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ABSTRACT: The aim of this study was to determine whether dynamic contrast-enhanced computed tomography (DCE-CT) and the slope method can provide absolute measures of hepatic blood perfusion from the hepatic artery (HA) and portal vein (PV) at experimentally varied blood flow rates.
Ten anesthetized 40-kg pigs underwent DCE-CT of the liver during periods of normocapnia (normal flow), hypocapnia (decreased flow), and hypercapnia (increased flow), which were induced by adjusting the ventilation. Reference blood flows in the HA and PV were measured continuously by surgically placed ultrasound transit-time flowmeters. For each capnic condition, the DCE-CT-estimated absolute hepatic blood perfusion from the HA and PV were calculated using the slope method and compared with flowmeter-based absolute measurements of hepatic perfusions and relative errors were analyzed.
The relative errors (mean ± SEM) of the DCE-CT based perfusion estimates were -21% ± 23% for HA and 81% ± 31% for PV during normocapnia, 9% ± 23% for HA and 92% ± 42% for PV during hypocapnia, and 64% ± 28% for HA and -2% ± 20% for PV during hypercapnia. The mean relative errors for HA were not significantly different from 0 during hypocapnia and normocapnia, and the DCE-CT slope method could detect relative changes in HA perfusion between scans. Infusion of contrast agent led to significantly increased hepatic blood perfusion, which biased the PV perfusion estimates.
Using the DCE-CT slope method, HA perfusion estimates were accurate at low and normal flow rates, whereas PV perfusion estimates were inaccurate and imprecise. At high flow rate, both HA perfusion estimates were significantly biased.
Investigative radiology 07/2012; 47(10):588-95. · 4.85 Impact Factor
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ABSTRACT: Intestinal ischemia is difficult to diagnose, and search for new biomarkers has led to interest in D-lactate, which arises from bacterial fermentation in the gastrointestinal tract.
The superior mesenteric artery was clamped in eight pigs for 6 h to induce ischemia of the intestine. Eight sham-operated pigs served as controls. Systemic and portal plasma D- and L-lactate were sampled in 1 h intervals. L-LDH was inactivated prior to D-lactate measurement by addition of NaOH.
In systemic vein samples, we found a significant mean difference in the change of D-lactate from baseline to 6 h between the sham and intervention group (.007 ± .011 mmol/l vs. .030 ± .013 mmol/l, respectively) (P = .020). Both systemic and portal circulation levels of plasma L-lactate increased significantly between the two groups within an hour. The mean difference for L-lactate were -.020 ± .215 mmol/l and 1.440 ± 1.454 mmol/l in the sham and intervention group, respectively (P = .009).
L-lactate was found to be a marker of arterial-induced intestinal ischemia in both the systemic and portal circulation. There was no significant elevation of D-lactate at either site during the 6 h of ischemia.
International journal of surgery (London, England) 05/2012; 10(6):296-300.
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ABSTRACT: BACKGROUND: Ischemic preconditioning (IPC) has been shown to protect the liver against ischemia-reperfusion (I/R) injuries. However, ischemic post-conditioning has received little attention. The aim of the present study was to quantify and compare the hepato-protective properties of IPC and IPO, for the first time, using unbiased design-based stereological methods. METHODS: We divided 67 rats into four groups: sham, liver ischemia (LI), IPC, and IPO. Rats were subjected to 60 min LI, followed by 4- or 24-h reperfusion. We performed quantification of (NVR) and apoptotic cell profile number. RESULTS: We observed no significant differences in NVR between ischemic groups after 4 h. After 24-h reperfusion, NVR had increased to 70% in the LI group, compared with 51% (P = 0.02) and 49% (P = 0.01) in the IPC and IPO groups, respectively. After 4-h reperfusion, the apoptotic cell number was significantly higher in all ischemic groups than in the sham group; we detected no difference between ischemic groups. After 24-h reperfusion, we detected a significantly lower number of apoptotic cell profiles in the IPC group than in the LI group (P = 0.02). The mean number of apoptotic cell profiles decreased insignificantly in the IPO group (P = 0.06). Liver parameters were at all time comparable between groups. CONCLUSIONS: After I/R, IPC and IPO reduce the degree of hepatocellular injury. Both methods are equally efficient at preventing hepatocellular necrosis. Furthermore, apoptosis is significantly lower after IPC.
Journal of Surgical Research 04/2012; · 2.25 Impact Factor
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ABSTRACT: To establish an automated plasma D-lactate assay without interference from L-lactate and L-lactate dehydrogenase (L-LDH).
The D-lactate assay was programmed as a 2-point endpoint assay on the Roche Modular P using the D-lactic acid kit from Biocontrol Systems, USA. In the chemical reaction, D-lactate was oxidized to pyruvate by NAD(+) in the presence of D-lactate dehydrogenase. The resultant pyruvate was converted to alanine in the presence of alanine aminotransferase. The amount of NADH formed in the coupled reaction, measured by the change in the absorbance at 340 nm, was proportional to the concentration of D-lactate in the sample. Human serum albumin (HSA) solutions and plasma from pigs with experimentally-induced gut ischemia were used in this study. Blood samples were collected into Venosafe® tubes.
The D-lactate assay was linear up to 1.000 mmol/L in HSA solutions and plasma. The detection limit was 0.003 mmol/L. Within-run CVs ≤ 2.0% and total CVs ≤ 3.2% were obtained in the control material. Recovery was 87.1 ± 5.2 % (Mean ± SD). The L-LDH activity was completely inactivated in plasma samples by the addition of 20 µL of a 5 mol/L NaOH solution to 500 µL of plasma (pH 11.5). No interference could be detected from concentrations of bilirubin < 450 µmol/L, haemoglobin < 0.2 mmol/L or Intralipid® < 2.5 g/L.
The performance of the established D-lactate assay meets the requirements to be implemented into hospital laboratories. The sample preparation method is simple, cheap and requires minimal labour.
Scandinavian journal of clinical and laboratory investigation 08/2011; 71(6):507-14. · 1.38 Impact Factor
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ABSTRACT: Intestinal ischemia is difficult to diagnose. The search for biomarkers has led to an increased interest in d-lactate. d-lactate measured in higher concentrations arises from bacterial fermentation in the gastrointestinal tract. Permeable intestinal wall is an early consequence of intestinal ischemia, which allows d-lactate to enter the portal circulation.
The superior mesenteric vein was clamped in eight pigs for two hours to induce ischemia of the intestine. Eight sham-operated pigs served as controls. Systemic and portal plasma d- and l-lactate, l-LDH and leukocytes were measured.
Plasma d-lactate increased significantly and nearly simultaneously in the systemic and portal circulation. After 75 min, samples from the jugular vein showed concentrations of .019 ± .008 mmol/L in the sham group and .042 ± .022 mmol/L in the intervention group (P = .023). A similar significant effect was seen in the portal circulation after 90 min. l-lactate increased five minutes after clamping in the portal circulation, with values of 3.396 ± 1.119 mmol/L in the intervention group compared to 1.696 ± .483 mmol/L in the control group (P = .006). l-LDH increased significantly in the intervention group, while leukocytes were unaffected. l-LDH and l-lactate in plasma led to an overestimation of d-lactate if not handled.
Both systemic d- and l-lactate were markers of venous-induced intestinal ischemia. We speculate that d-lactate may be a valuable aid to the clinician in search of the anaerobic focus, because it may be more specific for mesenteric ischemia than l-lactate, in the sense that it is of bacterial origin.
International journal of surgery (London, England) 04/2011; 9(5):428-32.
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ABSTRACT: We previously reported that both leukoreduced (LR) and buffy coat-depleted (BCD) blood transfusions had a detrimental effect on long-term overall survival in patients who underwent elective surgery for colorectal disease. This analysis investigates long-term cause-specific mortality in trial participants diagnosed with colorectal cancer (CRC).
We used the Danish Civil Registration System to follow 448 trial participants with CRC, from their enrollment in 1992 to 1995 until January 2007. A total of 108 patients were transfused with BCD blood, 94 with LR blood, and 246 did not receive a transfusion (NT). We reviewed death certificates for study patients who died during follow-up. Cause-of-death data were coded according to the International Classification of Diseases (ICD-8 and -10). The Charlson Comorbidity Index was used for risk adjustment.
A total of 43% of NT, 28% of BCD, and 27% of LR transfused patients were alive after 15 years of follow-up (p = 0.001 for transfused vs. NT patients). For LR-transfused versus NT patients the adjusted mortality ratio for death from rectal cancer was 1.81 (95% confidence interval [CI], 0.97-3.38), and for death from cardiovascular disease 2.12 (95% CI, 1.23-3.62). For BCD versus NT patients the adjusted mortality ratio for death from rectal cancer was 1.19 (95% CI, 0.61-2.33) and for cardiovascular disease it was 1.68 (95% CI, 0.97-2.91).
LR transfusion is associated with decreased long-term survival due to death from cardiovascular disease. A similar but weaker tendency was observed for BCD transfusion.
Transfusion 02/2011; 51(2):259-63. · 3.22 Impact Factor
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ABSTRACT: Ischemic pre- and postconditioning protects the liver against ischemia/reperfusion injuries. The aim of the present study was to examine how ischemic pre- and postconditioning affects gene expression of hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor A (VEGF-A) and transforming growth factor β (TGF-β) in liver tissue.
28 rats were randomized into five groups: control; ischemia/reperfusion; ischemic preconditioning (IPC); ischemic postconditioning (IPO); combined IPC and IPO. IPC consisted of 10 min of ischemia and 10 min of reperfusion. IPO consisted of three cycles of 30 sec. reperfusion and 30 sec. of ischemia.
HIF-1α mRNA expression was significantly increased after liver ischemia compared to controls (p = 0.010). HIF-1α mRNA expression was significantly lower in groups subjected to IPC or combined IPC and IPO when compared to the ischemia/reperfusion group (p = 0.002). VEGF-A mRNA expression increased in the ischemia/reperfusion or combined IPC and IPO groups when compared to the control group (p < 0.05).
Ischemic conditioning seems to prevent HIF-1α mRNA induction in the rat liver after ischemia and reperfusion. This suggests that the protective effects of ischemic conditioning do not involve the HIF-1 system. On the other hand, the magnitude of the HIF-1α response might be a marker for the degree of I/R injuries after liver ischemia. Further studies are needed to clarify this issue.
Comparative Hepatology 01/2011; 10(1):3. · 1.88 Impact Factor
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ABSTRACT: Pancreatic cancer has a relatively low incidence but ranks fourth among cancer- related deaths in western countries. In Denmark, cancer survival generally is lower than in other countries with comparable health care systems. As a result, in 2000, a national strategy to improve cancer survival was introduced. Here we examine time trends in survival and relative mortality among pancreatic cancer patients, using Danish population and medical databases.
Using the Danish National Patient Registry (DNPR), we identified all incident pancreatic cancer patients (n = 2968) diagnosed between 1998 and 2009 in the Central and North Denmark Regions. We computed the 1-, 3-, and 5-year survival and relative mortality (MRR) and associated 95% confidence intervals (CI) adjusting for age and gender. Among surgical patients, we also computed 30-day mortality and 30-day MRR.
Median age at diagnosis was approximately 71 years. The annual number of patients increased from 189 in 1998-2000 to 302 in 2007-2009. There was a slight improvement in 1-, 3-, and 5-year survival over time from 14.8% to 17.7%; 3.5% to a predicted 5.6%; and from 2.0% to a predicted 3.8%, from 1998-2000 to 2007-2009, respectively. Correspondingly, the adjusted relative mortality decreased from 1998-2000 to 2007-2009. Thirty-day post-operative mortality decreased from 12.2% in 1998-2000 to 5.8% in 2007-2009, corresponding to a 30-day MRR of 0.38, 95% CI = 0.09, 1.6 in 2007-2009.
There was a slight, albeit modest, improvement in survival and relative mortality in pancreatic cancer patients between 1998 and 2009. As we lacked staging information, it is not clear if this improvement is attributable to earlier stage at diagnosis. However, these improvements likely reflect the national cancer strategy which aimed to centralize cancer services and involved the introduction of palliative and adjuvant chemotherapy for pancreatic cancer in Denmark. The dismal prognosis of pancreatic cancer means that efforts to improve survival need to be intensified.
Clinical Epidemiology 01/2011; 3 Suppl 1:19-25.
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ABSTRACT: During surgery, ischaemic pre- (IPC) and post-conditioning (IPO) protects the liver against ischaemia/reperfusion injuries (I/R-injuries). The impact of ischaemic conditioning on liver regeneration has been less well studied. Angiogenesis is an important part of liver regeneration after hepatectomy. The aim of the present study was to investigate the effect of ischaemia/reperfusion and ischaemic conditioning on the expression of genes with angiogenic potential in a model of rat liver ischaemia.
A model of total liver ischaemia (30 min) and reperfusion (30 min) was employed using Wistar rats. Rats were randomized into five groups: (C) control (IRI) ischaemic, IPC, IPO and IPC + IPO. Liver enzymes were sampled at the end of reperfusion. Liver biopsies were analysed using cDNA microarrays.
Alanine aminotransferase (ALT) increased significantly in all the ischaemic groups compared with controls (P= 0.000). Searching databases 99 genes involved in rat liver angiogenesis were identified. Compared with group (C) the number of genes significantly up-regulated was as follows: IRI (n= 5), IPC (n= 24), IPO (n= 33) and IPC + IPO (n= 18). No genes were down-regulated in the four groups compared with controls.
Ischaemic conditioning, as demonstrated in the present study, seems to be potent activators of angiogenic genes. This might be favourable to the regenerating liver.
HPB 10/2010; 12(8):554-60. · 1.60 Impact Factor
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ABSTRACT: Cholangiocellular carcinoma accounts for 3% of gastrointestinal tumors. It is the second most common primary hepatic malignancy and is associated with primary sclerosing cholangitis.
We report a patient with primary sclerosing cholangitis and cholangiocellular carcinoma who underwent partial hepatectomy and postoperatively suffered life-threatening biliary stasis with cholascos and peritonitis. The patient had cholangiocellular carcinoma recurrence at the resection margins and local lymph node metastases, but chemotherapy was not possible because of elevated bilirubin and liver dysfunction. After successful percutaneous stenting and placement of an internal-external drainage tube from the biliary tree to the gastric ventricle, ascites and cholascos resolved completely and the patient was then referred for chemotherapy. The internal-external drainage tube was converted to an internal tube after 3 1/2 months. The patient received chemotherapy and survived 14 months after stenting.
Preferably, bile leaks should be detected preoperatively but the ongoing development of solutions to the postoperative biliary complications seen in these patients is extremely important.
Journal of Gastrointestinal Cancer 09/2010; 43(2):354-7.
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ABSTRACT: Acute cholecystitis can be the result of retention of bile in the gallbladder with possible secondary infection and ischaemia. The aim of the present study was to investigate whether internal drainage of the gallbladder could protect against the development of acute cholecystitis in a pig model.
Twenty pigs were randomized to either internal drainage (drained) or not (undrained). Day 0 acute cholecystitis was induced by ligation of the cystic artery and duct together with inoculation of bacteria. Four days later the pigs were killed and the gallbladders were removed and histologically scored for the presence of cholecystitis. Bile and blood samples were collected for bacterial culturing and biochemical analyses.
The histological examination demonstrated statistical significant differences in acute cholecystitis development between groups, the degree of inflammation being highest in undrained pigs. There were no differences in bacterial cultures between the two groups.
Internal drainage of the gallbladder protected against the development of acute cholecystitis in the present pig model. These findings support the theory that gallstone impaction of the cystic duct plays a crucial role as a pathogenetic mechanism in the development of acute cholecystitis and suggest that internal drainage may be a way to prevent and treat acute cholecystitis.
Annals of Surgical Innovation and Research 01/2010; 4:4.
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ABSTRACT: We evaluated the organisation, management and outcome for patients undergoing elective liver resection in Denmark in the period 2002-2007.
Nationwide data based on the National Patient Registry and discharge information from hospital departments in the period 1 January 2002 to 31 December 2007 were analysed.
Twenty-three departments performed 818 resections with five departments performing 96% and 18 departments performing 4% of the operations. The amount of non-anatomical resections constituted 30% (248 of 818) of the resections. The median postoperative stay was nine days, and the hospital mortality rate was 3.9%, distributed between 2.4% for non-anatomical resections, 2.9% for segmental resections and 5.2% for right-sided hepatectomy.
The number of treated patients was too small as was the number referred to highly specialised liver surgery units. Moreover, the amount of non-anatomical resections was too high as was the average postoperative stay and the hospital mortality rate. In future, we propose that liver resections be centralised in 2-3 hospitals each capable of providing all the following services: surgery, hepatology, oncology and interventional radiology.
Ugeskrift for laeger 05/2009; 171(17):1365-8.
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Ugeskrift for laeger 05/2008; 170(16):1321.
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ABSTRACT: In this consecutive, prospective study, the value of an FDG-PET scan acquired before treatment of liver metastases from colorectal cancer was tested in 54 patients. In 81% of the cases, PET findings were in concordance with CT. In 19% of the cases, the treatment plan was altered as more liver lesions were found by PET than by CT (4 patients), fewer or no liver lesions (3 patients), or extra-hepatic lesions (3 patients). PET used supplementary to CT improves the treatment decision in one fifth of patients with colorectal liver metastases.
Ugeskrift for laeger 05/2008; 170(16):1364-6.
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ABSTRACT: Because the liver has a remarkable ability to regenerate, extensive resections are possible. Most liver centres recommend that the remnant liver after resection in a non-cirrhotic liver constitutes at least 30% of the normal liver mass. Too extensive resection carries a risk of the small-for-size syndrome with coagulapathy, jaundice, multi-organ failure and high mortality. Resection in a liver with established cirrhosis is more difficult because the ability to regenerate is lost and function is reduced. Portal hypertension is considered a contraindication to resection.
Ugeskrift for laeger 05/2008; 170(16):1345-7.
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ABSTRACT: Obstruction often gives rise to disabling symptoms in non curable malignant upper gastrointestinal disease. Surgical relief is associated with high morbidity and mortality. We report outcomes of 24 patients palliated with endoscopic inserted stents. PATIENTS STUDIED: Thirteen females and 11 males, median age 66 years (range 24 to 88) suffered from gastroduodenal obstruction because of non curable malignant disease. All patients had nausea, repeated vomiting, and weight loss. The obstruction was localized in the stomach (n=5), gastrojejunostomy (n=3), or the duodenum (n=16). Self-expanding metal stents were delivered endoscopically under fluoroscopic control.
All patients got an improved quality of life and could eat at least semisolid food. All the patients were followed until they died. The median survival time after the procedure was 6.4 (range 0.5 to 23) months. In 1 patient stenting was complicated by perforation leading to death 2 weeks later. In another patient the stent migrated during the initial placement, but a secondary stent could be placed during the same procedure. Due to a long duodenal stenosis 2 patients got 2 stents under the primary procedure. During the follow-up period, 6 patients had supplementary gastroduodenal stents placed. Nine patients had biliary stents placed before the placement of the gastroduodenal stents, 2 after.
Our data suggest that endoscopic stenting for disabling symptoms due to gastroduodenal obstruction from non curable malignant disease, gives good symptomatic improvement with only few complications.
Surgical laparoscopy, endoscopy & percutaneous techniques 03/2007; 17(1):5-9. · 1.23 Impact Factor
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ABSTRACT: This study investigated the long-term survival rate of 589 patients enrolled in a trial in 1992-1995 who underwent colorectal surgery. The patients were randomised to receive leucocyte-depleted or buffy-coat-poor blood when transfusion was indicated. Significantly more of the non-transfused patients (59%) were alive seven years later compared to patients transfused with leucocyte-depleted blood (41%) and to patients transfused with buffy-coat-poor blood (45%).
Ugeskrift for laeger 01/2006; 168(5):481-4.
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ABSTRACT: A Danish clinical trial showed that transfusion with leucocyte-depleted red blood cells reduces postoperative infectious complications compared with cells without buffy-coat. However, the effect on long-term outcome is unknown. We followed up the 142 cancer patients transfused with buffy-coat-poor red cells, the 118 transfused with leucocyte-depleted blood, and the 329 who were not transfused, until 2003. After 7 years' follow-up, survival for those with leucocyte-depleted blood transfusion (46 [41%]) was not significantly different from transfusion of blood without buffy-coat (59 [45%], p=0.51). Although survival is reduced by blood transfusion, it does not differ between the two transfusion regimens.
The Lancet 365(9460):681-2. · 38.28 Impact Factor
