| 1. |
- Morner, Malin E. M., et al.
(författare)
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The Importance of Blood Loss During Colon Cancer Surgery for Long-Term Survival : An Epidemiological Study Based on a Population Based Register
- 2012
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 255:6, s. 1126-1128
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study tested the hypothesis that the amount of blood loss during surgery for colonic cancer influences long-term survival. Background: The perioperative blood loss during surgery for colorectal cancer relates to the risk for complications and early mortality. Methods: All patients who underwent surgery for colon cancer between 1997 and 2003 in the health-care region of Uppsala/Orebro were prospectively registered at the regional oncological center. Data on patients who underwent radical surgery for stages I to III disease were analyzed. Patients who died within 6 months after surgery were excluded. Hazard ratios were calculated with uni- and multivariate Cox proportional hazard regression. Because of covariation, blood loss, blood transfusion, and complications were tested in separate multivariate analyses. Results: Blood loss of 250 mL or more during surgery, male gender, occurrence of complications, age more than 75 years, and stage III disease were risk factors for overall mortality in the uni- and multivariate analyses. Perioperative blood transfusion was shown to be a risk factor in the univariate analysis only. Conclusions: The results support the hypothesis that degree of blood loss during surgery for colon cancer is a factor that influences long-term survival.
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| 2. |
- Svanfeldt, Monika, et al.
(författare)
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Effect of "preoperative" oral carbohydrate treatment on insulin action : a randomised cross-over unblinded study in healthy subjects
- 2005
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Ingår i: Clinical Nutrition. - Edinburgh, United Kingdom : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 24:5, s. 815-21
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Preoperative intake of a clear carbohydrate-rich drink reduces insulin resistance after surgery. In this study, we evaluated whether this could be related to increased insulin sensitivity at the onset of surgery. Furthermore, we aimed to establish the optimal dose-regimen.Methods: Six healthy volunteers underwent hyperinsulinaemic (0.8 mU/kg/min), normoglycaemic (4.5 mmol/l) clamps and indirect calorimetry on four occasions in a crossover-randomised order; after overnight fasting (CC), after a single evening dose (800 ml) of the drink (LC), after a single morning dose (400 ml, CL) and after intake of the drink in the evening and in the morning before the clamp (LL). Data are presented as mean+/-SD. Statistical analysis was performed using the Student's t-test and ANOVA.Results: Insulin sensitivity was higher in CL and LL (9.2+/-1.5 and 9.3+/-1.9 mg/kg/min, respectively) compared to CC and LC (6.1+/-1.6 and 6.6+/-1.9 mg/kg/min, P<0.01 vs. CL and LL).Conclusions: A carbohydrate-rich drink enhances insulin action 3 h later by approximately 50%. Enhanced insulin action to normal postprandial day-time level at the time of onset of anaesthesia or surgery is likely to, at least partly, explain the effects on postoperative insulin resistance.
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| 3. |
- Svanfeldt, Monika
(författare)
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Perioperative nutrition and insulin resistance
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgical trauma induces a catabolic response with development of insulin resistance as a central and well-characterised feature. In insulin resistance, the stimulating effect of insulin on peripheral glucose uptake and the suppressing effect of insulin on endogenous glucose release are decreased, resulting in hyperglycaemia. It is marked the first day after surgery and normalises within two to three weeks. Preoperative treatment with oral carbohydrates instead of traditional fasting and use of epidural anaesthesia reduce postoperative insulin resistance. Both starvation and bed rest are known to induce insulin resistance. In the first study, the effect of traditional post-surgical low caloric feeding and bed rest on insulin sensitivity (hyperinsulinaemic (0.8 mU/kg/min) normoglycaemic (4.5 mM) clamps) and substrate utilisation (indirect calorimetry) were studied in healthy volunteers in a control situation and after three days of low caloric feeding and bed rest. Half of the volunteers underwent a second protocol with identical low caloric feeding but without bed rest. Three days of low caloric feeding induced a decrease in insulin sensitivity by nearly 60 % and caused alterations in substrate utilisation both with and without bed rest. The metabolic effect of low caloric feeding and bed rest was not related to age in the present study. Thus, low caloric feeding might be of importance for development of postoperative insulin resistance. The use of total parenteral nutrition (TPN) in patients undergoing surgery in order to reduce catabolism has been shown to induce hyperglycaemia and increase the complication rate, mainly infectious. However, the effects of TPN have not been investigated in patients treated to proactively minimise development of postoperative insulin resistance. Insulin sensitivity, glucose kinetics (6,62H2-D-glucose) and substrate utilisation were studied before surgery and on the third postoperative day in 13 patients undergoing colorectal resections. Patients were randomised to postoperative hypocaloric glucose or TPN. All received preoperative oral carbohydrate treatment and epidural anaesthesia during and after surgery. Whole-body glucose disposal decreased by only approximately 25 % irrespective of whether or not TPN was given. Low caloric feeding resulted in changes in substrate utilisation and nitrogen balance resembling starvation, while TPN attenuated these changes. Preoperative oral carbohydrate treatment has been used as an evening dose the day before surgery (100 g) and a morning dose (50 g). The aim of study III was to investigate to what extent the two doses, respectively, affected insulin sensitivity at the time of onset of surgery. Insulin sensitivity and substrate utilisation were measured in six healthy volunteers on four occasions in a randomised order (in the overnight fasted state, after the evening dose only, after the morning dose only, and after both doses). Oral carbohydrate treatment given in the morning increased insulin sensitivity three hours later (corresponding to the time of onset of surgery) by approximately 50%. The evening dose did not affect insulin sensitivity the following day. Thus, increased insulin sensitivity at the onset of surgery might, at least in part, explain the positive effects of carbohydrate loading seen on postoperative insulin sensitivity. In paper IV, the effect of preoperative oral carbohydrate treatment on postoperative whole-body protein kinetics was evaluated. Insulin sensitivity, protein (2H5-phenylalanine, 2H2-tyrosine, 2H4-tyrosine) and glucose (6,62H2-D-glucose) kinetics and substrate utilisation were studied before surgery and on the first postoperative day in 12 patients undergoing colorectal resections. Patients were randomised between oral carbohydrate treatment and a placebo drink before surgery. Preoperative carbohydrate treatment improved postoperative whole-body protein balance. The effect of insulin on whole-body protein kinetics was not altered after surgery.
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| 4. |
- Svanfeldt, Monika, et al.
(författare)
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Postoperative parenteral nutrition while proactively minimizing insulin resistance
- 2006
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Ingår i: Nutrition (Burbank, Los Angeles County, Calif.). - New York, USA : Elsevier. - 0899-9007 .- 1873-1244. ; 22:5, s. 457-64
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We compared the metabolic effects of postoperative total parenteral nutrition (TPN) and hypocaloric glucose after treatment with oral carbohydrates preoperatively and epidural anesthesia to proactively minimize postoperative insulin resistance.Methods: Thirteen patients undergoing colorectal resections were given oral carbohydrates preoperatively and epidural anesthesia and randomized to TPN or hypocaloric glucose during and after surgery. Insulin sensitivity (hyperinsulinemic clamp [0.8 mU x kg(-1) x min(-1)], normoglycemic clamps [4.5 mM]), and glucose kinetics (6,6(2)H2-D-glucose), were studied before and on postoperative day 3. Indirect calorimetry was performed and nitrogen excretion in urine was measured. Values are presented as mean +/- standard deviation. Analysis of variance, planned comparison, and Bonferroni's correction were used for statistical analysis.Results: Three days after surgery insulin-stimulated whole-body glucose disposal decreased by 24 +/- 11% versus 28 +/- 23% in patients receiving TPN and hypocaloric glucose, respectively (P < 0.05 for both, not significant between groups). Endogenous glucose production during insulin stimulation was increased only in the glucose group after surgery (P < 0.05 versus before). After surgery, insulin-stimulated glucose oxidation was higher after treatment with TPN, whereas fat oxidation was lower (P < 0.05 for both versus glucose treatment). Fat oxidation increased in the glucose group at basal after surgery (P < 0.05 versus before). Nitrogen balance was less negative after treatment with TPN (P < 0.01).Conclusions: Treatment with TPN does not seem to improve postoperative peripheral insulin sensitivity in patients with minor insulin resistance after pretreatment with preoperative carbohydrates and perioperative epidural anesthesia. Hypocaloric nutrition results in changes in substrate utilization and nitrogen balance resembling starvation, whereas TPN attenuates these changes.
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| 5. |
- Zucchelli, Marco, et al.
(författare)
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PepT1 oligopeptide transporter (SLC15A1) gene polymorphism in inflammatory bowel disease
- 2009
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 15:10, s. 1562-1569
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human polymorphisms affecting gut epithelial barrier and interactions with bacteria predispose to the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). The intestinal transporter PepT1, encoded by the SLC15A1 gene, mediates intracellular uptake of bacterial products that can induce inflammation and NF-kappaB activation upon binding to NOD2, a protein often mutated in CD. Hence, we tested SLC15A1 polymorphisms for association with IBD.METHODS: Twelve SLC15A1 single nucleotide polymorphisms (SNPs) were genotyped in 1783 individuals from 2 cohorts of Swedish and Finnish IBD patients and controls. An in vitro system was set up to evaluate the potential impact of SLC15A1 polymorphism on PepT1 transporter function by quantification of NOD2-mediated activation of NF-kappaB.RESULTS: The common allele (C) of a coding polymorphism (rs2297322, Ser117Asn) was associated with CD susceptibility both in Sweden and in Finland, but with genetic effects in opposite directions (risk and protection, respectively). The best evidence of association was found in both populations when the analysis was performed on individuals not carrying NOD2 common risk alleles (Sweden allelic P = 0.0007, OR 1.97, 95% confidence interval [CI] 1.34-2.92; Finland genotype P = 0.0013, OR 0.63, 95% CI 0.44-0.90). The PepT1 variant encoded by the C allele (PepT1-Ser117) was associated with reduced signaling downstream of NOD2 (P < 0.0001 compared to Pept1-Asn117).CONCLUSIONS: A functional polymorphism in the SLC15A1 gene might be of relevance to inflammation and antibacterial responses in IBD. Whether this polymorphism truly contributes to disease susceptibility needs to be further addressed, and should stimulate additional studies in other populations.
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