The importance of blood loss during colon cancer surgery for long-term survival: an epidemiological study based on a population based register.

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/Örebro 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.

Intraoperative local insufflation of warmed humidified CO2 increases open wound and core temperatures: a randomized clinical trial.

BACKGROUND: The open surgical wound is exposed to cold dry ambient air, resulting in substantial heat loss through radiation, evaporation, and convection. At the same time, anesthesia decreases the patient's core temperature. Despite preventive measures, mild intraoperative hypothermia has been associated with postoperative morbidity. We hypothesized that local insufflation of warmed humidified carbon dioxide (CO(2)) would maintain wound and core temperature. METHODS: Eighty patients undergoing open colon surgery were randomized to standard warming measures, or to additional local wound insufflation of warmed (30 °C) humidified (93 % rH) CO(2) via a gas diffuser. Surface temperature of the open abdominal wound was measured with a heat-sensitive infrared camera, and core temperature was measured with an ear thermometer. RESULTS: Mean operative time was 219 ± 104 and 205 ± 85 min in the CO(2) group and the control group, respectively (p = 0.550). Clinical variables did not differ significantly between the groups. The median wound area and wound edge temperatures were 1.2 °C (p < 0.001) and 1.0 °C (p = 0.002) higher in the CO(2) group, respectively, than in the control group. The mean core temperature after intubation was the same (35.9 °C) in both groups, but at end of surgery core temperature in the two groups differed, with a mean of 36.2 ± 0.5 °C in the CO(2) group and a mean of 35.8 ± 0.5 °C in the control group (p = 0.003). CONCLUSIONS: Insufflation of warmed, humidified CO(2) in an open surgical wound cavity prevents intraoperative decrease in surgical wound temperature as well as core temperature.

Local insufflation of warm humidified CO2increases open wound and core temperature during open colon surgery: a randomized clinical trial.

BACKGROUND: The open surgical wound is exposed to cold and dry ambient air resulting in heat loss through radiation, evaporation, and convection. Also, general and neuraxial anesthesia decrease the patient's core temperature. Despite routine preventive measures mild intraoperative hypothermia is still common and contributes to postoperative morbidity and mortality. We hypothesized that local insufflation of warm fully humidified CO(2) would increase both the open surgical wound and core temperature. METHODS: Eighty-three patients undergoing open colon surgery were equally and parallelly randomized to either standard warming measures including forced-air warming, warm fluids, and insulation of limbs and head, or to additional local wound insufflation of warm (37°C) humidified (100% relative humidity) CO(2) at a laminar flow (10 L/min) via a gas diffuser. Wound surface and core temperatures were followed with a heat-sensitive infrared camera and a tympanic thermometer. RESULTS: The mean wound area temperature during surgery was 31.3°C in the warm humidified CO(2) group compared with 29.6°C in the control group (P < 0.001, 95% confidence interval [CI], 1.2°C to 2.3°C). Also, the mean wound edge temperature during surgery was 30.1°C compared with 28.5°C in the control group (P < 0.001, 95% CI, 0.2°C to 0.7°C). Mean core temperature before start of surgery was similar with 36.7°C ± 0.5°C in the warm humidified CO(2) group versus 36.6°C ± 0.5°C in the control group (95% CI, 0.4 to -0.1°C). At end of surgery, the 2 groups differed significantly with 36.9 ± 0.5°C in the warm humidified CO(2) group versus 36.3 ± 0.5°C in the control group (P < 0.001, 95% CI, 0.38°C to 0.82°C). Moreover, only 8 patients of 40 in the warm humidified CO(2) group had a core temperature <36.5°C (20%, 95% CI, 7 to 33%), whereas in the control group this was the case in 24 of 39 (62%, 95% CI, 46% to 78%, P = 0.001) patients (difference of the percentages between the groups 42%, 95% CI, 22% to 61%, P < 0.001). With a cutoff at <36.0°C none of the patients in the warm humidified CO(2) group compared with 7 patients (18%, 95% CI, 5% to 31%, P = 0.005) in the control group was hypothermic at end of surgery (difference of the percentages between the groups 18%, 95% CI, 6% to 30%, P = 0.005). The median (25th/75th percentile) operating time was 181.5 (147.5/288) minutes in the warm humidified CO(2) group versus 217 (149/288) minutes in the control group (P = 0.312). Clinical variables did not show any significant differences between the groups. CONCLUSIONS: Insufflation of warm fully humidified CO(2) in an open surgical wound cavity increases surgical wound and core temperatures and helps to maintain normothermia.

Postoperative parenteral nutrition while proactively minimizing insulin resistance.

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.

Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes.

Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK alpha2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK alpha2.

Effect of "preoperative" oral carbohydrate treatment on insulin action--a randomised cross-over unblinded study in healthy subjects.

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.

PepT1 oligopeptide transporter (SLC15A1) gene polymorphism in inflammatory bowel disease.

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.