Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients

Background: Pancreatic cancer is often accompanied by cachexia, a syndrome of severe weight loss and muscle wasting. A suboptimal response to nutritional support may further aggravate cachexia, yet the influence of nutrition on protein kinetics in cachectic patients is poorly understood. Methods: Eight cachectic pancreatic cancer patients and seven control patients received a primed continuous intravenous infusion of l‐[ring‐2H5]phenylalanine and l‐[3,3‐2H2]tyrosine for 8 h and ingested sips of water with l‐[1‐13C]phenylalanine every 30 min. After 4 h, oral feeding was started. Whole body protein breakdown, protein synthesis, and net protein balance were calculated. Results are given as median with interquartile range. Results: Baseline protein breakdown and protein synthesis were higher in cachectic patients compared with the controls (breakdown: 67.1 (48.1–79.6) vs. 45.8 (42.6–46.3) µmol/kg lean body mass/h, P = 0.049; and synthesis: 63.0 (44.3–75.6) vs. 41.8 (37.6–42.5) µmol/kg lean body mass/h, P = 0.021). During feeding, protein breakdown decreased significantly to 45.5 (26.9–51.1) µmol/kg lean body mass/h (P = 0.012) in the cachexia group and to 33.7 (17.4–37.1) µmol/kg lean body mass/h (P = 0.018) in the control group. Protein synthesis was not affected by feeding in cachectic patients: 58.4 (46.5–76.1) µmol/kg lean body mass/h, but was stimulated in controls: 47.9 (41.8–56.7) µmol/kg lean body mass/h (P = 0.018). Both groups showed a comparable positive net protein balance during feeding: cachexia: 19.7 (13.1–23.7) and control: 16.3 (13.6–25.4) µmol/kg lean body mass/h (P = 0.908). Conclusion: Cachectic pancreatic cancer patients have a higher basal protein turnover. Both cachectic patients and controls show a comparable protein anabolism during feeding, albeit through a different pattern of protein kinetics. In cachectic patients, this is primarily related to reduced protein breakdown, whereas in controls, both protein breakdown and protein synthesis alterations are involved

Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation

Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic–hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload

Laparoscopic fistula excision and omentoplasty for high rectovaginal fistulas: a prospective study of 40 patients

AIM: The aim of this study is to prospectively evaluate 40 patients with a high rectovaginal fistula treated by a laparoscopic fistula division and closure, followed by an omentoplasty. PATIENTS AND METHODS: Forty patients with a rectovaginal fistula, between the middle third of the rectum and the posterior vaginal fornix, resulting from different causes (IBD, iatrogenic and birth trauma) were treated by a laparoscopic excision of the fistula and insertion of an omentoplasty in the rectovaginal septum. The patients completed the gastrointestinal quality of life index questionnaire (GIQLI) and the Cleveland Clinic incontinence score (CCIS). All tests were performed at regular intervals after treatment. RESULTS: In 38 (95%) patients with a median age of 53 years (range 33-72), the surgical procedure was feasible. In two patients, the fistula was closed without an omentoplasty, and a diverting stoma was performed. The median follow-up was 28 months (range 10-35). Two patients (5%) developed a recurrent fistula. In one patient, the interposed omentum became necrotic and was successfully treated laparoscopically. In another patient, an abscess developed, which needed drainage procedures. The mean CCIS was 9 (range 7-10) before treatment and 10 (range 7-13) after treatment (p = 0.5 Wilcoxon). The median GIQLI score was 85 (range 34-129) before treatment and 120 (range75-142) after treatment (p = 0.0001, Wilcoxon). CONCLUSIONS: Laparoscopic fistula excision combined with omentoplasty is a good treatment modality with a high healing rate for high rectovaginal fistulas and an acceptable complication rate