutamine in total parenteral nutrition of bone marrow transplant patients

La glutamina es un amioácido esencial para la síntesis de nucleótidos y una fuente de energía para la replicación celular, existe evidencia contradictoria respecto a los beneficios de su administración como parte de la nutrición parenteral en pacientes sometidos a trasplante de médula ósea (TMO). Más del 75% de los pacientes sometidos a trasplante de precursores hematopoyéticos, presentan durante su evolución complicaciones que comprometen el tracto digestivo, principalmente mucositis, limitando la ingesta oral, de allí la necesidad del uso de nutrición parenteral total (NPT) en estos casos. Objetivo: Analizar la relación entre uso de glutamina en la NPT de TMO y la evolución de complicaciones agudas como mucositis, EICH e infecciones, así como la estancia hospitalaria y los días de nutrición parenteral total. Material y métodos: Estudio observacional retrospectivo. Se incluyeron la totalidad de TMO con NPT entre 2007 y 2013 en nuestro hospital. Se analizaron días de hospitalización, días de soporte nutricional, uso de glutamina y complicaciones agudas. Los resultados se analizaron con el programa SPSS 15.0. Resultados: Se incluyeron 73 pacientes trasplantados, se dividieron en dos grupos según el aporte de glutamina siendo ambos grupos comparables entre sí. La edad media fue de 36,96±12,89 años. El 47,9% de los pacientes estudiados recibió suplemento de glutamina en la NPT. Los pacientes que recibieron glutamina tuvieron una estancia media de 31,49±7,41 días con 14,11±5,87 días de NPT en comparación a los que no recibieron glutamina con 32,16±7,99 y 15,50±7,71 días respectivamente (p=0,71 y 0,39). La duración de la mucositis en los pacientes que recibieron glutamina fue de 12,23±5,66 días comparado con 15,50±7,71 días en los que no recibieron glutamina (p=0,042).Se observaron grados severos de EICH (II, III) en un 20,6% de los pacientes sin glutamina en comparación al 13,7% en los que la recibieron (p=0,636). Del total de los de los pacientes estudiados, el 13,7% sufrieron complicaciones infecciosas mientras recibían NPT con glutamina, comparado con 16,4% en pacientes que no recibieron (p=0,700). Conclusiones: En nuestra serie, se observó una reducción estadísticamente significativa en la duración de la mucositis en pacientes que recibieron NPT con glutamina

Glutamine is an essential amino acid for nucleotide synthesis and an important energy resource for cellular division. There is contradictory evidence about its benefits as part of parenteral nutrition. More than 75% of bone marrow transplant patients (BMTP) have, during their evolution, digestive tract complications limiting enteral nutrition, for this reason, sometimes total parenteral nutrition (TPN) is required. Objective: Our aim was to analyze the relation between the use of glutamine in TPN of BMTP, and the evolution of clinical acute complications as mucositis, graft versus host disease (GVHD) and infections days of stay and days of TPN. Materials and Methods: observational retrospective study. All BMTP with total parenteral nutrition during the period 2007-2013 were included. We analyzed days of stay, days of nutrition, glutamine use and acute complications. Results were analyzed in SPSS 15.0. Results: 73 BMTP were divided in two comparable groups depending on glutamine use. The mean age was 36,96 ± 12,89 years. 47,9% of patients received glutamine in TPN. Patients who received glutamine had a mean stay of 31,49±7,41 days with 14,11±5,87 days of TPN compared with the non-glutamine group with 32,16±7,99 and 15,50±7,71 days respectively (p=0,71 y 0,39). Mucositis lasted 12,23±5,66 days in the glutamine group, and 15,50±7,71 days in the non-glutamine group (p=0,042). Severe grades of GVHD (II,III) was observed in 20,6% of the non glutamine group compared with the 13,7% of the other group (p=0,636). In patients with glutamine suplementation, mucositis last 12,23±5,66 days compared with 15,50±7,71 days in the non-glutamine group (p=0,042).13,7% of all patients suffered infections while receiving TPN with glutamine compared with 16,4% in patients who did not receive glutamine (p=0,700). Conclusion: In our group, a statistically significant reduction in the duration of mucositis was observed in patients who received parenteral glutamine

Influence of an immuno-enhanced formula in postsurgical ambulatory patients with head and neck cancer / Influencia de una formula inmunoenriquecida en pacientes ambulatorios postquirurgicos con cancer de cabeza y cuello

Background: Patients with head and neck cancer undergoing surgery have a high incidence of ambulatory postoperative complications. Objective: The aim of our study was to investigate the influence of an oral immunoenhanced supplement (arginine and glutamine) on nutritional and biochemical parameters in postsurgical ambulatory patients with head and neck tumor. Design: A population of 39 ambulatory postsurgical patients with oral and laryngeal cancer was enrolled. At Hospital discharge postsurgical head and neck cancer patients were asked to consume two units per day of a specially designed enhanced supplement for a twelve week period. Results: The mean age was 60.2+/-13.1 years (9 female/30 males). Duration of supplementation was 90.8 + 20days. A significant increase of album in (3.1±0.6 g/dl vs 4.12+0.7g /dl;p<0.05), prealbumin (21.4±6.3 mg/dl vs22.4+5.9 mg/dl;p<0.05) and transferr in (198.8±45.2mg/dl vs 253.8+60.7 mg/dl; p<0.05) levels were observed. No differences were detected in weight and other anthropometric parameters. Ten patients (41.3%) received radiotherapy along the enhanced supplementation period and only 5 (20% of patients with radiotherapy) developed a clinical oral mucositis. Conclusions: At dose used, arginine and glutamine enhanced formula improved seric protein levels in ambulatory postoperative head and neck cancer patients with a low rate of oral mucositis in the subgroup with radiotherapy (AU)

Antecedentes: Los pacientes con tumores de cabeza y cuello sometidos a cirugía presentan una alta incidencia de complicaciones ambulatorias. Objetivo: El principal objetivo de nuestro trabajo fue evaluar la influencia de un suplemento oral inmunoenriquecido con arginina y glutamina en pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello. Diseño: Una muestra de 39 pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello fue evaluada. Tras el alta hospitalaria, los pacientes recibieron dos bricks al día de un suplemento inmuno enriquecido durante 12 semanas. Resultados: La edad media fue de 60,2+/-13,1 años (9mujeres/30 varones). La duración media de la suplementación fue de 90,8+20 días. Se detectó un aumento significativo en los niveles de albúmina (3,1±0,6 g/dl vs4,12+0,7 mg/dl; p<0,05), prealbúmina (21,4±6,3 mg/dl vs22,4+5,9 mg/dl;p<0,05) y transferrina (198,8±45,2 mg/dlvs 253,8+60,7 mg/dl; p<0,05). No se detectaron diferencias en el peso ni en otras variables antropométricas. Un total de 10 pacientes (41,3%) recibieron radioterapia durante la suplementación, de los cuales solo 2 (20% de los pacientes con radioterapia) desarrollaron mucositis oral con significación clínica. Conclusiones: A la dosis usada, la formula enriquecida con arginina y glutamina mejoró lo niveles de proteínas séricas. Por otra parte los pacientes suplementados presentaron una baja tasa de mucositis asociada a la radioterapia (AU)