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The Diagnosis of Small Gastrointestinal Subepithelial Lesions by Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy. Diagnostics (Basel) 2022; 12:diagnostics12040810. [PMID: 35453857 PMCID: PMC9027519 DOI: 10.3390/diagnostics12040810] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/21/2022] [Accepted: 03/23/2022] [Indexed: 12/02/2022] Open
Abstract
Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.
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Recent Progress and Challenges in the Diagnosis and Treatment of Gastrointestinal Stromal Tumors. Cancers (Basel) 2021; 13:cancers13133158. [PMID: 34202544 PMCID: PMC8268322 DOI: 10.3390/cancers13133158] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 12/31/2022] Open
Abstract
Simple Summary Gastrointestinal stromal tumors (GIST) are potentially malignant tumors and require evidence-based surgical and/or medical treatment. Laparoscopy has similar safety and prognostic outcomes to those of laparotomy and is currently a standard procedure for localized GISTs. However, surgery for gastric GISTs less than 2 cm may be re-evaluated due to the indolent nature of the GIST and other competing risks among GIST patients. A work-up with endoscopy and endoscopic ultrasonography as well as endoscopic or percutaneous biopsy is important for the preoperative diagnosis of GISTs. Medical treatment with tyrosine kinase inhibitors is the mainstay for recurrent/metastatic GISTs. The activity of an individual drug is well correlated with gene alterations, and, in the era of precision medicine, cancer genome profiling should be considered before medical treatment. Abstract Gastrointestinal stromal tumors (GISTs) are the most frequent malignant mesenchymal tumors in the gastrointestinal tract. The clinical incidence of GISTs is estimated 10/million/year; however, the true incidence is complicated by frequent findings of tiny GISTs, of which the natural history is unknown. The initial work-up with endoscopy and endoscopic ultrasonography plays important roles in the differential diagnosis of GISTs. Surgery is the only modality for the permanent cure of localized GISTs. In terms of safety and prognostic outcomes, laparoscopy is similar to laparotomy for GIST treatment, including tumors larger than 5 cm. GIST progression is driven by mutations in KIT or PDGFRA or by other rare gene alterations, all of which are mutually exclusive. Tyrosine kinase inhibitors (TKIs) are the standard therapy for metastatic/recurrent GISTs. Molecular alterations are the most reliable biomarkers for TKIs and for other drugs, such as NTRK inhibitors. The pathological and genetic diagnosis prior to treatment has been challenging; however, a newly developed endoscopic device may be useful for diagnosis. In the era of precision medicine, cancer genome profiling by targeted gene panel analysis may enable potential targeted therapy even for GISTs without KIT or PDGFRA mutations.
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Computed tomography-based radiomics model for discriminating the risk stratification of gastrointestinal stromal tumors. Radiol Med 2020; 125:465-473. [PMID: 32048155 DOI: 10.1007/s11547-020-01138-6] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/16/2020] [Indexed: 12/22/2022]
Abstract
PURPOSE The pathological risk degree of gastrointestinal stromal tumors (GISTs) has become an issue of great concern. Computed tomography (CT) is beneficial for showing adjacent tissues in detail and determining metastasis or recurrence of GISTs, but its function is still limited. Radiomics has recently shown a great potential in aiding clinical decision-making. The purpose of our study is to develop and validate CT-based radiomics models for GIST risk stratification. METHODS Three hundred and sixty-six patients clinically suspected of primary GISTs from January 2013 to February 2018 were retrospectively enrolled, among which data from 140 patients were eventually analyzed after exclusion. Data from patient CT images were partitioned based on the National Institutes of Health Consensus Classification, including tumor segmentation, radiomics feature extraction and selection. A radiomics model was then proposed and validated. RESULTS The radiomics signature demonstrated discriminative performance for advanced and nonadvanced GISTs with an area under the curve (AUC) of 0.935 [95% confidence interval (CI) 0.870-1.000] and an accuracy of 90.2% for validation cohort. The radiomics signature demonstrated favorable performance for the risk stratification of GISTs with an AUC of 0.809 (95% CI 0.777-0.841) and an accuracy of 67.5% for the validation cohort. Radiomics analysis could capture features of the four risk categories of GISTs. Meanwhile, this CT-based radiomics signature showed good diagnostic accuracy to distinguish between nonadvanced and advanced GISTs, as well as the four risk stratifications of GISTs. CONCLUSION Our findings highlight the potential of a quantitative radiomics analysis as a complementary tool to achieve an accurate diagnosis for GISTs.
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Martinez AP, Fritchie KJ, Weiss SW, Agaimy A, Haller F, Huang HY, Lee S, Bahrami A, Folpe AL. Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or rhabdomyoblastic tumor of uncertain malignant potential? A histologically distinctive rhabdomyoblastic tumor in search of a place in the classification of skeletal muscle neoplasms. Mod Pathol 2019; 32:446-457. [PMID: 30287926 DOI: 10.1038/s41379-018-0145-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 08/23/2018] [Accepted: 08/23/2018] [Indexed: 12/21/2022]
Abstract
Skeletal muscle tumors are traditionally classified as rhabdomyoma or rhabdomyosarcoma. We have identified an unusual adult rhabdomyoblastic tumor not clearly corresponding to a previously described variant of rhabdomyoma or rhabdomyosarcoma, characterized by a very striking proliferation of non-neoplastic histiocytes, obscuring the underlying tumor. Ten cases were identified in nine males and one female with a median age of 43 years (range 23-69 years). Tumors involved the deep soft tissues of the trunk (N = 4), lower limbs (N = 4), and neck (N = 2). Tumors were well-circumscribed, nodular masses, frequently surrounded by a fibrous capsule containing lymphoid aggregates and sometimes calcifications. Numerous foamy macrophages, multinucleated Touton-type giant cells, and sheets/fascicles of smaller, often spindled macrophages largely obscured the underlying desmin, MyoD1, and myogenin-positive rhabdomyoblastic tumor. Cases were wild type for MYOD1 and no other mutations or rearrangements characteristic of a known subtype of rhabdomyoma or rhabdomyosarcoma were identified. Two of four cases successfully analyzed using a next-generation sequencing panel of 170 common cancer-related genes harbored inactivating NF1 mutations. Next-generation sequencing showed no gene fusions. Clinical follow (nine patients; median 9 months; mean 23 months; range 3-124 months) showed all patients received wide excision; four patients also received adjuvant radiotherapy and none received chemotherapy. At the time of last follow-up, all patients were alive and without disease; no local recurrences or distant metastases occurred. We hypothesize that these unusual tumors represent rhabdomyoblastic tumors of uncertain malignant potential. Possibly over time they should be relegated to a new category of skeletal muscle tumors of intermediate (borderline) malignancy.
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Affiliation(s)
- Anthony P Martinez
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55902
| | - Karen J Fritchie
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55902
| | - Sharon W Weiss
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA, 30322
| | - Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital of Erlangen, 91054, Erlangen, Germany
| | - Florian Haller
- Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital of Erlangen, 91054, Erlangen, Germany
| | - Hsuan-Ying Huang
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-Pei Road, Niao-Sung District, Kaohsiung City, Taiwan
| | - Seungjae Lee
- Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
| | - Armita Bahrami
- Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
| | - Andrew L Folpe
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55902.
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Kim JJ, Lim JY, Nguyen SQ. Laparoscopic resection of gastrointestinal stromal tumors: Does laparoscopic surgery provide an adequate oncologic resection? World J Gastrointest Endosc 2017; 9:448-455. [PMID: 28979709 PMCID: PMC5605344 DOI: 10.4253/wjge.v9.i9.448] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 06/30/2017] [Accepted: 07/24/2017] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract. Surgical resection remains the mainstay of non-metastatic disease. However, the ability to provide an adequate oncologic resection using laparoscopic surgery is still an area of debate. This is a thorough review of the current literature, looking particularly at the use of laparoscopic surgery for larger GISTs and the long-term oncologic outcomes compared to the results of open surgery. Laparoscopic resections provide an adequate oncologic result for GISTs of all sizes, including those greater than 5 cm in size.
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Affiliation(s)
- Joseph J Kim
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - James Y Lim
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Scott Q Nguyen
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
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Harlan LC, Eisenstein J, Russell MC, Stevens JL, Cardona K. Gastrointestinal stromal tumors: treatment patterns of a population-based sample. J Surg Oncol 2015; 111:702-7. [PMID: 25900896 DOI: 10.1002/jso.23879] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 11/26/2014] [Accepted: 12/04/2014] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The National Cancer Institute (NCI) annually confirms therapy with treating physicians on a sample of patients diagnosed with a specific cancer. METHODS Using the NCI Patterns of Care data, treatment patterns were examined on a population-based sample of patients diagnosed with gastrointestinal stromal tumors (GIST) in 2008. RESULTS A random sample of 323 of 405 GIST patients registered in SEER was selected. Most patients had gastric GISTs, were ≥ 65 years, white, had private insurance, and treated in a hospital with a residency program. Surgery was primarily performed in patients with non-metastatic disease (94%), in which: 26, 12, and 36% were at low, intermediate, and high-risk of recurrence, respectively. Amongst low-risk patients, ∼ 30% received adjuvant therapy. Amongst patients at higher risk, 26-40% did not receive adjuvant therapy. Imatinib was the most common targeted therapy administered. On multivariate analysis, age and risk-group were associated with receipt of adjuvant targeted therapy. CONCLUSIONS Our study shows that in 2008, the majority of patients diagnosed with GIST received appropriate surgical and adjuvant therapies. However, a considerable subset may have been overtreated and undertreated. Future studies identifying factors that impact the delivery of adjuvant therapy should be conducted.
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Affiliation(s)
- Linda C Harlan
- Applied Research Program, National Cancer Institute, Bethesda, Maryland
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Lartigue L, Neuville A, Lagarde P, Brulard C, Rutkowski P, Tos PD, Wardelmann E, Debiec-Rychter M, Italiano A, Coindre JM, Chibon F. Genomic index predicts clinical outcome of intermediate-risk gastrointestinal stromal tumours, providing a new inclusion criterion for imatinib adjuvant therapy. Eur J Cancer 2015; 51:75-83. [DOI: 10.1016/j.ejca.2014.10.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Revised: 10/09/2014] [Accepted: 10/14/2014] [Indexed: 01/31/2023]
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microRNA-218 increase the sensitivity of gastrointestinal stromal tumor to imatinib through PI3K/AKT pathway. Clin Exp Med 2014; 15:137-44. [PMID: 24706111 DOI: 10.1007/s10238-014-0280-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Accepted: 03/25/2014] [Indexed: 02/08/2023]
Abstract
To detect the expressions of microRNA-218 (miR-218) in an imatinib mesylate-sensitive human gastrointestinal stromal tumor (GIST) cells (GIST882) and an imatinib mesylate-resistant cell line (GIST430) and explore the roles of miR-218 and GIST cells in the sensitivity of gastrointestinal stromal tumor to imatinib mesylate and its potential signaling pathways, with an attempt to provide new insights for the treatment of GIST. The GIST cell lines (GIST882 and GIST430) were cultured in vitro. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression profiles of miR-218 in both GIST cell lines. Forty-eight hours after the transfection of the miR-218 mimic or miR-218 inhibitor in the GIST cells, the changes in the expression of miR-218 in the GIST cells were detected with qRT-PCR. The effects of the ectopic expression of miR-218 in GIST882 or GIST430 cells on the imatinib mesylate-induced GIST cell viability were determined by MTT. The effects of miR-218 ectopic expression on the apoptosis of imatinib mesylate-induce GIST cells were determined by Annexin V/PI double staining method and flow cytometry. The effects of miR-218 ectopic expression on the AKT and phospho-AKT (p-AKT) expressions of imatinib mesylate-induce GIST cells were determined by Western blot and flow cytometry with the PI3K pathway inhibitor Wortmannin. As shown by qRT-PCR, compared with that in the imatinib mesylate-sensitive GIST882, the expression of miR-218 in imatinib mesylate-resistant GIST430 was significantly decreased (P < 0.01). Compared with the control group, the expression of miR-218 significantly increased in the GIST882 48 h after the transfection of miR-218 mimic (P < 0.01) and significantly declined after the transfection of miR-218 inhibitor (P < 0.01). As shown by MTT and flow cytometry, after the expression of miR-218 was inhibited in GIST882 under the effect of imatinib mesylate, the cell viability significantly increased (P < 0.01) and the number of apoptotic cells significantly decreased (P < 0.05); on the contrary, the over-expression of miR-218 in GIST430 under the effect of imatinib mesylate resulted in the significantly decreased cell viability (P < 0.01) and the significantly increased number of apoptotic cells (P < 0.05). Western blot and flow cytometry showed that, in comparison to the control group, Wortmannin could significantly inhibit the expression of p-AKT in GIST430 cells (P < 0.01) and stimulated apoptosis (P < 0.01). The expression of miR-218 is down-regulated in an imatinib mesylate-resistant GIST cell line (GIST430), whereas miR-218 over-expression can improve the sensitivity of GIST cells to imatinib mesylate, with PI3K/AKT signaling pathway possibly involved in the mechanism.
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