**Ascites in Advanced Ovarian Cancer**

**Ascites in Advanced Ovarian Cancer**

#### Katarina Cerne and Borut Kobal Katarina Cerne and Borut Kobal Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.72698

#### **Abstract**

The presence of ascites is one of the general ovarian cancer (OC) symptoms detected at initial diagnosis and can be present at an early stage but is most often seen in advanced disease. In newly diagnosed OC patients, ascites is treated by the standard treatment for the underlying disease. However, once the chemoresistant and recurrent features of the disease develop, management of a large volume of ascites can be a major problem. By increasing abdominal pressure, ascites can cause severe symptoms; thus, palliation of symptomatic patients is the main goal. The elimination of fluid accumulation in OC patients with these symptoms will certainly improve their quality of life and may even prolong survival. Unfortunately, no standard treatment for OC-associated ascites exists. There are several traditional therapies for ascites, with limited effectiveness and significant adverse effects. Catumaxomab is the only medicine approved for intraperitoneal treatment of malignant ascites in patients with EpCAM-positive carcinomas. Advances in our understanding of malignant ascites aetiology and more effective treatment strategies for ascites and OC will help reduce the symptoms associated with ascites.

DOI: 10.5772/intechopen.72698

**Keywords:** advanced ovarian cancer, malignant ascites, aetiology, treatment, diagnosis

#### **1. Introduction**

Ascites is an abnormal accumulation of serous fluid (>50 mL) in the peritoneal cavity between the membrane lining the abdominal wall and the membrane covering the abdominal organs. Although ascites is most commonly observed in patients with cirrhosis, 7–10% of patients with ascites develop it secondary to malignancy. The commonest primary tumour associated with the development of ascites is ovarian cancer (OC) [1]. Large amounts of ascites in a patient with OC usually indicate the presence of peritoneal metastasis; therefore, ascites is found in the majority of patients (89%) with advanced disease (FIGO stages III and IV). However, the absence of ascites may not exclude malignant disease, since ascites is rarely

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

(17%) observed in the early disease (FIGO stages I and II) and is absent in nearly half of borderline tumours. Unlike in primary OC, recurrent disease is not strongly associated with ascites, which was found in 38% of patients with recurrent OC [2].

Throughout history, ascites has always been regarded as a poor prognostic sign. In the 1700s, Sir Thomas Spencer Wells wrote "surgeons stood and trembled on the brink of ovarian waters" [3]. Studies addressing the prognostic significance of ascites in patients with stage III or IV have shown a significantly poorer survival [4]. Ascites is also associated with pharmacoresistance [4]. Patch et al. showed that matched primary ascites (tumour cells isolated from ascites) share most genomic changes of acquired resistance with primary tumour samples across the whole genome [5].

In newly diagnosed ovarian cancer patients, ascites is treated by using the standard treatment for the underlying disease. However, once the chemoresistant and recurrent features of the disease develop, management of a large volume of ascites can be a major problem. Palliation of symptomatic patients is therefore the foremost goal, and elimination of fluid accumulation in patients with these symptoms will certainly improve their quality of life and may even prolong survival [6, 7]. An understanding of malignant ascites aetiology is of utmost importance if more effective treatment strategies for ascites and OC are to emerge in the future.

This chapter considers the aetiology and pathophysiology of malignant ascites in OC as well as current diagnostic modalities and explores the best form of management.

> formation by Holm-Nielsen more than 60 years ago [12]. Published data using lymphoscintigraphy showed that patients with malignant ascites had no activity above the diaphragm after intraperitoneal injection of the isotope, in contrast to control patients with no ascites or cirrhotic ascites. Bronskill et al. [13] showed that OC patients with persistent, intractable ascites, who were approaching their terminal illness, had low peritoneal drainage rates (below 50 ml/h). This result generally indicates obstruction of the diaphragmatic plexus [13]. Initial events that lead to fluid accumulation were studied by Nagy et al. [14] who showed that in mice efflux the peritoneal cavity of <sup>125</sup>I-labelled human serum albumin and <sup>51</sup>Cr-labelled red blood cells is markedly reduced (fivefold) within 1 day of *i.p.* ovarian tumour cell line injection. A significant reduction preceding a detectable increase in tumour cell number was not attributable to the blockage of peritoneal lymphatics by tumour cells and by itself did not provoke peritoneal fluid accumulation. These results suggest a prominent role for nonobstructive mechanisms, including contraction of lymph vessels induced by secretion of tumour cell product(s). At later periods, the absorption of fluid from the peritoneal cavity might also be affected due to carcinomatosis [14].

Ascites in Advanced Ovarian Cancer http://dx.doi.org/10.5772/intechopen.72698 199

Nagy et al. studied the influx of fluid into the peritoneal cavity of mice [14]. They found that after *i.p.* ovarian tumour cell line injection, influx of 125I-labelled human serum albumin rose between days 5 and 7 to values 13- to 25-fold higher than control values, when the tumour cell number had increased >500-fold. By day 10, influx had increased sufficiently to exceed efflux,

**2.2. Influx into the peritoneal cavity**

**Figure 1.** Aetiology of malignant ascites in ovarian cancer.
