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Gong W, Liu H, Yin Z, Zhou F, Zhan C. 68Ga-FAPI-04 PET/CT Imaging of Multiple Lymph Node Metastases of Gastric Hepatoid Adenocarcinoma. Clin Nucl Med 2025:00003072-990000000-01746. [PMID: 40392199 DOI: 10.1097/rlu.0000000000005873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/23/2025] [Indexed: 05/22/2025]
Abstract
Hepatoid adenocarcinoma is a rare special type of adenocarcinoma with hepatic differentiation that occurs in extrahepatic organs or tissues. We present 68Ga-FAPI-04 findings of multiple lymph node metastases of gastric hepatoid adenocarcinoma in a 60-year-old man. In this case, 68Ga-FAPI PET/CT showed increased FAPI activity in the primary gastric lesions and multiple lymph nodes throughout the body. Our findings suggest the potential value of 68Ga-FAPI-04 in the diagnosis of hepatoid adenocarcinoma.
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Affiliation(s)
- Weidong Gong
- Department of Nuclear Medicine, The Second People's Hospital of Yibin, Yibin
| | - Huajun Liu
- Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province
- Academician (Expert) Workstation of Sichuan Province, Luzhou
| | - Zongyin Yin
- Department of Burn Plastic Surgery, The Second People's Hospital of Yibin, Yibin, Sichuan, PR China
| | - Fan Zhou
- Department of Nuclear Medicine, The Second People's Hospital of Yibin, Yibin
| | - Chunyin Zhan
- Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province
- Academician (Expert) Workstation of Sichuan Province, Luzhou
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Xiang ZY, Hu YY, Zheng Q, Yu WM, Liu XC, Chen P, Wu F, Pan JH, Ji SQ, Gu LH. Clinicopathological characteristics and prognostic outcomes of resectable hepatoid adenocarcinoma of the stomach: insights from a multicenter case-control study. Am J Cancer Res 2025; 15:1689-1704. [PMID: 40371156 PMCID: PMC12070091 DOI: 10.62347/dbfo6813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 03/22/2025] [Indexed: 05/16/2025] Open
Abstract
Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC). This multicenter case-control study aimed to elucidate the clinicopathological features and prognosis of patients with resectable HAS. This retrospective study included 1387 GC patients treated at Ningbo No. 2 Hospital between January 2016 and December 2023, among whom 23 were HAS cases and incorporated 61 HAS patients from three external centers. Prognostic factors were analyzed using the Cox proportional hazards model. Propensity score matching (PSM) at a ratio of 4:1 and Kaplan-Meier survival curves were employed for analysis. The prevalence of HAS in this cohort was 1.1%. Among the 84 HAS patients with a median follow-up of 28 months, 47.6% had serum alpha-fetoprotein (AFP) levels exceeding 20 ng/mL. During the follow-up period, 44.0% of patients experienced relapses, predominantly through hepatic metastasis (62.2%). Univariate and multivariate analyses identified preoperative serum AFP levels between 200-500 ng/mL and TNM stages III/IV as independent prognostic factors for overall survival (OS). Elevated preoperative levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and TNM stages III/IV were independently associated with poorer disease-free survival (DFS). Conversely, open surgery and a Ki-67 proliferation index exceeding 50% were found to act as protective factors for both OS and DFS, with postoperative chemotherapy improving OS outcomes. After PSM adjustment, the analysis included 248 non-HAS patients and 62 HAS patients, revealing significantly better OS (P=0.043) and DFS (P=0.009) among non-HAS patients. Open radical surgery followed by adjuvant chemotherapy is recommended for the treatment of resectable HAS. Overall, patients with HAS exhibit a less favorable prognosis compared to those with non-HAS.
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Affiliation(s)
- Zhi-Yi Xiang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou, Zhejiang, China
| | - Yu-Ying Hu
- Department of General Surgery, The First Affiliated Hospital of Ningbo UniversityNingbo, Zhejiang, China
| | - Qi Zheng
- Department of General Surgery, Ningbo No. 2 HospitalNingbo, Zhejiang, China
| | - Wei-Ming Yu
- Department of Gastrointestinal Surgery, The Affiliated Lihuili Hospital, Ningbo UniversityNingbo, Zhejiang, China
| | - Xing-Chen Liu
- Intensive Care Unit, Ningbo No. 2 HospitalNingbo, Zhejiang, China
| | - Ping Chen
- Department of General Surgery, Ningbo No. 2 HospitalNingbo, Zhejiang, China
| | - Feng Wu
- Department of General Surgery, Ningbo No. 2 HospitalNingbo, Zhejiang, China
| | - Jun-Hai Pan
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw HospitalHangzhou, Zhejiang, China
| | - Sheng-Qiang Ji
- Ningbo Clinical Pathology Diagnosis Center NingboNingbo, Zhejiang, China
| | - Li-Hu Gu
- Department of General Surgery, Ningbo No. 2 HospitalNingbo, Zhejiang, China
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Li L, Zhang D, Zhu J, Zhang G. Hepatoid adenocarcinoma of the stomach with ideal response to neoadjuvant chemo-immunotherapy: a case report. Front Immunol 2025; 15:1496342. [PMID: 39845967 PMCID: PMC11750875 DOI: 10.3389/fimmu.2024.1496342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 12/18/2024] [Indexed: 01/24/2025] Open
Abstract
Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer characterized by histological features resembling hepatocellular carcinoma. Surgical intervention remains the preferred treatment modality for eligible patients. However, the efficacy of neoadjuvant therapy and alternative treatment regimens has been found to be suboptimal. Consequently, due to the high metastatic potential and unfavorable biological behavior of HAS, the prognosis for affected patients is exceedingly poor. We present a case involving a 64-year-old male diagnosed with advanced HAS, who demonstrated significant antitumor responses following a preoperative regimen of chemotherapy combined with immunotherapy, specifically utilizing oxaliplatin, S-1, and sintilimab. Over a 2-month period of neoadjuvant therapy, the patient's serum α-fetoprotein level significantly decreased from 52,951.56 ng/mL to 241.04 ng/mL. Computed tomography scans revealed substantial tumor regression. Subsequent radical surgical intervention confirmed significant tumor shrinkage, with no evidence of lymph node metastasis upon pathological examination. This is the first report of chemotherapy combined with sintilimab in the treatment of gastric hepatoid adenocarcinoma, which may provide novel insights into the therapeutic strategy for HAS.
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Affiliation(s)
- Linchuan Li
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Laboratory of Metabolism and Gastrointestinal Tumor, Shandong, China
| | - Dexu Zhang
- Shandong Provincial Qianfoshan Hospital, Shandong University, Shandong, China
| | - Jiankang Zhu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Laboratory of Metabolism and Gastrointestinal Tumor, Shandong, China
| | - Guangyong Zhang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Laboratory of Metabolism and Gastrointestinal Tumor, Shandong, China
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Huang YQ, Huang ZN, Hong QQ, Zhang P, Zhang ZZ, He L, Shang L, Wang LJ, Sun YF, Li ZX, Liu JJ, Ding FH, Lin ED, Fu YA, Lin SM, Chen QY, Zheng CH, Huang CM, Li P. Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: a retrospective cohort study. Int J Surg 2025; 111:718-727. [PMID: 39316640 PMCID: PMC11745678 DOI: 10.1097/js9.0000000000001768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/27/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at two centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the eighth American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that the mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the eighth AJCC staging system (0.667, 95% CI: 0.610-0.723, P <0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the eighth AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively, the mpTNM staging system outperformed the eighth AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P <0.05). The time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the eighth AJCC staging system with increasing observation time. CONCLUSION The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the eighth AJCC staging system.
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Affiliation(s)
- Ying-Qi Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Qing-Qi Hong
- Department of Gastrointestinal Oncology Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Liang He
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
| | - Lin-Jun Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Ya-Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China
| | - Zhi-Xiong Li
- Gastrointestinal Surgery Unit 1, Teaching Hospital of Putian First Hospital of Fujian Medical University, Putian, People’s Republic of China
| | - Jun-Jie Liu
- Gastrointestinal Department of The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China
| | - En-De Lin
- Department of General Surgery, Zhongshan Hospital Affiliated with Xiamen University, Xiamen, People’s Republic of China
| | - Yong-An Fu
- Department of Gastrointestinal Surgery, Affiliated Quanzhou First Hospital to Fujian Medical University, Quanzhou, People’s Republic of China
| | - Shuang-Ming Lin
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated with Fujian Medical University, Longyan, People’s Republic of China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
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Ye ZY, Xu CH, Chen W, Shao ZM, Zhao X, Tang JL, Li XS, Wang X, Wang CN, Yang QQ, Huang Y, Xiao XY, Wu XD, Wu QB. α‑Fetoprotein‑positive hepatoid adenocarcinoma of the stomach and a new classification: A case report. Oncol Lett 2024; 28:586. [PMID: 39421320 PMCID: PMC11484300 DOI: 10.3892/ol.2024.14717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 09/12/2024] [Indexed: 10/19/2024] Open
Abstract
α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is a rare subtype of gastric cancer (GC) with controversial classification methods. Hepatoid adenocarcinoma of the stomach (HAS) is another rare subtype of GC. Its definition intersects with that of AFPGC, but it is much rarer. The present report describes the case of an elderly patient with GC and AFPGC and HAS features in a serum test and pathology, respectively, and proposes a new classification of GC subtypes based on histological and AFP-producing features. A 75-year-old woman presented with a history of polydipsia and polyuria for over a decade and dizziness for 1 day. Serum AFP levels gradually elevated from 183.70 to 397.70 ng/ml in 1 month after the patient's first clinic visit. Subsequent pathological findings from endoscopic biopsy samples confirmed a hepatoid focus with positive immunohistochemical staining for AFP. The patient underwent a laparoscopic-assisted radical total gastrectomy and esophagojejunal Roux-en-Y anastomosis, and the serum AFP levels decreased to the normal range after the surgery. The present case indicates the diagnostic value of both the serum AFP level and pathological examinations in the diagnosis of AFPGC and HAS, and also highlights the contemporary circumstances of the vague classification based on different criteria for these two subtypes. Furthermore, the present report proposes a new classification considering both histological and AFP-producing features (using both serum biomarkers and immunohistochemistry tests) to cover all cases encompassed by AFPGC and HAS under all definition methods. This new method would give more precise diagnoses and add value to the subsequent treatment decision-making.
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Affiliation(s)
- Zhen-Yu Ye
- Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macau SAR, P.R. China
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Chuan-Hai Xu
- Department of Pathology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Wang Chen
- Department of Medical Imaging, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Zhong-Ming Shao
- Department of Pathology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Xue Zhao
- Department of General Medicine, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Jin-Ling Tang
- Gastrointestinal Endoscopy Center, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Xiang-Su Li
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Xin Wang
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Chao-Nan Wang
- Department of General Medicine, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Qing-Qing Yang
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
- Department of Gastroenterology, Yancheng Clinical College of Xuzhou Medical University, Yancheng, Jiangsu 224005, P.R. China
| | - Yang Huang
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
- Department of Gastroenterology, Yancheng Clinical College of Xuzhou Medical University, Yancheng, Jiangsu 224005, P.R. China
| | - Xue-Yi Xiao
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
- Department of Gastroenterology, Yancheng Clinical College of Xuzhou Medical University, Yancheng, Jiangsu 224005, P.R. China
| | - Xu-Dong Wu
- Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macau SAR, P.R. China
- Department of Gastroenterology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China
| | - Qi-Biao Wu
- Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macau SAR, P.R. China
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Gu X, Rong J, Zhu L, Dai Z, Ren S, Chen J, Yin B, Wang Z. Hepatoid adenocarcinoma of the stomach: discrimination from conventional gastric adenocarcinoma with a computed tomography-based radiomics nomogram. J Gastrointest Oncol 2024; 15:2041-2052. [PMID: 39554578 PMCID: PMC11565099 DOI: 10.21037/jgo-24-210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 09/04/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND Previous studies found it difficult to differentiate hepatoid adenocarcinoma of the stomach (HAS) from conventional gastric adenocarcinoma (CGA). We aimed to assess the efficacy of a computed tomography (CT)-based radiomics nomogram in identifying HAS. METHODS Portal phase CT images were collected from 59 patients with HAS and 122 patients with CGA. HAS and CGA were differentiated through univariate analysis of clinical characteristics, serum biochemical biomarkers, and CT features. The construction of the radiomics signature involved the application of the least absolute shrinkage and selection operator (LASSO) regression model. Multivariable logistic regression analysis was employed to establish the CT-based radiomics nomogram. RESULTS The separation of HAS patients from CGA patients relied on the serum alpha-fetoprotein (AFP) level and radiomics signature. The area under the curve (AUC) of AFP was 0.726 [95% confidence interval (CI): 0.639-0.801] in the training cohort and 0.681 (95% CI: 0.541-0.800) in the test cohort, whereas the radiomic signature demonstrated a significantly higher AUC of 0.949 (95% CI: 0.895-0.980) in the training cohort and 0.868 (95% CI: 0.749-0.944) in the test cohort. The nomogram model yielded excellent accuracy for identifying HAS, achieving an AUC of 0.970 (95% CI: 0.923-0.992) in the training cohort and 0.905 (95% CI: 0.796-0.968) in the test cohort. CONCLUSIONS Radiomics analysis offers promise for differentiating HAS from CGA, and the CT-based radiomics nomogram is likely to have significant clinical implications on HAS distinction.
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Affiliation(s)
- Xiaoyu Gu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jian Rong
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Li Zhu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhaoyan Dai
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianxin Chen
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Bo Yin
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Wang QZ, Zhou YX, Mu XL, Wang JL, Zhang S, Chen Y. Development of dynamic nomogram for predicting cancer-specific survival in hepatoid adenocarcinoma: A comprehensive SEER-based population analysis. BIOMOLECULES & BIOMEDICINE 2024; 24:1350-1360. [PMID: 38577906 PMCID: PMC11379014 DOI: 10.17305/bb.2024.10445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/31/2024] [Accepted: 03/31/2024] [Indexed: 04/06/2024]
Abstract
Hepatoid adenocarcinoma (HAC) is a poorly differentiated extrahepatic tumor that can produce alpha-fetoprotein (AFP). The literature does not provide a comprehensive understanding of the prognostic factors for HAC. Therefore, we present a novel nomogram to predict the cancer-specific survival (CSS) of patients with HAC. We analyzed 265 cases of HAC from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. Using a Cox proportional hazard regression model, we identified several risk factors and incorporated them into our predictive nomogram. The nomogram's predictive ability was assessed by utilizing the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC). Results from a multivariate Cox regression showed that CSS was independently correlated with liver metastasis, surgery, and chemotherapy. Our nomogram had a C-index of 0.71 (95% CI 0.71-0.96). Furthermore, calibration curves demonstrated concordance between the predicted survival probability from the nomogram and the observed survival probability. The areas under the curve (AUC) for 6-month, 1-, and 3-year survival were 0.80, 0.82, and 0.88, respectively. Our study successfully formulated a prognostic nomogram that offers promising predictions for the 6-month, 1-, and 3-year CSS of patients with HAC. This nomogram holds potential for practical use in guiding treatment decisions and designing clinical trials.
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Affiliation(s)
- Qing-Zhe Wang
- Department of Targeting Therapy and Immunology, Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Yi-Xin Zhou
- Department of Targeting Therapy and Immunology, Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Li Mu
- Department of Targeting Therapy and Immunology, Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Jia-Ling Wang
- Department of Targeting Therapy and Immunology, Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Shuang Zhang
- Department of Targeting Therapy and Immunology, Cancer Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Ye Chen
- Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Zhu H, Li Q, Qian L. Liver metastasis from hepatoid adenocarcinoma of the stomach: a case report and literature review. Front Oncol 2024; 14:1297062. [PMID: 38993642 PMCID: PMC11236608 DOI: 10.3389/fonc.2024.1297062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 06/11/2024] [Indexed: 07/13/2024] Open
Abstract
Hepatoid adenocarcinoma of the stomach (HAS) represents a rare malignant neoplasm sharing morphological and immunophenotypic similarities with hepatocellular carcinoma (HCC). Pathological morphology serves as the cornerstone for diagnosis, often accompanied by elevated alpha-fetoprotein (AFP) levels, nonspecific clinical symptoms, and imaging features reminiscent of gastric adenocarcinoma (GA). Liver metastases from HAS can mimic the enhancement patterns of HCC, posing challenges in differentiation from high-risk HCC cases. Conversely, HAS typically exhibits poorer prognostic outcomes compared to HCC and GA. This report presents a case of HAS with liver metastasis alongside a comprehensive literature review covering its pathology, molecular mechanisms, clinical presentations, and treatment modalities. Special focus is given to imaging characteristics and the utilization of radiomics for early-stage detection. The integration of imaging findings with laboratory results aids in HAS diagnosis, while radiomics provides novel insights for precise discrimination. In conclusion, the identification of distinct imaging markers distinguishing HAS from HCC and GA shows promise in facilitating optimal treatment strategies and improving patient outcomes.
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Affiliation(s)
- Hui Zhu
- Department of Radiology, Suzhou Wuzhong People’s Hospital, Suzhou, China
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Yanagawa S, Tanabe K, Kano M, Hotta R, Saeki Y, Fujikuni N, Ohdan H. Clinicopathological features of hepatoid adenocarcinoma of the stomach: A multicenter retrospective study. Cancer Rep (Hoboken) 2024; 7:e2101. [PMID: 38831124 PMCID: PMC11147685 DOI: 10.1002/cnr2.2101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 04/20/2024] [Accepted: 05/05/2024] [Indexed: 06/05/2024] Open
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.
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Affiliation(s)
| | - Kazuaki Tanabe
- Department of Perioperative and Critical Care Management, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mikihiro Kano
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Ryuichi Hotta
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Japan
| | - Yoshihiro Saeki
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
| | - Nobuaki Fujikuni
- Department of Digestive Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
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Wei J, Ji K, Zhang Y, Zhang J, Wu X, Ji X, Zhou K, Yang X, Lu H, Wang A, Bu Z. Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach. Cell Oncol (Dordr) 2024; 47:677-693. [PMID: 37943484 DOI: 10.1007/s13402-023-00892-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2023] [Indexed: 11/10/2023] Open
Abstract
PURPOSE Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. METHODS Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. RESULTS A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53. In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2, FGFR2, MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. CONCLUSION Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2, FGFR2, MET and HGF gene amplification may be potential therapeutic targets for HAS.
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Affiliation(s)
- Jingtao Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Yue Zhang
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
- The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, 100037, China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Kai Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xuesong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Hongfeng Lu
- Berry Genomics Corporation, Beijing, 102206, China
| | - Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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11
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Yang X, Wu Y, Wang A, Ma X, Zhou K, Ji K, Ji X, Zhang J, Wu X, Li Z, Bu Z. Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases. J Pathol Clin Res 2024; 10:e343. [PMID: 37974386 PMCID: PMC10766033 DOI: 10.1002/cjp2.343] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/13/2023] [Accepted: 08/28/2023] [Indexed: 11/19/2023]
Abstract
Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.
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Affiliation(s)
- Xuesong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Yan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xiuli Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Kai Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - ZhongWu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
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12
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Huang ZN, Huang YQ, Hong QQ, Zhang P, Zhang ZZ, He L, Shang L, Wang LJ, Sun YF, Li ZX, Liu JJ, Ding FH, Lin ED, Fu YA, Lin SM, Lu J, Zheng CH, Huang CM, Li P. Long-term prognostic benefit of adjuvant chemotherapy for patients with hepatoid adenocarcinoma of the stomach after radical resection: A national multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106975. [PMID: 37474342 DOI: 10.1016/j.ejso.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/10/2023] [Accepted: 07/02/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND There is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. METHODS The clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). RESULTS Kaplan‒Meier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). CONCLUSION The current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.
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Affiliation(s)
- Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ying-Qi Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qing-Qi Hong
- Department of Gastrointestinal Oncology Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liang He
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lin-Jun Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ya-Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Zhi-Xiong Li
- Gastrointestinal Surgery Unit 1, Teaching Hospital of Putian First Hospital of Fujian Medical University, Putian, China
| | - Jun-Jie Liu
- Gastrointestinal Department of the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - En-De Lin
- Department of General Surgery, Zhongshan Hospital Affiliated with Xiamen University, Xiamen, China
| | - Yong-An Fu
- Department of Gastrointestinal Surgery, Affiliated Quanzhou First Hospital to Fujian Medical University, Quanzhou, China
| | - Shuang-Ming Lin
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated with Fujian Medical University, Longyan, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
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13
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Liu Y, Lai H, Zhang R, Xia L, Guo C, Liu L. Risk factors and a prognostic model for patients with borderline resectable locally advanced T3-4N0-1 non-small cell lung cancer: a population-based study. Transl Cancer Res 2023; 12:2837-2851. [PMID: 37969361 PMCID: PMC10643965 DOI: 10.21037/tcr-23-519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 08/25/2023] [Indexed: 11/17/2023]
Abstract
Background Non-small cell lung cancer (NSCLC) is a malignant disease with a significant morbidity rate. For patients diagnosed with borderline resectable locally advanced (T3-4 invasion and N0-1) NSCLC, the optimal treatment and prognosis are still under debate. This study aimed to develop a predictive nomogram that could assess the prognosis of these patients and optimize clinical decision-making. Methods Between 2010 to 2015, the survival, demographic and clinical characteristics of patients with borderline resectable locally advanced T3-4N0-1 NSCLC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression analyses were conducted to identify potential factors, which were further utilized to develop a dynamic nomogram for personalized prediction. Internal and external validation were conducted to verify the predictive accuracy of the nomogram. Results Totally, 5,054 eligible records were enrolled into the study cohort. The included patients were divided into a training cohort (n=3,538) and a validation cohort (n=1,516) in a 7:3 ratio. Nine independent prognostic factors (including age, gender, primary site, lymph node removal, differentiation grade, T stage, N stage, histology and adjuvant chemotherapy) were finally included into the nomogram. The developed nomogram exhibited favorable discriminative ability with the C-index =0.71. Moreover, the calibration curves demonstrated excellent agreement between predicted and observed outcomes in both the training and validation cohorts. Notably, subgroup analyses revealed that neoadjuvant chemotherapy was significantly associated with a better overall survival (OS) (P<0.05) in patients staged as T3-4N1. Conclusions In this study, we developed and validated a prognostic model to assist in clinical decision-making for patients with borderline resectable locally advanced T3-4N0-1 NSCLC. Our findings suggested that patients with T3-4N1 stage disease may derive significant benefits from neoadjuvant chemotherapy.
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Affiliation(s)
- Yi Liu
- Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hongjin Lai
- Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ren Zhang
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Liang Xia
- Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Chenglin Guo
- Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Lunxu Liu
- Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
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14
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Chang R, Qi S, Wu Y, Yue Y, Zhang X, Qian W. Nomograms integrating CT radiomic and deep learning signatures to predict overall survival and progression-free survival in NSCLC patients treated with chemotherapy. Cancer Imaging 2023; 23:101. [PMID: 37867196 PMCID: PMC10590525 DOI: 10.1186/s40644-023-00620-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 10/16/2023] [Indexed: 10/24/2023] Open
Abstract
OBJECTIVES This study aims to establish nomograms to accurately predict the overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) who received chemotherapy alone as the first-line treatment. MATERIALS AND METHODS In a training cohort of 121 NSCLC patients, radiomic features were extracted, selected from intra- and peri-tumoral regions, and used to build signatures (S1 and S2) using a Cox regression model. Deep learning features were obtained from three convolutional neural networks and utilized to build signatures (S3, S4, and S5) that were stratified into over- and under-expression subgroups for survival risk using X-tile. After univariate and multivariate Cox regression analyses, a nomogram incorporating the tumor, node, and metastasis (TNM) stages, radiomic signature, and deep learning signature was established to predict OS and PFS, respectively. The performance was validated using an independent cohort (61 patients). RESULTS TNM stages, S2 and S3 were identified as the significant prognosis factors for both OS and PFS; S2 (OS: (HR (95%), 2.26 (1.40-3.67); PFS: (HR (95%), 2.23 (1.36-3.65)) demonstrated the best ability in discriminating patients with over- and under-expression. For the OS nomogram, the C-index (95% CI) was 0.74 (0.70-0.79) and 0.72 (0.67-0.78) in the training and validation cohorts, respectively; for the PFS nomogram, the C-index (95% CI) was 0.71 (0.68-0.81) and 0.72 (0.66-0.79). The calibration curves for the 3- and 5-year OS and PFS were in acceptable agreement between the predicted and observed survival. The established nomogram presented a higher overall net benefit than the TNM stage for predicting both OS and PFS. CONCLUSION By integrating the TNM stage, CT radiomic signature, and deep learning signatures, the established nomograms can predict the individual prognosis of NSCLC patients who received chemotherapy. The integrated nomogram has the potential to improve the individualized treatment and precise management of NSCLC patients.
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Affiliation(s)
- Runsheng Chang
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Shouliang Qi
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China.
- Key Laboratory of Intelligent Computing in Medical Image, Ministry of Education, Northeastern University, Shenyang, China.
| | - Yanan Wu
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Yong Yue
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoye Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei Qian
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
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15
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Wang T, Li W, Wang Z, Wei X. A 47-year-old female with primary hepatoid adenocarcinoma in the pelvic retroperitoneum. Quant Imaging Med Surg 2023; 13:6317-6322. [PMID: 37711805 PMCID: PMC10498198 DOI: 10.21037/qims-22-1290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 07/31/2023] [Indexed: 09/16/2023]
Affiliation(s)
- Tao Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Weihua Li
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhenchang Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xuan Wei
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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16
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5323-5331. [DOI: 10.12998/wjcc.v11.i22.5323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer.
CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively.
CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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17
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5329-5337. [PMID: 37621602 PMCID: PMC10445072 DOI: 10.12998/wjcc.v11.i22.5329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer. CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively. CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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18
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Dong C, Wang Y, Gu X, Lv X, Ren S, Wang Z, Dai Z. Differential diagnostic value of tumor markers and contrast-enhanced computed tomography in gastric hepatoid adenocarcinoma and gastric adenocarcinoma. Front Oncol 2023; 13:1222853. [PMID: 37538113 PMCID: PMC10396771 DOI: 10.3389/fonc.2023.1222853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 06/29/2023] [Indexed: 08/05/2023] Open
Abstract
OBJECTIVE This study aimed to investigate the effectiveness of tumor markers and contrast-enhanced computed tomography (CE-CT) in differentiating gastric hepatoid adenocarcinoma (GHA) from gastric adenocarcinoma (GA). METHODS This retrospective study included 160 patients (44 with GHA vs. 116 with GA) who underwent preoperative CE-CT. Preoperative serum concentrations of tumor biomarkers and CT imaging features were analyzed, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), tumor location, growth pattern, size, enhancement pattern, cystic changes, and mass contrast enhancement. Multivariate logistic regression analyses were performed to evaluate useful tumor markers and CT imaging features for differentiating GHA from GA. RESULTS When compared to GA, GHA showed a higher serum AFP [13.27 ng/ml (5.2-340.1) vs. 2.7 ng/ml (2.2-3.98), P <0.001] and CEA levels [4.07 ng/ml (2.73-12.53) vs. 2.42 ng/ml (1.38-4.31), P <0.001]. CT imaging showed GHA with a higher frequency of tumor location in the gastric antrum (P <0.001). GHA had significantly lower attenuation values at the portal venous phase [PCA, (82.34 HU ± 8.46 vs. 91.02 HU ± 10.62, P <0.001)] and delayed phase [DCA, (72.89 HU ± 8.83 vs. 78.27 HU ± 9.51, P <0.001)] when compared with GA. Multivariate logistic regression analyses revealed that tumor location, PCA, and serum AFP level were independent predictors of differentiation between GHA and GA. The combination of these three predictors performed well in discriminating GHA from GA, with an AUC of 0.903, a sensitivity of 86.36%, and a specificity of 81.90%. CONCLUSIONS Integrated evaluation of tumor markers and CT features, including tumor location, PCA, and serum AFP, allowed for more accurate differentiation of GHA from GA.
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Affiliation(s)
- Congsong Dong
- Department of Radiology, Affiliated Hospital 6 of Nantong University (Yancheng Third People’s Hospital), Yancheng, China
| | - Yanling Wang
- Department of Radiology, The People’s Hospital of Suzhou New District, Suzhou, China
| | - Xiaoyu Gu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaojing Lv
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhenyu Dai
- Department of Radiology, Affiliated Hospital 6 of Nantong University (Yancheng Third People’s Hospital), Yancheng, China
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Mattiolo P, Scarpa A, Luchini C. Hepatoid tumors of the gastrointestinal/pancreatobiliary district: morphology, immunohistochemistry, and molecular profiles. Hum Pathol 2023; 132:169-175. [PMID: 35714834 DOI: 10.1016/j.humpath.2022.06.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/08/2022] [Indexed: 02/07/2023]
Abstract
Hepatoid tumors (HTs) histologically resemble hepatocellular carcinoma (HCC) but manifest outside the liver. Regarding immunohistochemistry (IHC), the classical markers of hepatoid differentiation are Hep Par-1, CD10, and arginase-1. This study provides a critical overview of HT in the gastrointestinal/biliopancreatic system, which is the most common site of origin. Gastric HTs are malignant neoplasms recognized by the current WHO classification as a variant of adenocarcinoma. In addition to the classic IHC markers, SALL4 and claudin-6 can help exclude a metastatic HCC at this site. Next-generation sequencing revealed the most common alterations, including TP53 mutation, microsatellite instability (MSI), and Her2 amplification. Esophageal HTs are exceptionally rare and usually arise in the context of Barrett's esophagus. In the intestine, HTs are classified within the adenocarcinoma spectrum and manifest more often in the background of inflammatory bowel disease. Regarding their molecular profile, recurrent alterations included MSI and NCOA4-RET fusions. In the pancreas, the current WHO classification acknowledges HT only as a possible variant of ductal adenocarcinoma, characterized by a poor prognosis. However, at this site, neuroendocrine tumors (NETs) and solid pseudopapillary neoplasms (SPNs) may also show hepatoid differentiation. Hepatoid NETs show aggressive behavior, whereas hepatoid SPNs harbor CTNNB1 mutations and are characterized by an indolent clinical course. Lastly, biliary HTs belong to the adenocarcinoma category and usually show a poor prognosis. In conclusion, gastrointestinal/pancreatobiliary HTs show specific histomolecular features, which should be considered for improving routine diagnostic activity and clinical management.
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Affiliation(s)
- Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy; ARC-Net Research Center for Applied Research on Cancer, University of Verona, Verona, 37134, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy; ARC-Net Research Center for Applied Research on Cancer, University of Verona, Verona, 37134, Italy.
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Relationships of tumor differentiation and immune infiltration in gastric cancers revealed by single-cell RNA-seq analyses. Cell Mol Life Sci 2023; 80:57. [PMID: 36729271 PMCID: PMC9894979 DOI: 10.1007/s00018-023-04702-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/08/2023] [Accepted: 01/17/2023] [Indexed: 02/03/2023]
Abstract
Gastric cancers are highly heterogeneous malignant tumors. To reveal the relationship between differentiation status of cancer cells and tumor immune microenvironments in gastric cancer, single-cell RNA-sequencing was performed on normal mucosa tissue, differentiated gastric cancer (DGC) tissue, poorly differentiated gastric cancer (PDGC) tissue and neuroendocrine carcinoma (NEC) tissue sampled from surgically resected gastric cancer specimens. We identified the signature genes for both DGC and PDGC, and found that signature genes of PDGC strongly enriched in the epithelial-mesenchymal transition (EMT) program. Furthermore, we found that DGC tends to be immune-rich type whereas PDGC tends to be immune-poor type defined according to the density of tumor-infiltrating CD8+ T cells. Additionally, interferon alpha and gamma responding genes were specifically expressed in the immune-rich malignant cells compared with immune-poor malignant cells. Through analyzing the mixed adenoneuroendocrine carcinoma, we identified intermediate state malignant cells during the trans-differentiation process from DGC to NEC, which showed double-negative expressions of both DGC marker genes and NEC marker genes. Interferon-related pathways were gradually downregulated along the DGC to NEC trans-differentiation path, which was accompanied by reduced CD8+ cytotoxic T-cell infiltration. In summary, molecular features of both malignant cells and immune microenvironment cells of DGC, PDGC and NEC were systematically revealed, which may partially explain the strong tumor heterogeneities of gastric cancer. Especially along the DGC to NEC trans-differentiation path, immune-evasion was gradually enhanced with the decreasing activities of interferon pathway responses in malignant cells.
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Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence. BMC Genomics 2022; 23:656. [PMID: 36114454 PMCID: PMC9482307 DOI: 10.1186/s12864-022-08880-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 09/08/2022] [Indexed: 11/23/2022] Open
Abstract
Background General transcription factor IIi (GTF2I) mutations are very common in thymic epithelial tumors (TETs) and are related to a more favorable prognosis in TET patients. However, limited research has been conducted on the role of GTF2I in the tumor immune microenvironment (TIME). Further, long non-coding RNAs (lncRNAs) have been associated with the survival of patients with TETs. Therefore, this study aimed to explore the relationship between GTF2I mutations and TIME and build a new potential signature for predicting tumor recurrence in the TETs. Research data was downloaded from The Cancer Genome Atlas database and the CIBERSORT algorithm was used to evaluate TIME differences between GTF2I mutant and wild-type TETs. Relevant differentially expressed lncRNAs based on differentially expressed immune-related genes were identified to establish lncRNA pairs. We constructed a signature using univariate and multivariate Cox regression analyses. Results GTF2I is the most commonly mutated gene in TETs, and is associated with an increased number of early-stage pathological types, as well as no history of myasthenia gravis or radiotherapy treatment. In the GTF2I wild-type group, immune score and immune cell infiltrations with M2 macrophages, activated mast cells, neutrophils, plasma, T helper follicular cells, and activated memory CD4 T cells were higher than the GTF2I mutant group. A risk model was built using five lncRNA pairs, and the 1-, 3-, and 5-year area under the curves were 0.782, 0.873, and 0.895, respectively. A higher risk score was related to more advanced histologic type. Conclusion We can define the GTF2I mutant-type TET as an immune stable type and the GTF2I wild-type as an immune stressed type. A signature based on lncRNA pairs was also constructed to effectively predict tumor recurrence.
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