Oral ω-3 PUFA supplementation modulates inflammation in adipose tissue depots in morbidly obese women: A randomized trial.

OBJECTIVES: Obesity is characterized by local and systemic low-grade inflammatory responses. Adipose tissue macrophages (ATM) play decisive roles in inflammation, insulin signaling, and various metabolic dysfunctions. Diets enriched with ω-3 polyunsaturated fatty acids (PUFAs) have been shown to improve health and mitigate pathologic conditions. However, the effects of ω-3 PUFA on adipose tissue inflammation, ATM number, and phenotype are poorly defined in human obesity. The aim of this study was to examine differences in expression of metabolic-inflammatory markers in omental, mesenteric, and subcutaneous fat depots of obese women supplemented with ω-3 PUFAs for 4 wk compared with a low-calorie diet before bariatric surgery. METHODS: In a randomized controlled trial, inflammatory markers in the abdominal adipose tissue and the systemic response in obese women were studied. Patients were treated with a 2-wk low-calorie diet (LCD) or a 4-wk ω-3 PUFA-enriched diet (920 mg eicosapentaenoic acid, 760 mg docosahexaenoic acid daily) before laparoscopic bypass surgery. Omental, mesenteric, and subcutaneous adipose tissue biopsies were collected during surgery and analyzed for quantity and phenotype of ATMs, and profiled for adipokines, cytokines, and signal transduction molecules. RESULTS: The chronic inflammatory state characterized by ATM markers was mostly improved by ω-3 PUFAs in visceral adipose tissue. We observed a decreased expression of CD45, CCL2, and CD68, indicating a lower inflammatory state. In patients with type 2 diabetes, ω-3 PUFAs lowered the expression of Netrin-1. CONCLUSIONS: Compared with an LCD, a diet enriched with ω-3 PUFAs influences the inflammatory state in different adipose tissue depots, by affecting markers of adipose tissue inflammation, macrophage phenotype, and retention. However, this was not reflected in clinical parameters such as insulin resistance and inflammatory cytokines. Subcutaneous adipose tissue and visceral adipose tissue have different responses to an LCD or a ω-3 PUFA-enriched diet. The presence of diabetes modifies the expression of inflammatory markers.

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.

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.

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.

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).

[A young woman with acute pain in the lower right abdomen]. / Een jonge vrouw met acute pijn rechtsonder in de buik.

A 19-year old woman with acute pain in the lower right quadrant of the abdomen was seen in the emergency room. Because we suspected an anomaly of the appendix, we performed a laparoscopy. We unexpectedly found a torsion of a Hydatid of Morgagni, a stalked cyst of the fallopian tube.

Risk of anastomotic leakage with nonsteroidal anti-inflammatory drugs within an enhanced recovery program.

INTRODUCTION: Anastomotic leakage is a serious complication after colorectal resection. Recent studies suggest that nonsteroidal anti-inflammatory drugs may increase the risk of anastomotic leakage. We investigated this association in our enhanced recovery population. MATERIAL AND METHODS: Patients undergoing an elective colon or rectal resection with primary anastomosis because of malignancy and treated within our enhanced recovery program were included. Univariable and multivariable logistic regression analyses were used to study risk factors for anastomotic leakage. RESULTS: Between 2006 and 2013, 856 patients were included. The anastomotic leakage rate was significantly higher in the group that received nonsteroidal anti-inflammatory drugs compared to patients who did not: 9.2 vs. 5.3%, p = 0.038. This higher rate was only seen in patients receiving diclofenac: for colonic resections, 11.8 vs. 6.0%, p = 0.016; for rectal resections, 13.1 vs. 0%, p = 0.017. Only male sex (odds ratio 2.20, p = 0.005) was also independently associated with anastomotic leakage. CONCLUSION: The results of this study are in line with other comparable studies in the literature, showing an increased risk for anastomotic leakage with diclofenac. The use of diclofenac in colorectal surgery can no longer be recommended. Alternatives for postoperative analgesia need to be explored within an enhanced recovery program.

Eight years of experience with Enhanced Recovery After Surgery in patients with colon cancer: Impact of measures to improve adherence.

BACKGROUND: Perioperative treatment of patients with colorectal cancer according to the Enhanced Recovery After Surgery (ERAS) protocol has proven to reduce complications and duration of stay. However, strict adherence remains a challenge and the benefits may decrease with lower adherence. In this study, we report on 8 years of adherence to the ERAS protocol and its effect on postoperative outcome in patients with colon cancer. METHODS: In 2006, the ERAS protocol was introduced for treatment of colon cancer patients in the Medical Center Alkmaar, a large teaching hospital. Patients scheduled for elective colon cancer resection were included in this study. Adherence to ERAS items was monitored and along with clinical data prospectively gathered in a database. In 2011, several measures to improve adherence were implemented. RESULTS: In total, 816 patients were included. Mean adherence rate was 73% in 2006 and 2007, 66% in 2008 and 2009, 63% in 2010 and 2011, and 82% in 2012 and 2013. There was a shorter duration of stay in the years with high adherence (5.7 days) compared with the years with low adherence (7.3 days; P < .001). The ERAS items that were the strongest predictors for a shorter duration of stay were no nasogastric tube, early mobilization, early oral nutrition, early removal of epidural, early removal of catheter, and nonopioid oral analgesia. CONCLUSION: It is possible to improve adherence to the ERAS protocol and related outcomes with specific measures. Adherence to the ERAS protocol was related inversely to duration of stay. Only postoperative items of the ERAS protocol were predictive for a shorter duration of stay. Keeping adherence optimal remains an ongoing challenge that requires repeated training and dedicated personnel.