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      Therapeutic Approaches to Gastric Hepatoid Adenocarcinoma: Current Perspectives

      review-article
      1 , 2
      Therapeutics and Clinical Risk Management
      Dove
      hepatoid adenocarcinoma, stomach, gastric, alpha-fetoprotein, therapy, prognosis

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          Abstract

          Hepatoid adenocarcinoma of the stomach (HAS) is a rare subgroup of gastric cancer (GC). Morphologically, this tumor exhibits both adenocarcinomatous and hepatocellular differentiation, and most tumors show immunohistochemical staining for alpha-fetoprotein (AFP) or elevated AFP serum levels. The diagnosis of HAS is frequently delayed, and at least half of patients have advanced disease at the time of diagnosis. Despite a lack of evidence, treatment approaches have mostly followed principles for the treatment of common gastric cancer (CGC), including radical surgery in eligible patients with curative intent. The indications for and the type of adjuvant systemic treatments remain unclear. Additionally, there is a lack of evidence allowing any firm conclusions to be drawn regarding the best treatment for patients with metastatic HAS (mHAS). Chemotherapy regimens, including cisplatin-based chemotherapy, are considered the most efficient first-line systemic treatment in advanced situations. Their combination with targeted therapy (i.e., trastuzumab) in HER2-positive tumors seems promising. The rarity of these patients and the scarce and heterogeneous literature on this particular subgroup of GC make it difficult to provide any robust evidence for the clinical management of patients with HAS.

          Most cited references40

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          How liquid biopsies can change clinical practice in oncology

          Cell-free DNA fragments are shed into the bloodstream by tumor cells. The analysis of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, can be exploited for a variety of clinical applications. ctDNA is being used to genotype solid cancers non-invasively, to track tumor dynamics and to detect the emergence of drug resistance. In a few settings, liquid biopsies have already entered clinical practice. For example, ctDNA is used to guide treatment in a subset of lung cancers. In this review, we discuss how recent improvements in the sensitivity and accuracy of ctDNA analyses have led to unprecedented advances in this research field. We further consider what is required for the routine deployment of liquid biopsies in the clinical diagnostic space. We pinpoint technical hurdles that liquid biopsies have yet to overcome, including preanalytical and analytical challenges. We foresee how liquid biopsies will transform clinical practice: by complementing (or replacing) imaging to monitor treatment response and by detecting minimal residual disease after surgery with curative intent.
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            An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report.

            A patient with primary gastric adenocarcinoma with extremely high serum alpha-fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic-type AFP and not germ-cell-type. Localization of alpha-1-antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid-Schiff (PAS)-positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.
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              Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: a literature review.

              Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be a challenge, especially in endemic areas with a high incidence of HCC. To date, HAC has only been reported in case series or single case reports, so we aimed to review the clinicopathological characteristics of HAC to obtain a more complete picture of this rare form of extrahepatic adenocarcinoma. All the articles about HAC published from 2001 to 2011 were reviewed, and clinicopathological findings were extracted for analysis. A late middle-aged male with high serum α-fetoprotein and atypical image finding of HCC should raise the suspicion of HAC, and characteristic pathological immunohistochemical stains can help with the differential diagnosis. Novel immunohistochemical markers may be useful to clearly differentiate HAC from HCC. Once metastatic HAC is diagnosed, the primary tumor origin should be identified for adequate treatment. The majority of HAC originates from the stomach, so panendoscopy should be arranged first.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                TCRM
                tcriskman
                Therapeutics and Clinical Risk Management
                Dove
                1176-6336
                1178-203X
                23 December 2019
                2019
                : 15
                : 1469-1477
                Affiliations
                [1 ]Department of Gastrointestinal Surgery, Stavanger University Hospital , Stavanger, Norway
                [2 ]Department of Clinical Medicine, University of Bergen , Bergen, Norway
                Author notes
                Correspondence: Jon Arne Søreide Department of Gastrointestinal Surgery, Stavanger University Hospital , POB 8100, StavangerN-4022, NorwayTel +47 905 31770Fax +47 51519919 Email jonarne.soreide@uib.no
                Author information
                http://orcid.org/0000-0001-7572-1089
                Article
                204303
                10.2147/TCRM.S204303
                6934111
                31920320
                b1a8a925-86a1-4ff3-8f3e-eeb22a35f4ec
                © 2019 Søreide.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 08 October 2019
                : 13 December 2019
                Page count
                Figures: 1, Tables: 1, References: 46, Pages: 9
                Categories
                Review

                Medicine
                hepatoid adenocarcinoma,stomach,gastric,alpha-fetoprotein,therapy,prognosis
                Medicine
                hepatoid adenocarcinoma, stomach, gastric, alpha-fetoprotein, therapy, prognosis

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