Reduction of peritoneal carcinomatosis by intraperitoneal administration of phospholipids in rats

Abstract

Background: Intraperitoneal tumor cell attachment after resection of gastrointestinal cancer may lead to a developing of peritoneal carcinosis. Intraabdominal application of phospholipids shows a significant decrease of adhesion formation even in case of rising tumor cell concentration.

Methods: In experiment A 2*106 colonic tumor cells (DHD/K12/Trb) were injected intraperitonely in female BD-IX-rats. A total of 30 rats were divided into three groups with treatments of phospholipids at 6% or 9% and the control group. In experiment B a total of 100 rats were divided into ten groups with treatments of phospholipids at 9% and the control group. A rising concentration of tumor cells (10,000, 50,000, 100,000, 250,000 and 500,000) were injected intraperitonely in female BD-IX-rats of the different groups. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of attachment and the Peritoneal Cancer Index (PCI).

Results: In experiment A, we found a significant reduction (control group: tumor volume: 12.0 +/- 4.9 ml; area of tumor adhesion: 2434.4 +/- 766 mm2; PCI 28.5 +/- 10.0) of peritoneal dissemination according to all evaluation methods after treatment with phospholipids 6% (tumor volume: 5.2 +/- 2.2 ml; area of tumor adhesion: 1106.8 +/- 689 mm2; PCI 19.0 +/- 5.0) and phospholipids 9% (tumor volume: 4.0 +/- 3.5 ml; area of tumor adhesion: 362.7 +/- 339 mm2; PCI 13.8 +/- 5.1). In experiment B we found a significant reduction of tumor volume in all different groups of rising tumor cell concentration compared to the control. As detected by the area of attachment we found a significant reduction in the subgroups 1*104, 25*104 and 50*104. The reduction in the other subgroups shows no significance. The PCI could be reduced significantly in all subgroups apart from 5*104.

Conclusion: In this animal study intraperitoneal application of phospholipids resulted in reduction of the extent of peritoneal carcinomatosis after intraperitoneal administration of free tumor cells. This effect was exceptionally noticed when the amount of intraperitoneal tumor cells was limited. Consequently, intraperitoneal administration of phospholipids might be effective in reducing peritoneal carcinomatosis after surgery of gastrointestinal tumors in humans.

Figure 1

Experiment A: Volume of intraperitoneal tumor (ml, SEM). (PL6% to control p = 0.001; PL9% to control p = 0.001; PL6% to PL9% no significance)

Figure 2

Experiment A: Area of tumor adhesion (mm², SEM). (PL6% to control p = 0.002; PL9% to control p = 0.001; PL6% to PL9% p = 0.006)

Figure 3

Experiment A: Peritoneal Cancer Index (PCI, SEM). (PL6% to control p = 0.027; PL9% to control p = 0.001; PL6% to PL9% p = 0.048)

Figure 4

Experiment B: Volume of intraperitoneal tumor (ml, SEM). (1*10⁴ p = 0,001; 5*10⁴ p = 0,0007; 1*10⁵ p = 0.007; 2,5*10⁵ p = 0,0031; 5*10⁵ p = 0,003)

Figure 5

Experiment B: Area of tumor adhesion (mm², SEM). (1*10⁴ p = 0,001; 5*10⁴ no significance; 1*10⁵ no significance; 2,5*10⁵ p = 0,0032; 5*10⁵ p = 0,0013)

Figure 6

Experiment B: Peritoneal Cancer Index (PCI, SEM). (1*10⁴ p = 0,001; 5*10⁴ no significance; 1*10⁵ p = 0.007; 2,5*10⁵ p = 0.001; 5*10⁵ p = 0.0011)