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      Rare Distant Metastatic Disease of Ovarian and Peritoneal Carcinomatosis: A Review of the Literature

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          Abstract

          Background: Although metastases of ovarian and peritoneal carcinomatosis are most commonly found within the peritoneal cavity, there is a number of other rare distant sites that have been reported. Our goal is to provide an evidence-based summary of the available literature considering the rare distant metastatic sites of ovarian and peritoneal carcinomatosis. Methods: A comprehensive search of the literature was conducted, with Medline/PubMed being searched for cases of rare metastatic disease originated from primary ovarian and peritoneal cancer with related articles up to 2019 including terms such as “ovarian cancer”, “metastases”, “peritoneal” and others. Results: The most common mechanism of ovarian cancer metastases consists of primarily dissemination within the peritoneal cavity, while, rare and distant sites can either occur at the beginning or during the course of the disease and they are usually associated with hematogenous route and lymphatic invasion, having poor prognosis, with the least common sites being skin, bone, CNS, eye, placenta, central airways, rare lymph nodes, intra-abdominal organs, heart and breast. Conclusions: The occurrence of metastatic sites described in this review represents the most common rare distant metastatic sites, and even though their patterns of metastases are still not fully clarified due to the rarity of the reports, they offer valuable information considering the pathophysiology of the disease.

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          Most cited references117

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          Ovarian cancer

          Epithelial ovarian cancer is the commonest cause of gynaecological cancer-associated death. The disease typically presents in postmenopausal women, with a few months of abdominal pain and distension. Most women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III), for which the standard of care remains surgery and platinum-based cytotoxic chemotherapy. Although this treatment can be curative for most patients with early stage disease, most women with advanced disease will develop many episodes of recurrent disease with progressively shorter disease-free intervals. These episodes culminate in chemoresistance and ultimately bowel obstruction, the most frequent cause of death. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Targeted treatments such as antiangiogenic drugs or poly (ADP-ribose) polymerase inhibitors offer potential for improved survival. The efficacy of screening, designed to detect the disease at an earlier and curable stage remains unproven, with key results expected in 2015. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Epidemiology of ovarian cancer: a review

            Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy, pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology, primary prevention, early detection, and possibly even therapeutic strategies.
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              The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome.

              A proportion of adenocarcinomas in prophylactic adnexectomies (bilateral salpingo-oophorectomies [BSOs]) from women with BRCA mutations (BRCA positive) occur in the fallopian tube. We analyzed a consecutive series of BSOs from BRCA-positive women following an index case of fimbrial serous carcinoma. To determine if the fimbria is a preferred site of origin, we followed a protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Immunostaining for p53 and Ki-67 was also performed. Thirteen BRCA-positive women (cases) and 13 women undergoing BSOs for other disorders (controls) were studied. Tubal carcinoma was detected in 4 cases at the initial histologic evaluation and in no controls. A fifth carcinoma was discovered following further sectioning of the fimbriae. Three were BRCA2 positive and two BRCA1 positive. Three were in the fimbria, one in both the fimbria and proximal tube, and one involved the ampulla. Four were serous carcinomas, four were confined to the tube, and three were noninvasive (intraepithelial). No ovarian carcinomas were identified. All tumors were Ki-67 positive (>75% of cell nuclei), and excluding one endometrioid carcinoma, p53 positive (>75% cell nuclei); p53 positivity in the absence of elevated Ki-67 did not correlate with morphologic neoplasia. The fimbria was the most common location for early serous carcinoma in this series of BRCA-positive women. Protocols that extensively examine the fimbria (SEE-FIM) will maximize the detection of early tubal epithelial carcinoma in patients at risk for ovarian cancer. Investigative strategies targeting the fimbriated end of the fallopian tube should further define its role in the pathogenesis of familial and sporadic ovarian serous carcinomas.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                24 July 2019
                August 2019
                : 11
                : 8
                : 1044
                Affiliations
                [1 ]1st Department of Obstetrics and Gynecology, Alexandra Hospital, Gynecologic Oncology Unit, University of Athens, Athens 115 28, Greece
                [2 ]Department of Obstetrics & Gynecology, Department of Obstetrics-Gynaecology, Royal Oldham Hospital, Pennine Accute Trust, Oldham OL12JH, UK
                [3 ]3rd Department of Surgery, “AHEPA” University Hospital, Aristotle University of Thessaloniki, Thessaloniki 546 36, Greece
                Author notes
                Author information
                https://orcid.org/0000-0003-1104-7739
                https://orcid.org/0000-0003-0216-3420
                https://orcid.org/0000-0001-5119-2207
                Article
                cancers-11-01044
                10.3390/cancers11081044
                6721345
                31344859
                9ff36e81-dd1c-477a-be73-bff3f41ae63e
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 June 2019
                : 22 July 2019
                Categories
                Review

                ovarian cancer,distant,metastases,peritoneal cancer
                ovarian cancer, distant, metastases, peritoneal cancer

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