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      Diagnostic and treatment strategy for small gastrointestinal stromal tumors

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          Abstract

          Gastrointestinal stromal tumors (GISTs) are considered to be potentially malignant mesenchymal tumors of the gastrointestinal tract. Clinically relevant GISTs are rare; however, subclinical GISTs (mini‐GISTs) (1‐2 cm) and pathologic GISTs (micro‐GISTs) (<1 cm) are frequently reported. Most mini‐GISTs and almost all micro‐GISTs of the stomach may exhibit benign clinical behavior, and only mini‐GISTs with high‐risk features may progress. For this review, a provisional algorithm was used to propose diagnostic and treatment strategies for patients with small GISTs. Because surgery is the only potentially curative treatment, in its application for small GISTs, the principles of sarcoma surgery should be maintained, and cost effectiveness should be considered. Indications for surgery include GISTs measuring ≥2 cm, symptomatic GISTs, and mini‐GISTs with high‐risk features (irregular borders, cystic spaces, ulceration, echogenic foci, internal heterogeneity, and tumor progression during follow‐up); however, a preoperative pathologic diagnosis is infrequently obtained. For small intestinal and colorectal GISTs, surgery is indicated irrespective of size because of their greater malignant potential. Otherwise, mini‐GISTs without high‐risk features, micro‐GISTs, and small submucosal tumors measuring <5 cm without high‐risk features may be followed by periodical endoscopic ultrasonography. Although surgical approaches and operative methods are selected according to tumor size, location, growth pattern, and surgical teams, laparoscopic surgery has produced similar oncologic outcomes and is less invasiveness compared with open surgery. After resection, pathologic examination for diagnosis and risk assessment is mandatory, and genotyping is also recommended for high‐risk GISTs. Endoscopic resection techniques, although feasible, are not routinely indicated for most mini‐GISTs or micro‐GISTs. Cancer 2016;122:3110–8 . © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

          Abstract

          Gastrointestinal stromal tumors (GISTs) are potentially malignant, and endoscopic ultrasonography and endoscopic ultrasound‐guided fine‐needle aspiration may play a major role in the diagnosis of small GISTs and submucosal tumors. Surgery is indicated for all intestinal GISTs and for small gastric GISTs in patients who have symptoms and/or high‐risk features.

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          Most cited references34

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          The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines

          Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines—for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry—their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.
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            Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

            (2014)
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              High incidence of microscopic gastrointestinal stromal tumors in the stomach.

              Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms with an annual incidence of approximately 10 to 20 per 1 million cases. Although pathologists have often observed incidental small GISTs in the stomach resected from patients with gastric cancer, no report on the real incidence of gastric GISTs is available. In this study, 100 whole stomachs resected from patients with gastric cancer were sectioned at 5-mm intervals and hematoxylin and eosin-stained slides (a mean of 130 slides for each case) were examined for microscopic GISTs. KIT (CD117), CD34, and desmin expression of the incidental tumors was evaluated by immunohistochemistry, and genomic DNA extracted from formalin-fixed and paraffin-embedded tumor tissues was analyzed for c-kit gene mutations in exon 11. In 35 of the 100 whole stomachs, we found 50 microscopic GISTs, all of which were positive for KIT and/or CD34 and negative for desmin. Most microscopic GISTs (45/50, 90%) were located in the upper stomach. Two of the 25 (8%) microscopic GISTs had c-kit gene mutations. Fifty-one leiomyomas with positive expression for desmin were observed in 28 of the 100 stomachs. Both leiomyomas and GISTs were found in 12 stomachs. These results indicate that microscopic GISTs are common in the upper portion of the stomach. Considering the annual incidence of clinical GISTs, only few microscopic GISTs may grow into a clinical size with malignant potential. Further studies are required to clarify the genetic events responsible for the transformation of microscopic GISTs to clinical GISTs.
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                Author and article information

                Contributors
                tnishida@ncc.go.jp
                Journal
                Cancer
                Cancer
                10.1002/(ISSN)1097-0142
                CNCR
                Cancer
                John Wiley and Sons Inc. (Hoboken )
                0008-543X
                1097-0142
                01 August 2016
                15 October 2016
                : 122
                : 20 ( doiID: 10.1002/cncr.v122.20 )
                : 3110-3118
                Affiliations
                [ 1 ] Department of SurgeryNational Cancer Center Hospital TokyoJapan
                [ 2 ] Division of Research and Development for Minimally Invasive TreatmentCancer Center, Keio University School of Medicine TokyoJapan
                [ 3 ] Division of Surgical OncologyBrigham and Women's Hospital, Center for Sarcoma and Bone Oncology, Dana‐Farber Cancer Institute, Harvard Medical School Boston Massachusetts
                Author notes
                [*] [* ] Corresponding author: Toshirou Nishida, MD, PhD, Department of Surgery, National Cancer Center Hospital, 5‐5‐1 Tsukiji, Chuoku, Tokyo 104‐0045, Japan; Fax: (011) 81‐3‐3543‐5321; tnishida@ 123456ncc.go.jp
                Article
                CNCR30239
                10.1002/cncr.30239
                5096017
                27478963
                98b798e3-2070-4e0f-bde9-b43bbc28d093
                © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 06 May 2016
                : 05 June 2016
                : 14 June 2016
                Page count
                Figures: 4, Tables: 0, Pages: 10, Words: 5522
                Funding
                Funded by: Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology
                Award ID: 16H05419
                Funded by: National Cancer Center Research and Development Fund
                Award ID: 26‐A‐21
                Funded by: Uehara Memorial Foundation
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                cncr30239
                October 15, 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.6 mode:remove_FC converted:04.11.2016

                Oncology & Radiotherapy
                endoscopic ultrasonography (eus),gastrointestinal stromal tumor (gist),high‐risk features,laparoscopic surgery,submucosal tumor (smt)

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