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      Predictive and prognostic value of serum AFP level and its dynamic changes in advanced gastric cancer patients with elevated serum AFP

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          Abstract

          AIM

          To investigate predictive and prognostic value of serum alpha-fetoprotein (AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP (AFPAGC).

          METHODS

          One hundred and five patients with AFPAGC were enrolled in the study, and all of them underwent at least one cycle of systemic chemotherapy at our institute and had serum AFP ≥ 20 ng/mL at diagnosis or recurrence. Clinicopathologic features, serum AFP level at diagnosis and changes during treatment, first-line chemotherapy regimens, efficacy and toxicity, and survival information were collected. A Person’s χ 2 or Fisher’s exact test was used to measure the differences between variables. Survival prognostic factors were investigated using the Kaplan-Meier method and Cox regression.

          RESULTS

          Median serum AFP level was 161.7 ng/mL (range, 22.9-2557110 ng/mL). Objective response rates (ORR) was significantly lower in the AFP ≥ 160 ng/mL group than in the AFP < 160 ng/mL group (30.4% vs 68.3%, P < 0.001). ORR to doublet regimens was significantly lower in the AFP ≥ 160 ng/mL group, whereas ORR to triplet regimens was similar between the two groups. Liver metastasis rate was significantly higher in the AFP ≥ 160 ng/mL group than in the AFP < 160 ng/mL (69.8% vs 50.0%, P < 0.001). Overall survival (OS) in the two cohorts did not show any significant difference ( P = 0.712). Dynamic changes of AFP were consistent with response to chemotherapy, and median OS of patients with a serum AFP decline ≥ 50% and those with a serum AFP decline < 50% was 17.5 m and 10.0 m, respectively ( P = 0.003). Hepatic ( P = 0.005), peritoneal ( P < 0.001), non-regional lymph node metastasis ( P < 0.001), and portal vein tumor thrombus (PVTT) ( P = 0.042) were identified as independent prognostic factors for AFPAGC.

          CONCLUSION

          Real-time examination of AFP has great predictive and prognostic value for managing AFPAGC. For those with markedly elevated AFP, triplet regimens may be a better choice.

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          Most cited references22

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          Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.

          We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC).
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            Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability.

            Blockade of the programmed death 1 (PD-1) pathway has emerged as a novel therapy for cancer. Therefore, development of biomarkers for response prediction, such as PD-ligand 1 (PD-L1) expression by immunohistochemistry, may help to stratify patients. Solid tumors with CD8 T-cell rich tumor microenvironment have been implicated to be associated with increased PD-L1 expression. We hypothesized that gastric cancers associated with Epstein-Barr virus infection (EBV+) or microsatellite instability (MSI), both of which are known to harbor such tumor microenvironment, are associated with increased PD-L1 expression. Forty-four resected gastric cancers including 7 EBV+, 16 MSI, and 21 microsatellite stable cancers without EBV (EBV-/MSS) were studied for PD-L1 expression and T-cell subpopulations by immunohistochemistry. Positive PD-L1 expression (PD-L1+), defined as membranous staining in either tumor cells or tumor immune infiltrates, was seen in 32 (72%) gastric cancers. EBV+ or MSI cancers showed significantly higher rates of PD-L1+ compared with EBV-/MSS cancers (7/7, 100%; 14/16, 87%; 11/21, 52%; P=0.013). PD-L1+/EBV+ and PD-L1+/MSI cancers had significantly more CD8 T cells at tumor invasive front than PD-L1+/EBV-/MSS cancers (P<0.001). PD-L1+ was not associated with the depth of invasion or nodal metastasis (P=0.534, 0.288). Multivariate analysis showed PD-L1+ was not an independent predictor of disease-free survival while MSI was (P=0.548, 0.043). In summary, EBV+ or MSI gastric cancers are more likely to express PD-L1 and have increased CD8 T cells at tumor invasive front than EBV-/MSS cancers. Our results suggest EBV infection and MSI should be investigated for predicting response to PD-1 blockade.
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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

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 January 2018
                14 January 2018
                : 24
                : 2
                : 266-273
                Affiliations
                Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
                Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
                Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
                Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China. zhangxiaotianmed@ 123456163.com
                Author notes

                Author contributions: Wang KY collected and analyzed the data and wrote the manuscript; Jiao X collected the data and revised the manuscript; Shen L and Zhang XT were in charge of the project and revised the manuscript.

                Correspondence to: Xiao-Tian Zhang, MD, Professor, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China. zhangxiaotianmed@ 123456163.com

                Telephone: +86-10-88196561 Fax: +86-10-88196561

                Article
                jWJG.v24.i2.pg266
                10.3748/wjg.v24.i2.266
                5768945
                29375212
                3b965c6d-7e06-48fd-b2ef-fed52339a52d
                ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 26 October 2017
                : 18 November 2017
                : 5 December 2017
                Categories
                Retrospective Study

                alpha-fetoprotein,afp-producing gastric cancer,predictive factor,prognostic factor,triplet regimen

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