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      Comparison of Safety and Outcomes between Endoscopic and Surgical Resections of Small (≤ 5 cm) Primary Gastric Gastrointestinal Stromal Tumors

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          Abstract

          Background and aims: Endoscopic resection is increasingly performed for gastric gastrointestinal stromal tumors (GIST). However, the safety and outcomes remain elusive. We aimed in this retrospective study to compare operative complications and prognosis between endoscopically and surgically resected small (≤ 5 cm) GIST tumor groups.

          Methods: In this single-center retrospective study, we compared demographics, clinical outcomes, and the R0 resection rate between the endoscopy (n =268) and surgery (n =141) groups. Only GIST tumors in size of ≤ 5.0 cm were recruited for this comparison study.

          Results: Overall, the mean age of patients was 59.0 years (range: 31.0-83.0). The male-female ratio was 0.68. The most common site of GIST was, in the descending order, the gastric fundus (55%), corpus (27.6%), cardia (10.8%), and antrum (6.6%). Compared with the surgery group, GIST tumors in the endoscopy group were significantly smaller (1.69±0.9 cm, vs. 3.20±1.2 cm in the surgery group; P <0.001) in size; postoperative hospital stay was significantly shorter (4.66±1.5 days, vs. 8.11±5.0; P <0.001); post-resection time to first liquid diet was significantly shorter (1.94±1.1 days, vs. 4.63±2.6; P < 0.001); the incidence of operative and post-operative complications was significantly fewer (p < 0.05), and hospital costs were significantly lower (20115.4±5113.5¥, vs. 43378.4±16795.7¥; P < 0.001). The R0 resection rate was significantly lower in the endoscopy (93.3%) than in the surgery (99.3%) groups (P< 0.01). In the endoscopy group, 176 (65.7%) and 69 (25.7%) patients were found to be at very low and low risk of aggressiveness, respectively, in comparison to 27(19.2%) and 86 (61.0%) patients in the surgery group, respectively (P <0.001). Among 409 cases, 50 (12.2%) were found to be at intermediate or high risk of aggressiveness, 20 of which were treated with adjuvant imatinib therapy and but only 8/20 taking imatinib for 1 to 3 months because of side effects and high costs. No local or distant tumor recurrence was observed over an average of 33.5-month follow-ups. Two patients died of other disease in the surgery group.

          Conclusions: Endoscopic resection of selected small gastric GISTs (≤ 5cm) was feasible, safe, and associated with better intraoperative results and an equal postoperative course, compared to surgical resection.

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          PDGFRA activating mutations in gastrointestinal stromal tumors.

          Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.
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            Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden.

            Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST. All patients (n=1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3-1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk-group stratifications, were analyzed statistically. Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty-four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor-related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor-related deaths occurred in only 2 of 170 of patients (1.2%) with very-low-risk, low-risk, or intermediate-risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high-risk group and the overtly malignant group). GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk-group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index. Copyright (c) 2005 American Cancer Society.
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              Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial.

              Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour. We undertook a randomised phase III, double-blind, placebo-controlled, multicentre trial. Eligible patients had complete gross resection of a primary gastrointestinal stromal tumour at least 3 cm in size and positive for the KIT protein by immunohistochemistry. Patients were randomly assigned, by a stratified biased coin design, to imatinib 400 mg (n=359) or to placebo (n=354) daily for 1 year after surgical resection. Patients and investigators were blinded to the treatment group. Patients assigned to placebo were eligible to crossover to imatinib treatment in the event of tumour recurrence. The primary endpoint was recurrence-free survival, and analysis was by intention to treat. Accrual was stopped early because the trial results crossed the interim analysis efficacy boundary for recurrence-free survival. This study is registered with ClinicalTrials.gov, number NCT00041197. All randomised patients were included in the analysis. At median follow-up of 19.7 months (minimum-maximum 0-56.4), 30 (8%) patients in the imatinib group and 70 (20%) in the placebo group had had tumour recurrence or had died. Imatinib significantly improved recurrence-free survival compared with placebo (98% [95% CI 96-100] vs 83% [78-88] at 1 year; hazard ratio [HR] 0.35 [0.22-0.53]; one-sided p<0.0001). Adjuvant imatinib was well tolerated, with the most common serious events being dermatitis (11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five [1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo group. Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour. US National Institutes of Health and Novartis Pharmaceuticals.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2019
                10 July 2019
                : 10
                : 17
                : 4132-4141
                Affiliations
                [1 ]Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School.
                [2 ]Department of Gastroenterology, Affiliated Chaohu Hospital of Anhui Medical University.
                [3 ]Department of Geriatric, Affiliated Drum Tower Hospital of Nanjing University Medical School.
                [4 ]Department of Gastroenterology, Nanjing Drum Tower Clinical College of Nanjing Medical University.
                [5 ]Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School.
                [6 ]VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA 02132, USA.
                Author notes
                ✉ Corresponding authors: Dr. Guifang Xu, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. Email: 13852293376@ 123456163.com or guifangxu136@ 123456sina.com . Telephone: +86-25-83105206 Fax: +86-25-83105206.Dr. Qin Huang, VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA 02132, USA. Email: qinhuang0122@ 123456gmail.com . Dr. Xiaoping Zou, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. Email: 13770771661@ 123456163.com . Telephone: +86-25-83105206 Fax: +86-25-83105206.Dr. Lei Wang, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. Email: 867152094@ 123456qq.com . Telephone: +86-25-83105206 Fax: +86-25-83105206.

                # These authors contributed equally to the work.

                Competing Interests: Drs. Taohong Pang, Yan Zhao, Ting Fan, Qingqing Hu, Dekusaah Raymond, Weijie Zhang, Yi Wang, Bin Zhang, Shouli Cao, Ying Lv, Xiaoqi Zhang, Tingsheng Ling, Yuzheng Zhuge, Lei Wang, Xiaoping Zou, Qin Huang, Guifang Xu have no conflicts of interest or financial ties to disclose.

                Article
                jcav10p4132
                10.7150/jca.29443
                6692613
                31417658
                89cfb1e9-4473-4b98-97c6-5a22f2dfd296
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 23 August 2018
                : 21 May 2019
                Categories
                Research Paper

                Oncology & Radiotherapy
                gastric gastrointestinal stromal tumors,endoscopic resection,surgical resection,operative complications,postoperative course,adjuvant therapy with imatinib

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