Perioperative lipid-enriched enteral nutrition versus standard care in patients undergoing elective colorectal surgery (SANICS II): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Postoperative ileus and anastomotic leakage severely impair recovery after colorectal resection. We investigated the effect of perioperative lipid-enriched enteral nutrition versus standard care on the risk of postoperative ileus, anastomotic leakage, and other clinical outcomes. METHODS: We did an international, multicentre, double-blind, randomised, controlled trial of patients (≥18 years) undergoing elective colorectal surgery with primary anastomosis at six clinical centres in the Netherlands and Denmark. Patients were randomly assigned (1:1), stratified by location (colonic and rectal) and type of surgery (laparoscopic and open), via online randomisation software, with block sizes of six, to receive either continuous lipid-enriched enteral tube feeding from 3 h before until 6 h after surgery (intervention) or no perioperative nutrition (control). Surgeons, patients, and researchers were masked to treatment allocation for the entire study period. The primary outcome was postoperative ileus. Secondary outcomes included anastomotic leakage, pneumonia, preoperative gastric volumes, time to functional recovery, length of hospital stay, the need for additional interventions, intensive care unit admission, postoperative inflammatory response, and surgical complications. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175979, and trialregister.nl, number NTR4670. FINDINGS: Between July 28, 2014, and February 20, 2017, 280 patients were randomly assigned, 15 of whom were excluded after random allocation because they fulfilled one or more exclusion criteria. 265 patients received perioperative nutrition (n=132) or standard care (n=133) and were included in the analyses. A postoperative ileus occurred in 37 (28%) patients in the intervention group versus 29 (22%) in the control group (risk ratio [RR] 1·09, 95% CI 0·95-1·25; p=0·24). Anastomotic leakage occurred in 12 (9%) patients in the intervention group versus 11 (8%) in the control group (RR 1·01, 95% CI 0·94-1·09; p=0·81). Pneumonia occurred in ten (8%) patients in the intervention group versus three (2%) in the control group (RR 1·06, 95% CI 1·00-1·12; p=0·051). All other secondary outcomes were similar between groups (all p>0·05). INTERPRETATION: Perioperative lipid-enriched enteral nutrition in patients undergoing elective colorectal surgery has no advantage over standard care in terms of postoperative complications. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW), Fonds NutsOhra, and Danone Research.

Effect of Early vs Late Start of Oral Intake on Anastomotic Leakage Following Elective Lower Intestinal Surgery: A Systematic Review.

BACKGROUND: Experimental and clinical studies have demonstrated a beneficial effect of early enteral nutrition (EN) on anastomotic leakage following colorectal surgery. Early oral intake is a common form of early EN with various clinical benefits, but the effect on anastomotic leakage is unclear. This systematic review investigates the effect of early vs late start of oral intake on anastomotic leakage following lower intestinal surgery. METHODS: A systematic literature search was performed using the PubMed, Embase, Medline, and Cochrane databases. Randomized controlled trials were included that compared early (within 24 hours) vs late start of oral intake following elective surgery of the small bowel, colon, or rectum. Meta-analysis was performed for anastomotic leakage, overall complications, length of stay, and mortality. Sensitivity analysis was performed in which studies of inferior methodological quality were excluded. RESULTS: Nine studies including 879 patients met eligibility criteria. Early start of oral intake significantly reduced overall complications (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.93; P = .02), length of stay (mean difference, -0.89; 95% CI, -1.22 to -0.57; P < .001), and anastomotic leakage (OR, 0.40; 95% CI, 0.17-0.95; P = .04) compared with late start of oral intake. However, in the sensitivity analysis only the overall reduction of length of stay remained significant. CONCLUSION: The effect of early oral intake on anastomotic leakage is unclear as existing studies are heterogeneous and at risk of bias. High-quality studies are needed to study the potential benefit of EN on anastomotic healing.

Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis.

BACKGROUND: Endotoxin is hypothesized to play an important role in the activation of inflammatory pathways associated with nonalcoholic steatohepatitis (NASH). However, demonstration of hepatic endotoxin exposure is challenging due to the inaccessibility of the portal circulation. Furthermore, reliable measurement of the relatively low endotoxin levels in plasma of patients with liver disease and subsequent interpretation remain difficult. GOALS: In this study, we used the EndoCab assay that measures endogenous antibodies to the core region of endotoxin to estimate hepatic endotoxin exposure over time. STUDY: IgG levels against endotoxin were measured in peripheral plasma obtained from 21 severely obese patients with NASH and 9 severely obese patients with healthy livers. RESULTS: Plasma IgG levels against endotoxin were significantly elevated in patients with NASH compared with patients with healthy livers (48±63 GMU/mL vs. 10±13 GMU/mL). Moreover, these IgG levels progressively increased with NASH grade (grade 1 29±37; grade 2 58±51; grade 3 84±132 GMU/mL, P<0.05). There was no relation between plasma IgG levels and NASH stage. CONCLUSIONS: Plasma IgG levels against endotoxin were found to be increased in biopsy-proven human NASH and increased with aggravated inflammation in NASH, suggesting a relationship between chronic endotoxin exposure and the severity of human NASH.

Biomarkers of abdominal aortic aneurysm progression. Part 2: inflammation.

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin.

Biomarkers of AAA progression. Part 1: extracellular matrix degeneration.

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individual's risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase-alpha1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin-antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.