Enteral nutrition for maintaining remission in patients with quiescent Crohn's disease: current status and future perspectives.

PURPOSE: The value of enteral nutrition (EN) as maintenance therapy in patients with quiescent Crohn's disease (CD) has not been fully evaluated. The purpose of this study was to review the efficacy of EN for the maintenance of remission in patients with quiescent CD. METHODS: Seven prospective cohort studies evaluating the efficacy of EN for the maintenance of remission in quiescent CD were included. Three of the seven studies were randomized-controlled trials (RCTs). In all studies, patients used EN as a supplement or as a nocturnal tube feeding in addition to their normal food. RESULTS: One study compared the efficacy of elemental diet and polymeric diet. Elemental and polymeric diets were equally effective for the maintenance of clinical remission and for allowing tapering and cessation of steroid therapy. The other six studies compared the outcomes between patients treated with and without EN. The maintained clinical remission rate at 1 year was significantly higher in patients treated with EN in four of the six studies. Quantitative pooling of the studies was not feasible due to a small number of RCTs and a narrative account of the study characteristics. CONCLUSIONS: Our review suggests that EN is useful for the maintenance of remission in patients with quiescent CD. However, there are several limitations in the reviewed studies. There are few RCTs. Further, the sample size is small, and the duration of intervention and follow-up is short. Large and well-designed RCTs should be conducted to rigorously evaluate the efficacy of EN for maintaining remission.

Inverse association of des-acyl ghrelin with worksite blood pressure in overweight/obese male workers.

BACKGROUND: Job strain, defined as a combination of high job demands and low job control, has been reported to elevate blood pressure (BP) during work. Meanwhile, a recent experimental study showed that ghrelin blunted the BP response to such mental stress. In the present study, we examined the hypothesis that des-acyl ghrelin may have some beneficial effects on worksite BP through modulating the BP response to work-related mental stress, i.e., job strain. METHODS: Subjects were 34 overweight/obese male day-shift workers (mean age 41.7 ± 6.7 years). No subjects had received any anti-hypertensive medication. A 24-h ambulatory BP monitoring was recorded every 30 min on a regular working day. The average BP was calculated for Work BP, Morning BP, and Home BP. Job strain was assessed using the short version of the Japanese Job Content Questionnaire. RESULTS: Des-acyl ghrelin showed significant inverse correlations with almost all BPs except Morning SBP, Morning DBP, and Home DBP. In multiple regression analysis, des-acyl ghrelin inversely correlated with Work SBP after adjusting for confounding factors. Des-acyl ghrelin was also negatively associated with BP changes from Sleep to Morning, Sleep to Work, and Sleep to Home. CONCLUSIONS: Des-acyl ghrelin was inversely associated with Worksite BP, suggesting a unique beneficial effect of des-acyl ghrelin on Worksite BP in overweight/obese male day-shift workers.

Enteral nutrition to suppress postoperative Crohn's disease recurrence: a five-year prospective cohort study.

PURPOSE: The aim of this study was to investigate the long-term effect of enteral nutrition (EN) as a maintenance therapy in Crohn's disease (CD) patients following surgery. METHODS: This study was an extension of our previous study to prolong the duration of intervention and follow-up from 1 to 5 years. Forty consecutive patients who underwent resection for ileal or ileocolic CD were included. Following surgery, 20 patients received continuous elemental diet infusion during the nighttime plus a low-fat diet during the daytime (EN group). Another 20 patients received neither nutritional therapy nor food restriction (control group). All patients were followed for 5 years after operation. No patient received corticosteroid, immunosuppressants, or infliximab except patients who developed recurrence. The end point of this study was recurrence requiring biologic therapy or reoperation. Recurrence rates were analyzed on an intention-to-treat basis. RESULTS: In the EN group, four patients could not continue tube intubation for elemental diet intake. Two patients (10 %) in the EN group and nine patients (45 %) in the control group developed recurrence requiring infliximab therapy (P = 0.03). The cumulative recurrence incidence rate requiring infliximab was significantly lower in the EN group vs the control group (P = 0.02). One patient (5 %) in the EN group and five patients (25 %) in the control group required reoperation for recurrence (P = 0.18). The cumulative incidence of reoperation was lower in the EN group vs the control group, the difference not being significant (P = 0.08). CONCLUSION: The outcomes of this study suggest that EN therapy reduces the incidence of postoperative CD recurrence.

Increases in body mass index during infliximab therapy in patients with Crohn's disease: an open label prospective study.

In the past, the impact of infliximab therapy on nutritional status in patients with Crohn's disease (CD) has not been assessed. This prospective study was to investigate the effect of infliximab on nutritional status in CD patients. Fifty consecutive patients with active CD received infliximab (5 mg/kg) at weeks 0, 2 and 6 as remission induction therapy, and then at 8 weeks intervals as maintenance therapy. Patients were followed for 60 weeks. CD activity index (CDAI) and body mass index (BMI) were monitored. A fall in CDAI by ≥70 was defined as response to therapy, while CDAI<150 meant clinical remission. At week 10, 39 patients (78%) responded to infliximab induction therapy. BMI significantly increased during these 10 weeks (P<0.0001). The mean increase in BMI was significantly higher in patients who responded to infliximab vs patients who did not (P=0.03). Further, at weeks 30 and 60, 35 patients (70%) and 33 (66%) were in remission, respectively. The mean increase in BMI was significantly higher in patients who maintained remission vs patients not in remission (week 30, P=0.02; week 60, P=0.01). Patients with a low baseline BMI (<18.5) and those with small bowel involvement achieved a higher increase in BMI as compared to patients with BMI≥18.5 or patients without small bowel involvement. In this study, infliximab therapy was associated with improvement of patients' nutritional status, notably patients who responded to this biologic. Additionally, in patients with malnutrition and small bowel involvement, the nutritional impact of infliximab was higher.

Enteral nutrition for the maintenance of remission in Crohn's disease: a systematic review.

OBJECTIVE: This review study was designed to evaluate the efficacy of enteral nutrition (EN) for the maintenance of remission in patients with Crohn's disease (CD) who achieved medically or surgically induced remission. METHODS: The Medline, Embase, Ovid, and Cochrane database search of literature was carried out to identify studies that reported the efficacy of EN for the maintenance of remission in CD. The main outcome measure was the occurrence of clinical or endoscopic relapse. RESULTS: Ten studies were included: one randomized controlled trial, three prospective non-randomized trials, and six retrospective studies. Elemental, semielemental or polymeric diets were used as an oral supplement or a nocturnal tube feeding in addition to ordinary foods. Comparing outcomes between patients who received EN and those who did not, the clinical remission rate was significantly higher in those with EN in all seven studies. In two studies, EN showed suppressive effects on endoscopic disease activity. In all four studies investigating impacts of the quantity of enteral formula on clinical remission, higher amounts of enteral formula were associated with higher remission rates: > or =30 kcal/kg ideal body weight/day (vs. <30 kcal/kg ideal body weight/day), > or =1200 kcal/day (vs. <1200 kcal/day), and > or =1600 kcal/day (vs. <1600 kcal/day). Quantitative pooling of studies was not feasible because of the diversity of interventions and outcome measures among the studies. CONCLUSION: Although the evidence level is not high, the available data suggest that EN may be useful for maintaining remission in patients with CD. Large randomized controlled trials are necessary to assess a definite efficacy of EN for the maintenance of remission.

Prospective clinical trial: enteral nutrition during maintenance infliximab in Crohn's disease.

PURPOSE: Hitherto, the efficacy of enteral nutrition (EN) on clinical outcomes during biological maintenance therapy in Crohn's disease (CD) has not been investigated. This prospective study was to assess the efficacy of EN on the maintenance rate of clinical remission in patients with quiescent CD receiving infliximab as maintenance therapy. METHODS: Fifty-six patients who achieved clinical remission with infliximab induction therapy received infliximab as maintenance therapy (5 mg/kg, every 8 weeks). Thirty-two of the 56 patients received concomitant EN: elemental diet infusion during night-time and a low fat diet during daytime (EN group), while the remaining 24 patients received neither nutritional therapy nor food restriction (non-EN group). All patients were followed for 56 weeks; CD activity index (CDAI) was assessed and CDAI < 150 was defined as clinical remission. RESULTS: During the 56-week observation, the mean CDAI was not significantly different between the 2 groups. Seven patients in the EN group ceased EN therapy because they maintained complete remission. On an intention-to-treat basis, 25 patients in the EN group (78%) and 16 patients in the non-EN group (67%) remained in clinical remission during the 56-week observation (P = 0.51). CONCLUSIONS: The outcomes of this prospective study showed that concomitant EN during infliximab maintenance therapy does not significantly increase the maintenance rate of clinical remission in patients with CD.

Impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal cytokines during remission in patients with Crohn's disease: a prospective study.

BACKGROUND: Long-term enteral nutrition may maintain clinical and endoscopic remission in patients with Crohn's disease (CD). The aim of this prospective study was to investigate the impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal tissue cytokines in patients with quiescent CD. METHODS: Forty patients with CD who achieved clinical remission were included. Of these, 20 received continuous elemental diet (Elental) infusion during the nighttime and a low-fat diet during the daytime (EN group) and 20 received neither nutritional therapy nor food restriction (non-EN group). With these regimens, all 40 patients were monitored for 1 year. Further, ileocolonoscopy was performed at entry, at 6 and 12 months, and mucosal biopsies were taken for cytokine assays. RESULTS: On an intention-to-treat basis, 5 patients (25%) in the EN group and 13 (65%) in the non-EN group had a clinical relapse during the 1-year observation (P = 0.03). The mean endoscopic inflammation (EI) scores were not significantly different between the groups at both entry and 6 months, but at 12 months EI scores were significantly higher in the non-EN group than in the EN group (P = 0.04). Additionally, the mucosal tissue interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha levels significantly increased with time in the non-EN group (entry versus 12 months, IL-1beta, P = 0.02; IL-6, P = 0.002; TNF-alpha, P = 0.001). In the EN group these cytokines did not show a significant increase. CONCLUSIONS: Long-term enteral nutrition in patients with quiescent CD has a clear suppressive effect on clinical and endoscopic disease activities and the mucosal inflammatory cytokine levels.

Acute duodenal Crohn's disease successfully managed with low-speed elemental diet infusion via nasogastric tube: a case report.

Duodenal Crohn's disease is rare, and patients without obstruction are treated medically. We herein report one case whose duodenal Crohn's disease was successfully managed with low-speed elemental diet infusion through a nasogastric tube. A 28-year-old female developed acute duodenal Crohn's disease. Upper GI radiologic and endoscopic examinations showed a stricture in the duodenal bulb. Using the duodenal biopsy specimens, mucosal cytokine levels were measured; interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha levels were remarkably elevated. For initial 2 wk, powdered mesalazine was orally given but it was not effective. For the next 2 wk, she was treated with low-speed elemental diet therapy using a commercially available Elental(TM), which was infused continuously through a nasogastric tube using an infusion pump. The tip of the nasogastric tube was placed at an immediate oral side of the pylorus. The infusion speed was 10 mL/h (usual speed, 100 mL/h). After the 2-wk treatment, her symptoms were very much improved, and endoscopically, the duodenal stricture and inflammation improved. The duodenal mucosal cytokine levels remarkably decreased compared with those before the treatment. Although our experience was limited, low-speed elemental diet infusion through a nasogastric tube may be a useful treatment for acute duodenal Crohn's disease.

Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: cytokine production and endoscopic and histological findings.

BACKGROUND: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. METHODS: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-alpha in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1beta ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1beta ratio. CONCLUSIONS: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD.