Immunonutrition stimulates immune functions and antioxidant defense capacities of leukocytes in radiochemotherapy-treated head & neck and esophageal cancer patients: A double-blind randomized clinical trial.

BACKGROUND: Immunonutrition has been reported to improve the immune status of perioperative cancer patients, thereby reducing complications and length of hospital stay. AIM: This study aimed to assess whether immunonutrition enriched in arginine, EPA & DHA and nucleotides could impact the immune cells responses in head & neck and esophageal cancer patients treated by radiochemotherapy (RCT). METHODS: A double-blind clinical trial was carried out in 28 patients randomized into two groups, receiving either an immunomodulating enteral nutrition formula (IEN, n = 13, Impact(®), Nestlé) or an isoenergetic isonitrogenous standard enteral nutrition formula (SEN, n = 15) throughout RCT (5-7 weeks). After isolation from whole blood, immune cells metabolism and functions were assessed at the beginning (Db) and at the end (De) of RCT. RESULTS: Immunonutrition maintained CD4(+)/CD8(+) T-lymphocyte counts ratio and CD3 membrane expression between Db and De. Polymorphonuclear cells CD62L and CD15 densities and ROS production were increased in IEN patients. Peripheral blood mononuclear cells (PBMC) production of pro-inflammatory prostaglandin-E2 was stable in IEN patients and lower than in SEN patients at De. Genes coding for immune receptors, antioxidant enzymes and NADPH oxidase subunits were overexpressed in the PBMC of IEN vs SEN patients at De. CONCLUSION: Immunonutrition can enhance immune cell responses through the modulation of their phenotypes and functions. By modulating the gene expression of immune cells, immunonutrition could make it easier for the organism to adapt to the systemic inflammation and oxidative stress induced by RCT. CLINICAL TRIAL REGISTRATION: This clinical trial has been registered on ClinicalTrial.gov website: NCT00333099.

Immunonutrition improves functional capacities in head and neck and esophageal cancer patients undergoing radiochemotherapy: a randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is frequent in head and neck (HN) and esophageal cancer patients and aggravated by radiochemotherapy (RCT), increasing morbi-mortality and treatment toxicity. Our goal was to investigate the effect of immunonutrition consisting of an arginine, omega-3 fatty acid, nucleotides-enriched diet on nutritional status, and functional capacity in HN or esophageal cancer patients undergoing RCT. METHODS: 37 patients were randomized in a double-blind clinical trial. 5 days before and until the end of RCT (5-7 weeks), they received either an Immunomodulating Enteral Nutrition (IEN) or an isonitrogenous, isoenergetic Standard Enteral Nutrition (SEN). Anthropometrical parameters, nutritional risk index (NRI), serum albumin, plasma antioxidant capacity, and functional capacity were recorded between the beginning and the end of RCT. RESULTS: A significant gain in total body weight (+2.1 ± 3.1 kg) was observed in IEN patients. Albuminemia and NRI were improved concomitantly in IEN malnourished patients. Plasma antioxidant capacity was improved (+100 ± 13 µM EqTrolox) in IEN patients. Functional capacity measured by WHO Performance Status and Karnofsky index was maintained in IEN patients but significantly reduced in SEN patients. CONCLUSIONS: These preliminary data show that immunonutrition could improve the nutritional status together with functional capacity in HN and esophageal cancer patients undergoing RCT. CLINICAL TRIAL REGISTRATION: This clinical trial promoted by the University Hospital Center of Clermont-Ferrand has been registered at ClinicalTrial.gov website under the following reference: NCT00333099.

Azacytidine and erlotinib exert synergistic effects against acute myeloid leukemia.

The term myelodysplastic syndrome (MDS) identifies a heterogeneous group of clonal disorders originating from bone marrow stem cells that often progress to acute myeloid leukemia (AML). The reference treatments for MDS include the DNA methyltransferase inhibitors azacytidine and decitabine. Recently, the epidermal growth factor receptor (EGFR) inhibitor erlotinib has been shown to exert antileukemic activity in vitro and in vivo, independent of the EGFR. Thanks to this feature, erlotinib is currently being tested as an antileukemic drug in clinical trials. Here, we report that azacytidine and erlotinib mediate synergistic antineoplastic effects in several primary or secondary (post-MDS) AML cell lines. The combination of azacytidine and erlotinib blocked cell-cycle progression and induced caspase-dependent apoptosis more consistently than either of the two agents alone. These effects were not a consequence of cellular differentiation and could be discriminated from each other, as the former depended on caspases whereas the latter did not. The synergy between azacitidine and erlotinib, which involved the proteasomal degradation of the anti-apoptotic Bcl-2 family members MCL-1 and BCL2L10 and the upregulation of their pro-apoptotic counterpart PUMA, was abolished when azacytidine was replaced by decitabine but persisted when erlotinib was substituted with gefitinib, another EGFR inhibitor. Of note, the intracellular accumulation of azacytidine was exacerbated by both erlotinib and gefitinib, pointing to a pharmacokinetic mechanism of synergy. In approximately half of the cases studied, marrow and circulating blasts from MDS and AML patients, respectively, exhibited hyperadditive cytotoxic responses to the combination of azacytidine and erlotinib. These results strongly suggest that the combination of azacytidine and erlotinib may exert clinically relevant antileukemic effects.

Hypermetabolism in ALS patients: an early and persistent phenomenon.

The malnutrition common among patients with ALS can be attributed in some cases to increased resting energy expenditure (REE). However, the origins and evolution of this hypermetabolism have yet to be fully elucidated. The aim of the present study was to monitor REE over time in patients with ALS and to identify factors that may explain any variation observed. ALS patients underwent nutritional, neurological and respiratory assessment every 6 months for 2 years (or until they died or became physically incapable of being examined). Sixty-one patients were studied. At inclusion, 47.5% exhibited hypermetabolism, with a mean measured REE (mREE) 19.7 +/- 6.4% higher than the mean calculated REE (cREE) (P < 0.0001). The hypermetabolism persisted when mREE was normalized for fat free mass (FFM): 35.1 +/- 4.2 versus 32.3 +/- 4.7 kcal/kg day(-1) (P = 0.02) in hypermetabolic and normometabolic patients, respectively. In univariate analysis, mREE was negatively correlated with age and positively correlated with BMI, FFM, energy and protein intakes, and albumin level. No correlation was found with neurological scores, disease characteristics, respiratory function and survival. Multivariate analysis revealed no significant factors. Only 10 of 45 patients in whom REE was measured at least twice changed their metabolic status. Neither mREE nor mREE/cREE varied significantly over time, despite deteriorating neurological, nutritional and respiratory parameters (P < 0.0001), and an increase in mREE/FFM (P = 0.01). This study confirms that about 50% of ALS patients are hypermetabolic, and 80% show no change in metabolic status over time. Thus, metabolic status (a clinically useful indicator of the need for nutritional support) can be determined early in the evolution of the disease. The origin of hypermetabolism in this context remains unknown, but growing evidence points to mitochondria as having an important role.

Relationship between nutritional status and quality of life in patients with cancer.

Patients with cancer frequently suffer a deteriorated quality of life and this is an important factor in the therapeutic decision. The correlation between quality of life and malnutrition seems obvious and bidirectional. The aim of our study was to describe the global quality of life and its various dimensions in patients with cancer, as a function of the nutritional status. A transversal observational study was performed in wards in hospitals in Clermont-Ferrand and Saint Etienne on 907 patients. The EORTC questionnaire, QLQ-C30, was used to assess the quality of life. The mean global quality of life score was 48.8 for patients who had a weight loss of more than 10% since the beginning of their illness, compared with 62.8 for the other patients (p<0.001). A significant association with weight was observed for the main dimensions of the quality of life: physical, functional, cognitive, social, fatigue, nausea, pain, loss of appetite, constipation and diarrhoea. This strong relation between quality of life and weight loss shows the importance of dietary management in patients with cancer.

[What are the means of alimentary function supply and their indications in amyotrophic lateral sclerosis?]. / Quels sont les moyens de suppléance de la fonction alimentaire et leurs indications?

Artificial nutrition is necessary when oral feeding becomes insufficient to cover protein and energetic needs and becomes dangerous (risk of malnutrition, dehydration and aspiration). In ALS patients, enteral nutrition is the method of choice and gastrostomy is preferable to nasogastric tube which must be limited for a short term enteral nutrition or if gastrostomy is at risk (because of pulmonary function) or refused by the patient. The percutaneous gastrostomy can be placed endoscopically (PEG) or radiologically (RIG), surgical gastrostomy has to be avoided because of general anaesthesia. Advantages of RIG are a success rate of about 100 percent and a placement feasible without sedation but its superiority on PEG in ALS patients especially if pulmonary functions are altered is not demonstrated. No objective criterion permits to define the exact moment of enteral nutrition. However, enteral nutrition is recommended when dysphagia becomes symptomatic (insufficient caloric intake with weight loss, dehydration, frequent choking and aspiration). Swallowing disorders must be detected early to give to patients and their family information about enteral nutrition and gastrostomy as soon as possible and to help them to decide. It is desirable to propose gastrostomy when forced vital capacity is yet above 50 percent and nutritional state not altered (body mass index>18kg/m2 and/or weight loss<10 percent). Enteral nutrition is not desirable in ALS patients with dementia or in the preterminal phase. Suitable enteral nutrition with regular nutritional evaluation can improve nutritional status. Currently, improvement of quality of life and survival due to enteral nutrition has not been proved in ALS patients.

[Prospective evaluation of three kits for endoscopic percutaneous gastrostomy (PEG)]. / Evaluation prospective de trois kits de gastrostomie percutanée endoscopique (GPE).

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) is often used for long-term enteral feeding. Various PEG kits are currently available. A technical evaluation could be useful in providing a criteria of choice between the different kits. METHODS: Therefore, from January 1995 to January 1998, we prospectively performed a short- and a mid-term technical evaluation of 150 PEG kits: 106 Compat Sandoz, 37 Flocare Nutricia et 7 Sherwood. RESULTS: In 20% of the patients studied, technical problems during endoscopic insertion of the probe were observed. Only minor incidents were found for Compat Sandoz and Flocare Nutricia kits. However, major problems occurred with the Sherwood kits leading to a very difficult (4 cases) or impossible (2 cases) transcutaneous introduction of the catheter into the stomach. Mid-term outcome was evaluated in 86 of the 150 patients (57%) with a median follow-up duration of 5 months (range: 1-24). The main finding of the mid-term evaluation was a significant alteration of the Compat Sandoz tube. CONCLUSION: This prospective evaluation shows that technical improvement of the available PEG kits are needed, that the PEG polyurethane tube could be preferred for long-term enteral feeding.

[Gallbladder involvement in Crohn disease]. / Atteinte vésiculaire au cours de la maladie de Crohn.

We report the case of a young woman with Crohn's disease involving the entire digestive tract and with associated lesions of the liver, pancreas and gallbladder. This latter lesion led to acute cholecystitis which required cholecystectomy. The histo-pathological examination showed granulomas with multinucleated giant cells in the lamina propria. This observation illustrates a severe and extended form of Crohn's disease involving the entire digestive tract as well as the liver, the pancreas and the gallbladder.

Duodenojejunal motility after oral and enteral nutrition in humans: a comparative study.

BACKGROUND: Small bowel motility during enteral nutrition (EN) remains poorly known. Our aim was to compare, in six healthy volunteers, the duodenojejunal motor patterns after a 750-kcal meal either ingested or infused intraduodenally at two different infusion rates: 2 kcal/min for 6 hours (6-hour EN) or 1 kcal/min for 12 hours (12-hour EN). METHODS: In each volunteer, the three manometric studies were carried out in a random order with an interval of > or = 1 week between each recording. Number of phase III (PIIIs), their characteristics, number of waves (NW), and area under the curve (AUC) were determined. RESULTS: PIIIs were interrupted by each type of nutrition in every volunteer. In five of six during 6-hour EN and in six of six during 12-hour EN, the first PIII returned before the end of EN. The mean duration of the fed pattern was similar in the three studies. During the interruption of PIIIs after oral meal, duodenojejunal motility was characterized by uninterrupted random contractions. By contrast, in four of six during the 6-hour EN and in five of six during 12-hour EN, it was organized as regular short bursts of contractions separated by motor quiescence. In all studies during the disruption of PIIIs, NW and AUC values decreased progressively with time and were higher at the jejunum level than in the duodenum (p < .001). However, at each level of recording, NW and AUC values were similar in the three types of feeding. After the return of PIIIs, the number, duration, and propagation velocity of PIIIs, NW, and AUC values were similar in the three studies. CONCLUSIONS: EN interrupts PIIIs, but, in most cases, PIIIs reappear before the end of EN. During the interruption of PIIIs, the organization of the contractions is qualitatively different from the fed pattern observed after oral feeding. For the same caloric value of the meal, the quantitative duodenojejunal motor response is not affected by the infusion rate, and the more important jejunal, rather than duodenal motor response found after an oral meal, is observed during EN. During EN, after the return of PIIIs, despite the persistence of a nutrient infusion into the duodenum, the small bowel motor patterns are not qualitatively or quantitatively different from those recorded in fasting subjects.