Revisiting the Use of Normal Saline for Peritoneal Washing in Ovarian Cancer

Abstract

The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing insights from clinical investigations of normal saline in fluid resuscitation and from the cytopathologic evaluation of peritoneal washings. We integrate these insights with the unique biology of the omentum and omental metastasis, highlighting the importance of considering the absorptive ability of the omentum when administering agents into the peritoneal cavity. Furthermore, we describe insights from preclinical studies regarding the mechanisms by which normal saline might render the omentum conducive for colonization by cancer cells. Importantly, we discuss the possibility that the risk of colonization of preserved omental tissues might be minimized by using balanced crystalloid solutions for peritoneal washing.

Keywords: crystalloid solutions; neoplasm metastasis; omentum; peritoneal cavity; peritoneal lavage; tumor microenvironment.

Figure 1

Omental metastasis in a syngeneic orthotopic mouse model of ovarian cancer. The bulky tumor mass involving the omentum is outlined in blue.

Figure 2

Immunofluorescence staining of normal omental tissue of an adult female C57BL/6 mouse, showing staining of the pan-leukocyte marker CD45 (red) and the endothelial cell marker CD31 (green). The tissue was counterstained with 4′,6-diamidino-2-phenylindole (blue). FALCs are indicated by arrows.

Figure 3

Normal saline remodels the omentum and stimulates its receptivity for ovarian cancer cells. Schematic representation of (A) the naïve omentum and (B) the omentum following administration of normal saline into the peritoneal cavity. Shown in (B) are the sequence of events following the absorption of normal saline by the omentum including (1) exfoliation of mesothelial cells through downregulation of the tight junction protein ZO-1, (2) induction of CX3CL1 expression in endothelial cells, (3) recruitment of CX3CR1+ monocytes/macrophages, (4) increased expression of pro-angiogenic cytokines in CX3CR1+ monocytes/macrophages through NF-κB activation, (5) stimulation of neoangiogenesis, and (6) implantation of ovarian cancer cells that circulate in the peritoneal fluid. This figure was created with BioRender.com (accessed on 6 October 2023).