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Chengbin Zheng,1,* Xingyu Feng,2,* Jiabin Zheng,2 Qian Yan,2 Xu Hu,2 Huolun Feng,2 Zhenru Deng,2 Qianchao Liao,2 Junjiang Wang,2 Yong Li1,2 1Department of General Surgery, Guangdong Provincial People’s Hospital; Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510080, People’s Republic of China; 2Department of General Surgery, Guangdong Provincial People’s Hospital; Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong LiDepartment of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, 106 Zhongshan Road 2, Guangzhou, Guangzhou 510080, People’s Republic of ChinaTel +86-13822177479Fax +86-020-83827812Email liyong@gdph.org.cnPurpose: Tumors with lymphovascular invasion (LVI) are thought to be associated with lymph node metastasis and to lead to a worse prognosis. However, the effect of LVI on the prognosis of adenocarcinoma of esophagogastric junction (AEG) is still unclear.Patients and Methods: We retrospectively analyzed 224 consecutive patients with non-metastatic AEG who underwent radical surgery in our hospital from 2004 to 2018. Inverse probability weighting (IPW) analysis was used to eliminate the selection bias. IPW-adjusted Kaplan–Meier curves and Cox proportional hazards models were used to compare disease-specific survival (DSS) and overall survival (OS) between patients with and without LVI.Results: A total of 224 patients with non-metastatic AEG who underwent radical resection were included in the study and 96 (42.9%) patients developed LVI. Survival analysis showed that LVI were associated with worse DSS (hazard ratio (HR) = 3.12; 95% CI: 1.93– 5.03) and worse OS (HR = 2.33; 95% CI: 1.61– 3.38). The results were consistent across subgroups stratified by pathologic N stage. Subgroup analysis demonstrated that Siewert type III (HR= 3.20, 95% CI: 1.45– 7.06) was associated with worse DSS, but not Siewert type I/II (HR= 1.46, 95% CI: 0.94– 2.31, P-interaction=0.047).Conclusion: LVI are associated with worse prognosis in AEG. LVI had a worse effect on DSS in Siewert type III AEG than Siewert type I/II AEG.Keywords: lymphovascular invasion, adenocarcinoma of esophagogastric junction, risk factor, overall survival, disease-specific survival

Weixian Hu,1,* Chengbin Zheng,1,* Renjie Li,2 Xingyu Feng,1 Guoliang Zheng,3 Zhichao Zheng,3 Wenjun Xiong,4 Guosheng Lin,5 Yongjian Zhou,5 Wei Wang,4 Yan Zhao,3 Yong Li1 1Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People’s Republic of China; 2Department of Bariatric and Metabolic Surgery, Klinikum Ernst von Bergmann, Potsdam 14467, Germany; 3Department of Gastric Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People’s Republic of China; 4Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, People’s Republic of China; 5Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, People’s Republic of China*These authors contributed equally to this work.Correspondence: Yong LiDepartment of General Surgery, Guangdong Provincial People’s Hospital; Guangdong Academy of Medical Sciences, 106 Zhongshan Road 2, Guangzhou, Guangdong 510080, People’s Republic of ChinaTel +86-13822177479Fax +86-83827812Email liyong@gdph.org.cnYan ZhaoDepartment of Gastric Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People’s Republic of ChinaTel +86-18900918909Email zhaoyan@CancerHosp-LN-CMU.comPurpose: Gastrointestinal stromal tumors (GISTs) are commonly known to be derived from the gastrointestinal (GI) tract, but recently there have been more and more literature describing lesions with similar pathological and immunohistochemical resembling GISTs but located outside the GI tract, and they have been termed as extra-GISTs (eGISTs). However, due to the rare incidence of eGISTs, its association with survival outcomes is poorly understood, especially in the Chinese population. Here, we aimed to identify the risk factors of eGISTs and to assess their association with overall survival (OS) and disease-free survival (DFS).Patients and Methods: Data of pathologically confirmed eGISTs cases, without radiological and perioperative evidence of other primary lesions, and with no microscopically identified adhesion between the tumor and the gastrointestinal serosa, which were surgically treated between January 2006 and September 2017 were retrieved from the database of four high-volume hospitals. Immunohistochemical and genetic testing were performed on the postoperative lesions and were staged using the National Institutes of Health (NIH) criteria.Results: A total of 55 cases were retrieved. eGISTs were identified from the retroperitoneum (36.4%), mesocolon (25.5%), small bowel mesentery (12.7%), abdominopelvic cavity (12.7%), lesser omental sac (5.5%), ovary (3.6%), pancreatic capsule (1.8%), or urinary bladder (1.8%). Based on the NIH risk classification, majority of the lesion were classified as high risk (85.5%). KIT 11 was the most common mutation site (76.5%) and 25.0% of the cases were wild-type eGISTs. Multivariate analyses showed that tumor location and size were independent factors affecting prognoses. Patients with tumors in the retroperitoneum had significantly poorer OS and DFS as compared to those in the non-retroperitoneum (HR [95% CI] for OS and DFS: 2.546 [1.023– 6.337] [P = 0.037] and 2.475 [0.975– 6.273] [P = 0.049], respectively). Similar findings were found for tumors of size > 15 cm, compared to ≤ 15 cm (HR [95% CI] for OS and DFS: 5.350 [2.022– 14.156] [P < 0.001] and 3.861 [1.493– 9.988] [P = 0.003], respectively).Conclusion: eGISTs were predominantly found from the retroperitoneum and mostly classified as high risk. Those located in the retroperitoneum and of size > 15 cm had the poorer OS and DFS as compared to those in the non-retroperitoneum and of size < 15 cm.Keywords: extra gastrointestinal stromal tumors, multicenter, immunohistopathology, gene mutation, National Institutes of Health criteria, risk factor, retroperitoneum, overall survival, disease-free survival, recurrence