Visceral Fat and Anastomotic Leakage After Colon Cancer Resection.

BACKGROUND: Visceral fat is considered a risk for postoperative complications in colon cancer surgery. However, the association with anastomotic leakage as the most worrisome complication is not clear mainly because of underpowered studies. OBJECTIVE: The purpose of this study was to analyze the effect of visceral fat as a continuous variable on anastomotic leakage in a large cohort of colon cancer resections. DESIGN: This was a retrospective, multicenter cohort study. SETTINGS: This study used data of the Dutch Surgical Colorectal Audit of the years 2011 through 2014 from 8 Dutch teaching hospitals. Visceral fat was assessed on the routine preoperative abdominal CT scan. PATIENTS: A total of 2370 patients underwent colon cancer resection with primary anastomosis. There were 2011 patients operated electively and 359 in an emergency setting. MAIN OUTCOME MEASURES: The effect of visceral fat on anastomotic leakage after multivariable analysis was measured. RESULTS: Visceral fat was associated with anastomotic leakage in the elective colon resection group (n = 2011) but not in emergency colon resections (n = 359). Significant confounding was found for type of resection, BMI, and sex. The association of male sex and BMI as previously reported risk factors for anastomotic leakage was explained by visceral fat. LIMITATIONS: The study was limited by its retrospective character and missing clinical data of known risk factors for anastomotic leakage, like smoking history and certain medication. CONCLUSIONS: The independent association of visceral fat with anastomotic leakage was confined to the elective colon cancer resection group. The previously reported associations of male sex and BMI with anastomotic leakage were explained by visceral fat. Visceral fat-associated comorbidities did not influence anastomotic leakage, suggesting that its effect on colon anastomotic healing is local rather than systemic. Future risk analysis for anastomotic leakage in colon cancer surgery should contain visceral fat values and consider subgroup differences. See Video Abstract at http://links.lww.com/DCR/B396. ADIPOSIDAD VISCERAL Y FUGA ANASTOMTICA EN CASOS DE RESECCIN DE CNCER DE COLON: ANTECEDENTES:La acumulación de grasa visceral se considera como un factor de riesgo en caso de complicaciones postoperatorias de cirugía de cáncer de colon. Sin embargo, la asociación con la fuga anastomótica como la complicación más preocupante no está clara principalmente debido a los estudios de bajo impacto disponibles.OBJETIVO:Analizar el efecto de la adiposidad visceral como una variable contínua sobre la fuga anastomótica en una gran cohorte de resecciones de cáncer de colon.DISEÑO:Estudio de cohorte multicéntrico retrospectivo.AJUSTES:Se utilizaron los datos de la Auditoría Colorrectal Quirúrgica Holandesa entre los años 2011 y 2014 en 8 hospitales de enseñanza de los Paises bajos. La grasa visceral fué evaluada por medio de la tomografía computada abdominal preoperatoria de rutina.PACIENTES:Un total de 2370 pacientes fueron sometidos a resección de cáncer de colon con anastomosis primaria. 2011 pacientes fueron operados electivamente y 359 en situación de emergencia.PRINCIPALES MEDIDAS DE RESULTADO:El efecto de la adiposidad visceral en la fuga anastomótica después del análisis multivariable.RESULTADOS:La grasa visceral se asoció con la fuga anastomótica en el grupo de resección electiva de colon (n = 2011) pero no en las resecciones de emergencia (n = 359). Se encontraron factores de confusión significativos para el tipo de resección, el índice de masa corporal y el género. La adiposidad visceral explica la asociación del género masculino y el índice de masa corporal como factores de riesgo reportados previamente en los casos de fugas anastomóticas.LIMITACIONES:Carácter retrospectivo del estudio y la falta de datos clínicos de factores de riesgo conocidos para la fuga anastomótica, como los antecedentes de tabaquismo y el consumo de ciertos medicamentos.CONCLUSIONES:La asociación independiente de la adiposidad visceral con la fuga anastomótica se limitó al grupo de resección electiva por cáncer de colon. Las asociaciones previamente reportadas de género masculino e índice de masa corporal con fuga anastomótica se explicaron por la grasa visceral. Las comorbilidades asociadas a la grasa visceral no influyeron en la fuga anastomótica, lo que sugiere que la cicatrisación anastomótica obedece más a un factor local que a un factor sistémico. Un análisis de riesgos previsibles para fugas anastomóticas en casos de resección de cáncer de colon deben involucrar los valores de la adiposidad visceral y considerar las diferencias entre subgrupos. Consulte Video Resumen en http://links.lww.com/DCR/B396. (Traducción-Dr Xavier Delgadillo).

Improving postoperative outcome in rectal cancer surgery: Enhanced Recovery After Surgery in an era of increasing laparoscopic resection.

PURPOSE: The Enhanced Recovery After Surgery (ERAS) protocol reduces complications and length of stay (LOS) in colon cancer, but implementation in rectal cancer is different because of neo-adjuvant therapy and surgical differences. Laparoscopic resection may further improve outcome. The aim of this study was to evaluate the effects of introducing ERAS on postoperative outcome after rectal cancer resection in an era of increasing laparoscopic resections. MATERIALS AND METHODS: Patients who underwent elective rectal cancer surgery from 2009 till 2015 were included in this observational cohort study. In 2010, ERAS was introduced and adherence to the protocol was registered. Open and laparoscopic resections were compared. With regression analysis, predictive factors for postoperative outcome and LOS were identified. RESULTS: A total of 499 patients were included. The LOS decreased from 12.3 days in 2009 to 5.7 days in 2015 (p = 0.000). Surgical site infections were reduced from 24% in 2009 to 5% in 2015 (p = 0.013) and postoperative ileus from 39% in 2009 to 6% in 2015 (p = 0.000). Only postoperative ERAS items and laparoscopic surgery were associated with an improved postoperative outcome and shorter LOS. CONCLUSIONS: ERAS proved to be feasible, safe, and contributed to improving short-term outcome in rectal cancer resections. The benefits of laparoscopic surgery may in part be explained by reaching better ERAS adherence rates. However, the laparoscopic approach was also associated with anastomotic leakage. Despite the potential of bias, this study provides an insight in effects of ERAS and laparoscopic surgery in a non-randomized real-time setting.

Preoperative Cerebrospinal Fluid Cortisol and the Risk of Postoperative Delirium: A Prospective Study of Older Hip Fracture Patients.

BACKGROUND: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. OBJECTIVES: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. METHODS: In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. RESULTS: Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. CONCLUSIONS: These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients.

The trajectory of C-reactive protein serum levels in older hip fracture patients with postoperative delirium.

OBJECTIVES: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. METHODS: This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C-reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. RESULTS: Forty-one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1-2 days) and more prolonged delirium (3 days or more). CONCLUSIONS: Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory-vascular) pathological pathway of postoperative delirium.

Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats.

Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.

Visceral obesity determined by CT scan and outcomes after colorectal surgery; a systematic review and meta-analysis.

BACKGROUND: Visceral obesity may affect outcome after colorectal surgery. The visceral fat area as determined by CT scanning is considered the standard in the detection of visceral obesity. METHOD: A systematic review was performed of trials investigating the effect of visceral obesity on outcomes of patients with colorectal cancer with no radiotherapy or chemotherapy and measured by CT scanning. The main endpoints were primary hospital stay, morbidity, operative time and blood loss. Quality assessment and data extraction were performed independently by two observers. RESULTS: Seven studies were eligible for analysis, including 1230 patients. Primary hospital stay (weighted mean difference 1.16 days, 95% CI 0.0.05 to 2.28 days, p = 0.04), morbidity rates (RR 0.15, 95% CI 0.10 to 0.21, p < 0.00001) and operative time (weighted mean difference 20.47 min, 95% CI 12.76 to 28.17 min, p < 0.00001) were significantly higher for visceral obese patients. No difference was found in blood loss. CONCLUSION: Visceral obesity leads to a longer hospital stay, higher morbidity and longer operative time after elective colon surgery. These findings show that the preoperative CT scan for detecting disseminated disease can be used to assess visceral obesity and helps in risk profiling patients undergoing elective colon surgery.

Effect of oral taurine on morbidity and mortality in elderly hip fracture patients: a randomized trial.

Hip fracture patients represent a large part of the elderly surgical population and face severe postoperative morbidity and excessive mortality compared to adult surgical hip fracture patients. Low antioxidant status and taurine deficiency is common in the elderly, and may negatively affect postoperative outcome. We hypothesized that taurine, an antioxidant, could improve clinical outcome in the elderly hip fracture patient. A double blind randomized, placebo controlled, clinical trial was conducted on elderly hip fracture patients. Supplementation started after admission and before surgery up to the sixth postoperative day. Markers of oxidative status were measured during hospitalization, and postoperative outcome was monitored for one year after surgery. Taurine supplementation did not improve in-hospital morbidity, medical comorbidities during the first year, or mortality during the first year. Taurine supplementation lowered postoperative oxidative stress, as shown by lower urinary 8-hydroxy-2-deoxyguanosine levels (Generalized estimating equations (GEE) analysis average difference over time; regression coefficient (Beta): -0.54; 95% CI: -1.08--0.01; p = 0.04), blunted plasma malondialdehyde response (Beta: 1.58; 95% CI: 0.00-3.15; p = 0.05) and a trend towards lower lactate to pyruvate ratio (Beta: -1.10; 95% CI: -2.33-0.12; p = 0.08). We concluded that peri-operative taurine supplementation attenuated postoperative oxidative stress in elderly hip fracture patients, but did not improve postoperative morbidity and mortality.

Diagnostic accuracy and patient acceptance of MRI in children with suspected appendicitis.

OBJECTIVE: To compare magnetic resonance imaging (MRI) and ultrasound in children with suspected appendicitis. METHODS: In a single-centre diagnostic accuracy study, children with suspected appendicitis were prospectively identified at the emergency department. All underwent abdominal ultrasound and MRI within 2 h, with the reader blinded to other imaging findings. An expert panel established the final diagnosis after 3 months. We evaluated the diagnostic accuracy of three imaging strategies: ultrasound only, conditional MRI after negative or inconclusive ultrasound, and MRI only. Significance between sensitivity and specificity was calculated using McNemar's test statistic. RESULTS: Between April and December 2009 we included 104 consecutive children (47 male, mean age 12). According to the expert panel, 58 patients had appendicitis. The sensitivity of MRI only and conditional MRI was 100% (95% confidence interval 92-100), that of ultrasound was significantly lower (76%; 63-85, P < 0.001). Specificity was comparable among the three investigated strategies; ultrasound only 89% (77-95), conditional MRI 80% (67-89), MRI only 89% (77-95) (P values 0.13, 0.13 and 1.00). CONCLUSION: In children with suspected appendicitis, strategies with MRI (MRI only, conditional MRI) had a higher sensitivity for appendicitis compared with a strategy with ultrasound only, while specificity was comparable. KEY POINTS: • In children, MRI has a higher sensitivity for appendicitis than ultrasound. • Ultrasound followed by MRI in negative or inconclusive findings is accurate. • The tolerance for ultrasound and MRI in children is comparable. • MRI can be performed in children in an emergency setting.

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.

BACKGROUND: Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. METHODS: Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. RESULTS: Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. CONCLUSIONS: Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. TRIAL REGISTRATION: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. REGISTRATION NUMBER: NCT00497978. Local ethical protocol number: NL16222.094.07.

Affective functioning after delirium in elderly hip fracture patients.

BACKGROUND: Delirium in elderly patients is associated with various long-term sequelae that include cognitive impairment and affective disturbances, although the latter is understudied. METHODS: For a prospective cohort study of elderly patients undergoing hip fracture surgery, baseline characteristics and affective and cognitive functioning were assessed preoperatively. During hospital admission, presence of delirium was assessed daily. Three months after hospital discharge, affective and global cognitive functioning was evaluated again in patients free from delirium at the time of this follow-up. This study compared baseline characteristics and affective functioning between patients with and without in-hospital delirium. We investigated whether in-hospital delirium is associated with increased anxiety and depressive levels, and post-traumatic stress disorder (PTSD) symptoms three months after discharge. RESULTS: Among 53 eligible patients, 23 (43.4%) patients experienced in-hospital delirium after hip fracture repair. Patients who had experienced in-hospital delirium showed more depressive symptoms at follow-up after three months compared to the 30 patients without in-hospital delirium. This association persisted in a multivariate model controlling for age, baseline cognition, baseline depressive symptoms, and living situation. The level of anxiety and symptoms of PTSD at follow-up did not differ between both groups. CONCLUSION: This study suggests that in-hospital delirium is associated with an increased burden of depressive symptoms three months after discharge in elderly patients who were admitted to the hospital for surgical repair of hip fracture. Symptoms of depression in patients with previous in-hospital delirium cannot be fully explained by persistent (sub)syndromal delirium or baseline cognitive impairment.

The neuropsychological sequelae of delirium in elderly patients with hip fracture three months after hospital discharge.

BACKGROUND: Delirium is a risk factor for long-term cognitive impairment and dementia. Yet, the nature of these cognitive deficits is unknown as is the extent to which the persistence of delirium symptoms and presence of depression at follow-up may account for the association between delirium and cognitive impairment at follow-up. We hypothesized that inattention, as an important sign of persistent delirium and/or depression, is an important feature of the cognitive profile three months after hospital discharge of patients who experienced in-hospital delirium. METHODS: This was a prospective cohort study. Fifty-three patients aged 75 years and older were admitted for surgical repair of acute hip fracture. Before the surgery, baseline characteristics, depressive symptomatology, and global cognitive performance were documented. The presence of delirium was assessed daily during hospital admission and three months after hospital discharge when patients underwent neuropsychological assessment. RESULTS: Of 27 patients with in-hospital delirium, 5 were still delirious after three months. Patients with in-hospital delirium (but free of delirium at follow-up) showed poorer performance than patients without in-hospital delirium on tests of global cognition and episodic memory, even after adjustment for age, gender, and baseline cognitive impairment. In contrast, no differences were found on tests of attention. Patients with in-hospital delirium showed an increase of depressive symptoms after three months. However, delirium remained associated with poor performance on a range of neuropsychological tests among patients with few or no signs of depression at follow-up. CONCLUSION: Elderly hip fracture patients with in-hospital delirium experience impairments in global cognition and episodic memory three months after hospital discharge. Our results suggest that inattention, as a cardinal sign of persistent delirium or depressive symptomatology at follow-up, cannot fully account for the poor cognitive outcome associated with delirium.

Imbalance of arginine and asymmetric dimethylarginine is associated with markers of circulatory failure, organ failure and mortality in shock patients.

In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (SD 17·9) µmol/l) while ADMA concentration was within the normal range (0·46 (SD 0·18) µmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.

Visceral fat loss by whole-body electromyostimulation is attenuated in male and absent in female older Non-Insulin-Dependent diabetes patients.

INTRODUCTION: Type 2 diabetes and its reversal correlate with increases and decreases in visceral fat (VF). Resistance exercise reduces VF in healthy persons, but little is known in type 2 diabetes. Muscle contractions induced by whole-body electromyostimulation (WB-EMS) provide a very effective form of resistance training. We hypothesized that WB-EMS reduces VF and improves plasma glucose measures in older non-insulin dependent diabetes mellitus (NIDDM) males and females. METHODS: A four-arm age-matched case control study was done on WB-EMS twice a week in older NIDDM patients (27 males, 18 females) compared with controls (15 males, 15 females). VAT area (VAT, cm2 ), total fat mass (TFM, kg) and lean body mass (LBM, kg) were assessed by DEXA-scanning. HbA1c, fasting glucose and plasma lipoproteins were measured at baseline and after 4 months. RESULTS: Baseline control VAT was higher in males than females (140.5 ± 35.6 vs. 96.7 ± 42.3, p < .001). In NIDDM, VAT was higher with no significant sex difference (206.5 ± 65.0 vs. 186.5 ± 60.5). In controls, WBEMS reduced VAT in males and females to similar extent (-16.9% and -16.4%, p < .001 vs. baseline) and in preference to TFM (-9.2% and -3.6%) or body weight loss (-2.8 and -2.1%). In NIDDM, VF loss was attenuated in males (-7.3%, p < .01) but completely absent in females. WBEMS reduced HbA1c and cholesterol and increased HDL levels (all p < .05) only in male NIDDM CONCLUSIONS: WBEMS induced VF loss in healthy older males and females an effect strongly attenuated in male and completely absent in female NIDDM patients. This questions the effectiveness of muscle contraction-induced VF lipolysis in NIDDM. Sex differences may dictate the success of resistance training in NIDDM, a subject that needs to be addressed in future studies.

Antioxidant-enriched enteral nutrition and immuno-inflammatory response after major gastrointestinal tract surgery.

Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery. The objective of the study was to investigate the effect of an enteral supplement, containing glutamine and antioxidants, on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery. Patients (n 21) undergoing major gastrointestinal tract surgery were randomised in a single-centre, open-label study. The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1, 3, 5 and 7 after surgery. Major gastrointestinal surgery increased IL-6, TNF receptor 55/60 (TNF-R55) and C-reactive protein (CRP). Surgery reduced human leucocyte antigen-DR (HLA-DR) expression on monocytes. CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group. In the treatment group, from the moment Module AOX was administered on day 1 after surgery, TNF receptor 75/80 (TNF-R75) level decreased until the third post-operative day and then stabilised, whereas in the control group the TNF-R75 level continued to increase. The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response (CRP, TNF-R75) after surgery.

Erythrocyte deformability and aggregability in patients undergoing colon cancer surgery and effects of two infusions with omega-3 fatty acids.

BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of omega-3 fatty acidsMETHODS:Forty-four patients undergoing elective laparoscopic colon resection for non-metastasized cancer were randomized between intravenous omega-3 poly-unsaturated fatty acids (n-3 PUFAs) or placebo (saline). Peri-operative blood samples were analyzed with a Lorrca MaxSIS Ektacytometer and erythrocyte membrane phospholipids were determined with gas chromatography. RESULTS: Patient and operation characteristics were equal between groups. There was a significant increase in erythrocyte membrane eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) in the n-PUFA group. There were no significant differences in erythrocyte deformability but the aggregation index (AI) was significantly lower and the aggregation half time (T½) was significantly higher in the n-3 PUFA group. CONCLUSION: This study confirms rapid changes in erythrocyte membrane phospholipid composition after administration of intravenous n-3 PUFAs. Erythrocyte deformability parameters were not affected but erythrocyte aggregability was decreased in the n-3 PUFA group. Further investigation is necessary to gain more insights in the effects of n-3 PUFA and the postoperative inflammatory response on erythrocyte function.

Erythrocyte deformability and aggregation in morbidly obese women undergoing laparoscopic gastric bypass surgery and effects of oral omega-3 fatty acid supplementation.

BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of oral omega-3 fatty acids in morbidly obese women undergoing gastric bypass surgeryMETHODS:Fifty-six morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery were randomized between a low calorie diet (LCD) during 2 weeks or oral omega-3 poly-unsaturated fatty acids (n-3 PUFAs) and a normal diet during 4 weeks. Peri-operative blood samples were analyzed with the Lorrca MaxSIS Ektacytometer for erythrocyte deformability and aggregability. RESULTS: There were no significant differences in erythrocyte function between the groups at any time point. Only erythrocyte aggregability parameters were affected by surgery. At six month follow-up, aggregation index (AI) and cholesterol, glucose and insulin were significantly improved. CONCLUSIONS: In this study, oral Omega-3 supplementation did not affect erythrocyte function compared to a LCD. Six months after surgery a significant improvement in AI and metabolic parameters was observed in both groups, contributing to a reduction in the risk at thromboembolic and cardiovascular complications.

Effects of perioperative intravenous ω-3 fatty acids in colon cancer patients: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The postoperative inflammatory response contributes to tissue healing and recovery but overwhelming inflammation is associated with postoperative complications. n-3 (ω-3) PUFAs modulate inflammatory responses and may help to prevent a proinflammatory cascade. OBJECTIVES: We aimed to investigate the effects of perioperative intravenous n-3 PUFAs on inflammatory cytokines in colon cancer surgery. METHODS: This study is a randomized, double-blind, placebo-controlled clinical trial. Forty-four patients undergoing elective colon resection for nonmetastasized cancer were randomly assigned to 2 intravenous n-3 PUFA or saline control infusions the night before and the morning after surgery. Blood was sampled at 6 perioperative time points for changes in cytokines in serum and in LPS-stimulated whole blood samples and leukocyte membrane fatty acid profiles. RESULTS: Twenty-three patients received saline and 21 patients received n-3 PUFAs. Patient and operation characteristics were equal between groups, except for open resection (saline n = 5 compared with n-3 PUFA n = 0, P = 0.056). Ex-vivo IL-6 after LPS stimulation was significantly higher in the n-3 PUFA group at the first day after surgery (P = 0.014), but not different at the second day after surgery (P = 0.467). White blood cell count was higher in the n-3 PUFA group at the fourth day after surgery (P = 0.029). There were more patients with infectious complications in the n-3 PUFA group (8 compared with 3, P = 0.036). There were no overall differences in serum IL-6, IL-10, C-reactive protein, and length of stay. The administration of n-3 PUFAs resulted in rapid increases in leukocyte membrane n-3 PUFA content. CONCLUSIONS: In the n-3 PUFA group a clear relation with serum and LPS-stimulated cytokines was not found but, unexpectedly, more infectious complications occurred. Caution is thus required with the off-label use of a perioperative intravenous n-3 PUFA emulsion as a standalone infusion in the time sequence reported in the present study in colon resections with primary anastomosis. This trial was registered at clinicaltrials.gov as NCT02231203.

Four Weeks of Preoperative Omega-3 Fatty Acids Reduce Liver Volume: a Randomised Controlled Trial.

PURPOSE: Weight loss before bariatric surgery with a low-calorie diet (LCD) has several advantages, including reduction of liver volume and an improved access to the lesser sac. Disadvantages include performing surgery in a state of undernutrition, side effects, costs and patient compliance. Omega-3 fatty acids may serve as an alternative to reduce liver steatosis. MATERIALS AND METHODS: A randomised controlled open-label trial was done to compare the effects of a LCD with Modifast (800 kcal/day) during 2 weeks with 2 g of omega-3 fatty acids a day and a normal diet (2000 kcal/day) during 4 weeks. Total liver volume (TLV) and volume of the left liver lobe (LLL), visceral fat area (VFA) and muscle area (SMA) at the L3-L4 level were measured with MRI before and after preoperative treatment. RESULTS: Sixty-two morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) were recruited. In both groups, there was a significant decrease in LLL, TLV and VFA. For LLL and TLV reduction, the LCD had a significantly larger effect (p < 0.05). Only in the LCD group was there a significant decrease in SMA with significantly more side effects and worse compliance. CONCLUSION: Both the LCD and omega-3 diet reduced LLL, TLV and VFA. The LCD outperformed the omega-3 diet in LLL and TLV reduction, but induced significant loss of SMA and had worse compliance due to more side effects. Omega-3 fatty acids may provide a safe and more patient-friendly alternative for a LCD and further research is indicated. TRIAL REGISTRATION: The study is registered at www.clinicaltrials.gov (NCT02206256).

Antioxidant enriched enteral nutrition and oxidative stress after major gastrointestinal tract surgery.

AIM: To investigate the effects of an enteral supplement containing antioxidants on circulating levels of antioxidants and indicators of oxidative stress after major gastrointestinal surgery. METHODS: Twenty-one patients undergoing major upper gastrointestinal tract surgery were randomised in a single centre, open label study on the effect of postoperative enteral nutrition supplemented with antioxidants. The effect on circulating levels of antioxidants and indicators of oxidative stress, such as F2-isoprostane, was studied. RESULTS: The antioxidant enteral supplement showed no adverse effects and was well tolerated. After surgery a decrease in the circulating levels of antioxidant parameters was observed. Only selenium and glutamine levels were restored to pre-operative values one week after surgery. F2-isoprostane increased in the first three postoperative days only in the antioxidant supplemented group. Lipopolysaccharide binding protein (LBP) levels decreased faster in the antioxidant group after surgery. CONCLUSION: Despite lower antioxidant levels there was no increase in the circulating markers of oxidative stress on the first day after major abdominal surgery. The rise in F2-isoprostane in patients receiving the antioxidant supplement may be related to the conversion of antioxidants to oxidants which raises questions on antioxidant supplementation. Module AOX restored the postoperative decrease in selenium levels. The rapid decrease in LBP levels in the antioxidant group suggests a possible protective effect on gut wall integrity. Further studies are needed on the role of oxidative stress on outcome and the use of antioxidants in patients undergoing major abdominal surgery.

Effects of a Carbohydrate-, Glutamine-, and Antioxidant-Enriched Oral Nutrition Supplement on Major Surgery-Induced Insulin Resistance: A Randomized Pilot Study.

BACKGROUND: Insulin resistance after surgery hampers recovery. Oxidative stress is shown to be involved in the occurrence of postoperative insulin resistance. Preoperative carbohydrate-rich oral nutrition supplements reduce but do not prevent insulin resistance. The aim of the present study was to investigate the effect of a carbohydrate-, glutamine-, and antioxidant-enriched preoperative oral nutrition supplement on postoperative insulin resistance. METHODS: A double-blind randomized controlled pilot study in 18 patients with rectal cancer, who received either the supplement (S) or the placebo (P) 15, 11, and 4 hours preoperatively, was conducted. Insulin sensitivity was studied prior to surgery and on the first postoperative day using a hyperinsulinemic euglycemic 2-step clamp. RESULTS: Hepatic insulin sensitivity (insulin-mediated suppression of glucose production) decreased significantly after surgery in both groups, with no differences between the groups. Peripheral insulin sensitivity (glucose rate of disappearance, Rd) was significantly decreased after surgery in both groups (S: 37.2 [19.1-50.9] vs 20.6 [13.9-27.9]; P: 23.8 [15.7-35.5] vs 15.3 [12.6-19.1] µmol/kg·min) but less pronounced in the supplemented group (P = .04). The percentage decrease in glucose Rd did not differ between the groups. Adipose tissue insulin sensitivity (insulin-mediated suppression of plasma free fatty acids) decreased to the same extent after surgery in both groups. CONCLUSION: Rectal cancer surgery induced profound insulin resistance, affecting glucose and fatty acid metabolism. The preoperative nutrition supplement somewhat attenuated but did not prevent postoperative peripheral insulin resistance.