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      Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020


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          We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.


          We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.


          A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% ( p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients ( p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis ( p = 0.82, p = 0.96, p = 0.25).


          HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.

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          Most cited references52

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          The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

          Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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            Lung cancer mutation profile of EGFR, ALK, and KRAS: Meta-analysis and comparison of never and ever smokers.

            Lung cancer is the leading cause of cancer-related mortality. While the majority of lung cancers are associated with tobacco smoke, approximately 10-15% of U.S. lung cancers occur in never smokers. Evidence suggests that lung cancer in never smokers appears to be a distinct disease caused by driver mutations which are different than the genetic pathways observed with lung cancer in smokers. A meta-analysis of human epidemiologic data was conducted to evaluate the profile of common or therapy-targetable mutations in lung cancers of never and ever smokers. Epidemiologic studies (N=167) representing over 63,000 lung cancer cases were identified and used to calculate summary odds ratios for lung cancer in never and ever smokers containing gene mutations: EGFR, chromosomal rearrangements and fusion of EML4 and ALK, and KRAS. This analysis also considered the effect of histopathology, smoking status, sex, and ethnicity. There were significantly increased odds of presenting the EGFR and ALK-EML4 mutations in 1) adenocarcinomas compared to non-small cell lung cancer and 2) never smokers compared to ever smokers. The prevalence of EGFR mutations was higher in Asian women as compared to women of Caucasian/Mixed ethnicity. As the smoking history increased, there was a decreased odds for exhibiting the EGFR mutation, particularly for cases >30 pack-years. Compared to ever smokers, never smokers had a decreased odds of KRAS mutations among those of Caucasian/Mixed ethnicity (OR=0.22, 95% CI: 0.17-0.29) and those of Asian ethnicity (OR=0.39, 95% CI: 0.30-0.50). Our findings show that key driver mutations and several patient features are highly prevalent in lung cancers of never smokers. These associations may be helpful as patient demographic models are developed to predict successful outcomes of targeted therapeutic interventions NSCLC.
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              Hepatoid Adenocarcinoma – Review of the Literature Illustrated by a Rare Case Originating in the Peritoneal Cavity

              Hepatoid adenocarcinoma (HAC) is a rare and aggressive extrahepatic tumour, morphologically mimicking hepatocellular carcinoma (HCC). However, immunophenotype and location are heterogeneous. We report the case of a 21-year-old man with HAC of the peritoneal cavity and summarize data from the 261 HAC cases published so far. The most common HAC locations were stomach (63%), ovaries (10%), lung (5%), gallbladder (4%), pancreas (4%), and uterus (4%). With the exception of gallbladder HAC, there was a male predominance (M:F = 2.4:1). Median age was 65 years (range 21–88). Fatigue, weight loss, abdominal masses, and pain were common findings. One-year survival was 55% and median overall survival 11 months (range 0.1–102). The outstanding diagnostic feature of HAC is positivity for alphafetoprotein (AFP) (88%), HepPar1 (63%), and EpCAM antibodies HEA125 or MOC31 which show no reactivity with hepatocytes. Due to the beneficial effect of sorafenib in HCC and strong activation of EGFR, ERK1 and AKT1, our patient received sorafenib. Despite temporary clinical improvement, he died 6 months after the diagnosis. The diagnostic panel of HAC should include AFP, HepPar1, and EpCAM antibodies. EpCAM reactivity excludes HCC. HAC has a poor prognosis.

                Author and article information

                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                06 August 2021
                : 11
                : 702216
                [1] 1Department of Oncology, The Affiliated Fifth People’s Hospital of Chengdu University of TCM, Chengdu Fifth People’s Hospital , Chengdu, China
                [2] 2Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center , Guangzhou, China
                [3] 3Department of Clinical Laboratory, The Affiliated Fifth People’s Hospital of Chengdu University of TCM, Chengdu Fifth People’s Hospital , Chengdu, China
                [4] 4Department of Pathology, The Affiliated Fifth People’s Hospital of Chengdu University of TCM, Chengdu Fifth People’s Hospital , Chengdu, China
                Author notes

                Edited by: Junji Uchino, Kyoto Prefectural University of Medicine, Japan

                Reviewed by: Federica Pezzuto, University of Padua, Italy; Janaki Deepak, University of Maryland, Baltimore, United States

                *Correspondence: Lang He, helang126@ 123456outlook.com

                †These authors have contributed equally to this work

                This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology

                Copyright © 2021 Hou, Xie, Zhang, Dai, Chen and He

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 29 April 2021
                : 20 July 2021
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 53, Pages: 10, Words: 4544
                Systematic Review

                Oncology & Radiotherapy
                hepatoid adenocarcinoma of the lung,clinical features,treatment,prognosis,case report,systematic review


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