| 1. |
- Bergström, Maria, 1964, et al.
(författare)
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Effect of acidosis on expression of mesothelial cell plasminogen activator inhibitor type-1.
- 2006
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Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 20:9, s. 1448-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Abdominal mesothelial cells are exposed to carbon dioxide during laparoscopy. Previous data indicate that carbon dioxide increases release and expression of plasminogen activator inhibitor type-1 (PAI-1) and induces acidification. METHODS: To assess the impact resulting from a range of pH, human mesothelial cells were exposed to culturing media balanced to pH levels of 6.0 to 8.0 for 90 min. Samples from cell media were withdrawn at several time points. Concentrations of PAI-1 and PAI-1 activity were measured using enzyme-linked immunoassay techniques. To focus on the effect of clinically relevant pH, cells were subjected to pH 6.4 and 7.4. Samples were withdrawn for PAI-1 assessments and for PAI-1 mRNA analyses. RESULTS: During exposure to various levels of pH, PAI-1 secretion and activity were variable. However, 5 h after exposure, greater concentration and activity of PAI-1 were observed in acidified cultures. More PAI-1 mRNA was isolated after exposure of cells to a pH of 6.4, apparently indicating transcriptional regulation. CONCLUSIONS: Mesothelial cells seem to respond to acidification by an increased release and production of PAI-1 in vitro.
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| 2. |
- Bergström, Maria, 1964, et al.
(författare)
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Peritoneal and systemic pH during pneumoperitoneum with CO(2) and helium in a pig model.
- 2008
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 22:2, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Local peritoneal effects of laparoscopic gases might be important in peritoneal biology during and after laparoscopic surgery. The most commonly used gas, CO(2), is known to be well tolerated, but also causes changes in acid-base balance. Helium is an alternative gas for laparoscopy. Although safe, it is not widely used. In this study a method for monitoring peritoneal pH during laparoscopy was evaluated and peritoneal pH during CO(2) and helium pneumoperitoneum was studied as well as its systemic reflection in arterial pH. METHODS: For these experiments 20 pigs were used, with ten exposed to pneumoperitoneum with CO(2), and ten to helium. Peritoneal and sub-peritoneal pH were continuously measured before and during gas insufflation, during a 30-minute period with a pneumoperitoneum and during a 30-minute recovery period. Arterial blood-gases were collected immediately before gas insufflation, at its completion, at 30 minutes of pneumoperitoneum and after the recovery period. RESULTS: Peritoneal pH before gas insufflation was in all animals 7.4. An immediate local drop in pH (6.6) occurred in the peritoneum with CO(2) insufflation. During pneumoperitoneum pH declined further, stabilising at 6.4, but was restored after the recovery period (7.3). With helium, tissue pH increased slightly (7.5) during insufflation, followed by a continuous decrease during pneumoperitoneum and recovery, reaching 7.2. Systemic pH decreased significantly with CO(2) insufflation, and increased slightly during helium insufflation. Systemic pH showed co-variation with intra-peritoneal pH at the the end of insufflation and after 30 minutes of pneumoperitoneum. CONCLUSIONS: Insufflation of CO(2) into the peritoneal cavity seemed to result in an immediate decrease in peritoneal pH, a response that might influence biological events. This peritoneal effect also seems to influence systemic acid-base balance, probably due to trans-peritoneal absorption.
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| 3. |
- Brokelman, Walter J A, et al.
(författare)
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Decreased peritoneal tissue plasminogen activator during prolonged laparoscopic surgery.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 151:1, s. 89-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peritoneal fibrinolysis is crucial in the peritoneal healing processes and subsequent adhesion formation. During conventional surgery, the peritoneal fibrinolytic system is rapidly disturbed. Short-term laparoscopy does not seem to affect peritoneal fibrinolysis. The aim of the present study was to assess the effect of prolonged laparoscopic surgery on peritoneal fibrinolysis. METHODS: Twelve consecutive patients undergoing laparoscopic gastric bypass surgery for morbid obesity were included in the study. During the procedure, biopsies of the parietal peritoneum were taken at the start of the procedure and each 45 min afterward. Tissue samples were homogenized and tissue-type plasminogen activator (tPA) antigen, tPA activity, urokinase-type PA antigen, and plasminogen activating inhibitors type 1 antigen were measured using commercial assay techniques. RESULTS: Both tPA antigen and its activity progressively decreased during the procedure, reaching significant levels after 90 min of surgery. The levels of uPA antigen and plasminogen activating inhibitors antigen did not significantly change throughout the procedure. CONCLUSIONS: As for conventional surgery, prolonged laparoscopic surgery causes a decreased fibrinolytic activity in the peritoneum due to decreased tPA levels.
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| 4. |
- Brokelman, Walter J A, et al.
(författare)
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Peritoneal fibrinolytic response to various aspects of laparoscopic surgery: a randomized trial.
- 2006
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 0022-4804. ; 136:2, s. 309-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peritoneal fibrinolysis is important in peritoneal wound healing processes and adhesion formation. The peritoneal fibrinolytic response to laparoscopy is merely unknown. In the present study we investigate the effect of short-term laparoscopy on the peritoneal fibrinolytic response and the influence of intra-abdominal pressure, light intensity and choice of dissection device on this response. METHODS: There were 50 patients scheduled for laparoscopic cholecystectomy randomized in five groups operated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and the end of the procedure. Tissue concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and the tPA-activity were measured using ELISA techniques. RESULTS: There were no differences in tPA antigen, tPA-activity, uPA antigen, or PAI-1 antigen concentrations in biopsies taken at the beginning compared to samples taken at the end of the operation. Different intra-abdominal pressures, light intensities and the choice dissection device did not affect any of the measured parameters. CONCLUSION: Short-term laparoscopy does not affect the peritoneal fibrinolytic activity. The used intra-abdominal pressure, light intensity and choice of dissection device do not affect peritoneal activity during short-term laparoscopy.
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| 5. |
- Brokelman, Walter J A, et al.
(författare)
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Peritoneal transforming growth factor beta-1 expression during laparoscopic surgery: a clinical trial.
- 2007
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Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 21:9, s. 1537-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) is a growth factor involved in various biologic processes, including peritoneal wound healing and dissemination of malignancies. Laparoscopic surgery is evolving rapidly, and indications are increasing. The peritoneal TGF-beta1 expression during laparoscopic surgery is unknown. METHODS: For this study, 50 patients scheduled for laparoscopic cholecystectomy were randomized into five groups, then surgically treated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and end of surgery. Tissue concentrations of total and active TGF-beta1 were measured using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: There was no significant difference in either total or active TGF-beta1 concentration between peritoneal biopsies taken at the start of surgery and samples taken at the end of the procedure. Patients who underwent surgery with the ultrasonic scalpel had significant lower levels of both active (p < 0.005) and total (p < 0.01) TGF-beta1 at the end of surgery than patients treated with electrocautery. Patients who had surgery with a high light intensity had significantly lower levels of total TGF-beta1 levels (p < 0.005) with an unchanged active part than patients who had surgery with low light intensity. CONCLUSION: The choice of dissection device and the light intensity used in laparoscopic surgery affect peritoneal TGF-beta1 concentrations, indicating that peritoneal biology can be affected by laparoscopic surgery. Because TGF-beta1 is involved in various biologic processes in the peritoneal cavity, this observation may have important clinical consequences.
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| 6. |
- Brokelman, Walter, et al.
(författare)
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The peritoneal fibrinolytic response to conventional and laparoscopic colonic surgery.
- 2009
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Ingår i: Journal of laparoendoscopic & advanced surgical techniques. Part A. - : Mary Ann Liebert Inc. - 1092-6429 .- 1557-9034. ; 19:4, s. 489-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laparoscopic surgery is considered to induce less peritoneal trauma than conventional surgery. The peritoneal plasmin system is important in the processes of peritoneal healing and adhesion formation. The present study assessed the peritoneal fibrinolytic response to laparoscopic and conventional colonic surgery. METHODS: Twenty-four patients scheduled for a right colonic resection were enrolled in the trial. Twelve underwent conventional surgery and 12 were operated laparoscopically. Biopsies of the parietal peritoneum were taken at standardized moments during the procedure. Tissue concentrations of tissue-type plasminogen activator (tPA) and its specific activity (tPA-activity), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured, using commercial assays. RESULTS: After mobilization of the colon, peritoneal levels of tPA antigen and activity were significantly higher in the laparoscopic group (p < 0.005) due to a decrease in the conventional group (p < 0.05). At the end of the procedure, the concentrations of tPA antigen and activity significantly (p < 0.05) decreased in the laparoscopic group to levels comparable with the conventional group. Neither uPA antigen nor PAI-1 antigen changed throughout the procedures. CONCLUSIONS: Both conventional and laparoscopic surgery inflict a decrease in tPA antigen and its specific activity. Peritoneal hypofibrinolysis initiates more rapidly during conventional, compared to laparoscopic, surgery, but at the conclusion of the surgery, the effect was the same.
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| 7. |
- Falk, Peter, 1962, et al.
(författare)
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Studies of TGF-beta(1-3) in serosal fluid during abdominal surgery and their effect on in vitro human mesothelial cell proliferation.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 154:2, s. 312-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased transforming growth factor-beta (TGF-beta) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-beta response to the surgical trauma is limited. This study investigated TGF-beta(1-3) isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-beta(1-3) on human mesothelial cell proliferation. MATERIALS AND METHODS: Total as well as biologically active TGF-beta(1-3) and fibrinolytic factors: t-PA, uPA, and PAI-1 were measured in serosal fluid and plasma from 23 patients undergoing colorectal cancer surgery. In vitro proliferation of human primary mesothelial cell cultures upon TGF-beta(1-3) stimulation was also investigated. RESULTS: Total TGF-beta1 and TGF-beta2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-beta3 was higher in serosal fluid compared with plasma, while levels of active fractions did not differ. Plasminogen activators (t-PA, uPA) were elevated while the inhibitor (PAI-1) was decreased in serosal fluid compared with plasma. The in vitro mesothelial cell proliferation studies revealed that high TGF-beta(1-3) concentrations decreased cell proliferation, while lower concentrations of TGF-beta1 increased mesothelial cell proliferation. CONCLUSIONS: This human study shows increased active TGF-beta levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-beta1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-beta cytokines may be involved in postsurgical adhesion formation.
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| 8. |
- Langenskiöld, Marcus, 1972, et al.
(författare)
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Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer.
- 2009
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380. ; 30:4, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Degradation of extracellular matrix is important for tumour growth and invasion, which in part is regulated by the plasminogen activation system. The aim of the study was to evaluate the protein expression of urokinase plasminogen activator (uPA) and plasminogen-activating inhibitor-1 (PAI-1) in plasma, tumour-free mucosa and tumour tissue regarding their prognostic value in colon and rectal cancer. Methods: Patients (n = 221) undergoing surgery for colorectal cancer were prospectively included. Samples were assayed by ELISA technique. Results: PAI-1 in tumour tissue (p = 0.006), plasma (<0.0001) and uPA in tumour-free mucosa (p = 0.006) were associated with survival in rectal cancer in univariate analysis. An uPA expression level below 1.1 ng/mg (log rank test, p < 0.0001) in tumour-free mucosa was associated with poor survival in rectal cancer. This was true also for patients without disseminated disease (M(0), p = 0.02). PAI-1 in plasma correlated with metastatic disease (p < 0.0001). uPA and PAI-1 were not associated with survival in either tumour tissue, mucosa or plasma in patients with colon cancer. Conclusions: uPA and PAI-1 have a differential prognostic impact in colon and rectal cancer. Preoperative mucosal uPA and plasma PAI-1 protein expression could possibly be used as prognostic factors in rectal cancer.
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| 9. |
- Langenskiöld, Marcus, 1972, et al.
(författare)
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Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer
- 2005
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Ingår i: International journal of colorectal disease. - 0179-1958. ; 20:3, s. 245-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Degradation of the extracellular matrix plays an important part during the invasion of cancer cells into the surrounding tissue. The matrix metalloproteinases (MMPs) have a central role in this process as demonstrated in different malignancies. The aim of this study was to investigate the presence of several MMPs from tumour, adjacent tumour-free colon segment and from plasma, in order to evaluate how these factors might be used as predictors in colorectal malignancy. METHODS: Seventy-two patients who underwent surgery because of a colorectal carcinoma were included. Biopsies from the tumour, macroscopically tumour-free bowel and plasma samples were analysed with enzyme-linked immunosorbent assay tests (ELISAs) quantifying protein expression of several MMPs. RESULTS: We found highly elevated concentrations of MMP-1, MMP-2, MMP-3 and MMP-9 protein expression in tumour tissue compared with tumour-free tissue (p<0.0001). Elevated MMP-1 tumour levels were found in patients with Dukes' C cancers (p=0.02). Lymph node status correlated with the expression of MMP-2 in plasma, which was significantly increased in patients with lymph node metastasis compared with those without (p=0.002). MMP-2 in plasma was higher in T3 and T2 tumours than in T4 tumours (p=0.0083). CONCLUSION: The MMPs we investigated were strongly elevated in tumour tissue compared with tumour-free bowel wall. Our results indicate that MMP-2 in plasma may possibly be used as a predictor in colorectal malignancy. The use of MMP-2 as a predicting tool in combination with different imaging techniques may give important preoperative information in patients with colorectal cancer.
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| 10. |
- Langenskiöld, Marcus, 1972, et al.
(författare)
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Increased TGF-beta 1 protein expression in patients with advanced colorectal cancer.
- 2008
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Ingår i: Journal of surgical oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 97:5, s. 409-15
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is evidence that TGF-beta 1 plays a role as a tumor suppressor in early disease and has pro-oncogenic effects in advanced tumor stage. The aim of the study was to correlate TGF-beta 1 in plasma and tissue to clinical and pathological parameters in patients with various stages of disease progression. METHODS: One hundred sixty-nine patients who underwent surgery for a colorectal carcinoma were prospectively included. Blood samples, tumor free mucosa and tumor biopsies were assayed. RESULTS: TGF-beta 1 protein expression in tumors increased with increasing T-stage regardless of whether patients with metastatic disease were included or not (P = 0.0006). Patients with metastatic disease showed elevated TGF-beta 1 protein expression in both tumor tissue (P = 0.004) and plasma (P = 0.001) compared to those without metastatic disease. TGF-beta 1 protein expression was higher in the colon compared with the rectum in both tumor tissue and tumor-free bowel (P = 0.03), regardless of whether patients with metastatic disease were included or not. This difference was mainly attributable to a higher TGF-beta 1 protein expression in non-metastatic patients with lymph node positivity (P = 0.005). CONCLUSIONS: Higher TGF-beta 1 protein expression is associated with increasing T-stage and metastatic disease, indicating that TGF-beta 1 is of importance in tumor progression. The localization of the tumor seems to influence the TGF-beta 1 protein expression in patients with tumor cell-positive lymph nodes.
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