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Metastatic Ovarian Carcinoma

Ovarian Epithelial Cancer Stage IV

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.

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Presentation

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%) [9]. Ascites is a valuable clinical sign that is present in two-thirds of cases [9]. Additionally, altered bowel and bladder habits may be encountered.

Pleural Effusion
  • Pleural effusions constitute the most frequent site of distant metastasis (FIGO stage IV disease).[ncbi.nlm.nih.gov]
  • Higher levels were detected in peritoneal compared to pleural effusions (p 0.031).[ncbi.nlm.nih.gov]
  • After drainage, chest X-ray showed a massive pleural effusion and thoracic Computed Tomography (CT) scan demonstrated a gastropleural fistula.[jpmsonline.com]
  • A 41-year-old previously hysterectomized women presented with pelvic mass and malignant pleural effusion.[link.springer.com]
  • Stage IV - Distant metastatic spread, with either pleural effusion that contains malignant cells (IVA) or involvement of extra-abdominal organs (IVB). Metastatic ovarian carcinoma carries a very poor prognosis.[symptoma.com]
Dyspnea
  • CASE REPORT In April 2015, a 59-year old woman was referred to the Oncological Department after onset of dyspnea, tachycardia, polypnea and cachexia.[jpmsonline.com]
Pain
  • A woman with stage IV metastatic papillary serous ovarian cancer presented with fever, altered mental status, difficulty with vision and right knee pain.[ncbi.nlm.nih.gov]
  • We report on a 58-years-old woman with a metastatic ovarian carcinoma who had chest pain, nausea and collapse during their first Taxol infusion.[ncbi.nlm.nih.gov]
  • 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.[symptoma.com]
  • Most patients had abdominal pain and a pelvic mass. In 56%, the ovarian tumors and the large bowel carcinomas were discovered synchronously; 44% were metachronous. Seventy-five percent of the tumors were unilateral.[ncbi.nlm.nih.gov]
  • Concurrently, she had periods of abdominal pain. This was diffuse, although largely right-sided, was of insidious onset and dull in nature. There was some pain relief with oral analgesics.[jmedicalcasereports.biomedcentral.com]
Fatigue
  • In our practice, patients who experience fatigue from DCA generally do feel better after the DCA treatment is stopped.[medicorcancer.com]
  • Five years after the initial diagnosis, the patient was admitted to the hospital with anemia, hemoglobin of 7.0 gm/dl, fatigue, and melena.[hindawi.com]
  • Associated symptoms included yellowing of the eyes and skin, nausea with non-bilious and non-bloody vomiting, and generalized fatigue for the past 3 days. She denied pruritis, bowel habit changes, fevers, chills, night sweats, or recent travel.[acgcasereports.gi.org]
  • Viral platforms under evaluation in ovarian cancer clinical trials include: Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms Measles virus: a highly contagious[cancerresearch.org]
  • Also consider testing women who present with unexplained fatigue, weight loss or change in bowel habit.[patient.info]
Weight Loss
  • Signs and symptoms of ovarian cancer may include: Abdominal bloating or swelling Quickly feeling full when eating Weight loss Discomfort in the pelvis area Changes in bowel habits, such as constipation A frequent need to urinate When to see a doctor Make[mayoclinic.org]
  • Also consider testing women who present with unexplained fatigue, weight loss or change in bowel habit.[patient.info]
  • She felt weaker, spent more time in bed, and reported progressive anorexia and weight loss. Bowel habits were essentially normal. On examination, she was sick looking, wasted and had bilateral pedal edema.[jmedicalcasereports.biomedcentral.com]
  • loss Unexplained abdominal pain An ovarian mass is more likely to be cancer in older women.[merckmanuals.com]
Anorexia
  • She felt weaker, spent more time in bed, and reported progressive anorexia and weight loss. Bowel habits were essentially normal. On examination, she was sick looking, wasted and had bilateral pedal edema.[jmedicalcasereports.biomedcentral.com]
  • Constitutional symptoms include fatigue, weight loss, anorexia and depression. It most commonly presents with a pelvic or abdominal mass that may be associated with pain.[patient.info]
Abdominal Pain
  • 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.[symptoma.com]
  • Most patients had abdominal pain and a pelvic mass. In 56%, the ovarian tumors and the large bowel carcinomas were discovered synchronously; 44% were metachronous. Seventy-five percent of the tumors were unilateral.[ncbi.nlm.nih.gov]
  • At the time, she had complaints of on-and-off partial constipation for 2 weeks, abdominal pain and distension for 2 days, and vomiting for 1 day. She was dehydrated and wasted.[jmedicalcasereports.biomedcentral.com]
  • The definitive treatment for advanced cases is liver transplantation. 3 Case Report A 53-year-old woman with a history of BRCA2 stage III recurrent ovarian cancer presented with complaints of abdominal pain for the past 3 weeks.[acgcasereports.gi.org]
  • The patient could only tolerate a liquid diet due to generalized cramping abdominal pain after meals. There were no significant prior health problems except for hypothyroidism. Medications included L-thyroxine, hydromorphone, and bromazepam.[medicorcancer.com]
Pelvic Mass
  • A 49-year-old woman presented with ascites and a left pelvic mass. Optimal debulking surgery was carried out including a segmental resection of segment 5/6 of the liver.[ncbi.nlm.nih.gov]
  • Most patients had abdominal pain and a pelvic mass. In 56%, the ovarian tumors and the large bowel carcinomas were discovered synchronously; 44% were metachronous. Seventy-five percent of the tumors were unilateral.[ncbi.nlm.nih.gov]
  • A 41-year-old previously hysterectomized women presented with pelvic mass and malignant pleural effusion.[link.springer.com]
  • A pelvic mass plus ascites usually indicates ovarian cancer but sometimes indicates Meigs syndrome (a benign fibroma with ascites and right hydrothorax).[merckmanuals.com]
  • ., pelvic masses, ascites, or vaginal bleeding. 17 , 19 Some patients with ovarian metastases have menstrual abnormalities, postmenopausal bleeding, and virilization, or they deliver a masculinized female fetus.[clinicalgate.com]
Nausea
  • We report on a 58-years-old woman with a metastatic ovarian carcinoma who had chest pain, nausea and collapse during their first Taxol infusion.[ncbi.nlm.nih.gov]
  • Ovarian Cancer Overview Ovarian cancer warning signs include ongoing pain or cramps in the belly or back, abnormal vaginal bleeding, nausea, and bloating. Depending on the cancer stage, ovarian cancer treatment includes surgery and chemotherapy.[webmd.com]
  • Clinical manifestations of metastasis to stomach are variable and include epigastric pain, melena, anemia from occult gastrointestinal blood loss, nausea, and vomiting [ 1 – 3 , 6 , 7 ].[hindawi.com]
  • Associated symptoms included yellowing of the eyes and skin, nausea with non-bilious and non-bloody vomiting, and generalized fatigue for the past 3 days. She denied pruritis, bowel habit changes, fevers, chills, night sweats, or recent travel.[acgcasereports.gi.org]
  • […] intercourse Abdominal swelling and bloating Urinary frequency Constipation Ascites : Collection of fluid in the abdomen , contributing to abdominal distension and shortness of breath Loss of appetite Feeling full after eating little Gas and/or diarrhea Nausea[emedicinehealth.com]
Abdominal Distension
  • Abdominal distension progressively increased and she had to have regular peritoneocentesis for ascitic relief. In May 2012 her condition was re-evaluated. She was frail and had grade 2 edema.[jmedicalcasereports.biomedcentral.com]
  • Early symptoms are often vague, such as abdominal discomfort, abdominal distension or bloating, urinary frequency or dyspepsia. Constitutional symptoms include fatigue, weight loss, anorexia and depression.[patient.info]
  • All cases presented with similar symptomatology: pelvic pain, abdominal distension and ascites in two cases. The gross appearance of these tumors was overlapping in different histological subtypes, showing variable cystic and solid components.[medichub.ro]
  • Symptoms that come later include the following: Pelvic pain or pressure Pain with intercourse Abdominal swelling and bloating Urinary frequency Constipation Ascites : Collection of fluid in the abdomen , contributing to abdominal distension and shortness[emedicinehealth.com]
  • The mass may lead to acute pain due to torsion, rupture, or hemorrhage, or, patients may have abdominal distension, vaginal bleeding, or fever. Most are stage I and confined to the ovary at the time of diagnosis.[emedicine.medscape.com]
Abdominal Mass
  • mass / pain / rectal bleeding / jaundice Diagnosis Final diagnosis by histology and immunohistochemistry Treatment Debulking surgery with or without chemotherapy Clinical images Images hosted on other servers: Solid cystic bilateral ovarian mass Gross[pathologyoutlines.com]
  • Investigations [ 4 , 14 ] In primary care Refer urgently any woman with ascites and/or a pelvic or abdominal mass not obviously fibroids.[patient.info]
  • The main symptoms are abdominal pain, palpable abdominal mass, or vaginal bleeding, which are predominantly found in borderline and malignant tumors (8) . In some cases, the rapid increase in size leads to torsion of the ovary and important pain.[medichub.ro]
  • The patient may feel an abdominal mass. Most cases are diagnosed in an advanced stage.[emedicine.medscape.com]
Subcutaneous Nodule
Back Pain
  • pain menstrual irregularities painful intercourse dermatomyositis (a rare inflammatory disease that can cause skin rash, muscle weakness, and inflamed muscles) These symptoms may occur for any number of reasons.[healthline.com]
  • Abdominal, pelvic or back pain is usually a late sign and seen only with early disease that is complicated by torsion, rupture, or infection. It may cause abnormal uterine bleeding. Often associated with ascites.[patient.info]
  • Particularly large masses tend to be benign or borderline. [19] [16] The most typical symptoms of ovarian cancer include bloating , abdominal or pelvic pain or discomfort, back pain, irregular menstruation or postmenopausal vaginal bleeding, pain or bleeding[en.wikipedia.org]
Knee Pain
  • A woman with stage IV metastatic papillary serous ovarian cancer presented with fever, altered mental status, difficulty with vision and right knee pain.[ncbi.nlm.nih.gov]
Breast Mass
  • Initially, the patient was treated with antibiotic therapy, presenting improvement of the flogistic signs, but without regression of the breast mass. Then, the patient was submitted to imaging studies.[scielo.br]
  • Mastectomy of the breast mass is likely best reserved for patients who are unresponsive to systemic therapy and require palliation [ 11 ].[jcancer.org]
Altered Mental Status
  • A woman with stage IV metastatic papillary serous ovarian cancer presented with fever, altered mental status, difficulty with vision and right knee pain.[ncbi.nlm.nih.gov]
Vaginal Bleeding
  • Ovarian Cancer Overview Ovarian cancer warning signs include ongoing pain or cramps in the belly or back, abnormal vaginal bleeding, nausea, and bloating. Depending on the cancer stage, ovarian cancer treatment includes surgery and chemotherapy.[webmd.com]
  • The main symptoms are abdominal pain, palpable abdominal mass, or vaginal bleeding, which are predominantly found in borderline and malignant tumors (8) . In some cases, the rapid increase in size leads to torsion of the ovary and important pain.[medichub.ro]
  • ., pelvic masses, ascites, or vaginal bleeding. 17 , 19 Some patients with ovarian metastases have menstrual abnormalities, postmenopausal bleeding, and virilization, or they deliver a masculinized female fetus.[clinicalgate.com]
  • Vaginal bleeding that is heavy or irregular, especially after menopause. Vaginal discharge that is clear, white, or colored with blood. A lump in the pelvic area. Gastrointestinal problems, such as gas, bloating, or constipation.[northshore.org]
Pelvic Pain
  • All cases presented with similar symptomatology: pelvic pain, abdominal distension and ascites in two cases. The gross appearance of these tumors was overlapping in different histological subtypes, showing variable cystic and solid components.[medichub.ro]
  • Later, pelvic pain, anemia, cachexia, and abdominal swelling due to ovarian enlargement or ascites usually occur. Germ cell or stromal tumors may have functional effects (eg, hyperthyroidism, feminization, virilization).[merckmanuals.com]
  • Symptoms that come later include the following: Pelvic pain or pressure Pain with intercourse Abdominal swelling and bloating Urinary frequency Constipation Ascites : Collection of fluid in the abdomen , contributing to abdominal distension and shortness[emedicinehealth.com]
  • The typical symptoms of an LMP tumor can include abdominal distension or pelvic pain.[en.wikipedia.org]
  • Also, obtain a urinalysis to exclude other possible causes of abdominal/pelvic pain, such as urinary tract infections or kidney stones. Imaging studies Routine imaging is not required in all patients in whom ovarian cancer is highly suggested.[emedicine.medscape.com]
Adnexal Mass
  • A pelvic computed tomography scan revealed a 7-cm complex, right adnexal mass.[scholars.northwestern.edu]
  • Diagnosis Ultrasonography (for suspected early cancers) or CT or MRI (for suspected advanced cancers) Tumor markers (eg, cancer antigen [CA] 125) Surgical staging Ovarian cancer is suspected in women with the following: Unexplained adnexal masses Unexplained[merckmanuals.com]
  • Management of adnexal masses. Obstet Gynecol . 2007 Jul. 110 (1):201-14. [Medline] . Suh-Burgmann E, Kinney W. Potential harms outweigh benefits of indefinite monitoring of stable adnexal masses. Am J Obstet Gynecol . 2015 Dec. 213 (6):816.e1-4.[emedicine.medscape.com]
  • mass is a significant finding that often indicates ovarian cancer, especially if it is fixed, nodular, irregular, solid, and/or bilateral. 13–21% of adnexal masses are caused by malignancy; however, there are other benign causes of adnexal masses, including[en.wikipedia.org]
Amenorrhea
  • Adolescents with sex cord-stromal tumors may experience amenorrhea . As the cancer becomes more advanced, it can cause an accumulation of fluid in the abdomen.[en.wikipedia.org]
Ovarian Disorder
  • Altchek's Diagnosis and Management of Ovarian Disorders Online ISBN: 9781139003254 Book DOI: Unfortunately you do not have access to this title, please use the Get access link below for information on how to access this content.[cambridge.org]

Workup

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 [10], 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 [6]. 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 [7]. Although biopsy is not recommended for patients with this type of tumor, lymph node sampling or dissection may be performed [9].

Ovarian Mass
  • Work up had revealed bilateral ovarian masses with peritoneal spread. She underwent an exploratory laparotomy 3 weeks prior which revealed ovarian, peritoneal, omental, liver, gallbladder and small bowel tumor studding.[arizona.pure.elsevier.com]
  • In a few cases, the ovarian mass is the presenting feature.[e-immunohistochemistry.info]
  • The initial assessment demonstrates that the patient has a right-sided hydrothorax, ascites, and a large ovarian mass. Surgery is performed to remove the ovarian mass, and the patient's ascites and pleural effusion resolve promptly.[medbullets.com]
  • Seite 112 - Transvaginal ultrasonographic characterization of ovarian masses by means of color flow-directed Doppler measurements and a morphologic scoring system. Am J Obstet Gynecol 1 993; 1 68:909. ‎[books.google.de]
  • mass Gross description Laterality: mostly bilateral Size: mostly 10cm Surface involvement: mostly multiple small nodules on surface Extensive intraabdominal spread: mostly true for metastatic mucinous tumor Hilar involvement common in hematogenous spread[pathologyoutlines.com]
ST Elevation
  • The electrocardiography (ECG) showed a third-degree heart block and ST elevation in II, III and avF. In the initial and in the control laboratory investigation values of cardiac enzymes (creatininkinase and Troponine T) remained normal.[ncbi.nlm.nih.gov]
Pleural Effusion
  • Pleural effusions constitute the most frequent site of distant metastasis (FIGO stage IV disease).[ncbi.nlm.nih.gov]
  • Higher levels were detected in peritoneal compared to pleural effusions (p 0.031).[ncbi.nlm.nih.gov]
  • After drainage, chest X-ray showed a massive pleural effusion and thoracic Computed Tomography (CT) scan demonstrated a gastropleural fistula.[jpmsonline.com]
  • A 41-year-old previously hysterectomized women presented with pelvic mass and malignant pleural effusion.[link.springer.com]
  • Stage IV - Distant metastatic spread, with either pleural effusion that contains malignant cells (IVA) or involvement of extra-abdominal organs (IVB). Metastatic ovarian carcinoma carries a very poor prognosis.[symptoma.com]

Treatment

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 [5], and the extent of cytoreduction directly prolongs survival rates [11]. To maximize the effects of surgery, radical oophorectomy and primary stapled anastomosis are considered as effective technique [12], 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 [5]. Bleeding, infection and anastomotic dehiscence may be frequently seen and because ostomy is often necessary, the quality of life is severely impaired [5].

Prognosis

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 [9]:

  • Stage I - The primary tumor is confined to either a single ovary (with an intact capsule) or Fallopian tube (IA) or both (IB), with absence of malignant cells in the peritoneal fluid. Surgical spill, capsular rupture, presence of the tumor on the ovarian or tubal surface and malignant cells in peritoneal samples classify this tumor in stage IC1, IC2 and IC3, respectively.
  • Stage II - Involvement of one or both ovaries or Fallopian tubes, as well as pelvic extension (below the pelvic brim, for ex. spread to sigmoid colon), or presence of primary peritoneal malignancy (IIA), whereas stage IIB implies spread to other intraperitoneal tissues in the pelvis.
  • Stage III - In addition to involvement of the ovaries and/or Fallopian tubes or primary peritoneal cancer, a cytologic or histologic confirmation of tumor spread to the peritoneum (including the omentum, surfaces of the small and large intestines, mesentery, diaphragm and peritoneal surface of the spleen and liver) and/or metastatic spread to retroperitoneal lymph nodes. If only retroperitoneal lymph node spread is present, the tumor is staged as IIIA1, whereas metastatic spread up to 10 mm or more than 10 mm implies stages IIIA1 (ii) and IIIA1 (iii), respectively. IIIA2 stage includes extrapelvic peritoneal involvement, with or without nodal spread, while IIIB stage is demarcated by macroscopic pelvic involvement up to 2 cm. Pelvic spread of more than 2 cm (including the capsules of the liver and spleen, but without parenchymal spread) is termed as stage IIIC.
  • Stage IV - Distant metastatic spread, with either pleural effusion that contains malignant cells (IVA) or involvement of extra-abdominal organs (IVB).

Metastatic ovarian carcinoma carries a very poor prognosis [8]. When non-peritoneal metastases are present, the prognosis is significantly worse and mean survival rates are around 4 months from the diagnosis [2]. The devastating nature of this disease is further shown by the fact that long-term survival rates are only 30% [1].

Etiology

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 [1]:

  • Serous-papillary, endometrioid and borderline tumors that have low malignant potential are considered as type I tumors and they seem to arise from initially benign lesions under mutations of BRAF, KRAS, ERBB2 and expression of mitogen-activated protein kinases [1].
  • Type II included high-grade serous carcinomas that presumably contain mutations of RB1 and p16 proteins, but much less is known about the genetic mechanisms of this tumor.

Epidemiology

Reports from 2015 show that 22,280 new cases and 14,240 deaths from this malignancy were detected in the United States [4]. 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 [1]. Ethnic predilection in terms of longer survival rates has not been established [4].

Sex distribution
Age distribution

Pathophysiology

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 [1]. 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 [1]. 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 [1]. 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 [1]. 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 [1]. 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 [1].

Prevention

Having in mind the fact that 70% of women in European studies were diagnosed in advanced stages of the diseases (III and IV) [5], 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% [13]. 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 [14].

Summary

Metastatic ovarian carcinoma is a rare but devastating malignant disease due to its insidious onset and late clinical presentation [1]. 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 [1]. Ovarian carcinoma may arise from the surface epithelium of the ovaries, the Fallopian tubes and the mesothelium lining of the peritoneal cavity [1], 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 [1]. Additionally, BRCA 1 and 2 have also been identified [1]. 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 [1]. 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 [1]. 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 [2] [3]. 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 [4] [5]. But what is more worrisome is that almost 15,000 deaths occurred, signalizing that the case fatality ratio is very high [4]. 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 [6], 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 [7], 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 [5]. 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 [8].

Patient Information

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.

References

Article

  1. Lengyel E. Ovarian Cancer Development and Metastasis. Am J Pathol. 2010;177(3):1053-1064.
  2. Cormio G, Capotorto M, Di Vagno G, et al. Skin metastases in ovarian carcinoma: a report of nine cases and a review of the literature. Gynecol Oncol. 2003;90:682-685.
  3. Geisler JP, Geisler HE. Brain metastases in epithelial ovarian carcinoma. Gynecol Oncol. 1995;57:246-249.
  4. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.
  5. Derlatka P, Sienko J, Grabowska-Derlatka L, et al. Results of optimal debulking surgery with bowel resection in patients with advanced ovarian cancer. World J Surg Oncol. 2016;14:58.
  6. Yazbek J, Raju SK, Ben-Nagi J, et al. Effect of quality of gynaecological ultrasonography on management of patients with suspected ovarian cancer: a randomised controlled trial.Lancet Oncol. 2008;9(2):124-131.
  7. Iyer VR, Lee SI. MRI, CT, and PET/CT for ovarian cancer detection and adnexal lesion characterization.AJR Am J Roentgenol. 2010;194(2):311-321.
  8. Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol. 2000;19(1):3-10.
  9. Prat J. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynecol Obstet. 2014;124(1):1–5.
  10. Stany MP, Maxwell GL, Rose GS. Clinical decision making using ovarian cancer risk assessment. AJR Am J Roentgenol. 2010;194(2):337-432.
  11. Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20:1248–1259.
  12. Bristow RE, del Carmen M, Kaufman H, et al. Radical oophorectomy with primary stapled colorectal anastomosis for resection of locally advanced epithelial ovarian cancer. J Am Coll Surg. 2003;197:565–574.
  13. Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616-1622.
  14. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303-314.

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Last updated: 2018-06-21 19:50