**3. Diagnosis**

The absence of symptoms or the presence of symptoms that mimic other conditions often results in diagnostic delay with OC, and this worsens prognosis. Evaluation consists of physical examination, imaging [ultrasonography, computerized tomography (CT), magnetic resonance image (MRI)], serum tumour markers analysis and ascitic fluid analysis (visual inspection, biochemical analysis, cytology and tumour markers). Diagnostic laparoscopy is an additional investigation and may be useful in patients with whom simple investigations have failed to determine the cause of ascites (**Figure 2**) [6, 17–21].

(**Figure 3A**) [20]. Sometimes, bowel loops do not float freely but may be tethered along the posterior abdominal wall, plastered to organs or surrounded by loculated fluid collections (**Figure 3B**) [21]. When small amounts of ascitic fluid localise in the Morison pouch and the

**Figure 3.** Ultrasound images of ascites. (A) Transabdominal ultrasound image demonstrates ascites and ovarian tumour.

Ascites in Advanced Ovarian Cancer http://dx.doi.org/10.5772/intechopen.72698 201

In patients with new-onset ascites of unknown origin, peritoneal fluid analysis may provide some information regarding the origin of the disease. However, it remains difficult to differen-

On inspection, most ascitic fluids are transparent and tinged yellow. In the case of malignancy, it could also appear pink or red (when at least 10,000 red blood cells/μL are present). Any inflammatory condition can cause an elevated white blood cell count. In case of malig-

Conventional cytological examination shows high specificity, but its sensitivity is low (58– 75%) [23]. The cellular components of malignant ascites contain a complex mixture of cell populations, including tumour cells and stromal cells [25]. Immunohistochemistry (ICH) staining and cytological diagnosis by using cell block (CB) sections prepared with the ascites cytological specimen are useful in delineation of the primary origin of the tumour cells. Since

pouch of Douglas, CT scan demonstrated the best sensitivity [21, 22].

(B) Transvaginal ultrasound image demonstrates ascites and intestinal carcinosis.

**Figure 2.** Diagnostic laparoscopy showing ascites and peritoneal carcinosis.

**3.3. Ascitic fluid analysis**

tiate malignant ascites from other types [23].

nant ascites, lymphocytes usually predominate [24].

#### **3.1. Symptoms**

The most common complaint in the presentation of OC is abdominal swelling or bloating [17]. These symptoms are commonly associated with the physical and surgical finding of ascites. As the amount of fluid increases, ascites can cause significant symptoms referable to the gastrointestinal and genitourinary tracts. Malignant ascites is associated with abdominal and pelvic pain, while liver disease tends to be relatively painless [6, 17].

#### **3.2. Imaging**

Transabdominal and transvaginal ultrasonographies are the most sensitive techniques for the detection of ascitic fluid (**Figure 3**) [19]. Uncomplicated ascites appears as ahomogeneous, freely mobile, anechoic collection in the peritoneal cavity that demonstrates deep acoustic enhancement. Generally, free ascites do not displace organs situated between them

**Figure 2.** Diagnostic laparoscopy showing ascites and peritoneal carcinosis.

**Figure 3.** Ultrasound images of ascites. (A) Transabdominal ultrasound image demonstrates ascites and ovarian tumour. (B) Transvaginal ultrasound image demonstrates ascites and intestinal carcinosis.

(**Figure 3A**) [20]. Sometimes, bowel loops do not float freely but may be tethered along the posterior abdominal wall, plastered to organs or surrounded by loculated fluid collections (**Figure 3B**) [21]. When small amounts of ascitic fluid localise in the Morison pouch and the pouch of Douglas, CT scan demonstrated the best sensitivity [21, 22].

#### **3.3. Ascitic fluid analysis**

resulting in net accumulation of fluid [14]. An increase in influx is a result of various factors: (1) increased capillary permeability, (2) angiogenesis, (3) increased area for filtration and (4) decreased oncotic pressure difference. In malignant ascites, various factors secreted by tumour cells are present, which increase vascular permeability and induce angiogenesis. An early step leading to angiogenesis is partial proteolysis of vascular basal lamina, resulting in hyperpermeability. Vascular endothelial growth factor (VEGF) is the most potent and specific angiogenic factor, secreted by a large variety of tumours, peritoneal mesothelial cells, monocyte/ macrophages in malignant ascites and even tumour-infiltrating T cells [7]. Additionally, VEGF increases the permeability of vessels to plasma proteins, including albumin and fibrinogen, with a potency 10,000 times higher than histamine [15, 16]. Other factors that may also induce angiogenesis have been identified in malignant ascites and include basic fibroblast growth factor (bFGF), angiogenin, transforming growth factor alpha and beta (TGF-alpha, TGF-beta), interleukin-8, placental growth factor (PIGF) and platelet-derived endothelial cell growth factor (PD-EGF) [11]. Influx into the peritoneal cavity after *i.p.* ovarian tumour cell line injection rose significantly when the surface area for filtration also increased; the size and number of vessels lining the peritoneal cavity increased as much as 15-fold [16]. The protein content of malignant ascites is greater than in peritoneal fluid of healthy women [11]. The oncotic pressure difference between plasma and ascites therefore decreases, and as a consequence, reabsorption decreases and interstitial fluid accumulation results [11]. Liver metastasis causing hepatic vein obstruction may be an important aetiology factor in some cases of malignant ascites [1].

The absence of symptoms or the presence of symptoms that mimic other conditions often results in diagnostic delay with OC, and this worsens prognosis. Evaluation consists of physical examination, imaging [ultrasonography, computerized tomography (CT), magnetic resonance image (MRI)], serum tumour markers analysis and ascitic fluid analysis (visual inspection, biochemical analysis, cytology and tumour markers). Diagnostic laparoscopy is an additional investigation and may be useful in patients with whom simple investigations

The most common complaint in the presentation of OC is abdominal swelling or bloating [17]. These symptoms are commonly associated with the physical and surgical finding of ascites. As the amount of fluid increases, ascites can cause significant symptoms referable to the gastrointestinal and genitourinary tracts. Malignant ascites is associated with abdominal

Transabdominal and transvaginal ultrasonographies are the most sensitive techniques for the detection of ascitic fluid (**Figure 3**) [19]. Uncomplicated ascites appears as ahomogeneous, freely mobile, anechoic collection in the peritoneal cavity that demonstrates deep acoustic enhancement. Generally, free ascites do not displace organs situated between them

have failed to determine the cause of ascites (**Figure 2**) [6, 17–21].

and pelvic pain, while liver disease tends to be relatively painless [6, 17].

**3. Diagnosis**

200 Ovarian Cancer - From Pathogenesis to Treatment

**3.1. Symptoms**

**3.2. Imaging**

In patients with new-onset ascites of unknown origin, peritoneal fluid analysis may provide some information regarding the origin of the disease. However, it remains difficult to differentiate malignant ascites from other types [23].

On inspection, most ascitic fluids are transparent and tinged yellow. In the case of malignancy, it could also appear pink or red (when at least 10,000 red blood cells/μL are present). Any inflammatory condition can cause an elevated white blood cell count. In case of malignant ascites, lymphocytes usually predominate [24].

Conventional cytological examination shows high specificity, but its sensitivity is low (58– 75%) [23]. The cellular components of malignant ascites contain a complex mixture of cell populations, including tumour cells and stromal cells [25]. Immunohistochemistry (ICH) staining and cytological diagnosis by using cell block (CB) sections prepared with the ascites cytological specimen are useful in delineation of the primary origin of the tumour cells. Since multiple sections can be obtained by the CB method, this technique is particularly valuable when the ICH staining is required for a battery of markers. Typically, primary ovarian epithelial cancers are positive for ER/PR, PAX8, CK7 and negative for CK20 and CDX2. The reverse is true for gastrointestinal cancers. By using a combination of cytological conventional smears and CB methods, the primary site could be detected with 81% accuracy [26, 27].

malignant ascites, even though many studies focusing on cirrhosis related ascites have demonstrated great benefits of albumin infusion (6–8 g per litre of ascites removed) to maintain

Ascites in Advanced Ovarian Cancer http://dx.doi.org/10.5772/intechopen.72698 203

Common peritoneal-venous shunts drain ascites from the peritoneal cavity into the superior vena cava and have a one-way valve that prevents reflux of blood [32, 34]. They are rarely used due to the high rate of complications such as occlusion, infection, coagulopathy and the widespread dissemination of malignant cells [35]. The only advantage compared to other techniques is related to saving electrolytes and proteins, preserving the body fluid balance [30, 32]. Two shunts are commonly used: the older LeVeen and the most recent Denver shunt,

Contraindications of shunt positioning are as follows: congestive heart disease or renal failure due to the significant hemodilution and blood volume overload produced by the shunt, portal

A novel type of technique, automated low-flow ascites pump, drains ascites from the peritoneal cavity to the bladder. This novel device seems effective (even though tested only on liver disease patients) for symptom relief, although data about safety (especially linked to catheter

In cases of recurrent or refractory malignant ascites, when frequent paracentesis is required, patients may benefit from an indwelling catheter [32]. This device allows easy and self-drainage, eliminating the need for hospitalisation and frequent paracentesis. The most common permanent catheters are the tunnelled PleurX®, Tenckhoff, Port-a-Cath and cope-type loop catheters [30, 38]. Most authors prefer tunnelled catheters due to greater stability (higher long-term patency rate and success rate) and lower infection rate [30, 39]. Recent trials have suggested that untunnelled catheters have a 21–34% risk of developing peritonitis compared

Catheter placement can be performed with ultrasound guidance or with CT guidance in cases of particular anatomical conditions or widespread carcinomatosis [30]. Antibiotic prophylaxis is recommended for catheter placement [39]. Patients should be instructed to drain the fluid frequently enough to avoid the development of tense ascites, usually once or twice per week. Intravenous fluid replacement and/or albumin supplementation is indicated according

The safety and cost-effective profiles of tunnelled catheters for the management of recurrent

If the patient's malignant disease is sensitive to chemotherapy, reduction of ascites production and relief of symptoms may be achieved. However, most patients with ascites have already been treated with several lines of treatment, and their disease has become refractory

malignant ascites have been demonstrated by several observational studies [38, 40].

intravascular volume [30].

*4.1.3. Catheter drainage*

*4.1.2. Peritoneal-venous shunting*

which require different pressures to open the valves [32, 36].

dislodgement and infections) are only preliminary [37].

to clinical conditions and ascites volume [30, 39].

**4.2. Pharmacological treatment of ascites**

hypertension, and severe pleural effusion and clotting disorders [35].

to 4.4% with tunnelled Tenckhoff and 2.5% for tunnelled PleurX® [30].

A number of soluble factors are present in abundance in malignant ascites, but few have been validated for their biomarker potential [28].
