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Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial.

Braumann C, Gutt CN, Scheele J, Menenakos C, Willems W, Mueller JM, Jacobi CA - World J Surg Oncol (2009)

Bottom Line: The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear.Perioperative complications did not differ.Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General, Visceral, Vascular and Thoracic Surgery, Universitaetsmedizin Berlin, Charité Campus Mitte, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany. chris.braumann@charite.de

ABSTRACT

Background: The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe.

Methods: In the settings of a multicentre (three University Hospitals) prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD) or 0.25% povidone-iodine (control) intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages) is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall) level of IL-1beta in peritoneal fluid.

Results: Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36), the cancer-related death rate (17 vs. 19, p = .2), the local recurrence rate (7 vs. 12, p = .16), the distant metastasis rate (13 vs. 18, p = 0.2) as well as the time to relapse were not statistically significant different.

Conclusion: Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection.

Trial registration: ISRCTN66478538.

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Schematic diagram illustrating the study protocol.
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Figure 1: Schematic diagram illustrating the study protocol.

Mentions: The patients were randomized into TRD group (n = 60) or povidone-iodine group (control group, n = 60). All operations were performed conventionally. Immediately after opening the abdomen, 200 ml of Ringer's solution was instilled into the peritoneal cavity for 2 minutes in both groups. 30 ml of peritoneal fluid was collected (measurement time T1) to evaluate different cytokine levels (IL-1β, IL-6, and IL-10). After removal of the residual fluid the therapeutic substances were administered intraperitoneally and left for 10 minutes: either 500 ml of 0.5% TRD solution or 500 ml of Ringer's solution (control group). Again 30 ml of peritoneal fluid was aspirated and analyzed (T2). A subsequent tumor resection was then carried out according to the principles of surgical oncology. 30 ml of peritoneal fluid was then absorbed (measurement T3). At the end of the operation patients underwent a second therapeutic peritoneal irrigation for 10 minutes: either 1,500 ml 0.5% TRD with 2,500 IU heparin (TRD group) or 1,500 ml 0.25% povidone-iodine solution (control group). Again 30 ml of fluid was removed and analyzed (T4). Before the incision was closed in layers, either 500 ml of 0.5% TRD with 2,500 IU heparin (TRD group) or 500 ml of Ringer's solution (control group) were instilled. One drainage was placed in Douglas' space and barred in all patients. 2 hours (h) and 6 h after the operation 30 ml of peritoneal fluid were taken from the drainage in order to measure T5 and T6, respectively (Figure 1). Samples were any time identical diluted, immediately cooled (4° Celsius; C), centrifuged, and supernatants were stored (-25°C). The remaining of the intraperitoneal fluid was collected to determine intraabdominal viable tumor cells (in T1 and T4). The volume of the removed material was 30 ml in all measurements and standardized aspiration after insertion of the same quantity either of TRD or Ringer's solution permitted a balanced aspiration from an equal dilution in all cases. Central venous blood was also taken at the same assessment points for the determination of the cytokine levels. Peri- and postoperative coagulation status, and peritoneal and serum cytokine concentrations (IL-1β, IL-6, and IL-10) were investigated.


Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial.

Braumann C, Gutt CN, Scheele J, Menenakos C, Willems W, Mueller JM, Jacobi CA - World J Surg Oncol (2009)

Schematic diagram illustrating the study protocol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667516&req=5

Figure 1: Schematic diagram illustrating the study protocol.
Mentions: The patients were randomized into TRD group (n = 60) or povidone-iodine group (control group, n = 60). All operations were performed conventionally. Immediately after opening the abdomen, 200 ml of Ringer's solution was instilled into the peritoneal cavity for 2 minutes in both groups. 30 ml of peritoneal fluid was collected (measurement time T1) to evaluate different cytokine levels (IL-1β, IL-6, and IL-10). After removal of the residual fluid the therapeutic substances were administered intraperitoneally and left for 10 minutes: either 500 ml of 0.5% TRD solution or 500 ml of Ringer's solution (control group). Again 30 ml of peritoneal fluid was aspirated and analyzed (T2). A subsequent tumor resection was then carried out according to the principles of surgical oncology. 30 ml of peritoneal fluid was then absorbed (measurement T3). At the end of the operation patients underwent a second therapeutic peritoneal irrigation for 10 minutes: either 1,500 ml 0.5% TRD with 2,500 IU heparin (TRD group) or 1,500 ml 0.25% povidone-iodine solution (control group). Again 30 ml of fluid was removed and analyzed (T4). Before the incision was closed in layers, either 500 ml of 0.5% TRD with 2,500 IU heparin (TRD group) or 500 ml of Ringer's solution (control group) were instilled. One drainage was placed in Douglas' space and barred in all patients. 2 hours (h) and 6 h after the operation 30 ml of peritoneal fluid were taken from the drainage in order to measure T5 and T6, respectively (Figure 1). Samples were any time identical diluted, immediately cooled (4° Celsius; C), centrifuged, and supernatants were stored (-25°C). The remaining of the intraperitoneal fluid was collected to determine intraabdominal viable tumor cells (in T1 and T4). The volume of the removed material was 30 ml in all measurements and standardized aspiration after insertion of the same quantity either of TRD or Ringer's solution permitted a balanced aspiration from an equal dilution in all cases. Central venous blood was also taken at the same assessment points for the determination of the cytokine levels. Peri- and postoperative coagulation status, and peritoneal and serum cytokine concentrations (IL-1β, IL-6, and IL-10) were investigated.

Bottom Line: The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear.Perioperative complications did not differ.Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General, Visceral, Vascular and Thoracic Surgery, Universitaetsmedizin Berlin, Charité Campus Mitte, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany. chris.braumann@charite.de

ABSTRACT

Background: The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe.

Methods: In the settings of a multicentre (three University Hospitals) prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD) or 0.25% povidone-iodine (control) intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages) is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall) level of IL-1beta in peritoneal fluid.

Results: Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36), the cancer-related death rate (17 vs. 19, p = .2), the local recurrence rate (7 vs. 12, p = .16), the distant metastasis rate (13 vs. 18, p = 0.2) as well as the time to relapse were not statistically significant different.

Conclusion: Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection.

Trial registration: ISRCTN66478538.

Show MeSH
Related in: MedlinePlus