Metastatic ovarian carcinoma is a rare malignant disease confined to the peritoneum, as metastases are not spread through the typical hematogenous route. Abdominal pain may be the only symptom. Ultrasound, CT and MRI are needed for tumor staging, whereas cytoreductive surgery is the main form of treatment. The diagnosis carries a very poor prognosis, primarily because almost 75% of patients are diagnosed in advanced stages of the disease.
The clinical presentation gives little insight into the underlying cause, as nonspecific symptoms such as abdominal pain and discomfort are often the sole complaints, which could be the reason why ovarian cancers are most commonly detected in stage III (85%) . Ascites is a valuable clinical sign that is present in two-thirds of cases . Additionally, altered bowel and bladder habits may be encountered.
A careful physical examination and a properly obtained patient history are the first steps in the diagnostic workup, but clinical suspicion toward a malignant disease of the ovaries may be difficult to attain based solely on clinical findings. Levels of CA-125, an ovarian tumor marker, should be evaluated , but imaging studies are necessary for confirmation. The role of ultrasonography is pivotal in the diagnosis of ovarian cancer, but studies have determined that the level of expertise by the radiologist is detrimental in achieving a proper diagnosis . CT and/or MRI are highly useful methods in assessing tumor stage and treatment planning, while PET scan is not recommended due to very high false-positive rates . Although biopsy is not recommended for patients with this type of tumor, lymph node sampling or dissection may be performed .
Unlike other malignant diseases in their advanced stages, the role of surgery in metastatic ovarian carcinoma is considered as the most important. Cytoreductive surgery is performed in all patients, with a goal of reducing residual disease to 10 mm or less , and the extent of cytoreduction directly prolongs survival rates . To maximize the effects of surgery, radical oophorectomy and primary stapled anastomosis are considered as effective technique , while chemotherapy using platinum-based agents is frequently used following these procedures. However, this type of surgery possesses much higher complication rates, both intraoperative and postoperative . Bleeding, infection and anastomotic dehiscence may be frequently seen and because ostomy is often necessary, the quality of life is severely impaired .
Survival time directly depends on the stage of disease at the diagnosis. According to the the International Federation of Gynecology and Obstetrics (FIGO), ovarian carcinoma is classified into four stages :
Metastatic ovarian carcinoma carries a very poor prognosis . When non-peritoneal metastases are present, the prognosis is significantly worse and mean survival rates are around 4 months from the diagnosis . The devastating nature of this disease is further shown by the fact that long-term survival rates are only 30% .
The exact cause of this tumor remains unknown. Current theories propose that the effects of constant damage and repair of the ovarian epithelium during normal ovulatory cycles are main contributing factors to its pathogenesis. On the basis of histologic appearance and underlying genetic mutations, tumors are classified into two groups :
Reports from 2015 show that 22,280 new cases and 14,240 deaths from this malignancy were detected in the United States . Age is a significant factor when it comes to metastatic ovarian carcinoma. Young adult women were shown to be at the highest risk for type I cancers, whereas postmenopausal women are the population in which high-grade serous carcinomas appear . Ethnic predilection in terms of longer survival rates has not been established .
Much has been revealed regarding the pathogenesis of ovarian cancer and its unique metastatic spread. Type I tumors arise from a benign epithelial lesion into a low-grade malignant tumor, a phenomenon seen in adenocarcinoma of the colon and several other. BRAF, β-catenin and KRAS mutations, microsatellite instability and increased activity of mitogen-activated protein kinases are established as key events in further proliferation of the tumor . On the other hand, p16, p53 and RB1 genes are thought to be involved in type II tumor growth, but also BRCA1 and 2, one of the most important genes in the pathogenesis of breast cancer. Once the primary tumor has proliferated sufficiently to produce metastases, cells reach other sites in the peritoneum through passive transit in the peritoneal fluid and they almost invariably deposit on intraperitoneal tissues . To facilitate easier basement membrane adhesion, but also detachment from the primary tumor, a transformation from epithelial to mesenchymal cells occurs prior to their metastatic spread . Once they are situated in the peritoneal fluid, they seek for the mesothelium, on which they bind through β1-integrins and CD44, main adhesion molecules . When malignant cells attach to the mesothelium, they release matrix metalloproteinases (MMPs) 2 and 9, substances that cleave fibronectin and laminin in the mesothelium, thus contributing to further binding to this cellular layer . In the setting of extensive tumor growth, the need for additional blood supply calls for production of several vascular endothelial growth factors (VEGFs), which sustain their proliferation and further metastatic spread .
Having in mind the fact that 70% of women in European studies were diagnosed in advanced stages of the diseases (III and IV) , the aspect of an early diagnosis must be emphasized, as significantly longer survival rates have been observed in such cases. Prophylactic oophorectomy in women with confirmed BRCA1 or BRCA2 mutations has shown to reduce the risk of ovarian cancer by 50% . Additionally, the role of contraceptives in long-term prevention of ovarian cancer and the duration of contraceptive use directly correlates with a further risk reduction .
Metastatic ovarian carcinoma is a rare but devastating malignant disease due to its insidious onset and late clinical presentation . Based on histologic differentiation of tumors, it may be classified into type I - low-grade differentiating tumors of a reduced malignant potential that are most frequently diagnosed in younger women; and type II, most prevalent in postmenopausal women, carrying a much poorer prognosis . Ovarian carcinoma may arise from the surface epithelium of the ovaries, the Fallopian tubes and the mesothelium lining of the peritoneal cavity , and current theories regarding its pathogenesis lean toward "incessant ovulation". This hypothesis claims that the cumulative effects of the ovulatory cycles on the epithelial surfaces prone this layer to malignant transformation. Tumor growth and its specific metastatic spread have been extensively researched. Homeobox (HOX) genes responsible for morphogenesis of tissues in the female reproductive tract, p53 tumor suppressor gene, BRAF, KRAS, ERBB2, β-catenin and numerous other genes involved in the cell cycle have been determined as important constituents of tumor proliferation and differentiation . Additionally, BRCA 1 and 2 have also been identified . Interestingly, metastatic spread of cancer cells is not achieved by hematogenous spread, but through passive movement of the peritoneal fluid into which malignant cells immerse themselves from the primary tumor . For some reason, metastatic cells posses affinity for the mesothelium only, a cellular layer covering all intraperitoneal organs, such as the omentum, the capsules of the liver and spleen and serous layers of the large intestine, but secondary deposits are most commonly found on the diaphragm and the mesentery . In very rare cases, metastatic spread to non-peritoneal sites, including the skin and the brain, may be observed and such findings carry an even worse prognosis  . Most recent reports suggest that ovarian carcinoma is rarely encountered in clinical practice, comprising about 4% of all female cancers in Europe, while approximately 22,000 new cases were discovered in the United States in 2015  . But what is more worrisome is that almost 15,000 deaths occurred, signalizing that the case fatality ratio is very high . One of the reasons might be a very non-specific clinical presentation including abdominal pain and discomfort, as well as altered bowel habits. Ultrasonography is one of the most important initial diagnostic methods , and should be performed in all patients in whom the cause of such symptoms remains undisclosed. Computed tomography (CT) and magnetic resonance imaging (MRI) are highly useful in determining the stage of the tumor , but in deciding on the optimal treatment strategy as well. Because of extensive involvement of organs and tissues in the peritoneum, the principle of cytoreductive surgery, defined as residual disease of 1 cm or less, is implemented in the setting of metastatic carcinoma, while chemotherapy is also used . The prognosis is poor in the setting of metastatic ovarian cancer, as five-year survival rates of stages III and IV are 37% and 25%, respectively .
Metastatic ovarian carcinoma is a rare but devastating malignant disease. In the United States, approximately 22,000 new cases are documented every year and only 4% of all tumors in women are attributed to this cancer, but its long term survival rates barely reach 30%. The primary reason is that up to 80% of diagnoses are made in advanced stages of the disease, when therapy is of little efficacy. Ovarian carcinomas are divided into two types - one that is seen in younger women that possesses a lower malignant potential (and thus shows longer survival rates) and a high-grade serous carcinoma that is diagnosed in postmenopausal women, with a much poorer prognosis. One of the unique features of this tumor is that the metastases develop only in the organs within the peritoneum - a fluid-filled sac that contains most of the abdominal organs, primarily because the tumor spreads from the ovaries through the peritoneal fluid by passive mechanism. The clinical presentation of metastatic ovarian carcinoma may only include non-specific symptoms such as abdominal pain, discomfort and bloating, which may be one of the reasons why this tumor is diagnosed in later stages. To make the diagnosis, it is necessary to obtain a full patient history and conduct a proper physical examination, but imaging studies such as ultrasonography, computed tomography (CT scan) and magnetic resonance imaging (MRI) are vital in visualizing the tumor and determine its stage. More importantly, imaging studies are essential in determining optimal surgical approaches, which is the mainstay of therapy regardless of the stage. A specific procedure called cytoreductive surgery is performed and implies removal of as much tumor tissue as possible, is readily performed, together with removal of the ovaries and other organs, if necessary. Despite treatment, survival rates are poor, especially if the diagnosis is made in advanced stages of the disease. Since prevention of this tumor is highly unlikely, an early diagnosis is the single most important step in providing longer survival rates. Strategies that have proven to reduce the risk of this malignancy include prophylactic removal of ovaries in patients with known breast cancer antigen (BRCA) mutations, whereas the role of contraceptives in reducing the risk has been well-established.