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      Surgical Management of Gastrointestinal Stromal Tumors

      research-article
      , MPAP, PA-C
      Journal of the Advanced Practitioner in Oncology
      Harborside Press LLC

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          Abstract

          Gastrointestinal stromal tumors (GISTs) are considered rare, but they are one of the most common malignant mesenchymal tumors within the gastrointestinal tract, affecting 4,000 to 6,000 adults in the United States each year. Because gastrointestinal bleeding is often the initial symptom, a thorough and timely diagnostic workup is imperative to accurately diagnose a potentially deadly tumor. Endoscopic ultrasound is helpful when working through a differential diagnosis of subepithelial lesions and can help identify which mucosal layer the lesion originates from, as well as the density of the lesion; however, surgical resection is the standard of care for the treatment of a resectable nonmetastatic GIST. For recurrent GISTs, metastatic disease, or GISTs not amendable to resection, tyrosine kinase inhibitors are frequently used, with imatinib being used in the first-line setting. A multimodal treatment approach is often necessary to increase the chances of a permanent cure.

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          Most cited references15

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          Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor.

          Most gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor alpha (PDGFRA) kinases, which are imatinib targets. Sunitinib, which targets KIT, PDGFRs, and several other kinases, has demonstrated efficacy in patients with GIST after they experience imatinib failure. We evaluated the impact of primary and secondary kinase genotype on sunitinib activity. Tumor responses were assessed radiologically in a phase I/II trial of sunitinib in 97 patients with metastatic, imatinib-resistant/intolerant GIST. KIT/PDGFRA mutational status was determined for 78 patients by using tumor specimens obtained before and after prior imatinib therapy. Kinase mutants were biochemically profiled for sunitinib and imatinib sensitivity. Clinical benefit (partial response or stable disease for > or = 6 months) with sunitinib was observed for the three most common primary GIST genotypes: KIT exon 9 (58%), KIT exon 11 (34%), and wild-type KIT/PDGFRA (56%). Progression-free survival (PFS) was significantly longer for patients with primary KIT exon 9 mutations (P = .0005) or with a wild-type genotype (P = .0356) than for those with KIT exon 11 mutations. The same pattern was observed for overall survival (OS). PFS and OS were longer for patients with secondary KIT exon 13 or 14 mutations (which involve the KIT-adenosine triphosphate binding pocket) than for those with exon 17 or 18 mutations (which involve the KIT activation loop). Biochemical profiling studies confirmed the clinical results. The clinical activity of sunitinib after imatinib failure is significantly influenced by both primary and secondary mutations in the predominant pathogenic kinases, which has implications for optimization of the treatment of patients with GIST.
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            Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies.

            Gastrointestinal stromal tumours (GISTs) are rare, yet the most common mesenchymal tumour within the digestive tract. Lack of diagnostic criteria and no specific code in the ICD system has prevented epidemiological evaluation except from overt malignant cases in the past. A global estimate of incidence and disease patterns has thus not been available.
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              Current clinical management of gastrointestinal stromal tumor

              Gastrointestinal stromal tumors (GISTs) are the most common malignant subepithelial lesions (SELs) of the gastrointestinal tract. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Pathologically, diagnosis of a GIST relies on morphology and immunohistochemistry [KIT and/or discovered on gastrointestinal stromal tumor 1 (DOG1) is generally positive]. The prognosis of this disease is associated with the tumor size and mitotic index. The standard treatment of a GIST without metastasis is surgical resection. A GIST with metastasis is usually only treated by tyrosine kinase inhibitors without radical cure; thus, early diagnosis is the only way to improve its prognosis. However, a GIST is usually detected as a SEL during endoscopy, and many benign and malignant conditions may manifest as SELs. Conventional endoscopic biopsy is difficult for tumors without ulceration. Most SELs have therefore been managed without a histological diagnosis. However, a favorable prognosis of a GIST is associated with early histological diagnosis and R0 resection. Endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration (EUS-FNA) are critical for an accurate diagnosis of SELs. EUS-FNA is safe and effective in enabling an early histological diagnosis and adequate treatment. This review outlines the current evidence for the diagnosis and management of GISTs, with an emphasis on early management of small SELs.
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                Author and article information

                Journal
                J Adv Pract Oncol
                J Adv Pract Oncol
                J Adv Pract Oncol
                JADPRO
                Journal of the Advanced Practitioner in Oncology
                Harborside Press LLC
                2150-0878
                2150-0886
                September 2023
                1 September 2023
                : 14
                : 6
                : 541-547
                Affiliations
                [1]From Atrium Health Carolinas Medical Center, Charlotte, North Carolina
                Author notes
                Correspondence to: Heather Townsend, MPAP, PA-C, 1000 Blythe Boulevard, Charlotte, NC 28203 E-mail: h.drephal@ 123456gmail.com
                Article
                2023.14.6.7
                10.6004/jadpro.2023.14.6.7
                10558015
                37808075
                c926b03f-af0a-418f-98f2-2b3ddbcbb938
                © 2023 Harborside™

                This article is distributed under the terms of the Creative Commons Attribution Non-Commercial Non-Derivative License, which permits unrestricted non-commercial and non-derivative use, distribution, and reproduction in any medium, provided the original work is properly cited.

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