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      Long-Term Surgical Outcome of 1057 Gastric GISTs According to 7th UICC/AJCC TNM System : Multicenter Observational Study From Korea and Japan

      , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD

      Medicine

      Wolters Kluwer Health

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The aim of this study was to evaluate the treatment and prognosis of gastric gastrointestinal stromal tumors (GISTs) according to the 7th UICC/AJCC tumor-node-metastasis (TNM) system and the modified National Institutes of Health (NIH) risk classification. The study cohort consisted of 1057 patients with gastric GIST who underwent surgery between January 2000 and December 2007 from 13 institutions in Korea and 2 in Japan. Clinicopathologic characteristics, surgical outcomes, recurrence, and 5-year recurrence-free survival were evaluated.

          The mean age of the patients was 58.6 years. Thirty patients (2.8%) had distant metastasis preoperatively. Median tumor size was 4.0 cm. Complete resection (R0 resection) was achieved in 1018 patients (96.3%). Eighty-six patients (8.1%) had postoperative complications, and 2 patients (0.2%) died within 30 days after surgery. According to the 7th UICC/AJCC TNM system, 5-year recurrence-free survival rates were 95% to 99% in stage I, 94.1% in stage II, 74.1% in stage IIIA, 48.6% in stage IIIB, and 50.0% in stage IV patients. On survival analysis of high-risk patients according to the TNM system, the 5-year recurrence-free survival rates were 91.6% in stage II, 74.1% in stage IIIA, and 48.6% in stage IIIB patients. Independent factors of recurrence following surgery for gastric GIST were gender, tumor size, mitotic count, and radicality on multivariate analysis.

          The treatment outcome and prognosis of gastric GIST in Korea and Japan seem more favorable compared to those in Western countries. Compared to the modified NIH risk classification, the 7th UICC/AJCC TNM system is more reflective of the 5-year recurrence-free survival of patients with gastric GIST.

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          Most cited references 11

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          Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

          The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.
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            The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000.

            The epidemiology of gastrointestinal stromal tumor has not been well examined, and prior studies often provide conflicting results. We conducted the first population-based study to evaluate the incidence and survival of malignant gastrointestinal stromal tumor in the United States. We utilized the Surveillance, Epidemiology, and End Results registry from the National Cancer Institute to identify all cases of malignant gastrointestinal stromal tumor diagnosed from 1992 to 2000. The age-adjusted incidence rates and the survival rates were calculated. Cox proportional hazards models were used to examine the risk of mortality. Between 1992 and 2000, there were 1,458 cases of diagnosed gastrointestinal stromal tumor. The age-adjusted yearly incidence rate was 0.68/100,000. The mean age at diagnosis was 63 yr. Fifty-four percent were men and 46% were women. The incidence rate was higher among men and among Blacks. Fifty-one percent of cases were in the stomach, 36% small intestine, 7% colon, 5% rectum, and 1% in the esophagus. Fifty-three percent of cases were staged as localized, 19% regional, 23% distant, and 5% unstaged. The 1- and 5-yr relative survival rates were 80% and 45%, respectively. The Cox analysis showed that older age, Black race, advanced stage, and receipt of therapy were independent predictors of mortality. Malignant gastrointestinal stromal tumors rare, but are more common in the older population, men, and Blacks. Risk factors for mortality include older age, Black race, advanced stage, and no surgical intervention.
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              Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors.

              While targeted inhibitors of tyrosine kinase activity demonstrate dramatic efficacy in the majority of patients with advanced gastrointestinal stromal tumors (GISTs), cure remains elusive and resistance to systemic therapy is a challenge. To assess the role of surgery in multimodality management of GISTs, we studied postoperative outcomes in patients treated with targeted kinase inhibitors for advanced GIST. We evaluated outcomes in a single institution series of 69 consecutive patients who underwent surgery for advanced GISTs while receiving kinase inhibitors. Patients were categorized based on extent of disease before surgery (stable disease, limited disease progression, generalized disease progression) and surgical result (no evidence of disease, minimal residual disease, bulky residual disease). Disease status before surgery was associated with surgical result (P < .0001; median follow-up, 14.6 months). After surgery, there was no evidence of disease in 78%, 25%, and 7% of patients with stable disease, limited progression, and generalized progression, respectively. Bulky residual disease remained after surgery in 4%, 16%, and 43% of the patients with stable disease, limited progression, and generalized progression. Twelve-month progression-free survival was 80%, 33%, and 0% for patients with stable disease, limited progression, and generalized progression (P < .0001). Twelve-month overall survival was 95%, 86%, and 0% for patients with stable disease, limited progression, and generalized progression (P < .0001). Patients with advanced GISTs exhibiting stable disease or limited progression on kinase inhibitor therapy have prolonged overall survival after debulking procedures. Surgery has little to offer in the setting of generalized progression.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                October 2015
                16 October 2015
                : 94
                : 41
                Affiliations
                From the Department of Surgery, Dong-A University College of Medicine, Seoul, Korea (M-CK, K-HK); Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea (J-HY, M-WY); Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (H-KY, H-JL); Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea (T-SS); Department of Surgery, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Korea (W-JH); Department of Surgery, Keimyung University School of Medicine, Seoul, Korea (S-WR); Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Seoul, Korea (YK); Center for Gastric Cancer, National Cancer Center, Seoul, Korea (Y-WK); Department of Surgery, School of Medicine, Ajou University, Seoul, Korea (S-UH); Department of Surgery, Seoul National University Bundang Hospital, Seoul, Korea (H-HK, D-JP); Department of Surgery, Yeouido St. Mary's Hospital, College of Medicine, The Cathoilc University of Korea, Seoul, Korea (WK); Department of Surgery, Chungnam National University Hospital, Seoul, Korea (S-IL); Department of Gastrointestinal Surgery, Kanagawa Cancer center, Seoul, Korea (HC); Department of Surgery, Soonchunhyang University College of Medicine, Seoul, Korea (G-SC); and Division of Gastrointestinal Surgery, Department of Surgery, Incheon St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (J-JK).
                Author notes
                Correspondence: Jeong-Hwan Yook, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 138-736 Seoul, Korea (e-mail: jhyook@ 123456amc.seoul.kr ).
                Article
                01526
                10.1097/MD.0000000000001526
                4616782
                26469894
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0

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