liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Winbladh, Anders
Publications (10 of 10) Show all publications
Brannstrom, F., Bjerregaard, J. K., Winbladh, A., Nilbert, M., Revhaug, A., Wagenius, G. & Morner, M. (2015). Multidisciplinary team conferences promote treatment according to guidelines in rectal cancer. Acta Oncologica, 54(4), 447-453
Open this publication in new window or tab >>Multidisciplinary team conferences promote treatment according to guidelines in rectal cancer
Show others...
2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 4, p. 447-453Article in journal (Refereed) Published
Abstract [en]

Background. Multidisciplinary team (MDT) conferences have been introduced into standard cancer care, though evidence that it benefits the patient is weak. We used the national Swedish Rectal Cancer Register to evaluate predictors for case discussion at a MDT conference and its impact on treatment. Material and methods. Of the 6760 patients diagnosed with rectal cancer in Sweden between 2007 and 2010, 78% were evaluated at a MDT. Factors that influenced whether a patient was discussed at a preoperative MDT conference were evaluated in 4883 patients, and the impact of MDT evaluation on the implementation of preoperative radiotherapy was evaluated in 1043 patients with pT3c-pT4 M0 tumours, and in 1991 patients with pN + M0 tumours. Results. Hospital volume, i.e. the number of rectal cancer surgical procedures performed per year, was the major predictor for MDT evaluation. Patients treated at hospitals with less than 29 procedures per year had an odds ratio (OR) for MDT evaluation of 0.15. Age and tumour stage also influenced the chance of MDT evaluation. MDT evaluation significantly predicted the likelihood of being treated with preoperative radiotherapy in patients with pT3c-pT4 M0 tumours (OR 5.06, 95% CI 3.08 - 8.34), and pN + M0 (OR 3.55, 95% CI 2.60 -4.85), even when corrected for co-morbidity and age. Conclusion. Patients with rectal cancer treated at high-volume hospitals are more likely to be discussed at a MDT conference, and that is an independent predictor of the use of adjuvant radiotherapy. These results indirectly support the introduction into clinical practice of discussing all rectal cancer patients at MDT conferences, not least those being treated at low-volume hospitals.

Place, publisher, year, edition, pages
Informa Healthcare, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117203 (URN)10.3109/0284186X.2014.952387 (DOI)000351533600003 ()25291075 (PubMedID)
Available from: 2015-04-22 Created: 2015-04-21 Last updated: 2017-12-04
Björnsson, B., Winbladh, A., Bojmar, L., Sundqvist, T., Gullstrand, P. & Sandström, P. (2014). Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion. World Journal of Gastroenterology, 20(28), 9506-9512
Open this publication in new window or tab >>Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion
Show others...
2014 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 28, p. 9506-9512Article in journal (Refereed) Published
Abstract [en]

AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

Place, publisher, year, edition, pages
Baishideng Publishing Group Co. Limited, 2014
Keywords
Ischemia-reperfusion injury; Preconditioning; Remote preconditioning; Liver ischemia; Liver surgery; Microdialysis; Nitric oxide; inducible nitric oxide synthase; interleukin-1 receptor
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-109589 (URN)10.3748/wjg.v20.i28.9506 (DOI)000339389800032 ()25071345 (PubMedID)
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-12-05
Winbladh, A., Björnsson, B., Trulsson, L., Offenbartl, K., Gullstrand, P. & Sandström, P. (2012). Ischemic Preconditioning Prior to Intermittent Pringles Maneuver in Liver Resections. Journal of Hepato-Biliary-Pancreatic Sciences, 19(2), 159-170
Open this publication in new window or tab >>Ischemic Preconditioning Prior to Intermittent Pringles Maneuver in Liver Resections
Show others...
2012 (English)In: Journal of Hepato-Biliary-Pancreatic Sciences, ISSN 1868-6982, Vol. 19, no 2, p. 159-170Article in journal (Refereed) Published
Abstract [en]

Background: Continuous inflow vascular occlusion during liver resections causes less severe ischemia and reperfusion injury (IRI) if it is preceded by ischemic preconditioning (IP) or if intermittent inflow occlusion is used during the resection. No previous clinical trial has studied the effects of adding IP to intermittent inflow occlusion.

Methods: Consecutive patients (n=32) with suspicion of malignant liver disease had liver resections (minimum 2 segments) performed with inflow occlusion 15/5. Half of the patients were randomized to receive IP (10/10). The patients were stratified according to volume of resection and none had chronic liver disease. The patients were followed for 5 days with microdialysis (μD).

Results: All patients completed the study and there were no deaths. No differences were seen between the groups regarding demographics or perioperative parameters (bleeding, duration of ischemia, resection volume, complications and serum lab tests). There were no differences in ALT, AST, Bilirubin or PT-INR levels, but μD revealed lower levels of lactate, pyruvate and glucose in the IP group having major liver resections (ANOVA). Nitrite and nitrate levels in μD decreased postoperatively but no differences were seen between the groups. In one patient an elevated μDglycerol curve was seen before the diagnosis of a stroke was made.

Conclusions: IP before intermittent vascular occlusion does not reduce the serum parameters used to assess IRI. IP seems to improve aerobic glucose metabolism as the levels of glucose, pyruvate and lactate locally in the liver were reduced compared to controls in patients having resected >3 segments. μD may be used to monitor metabolism locally.

Place, publisher, year, edition, pages
Springer, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68650 (URN)10.1007/s00534-011-0402-9 (DOI)000302092500011 ()
Available from: 2011-05-26 Created: 2011-05-26 Last updated: 2014-09-08Bibliographically approved
Winbladh, A., Björnsson, B., Trulsson, L., Bojmar, L., Sundqvist, T., Gullstrand, P. & Sandström, P. (2012). N-acetyl cysteine improves glycogenesis after segmental liver ischemia and reperfusion injury in pigs. Scandinavian Journal of Gastroenterology, 47(2), 225-236
Open this publication in new window or tab >>N-acetyl cysteine improves glycogenesis after segmental liver ischemia and reperfusion injury in pigs
Show others...
2012 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 2, p. 225-236Article in journal (Refereed) Published
Abstract [en]

Abstract Objective. N-acetylcysteine (NAC) is an antioxidative molecule known to protect liver tissue from oxygen radical species generated during ischemia and reperfusion (IR). Nutritional and toxicology studies have shown that NAC also improves glucose metabolism and glycogen stores. We hypothesized that NAC improves glycogenesis and that impaired glycogenesis is a key element in IR injury. Material and Methods. In an experimental model, 80 min of segmental liver ischemia was induced in 16 pigs and the reperfusion was followed for 360 min. Eight animals received NAC 150 mg/kg as a bolus injection followed by an infusion of NAC 50 mg/kg/h intravenously. Results. AST and leukocyte density were lower in the NAC-treated animals, unrelated to the glutathione levels or apoptosis. Glycogen stores returned to a higher degree in the NAC-treated animals and microdialysis revealed lower levels of lactate during the reperfusion phase. Nitrite/Nitrate levels in the NAC group were lower in both serum and microdialysates, indicating that NAC scavenges radical nitrosative species. Conclusions. NAC treatment improves glycogenesis after liver IR injury and reduces the level of intraparenchymal lactate during reperfusion, possibly due to the scavenging of radical nitrosative species.

Place, publisher, year, edition, pages
Informa Healthcare, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74184 (URN)10.3109/00365521.2011.643480 (DOI)
Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08
Björnsson, B., Winbladh, A., Bojmar, L., Trulsson, L., Olsson, H., Sundqvist, T., . . . Sandström, P. (2012). Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis. Journal of Surgical Research, 176(1), 55-62
Open this publication in new window or tab >>Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis
Show others...
2012 (English)In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 176, no 1, p. 55-62Article in journal (Refereed) Published
Abstract [en]

Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
ischemia-reperfusion injury; preconditioning; remote preconditioning; liver ischemia; liver surgery; microdialysis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79791 (URN)10.1016/j.jss.2011.07.038 (DOI)000305210100018 ()
Available from: 2012-08-17 Created: 2012-08-14 Last updated: 2017-12-07
Winbladh, A. (2011). Microdialysis in Liver Ischemia and Reperfusion injury. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Microdialysis in Liver Ischemia and Reperfusion injury
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: New chemotherapy regimens and improvements in surgical technique have increased the number of patients with liver tumours eligible for curative liver resection. There is a significant risk of bleeding during liver surgery, but this risk can be reduced if the portal inflow is temporarily closed; i.e. the Pringles maneuver (PM). If the PM is used, the liver will suffer from ischemia and reperfusion injury (IRI). If the liver remnant is too small or if the patient has chronic liver disease, the IRI may inhibit the regeneration of the liver remnant. The patient may then die from postoperative liver failure. Several strategies have been tried to protect the liver from IRI. For instance can the PM be applied in short intervals or reactive oxygen species can be scavenged by antioxidants. There are no sensitive methods available for studying IRI in patients and little is known how IRI affects the metabolism in the liver. Microdialysis is a technique that allows for continuous sampling of interstitial fluid in the organ of interest

Aim: To investigate the effects of ischemia and reperfusion on glucose metabolism in the liver using the microdialysis technique.

Method: A porcine model of segmental ischemia and reperfusion was developed. The hepatic perfusion and glucose metabolism was followed for 6-8 hours by placing microdialysis catheters in the liver parenchyma (studies I-III). In study IV, 16 patients were randomized to have 10 minutes of ischemic preconditioning prior to the liver resection, which was performed with 15 minutes of ischemia and 5 minutes of reperfusion repetitively until the tumour(s) were resected.

Results: During ischemia the glucose metabolism was anaerobic in the ischemic segment, while the perfused segment had normal glucose metabolism. Urea was added in the perfusate of the microdialysis catheters and was found to be a reliable marker of liver perfusion. The antioxidant NAcetylcystein (NAC) improved the hepatic aerobic glucose metabolism in the pig during the reperfusion, shown as reduced levels of lactate and improved glycogenesis in the hepatocytes. This can be explained by the scavenging of nitric oxide by NAC as nitric oxide otherwise would inhibit mitochondrial respiration. Also IP improved aerobic glucose metabolism resulting in lower hepatic lactate levels in patients having major liver resections.

Conclusion: Microdialysis can monitor the glucose metabolism both in animal experimental models and in patients during and after hepatectomy. Both NAC and IP improves aerobic glucose metabolism, which can be of value in patients with compromised liver function postoperatively.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. p. 86
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1238
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68651 (URN)978-91-7393-190-8 (ISBN)
Public defence
2011-06-10, Nils Holger, Hälsouniversitetet, Campus US. Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2011-05-26 Created: 2011-05-26 Last updated: 2020-02-03Bibliographically approved
Farnebo, S., Winbladh, A., Zettersten, E., Sandström, P., Gullstrand, P., Samuelsson, A., . . . Sjöberg, F. (2010). Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion. EUROPEAN SURGICAL RESEARCH, 45(2), 105-112
Open this publication in new window or tab >>Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion
Show others...
2010 (English)In: EUROPEAN SURGICAL RESEARCH, ISSN 0014-312X, Vol. 45, no 2, p. 105-112Article in journal (Refereed) Published
Abstract [en]

Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

Place, publisher, year, edition, pages
S. Karger AG, 2010
Keywords
Liver perfusion, Lactate, Ethanol, Metabolism, Recovery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-62299 (URN)10.1159/000319868 (DOI)000283851400006 ()
Available from: 2010-11-26 Created: 2010-11-26 Last updated: 2012-03-20
Winbladh, A., Sandström, P., Olsson, H., Svanvik, J. & Gullstrand, P. (2009). Segmental ischemia of the liver - microdialysis in a novel porcine model.. European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes, 43(3), 276-285
Open this publication in new window or tab >>Segmental ischemia of the liver - microdialysis in a novel porcine model.
Show others...
2009 (English)In: European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes, ISSN 1421-9921, Vol. 43, no 3, p. 276-285Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Segmental liver ischemia is often used in rodents to study ischemia and reperfusion injuries (IRI). There are no reports of protocols using segmental ischemia in porcine models. Microdialysis (MD) provides the opportunity to study local effects of IRI in vivo. METHODS: Eight pigs received an MD catheter placed in liver segments IV and V, respectively. All circulation to segment IV was stopped for 80 min, and reperfusion was followed for 240 min. RESULTS: During ischemia the levels of lactate, glycerol and glucose increased 3-fold (p < 0.001), 40-fold (p < 0.001) and 4-fold (p < 0.01), respectively, in the ischemic segment compared to the perfused segment, whereas the levels of pyruvate fell to a tenth of the preischemic level (p < 0.001). All values returned to baseline after reperfusion. Serum levels of aspartate aminotransferase increased (p < 0.05). Polymorphonuclear cells increased in both segments, although the density was significantly higher in segment IV. CONCLUSION: Clamping of one liver segment in pigs is a simple, stable and reproducible model to study IRI with minimal systemic effects. MD revealed no signs of anaerobic metabolism in the perfused segment but still there was an increase in the number of polymorphonuclear neutrophils in this segment, although it was lower than that in the ischemic segment.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21350 (URN)10.1159/000230675 (DOI)19641322 (PubMedID)
Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2011-05-26
Winbladh, A., Gullstrand, P., Svanvik, J. & Sandström, P. (2009). Systematic review of cholecystostomy as a treatment option in acute cholecystitis. HPB, 11(3), 183-193
Open this publication in new window or tab >>Systematic review of cholecystostomy as a treatment option in acute cholecystitis
2009 (English)In: HPB, ISSN 1365-182X, Vol. 11, no 3, p. 183-193Article, review/survey (Refereed) Published
Abstract [en]

Objectives: Percutaneous cholecystostomy (PC) is an established low-mortality treatment option for elderly and critically ill patients with acute cholecystitis. The primary aim of this review is to find out if there is any evidence in the literature to recommend PC rather than cholecystectomy for acute cholecystitis in the elderly population. Methods: In April 2007, a systematic electronic database search was performed on the subject of PC and cholecystectomy in the elderly population. After exclusions, 53 studies remained, comprising 1918 patients. Three papers described randomized controlled trials (RCTs), but none compared the outcomes of PC and cholecystectomy. A total of 19 papers on mortality after cholecystectomy in patients aged greater than65 years were identified. Results: Successful intervention was seen in 85.6% of patients with acute cholecystitis. A total of 40% of patients treated with PC were later cholecystectomized, with a mortality rate of 1.96%. Procedure mortality was 0.36%, but 30-day mortality rates were 15.4 % in patients treated with PC and 4.5% in those treated with acute cholecystectomy (P less than 0.001). Conclusions: There are no controlled studies evaluating the outcome of PC vs. cholecystectomy and the papers reviewed are of evidence grade C. It is not possible to make definitive recommendations regarding treatment by PC or cholecystectomy in elderly or critically ill patients with acute cholecystitis. Low mortality rates after cholecystectomy in elderly patients with acute cholecystitis have been reported in recent years and therefore we believe it is time to launch an RCT to address this issue.

Keywords
Acute; Cholecystitis; Cholecystostomy; Elderly; Review
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-21320 (URN)10.1111/j.1477-2574.2009.00052.x (DOI)000207814100001 ()19590646 (PubMedID)
Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2017-01-16Bibliographically approved
Winbladh, A., Björnsson, B., Trulsson, L., Bojmar, L., Sundqvist, T., Gullstrand, P. & Sandström, P.N-Acetylcysteine Improves Glycogenesis after Segmental Liver Ischemia and Reperfusion Injury in Pigs.
Open this publication in new window or tab >>N-Acetylcysteine Improves Glycogenesis after Segmental Liver Ischemia and Reperfusion Injury in Pigs
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: N-Acetylcysteine (NAC) is an antioxidative molecule known to protect liver tissue from oxygen radical species generated during ischemia and reperfusion. Nutritional and toxicology studies have shown that NAC also improves glucose metabolism and glycogen stores. We hypothesized that NAC improves glycogenesis and that impaired glycogenesis is a key element in ischemia-reperfusion injury.

Material and Methods: In an experimental model, 80 minutes of segmental liver ischemia was induced in 16 pigs and the reperfusion was followed for 360 minutes. Eight animals received NAC 150 mg/kg as a bolus injection followed by an infusion of NAC 50 mg/kg/h intravenously.

Results: AST and leukocyte density were lower in the NAC-treated animals, unrelated to the glutathione levels or apoptosis. Glycogen stores returned to a higher degree in the NAC treated animals and microdialysis revealed lower levels of lactate during the reperfusion phase. Nitrite/Nitrate levels in the NAC group were lower in both serum and microdialysate, indicating that NAC scavenges radical nitrosative species (RNS).

Conclusions: NAC treatment improves glycogenesis after liver ischemia and reperfusion injury and reduces the level of intraparenchymal lactate during reperfusion, possibly due to the scavenging of RNS.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68649 (URN)
Available from: 2011-05-26 Created: 2011-05-26 Last updated: 2011-05-26Bibliographically approved
Organisations

Search in DiVA

Show all publications