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Penel N, Le Cesne A, Blay JY. Adjuvant treatment of gastrointestinal stromal tumor: State of the art in 2025. Eur J Cancer 2025; 222:115473. [PMID: 40306119 DOI: 10.1016/j.ejca.2025.115473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/10/2025] [Accepted: 04/21/2025] [Indexed: 05/02/2025]
Abstract
The management of gastrointestinal stromal tumors (GISTs) has been revolutionized by the discovery of their sensitivity to imatinib. Most localized GISTs can be cured by surgery alone. The present overview aims to discuss the results of four recent randomized trials or updates assessing adjuvant imatinib. The duration of adjuvant treatments varied in these 4 trials (1 year versus zero, 2 years versus zero, 3 years versus 1 year and 6 years versus 3 years). All these trials showed that adjuvant imatinib improves disease/relapse-free survival in patients at high-risk of GIST relapse. Nevertheless, only one trial showed an overall survival improvement, in favor of 3-year treatment compared to 1-year treatment. But these randomized trials did not assess KIT or PDGFRA mutational status at study entry. Moreover, the definition of high-risk GIST differed across these trials. So, the patient subset that benefits the most from adjuvant imatinib therapy remains undetermined. The optimal duration of adjuvant imatinib therapy remain unclear.
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Affiliation(s)
- Nicolas Penel
- ULR 2694 - Metrics: Evaluation des technologies de santé et des pratiques médicales, Lille University Hospital, University of Lille, France; Medical Oncology Department, Centre Oscar Lambret, Lille, France, Lille University Hospital, University of Lille, France.
| | - Axel Le Cesne
- Medical Oncology Department, Institut Gustave Roussy, Villejuif, France
| | - Jean-Yves Blay
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
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Zhou Y, Peng R, Chen X, Xie X, Chen J, Li R. The feasibility of endoscopic resection for esophageal gastrointestinal stromal tumor. Surg Endosc 2025; 39:3718-3726. [PMID: 40316748 DOI: 10.1007/s00464-025-11763-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 04/20/2025] [Indexed: 05/04/2025]
Abstract
OBJECTIVES Esophageal gastrointestinal stromal tumor (e-GIST) is a rare type that is distinct from gastric GIST (g-GIST), and comprehensive studies are limited. The present study aims to compare the clinicopathological characteristics between e-GIST and g-GIST, evaluate the feasibility of using endoscopic resection (ER) to treat e-GIST, and explore its clinical implications. METHODS Patients with GISTs from January 2010 to May 2019 were enrolled in this study. Comprehensive clinicopathological, endoscopic, and follow-up data were collected and systematically analyzed. RESULTS There were 46 e-GIST patients and 366 g-GIST patients were enrolled. The distinct characteristics of e-GIST were as follows: (1) greater prevalence in male patients than in female patients, in contrast with the predominance of females among patients with g-GIST; (2) the median onset age was 61 years (range 20 to 80 years), with 58.7% of patients aged > 65 years in e-GIST; (3) the proportion of larger tumors was much more frequent in the esophagus; (4) greater incidence of ulceration/bleeding than in g-GIST; (5) increased mitotic count (≥ 5/50HPF). These factors collectively contribute to significantly shorter overall survival in e-GIST patients. Importantly, our analysis revealed that the outcomes of endoscopic resection (ER) were comparable to those of surgical resection for selected e-GISTs (tumor diameter ≤ 5 cm, without ulceration/bleeding, and mitotic count < 5/50HPF), with no significant differences in recurrence rate or survival time between these procedures. CONCLUSIONS This study highlights the distinct clinicopathological features of e-GIST from those of g-GIST with increased tumor size, ulceration/bleeding, and higher mitotic counts identified as significant prognostic factors. Our findings suggest that ER is a feasible and effective treatment approach for carefully selected e-GIST cases (tumor diameter ≤ 5 cm, without ulceration/bleeding), as assessed by endoscopic ultrasound (EUS). These results provide valuable insights for the management of this rare tumor subtype.
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Affiliation(s)
- Yanwu Zhou
- Department of Thoracic Surgery, Xiangya Hospital of Central South University, Changsha, China
| | - Ruyi Peng
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
- Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, China
| | - Xingcen Chen
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China
- Research Center of Digestive Disease, Central South University, Changsha, China
- Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, China
| | - Xinxin Xie
- Department of Otolaryngology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Jiefei Chen
- Department of Laboratory Medicine, Xiangya Medical School, Changsha, China
| | - Rong Li
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China.
- Research Center of Digestive Disease, Central South University, Changsha, China.
- Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, China.
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Joensuu H, Miyashita H, George S, Sicklick J. Navigating Ongoing Challenges in GI Stromal Tumors. Am Soc Clin Oncol Educ Book 2025; 45:e473224. [PMID: 40393024 DOI: 10.1200/edbk-25-473224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
GI stromal tumors (GISTs) are mesenchymal neoplasms with variable natural histories, originating in the GI tract, most commonly in the stomach. They are frequently characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) oncogenic mutations. Surgical resection remains the cornerstone treatment for localized GISTs. Clinical trials have demonstrated the benefits of adjuvant imatinib in patients selected on the basis of recurrence risk and gene mutations, although the optimal duration of therapy is yet to be established. Some data suggest that longer durations of adjuvant imatinib (>3 years) may provide additional benefit, which is being investigated in ongoing trials. Management of imatinib-related adverse effects is essential during treatment, and longitudinal abdominal imaging is mandatory both during and after adjuvant therapy. Once GISTs are more advanced and unresectable, KIT- and PDGFRA-directed tyrosine kinase inhibitors (TKIs) become the key treatment in most patients with KIT mutation. Several TKIs have regulatory approval for advanced GISTs, but in most patients, resistance to TKIs eventually emerges, mainly from secondary resistance mutations in KIT. Each TKI has different coverage of oncogenic KIT mutations, suggested by preclinical and clinical findings, which has given rationale to an ongoing clinical trial that includes molecular selection as eligibility criteria. Furthermore, novel treatment approaches, from TKI combinations to an antibody-drug conjugate, are being investigated. Despite the significant advance in managing GISTs with KIT mutations, those without KIT or PDGFRA mutation, which consists of 10%-15% of patients with GIST, can be a clinical challenge in the advanced setting. These non-KIT/PDGFRA GISTs could be driven by genomic or epigenomic alterations in SDHx, NF1 mutations, and other genomic alterations. Non-KIT/PDGFRA GISTs are less responsive to currently available TKIs than GISTs driven by KIT/PDGFRA mutations, and each subset of non-KIT/PDGFRA GIST has distinctive biology and clinical features. Therefore, individualized, multidisciplinary, biology-based management and consideration for clinical trial enrollment are critical for non-KIT/PDGRFA GISTs.
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Affiliation(s)
- Heikki Joensuu
- Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | | | - Suzanne George
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Jason Sicklick
- Department of Surgery, University of California San Diego, San Diego, CA
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Bourgeois AD, Skinner OT, Karnia JJ, Smith AC, Kim DY, Gallastegui A, Griffin MA, O'Neill M, Wustefeld-Janssens BG, Fontes GS, Selmic LE, Traverson M, de M Souza CH, Bertran J, Thomsen B, Vinayak A, Mickelson MA. Contrast-Enhanced Computed Tomography for Identification of Potential Malignancy in Canine Colorectal Mesenchymal Tumours. Vet Comp Oncol 2025; 23:216-223. [PMID: 40056897 DOI: 10.1111/vco.13047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 02/17/2025] [Accepted: 02/18/2025] [Indexed: 03/10/2025]
Abstract
Cross-sectional imaging may be used to characterise the location and extent of colorectal mesenchymal tumours (CRMTs). Given the anticipated variation in tumour behaviour and varying morbidity based on surgical margins, a reliable, non-invasive means of predicting malignant potential could facilitate case management. The purpose of this multi-institutional, retrospective study was to determine the diagnostic accuracy of contrast-enhanced CT for distinguishing benign and malignant CRMTs. Twenty-seven dogs with CRMTs were included. Initial diagnoses were reviewed, and slides or blocks were available for 24/27 dogs for further histologic review and immunohistochemical labelling for smooth muscle actin, KIT and vimentin. Two masked radiologists reviewed DICOM images for tumour characteristics, including a final, binary, consensus, subjective interpretation of malignancy. Eighteen tumours (66.7%) were classified as leiomyoma, one (3.7%) as a benign other non-lymphogenic intestinal mesenchymal tumour (benign), one (3.7%) as leiomyosarcoma, and seven (25.9%) as gastrointestinal stromal tumour (malignant). Agreement between radiologists ranged from none to weak for categorical variables, with no agreement (κ = 0.135) for the final assessment of a tumour as benign or malignant. Substantial overlap was noted between groups, with no single categorical variable demonstrating high accuracy as a predictor of malignancy. Consensus final assessment was a sensitive (80.0%) but not specific (29.4%) predictor of malignancy (accuracy: 48.2%). No association was identified between CT determination of malignancy and histologic determination of malignancy (p = 0.678). Non-standardised contrast-enhanced CT was ineffective at distinguishing malignant from benign CRMTs in this study.
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Affiliation(s)
- Alexandria D Bourgeois
- Department of Veterinary Medicine and Surgery, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
| | - Owen T Skinner
- Department of Veterinary Medicine and Surgery, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
| | - James J Karnia
- Department of Veterinary Medicine and Surgery, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
| | - Amanda C Smith
- Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
| | - Dae Young Kim
- Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
| | - Aitor Gallastegui
- Department of Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
| | - Maureen A Griffin
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Meaghan O'Neill
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Brandan G Wustefeld-Janssens
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Gabrielle S Fontes
- Department of Clinical Sciences, The Ohio State University, Columbus, Ohio, USA
| | - Laura E Selmic
- Department of Clinical Sciences, The Ohio State University, Columbus, Ohio, USA
| | - Marine Traverson
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA
| | - Carlos H de M Souza
- Department of Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
| | - Judith Bertran
- Department of Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
| | - Brian Thomsen
- VCA West Coast Specialty and Emergency Animal Hospital, Fountain Valley, California, USA
| | - Arathi Vinayak
- VCA West Coast Specialty and Emergency Animal Hospital, Fountain Valley, California, USA
| | - Megan A Mickelson
- Department of Veterinary Medicine and Surgery, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
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Zhao Z, Qiu S, Zhang X, Liu S, Wang L, Guan H, He J, Hu Y, Li X, Luo S, Chen Z, Mo T, Zhang Y, Zhao X, Pan Y, Ding H, Cao J, Pan J. Characterization of a novel cell line established from mice gastrointestinal stromal model by chemical induction. Transl Oncol 2025; 56:102388. [PMID: 40233502 PMCID: PMC12022689 DOI: 10.1016/j.tranon.2025.102388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 02/03/2025] [Accepted: 04/05/2025] [Indexed: 04/17/2025] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are a type of tumor that originates from gastrointestinal mesenchymal tissue. Although several somatic or germline mutation GIST mice were established, however, there is still a lack of an authentic mice GIST cell lines for further experimental study. METHODS We developed a chemically induced C57BL/6 J GIST model using 3- methylcholanthrene. Tumor characteristics were confirmed through histology and IHC. Primary cells were isolated to establish the mGSTc01 cell line, and molecular profiling was conducted. Additionally, we established GIST model in immunocompetent mice to evaluate their sensitivity to imatinib. RESULTS Our study successfully developed a chemically induced murine GIST model, characterized by positive staining of c-kit and DOG-1. The mGSTc01 monoclonal cell line exhibited slender morphology and expressed the c-kit marker, Whole exome sequencing uncovered mutations of Lamb1, MMP9, and c-kit in GIST cells and provided a detailed picture of the entire genome's copy number variations. RNA sequencing indicated genes associated with cell adhesion and focal adhesion were enriched in mGSTc01 cells. The mGSTc01 cells demonstrated obvious malignant behaviors, notably elevated migration, adhesion, and proliferation. In immunocompetent mice, subcutaneous xenografts not only reserved the aggressive phenotype but also displayed a response to imatinib, underscoring the model's applicability for advancing therapeutic research. CONCLUSION We firstly established a mGSTc01 cell line derived from C57BL/6 J mice GIST tumor offers, which closely mimicking human disease characteristics. It is a potent platform for investigating tumor microenvironment of GIST in mice model, and provides a novel way for new therapeutic discoveries in GIST.
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Affiliation(s)
- Zhan Zhao
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Shenghui Qiu
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China; Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, 510180, PR China
| | - Xiangwei Zhang
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Shijin Liu
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Lu Wang
- Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, 510632, PR China
| | - Hanyang Guan
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Jiashuai He
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Yangzhi Hu
- The Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, PR China
| | - Xiaobo Li
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China
| | - Simin Luo
- Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, China
| | - Zuyang Chen
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Tianmu Mo
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Yiran Zhang
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Xiaoxu Zhao
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Yunlong Pan
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China
| | - Hui Ding
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China.
| | - Jie Cao
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China; Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, 510180, PR China.
| | - Jinghua Pan
- Department of General Surgery, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, Guangdong, PR China.
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Rodriguez Pena MDC, Papke DJ. When Is It Important to Sequence Sarcomas and Other Mesenchymal Neoplasms? A Practical Guide to Molecular Testing. Hematol Oncol Clin North Am 2025:S0889-8588(25)00039-5. [PMID: 40374391 DOI: 10.1016/j.hoc.2025.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2025]
Abstract
The increasingly widespread availability of next-generation sequencing has led to its incorporation as a diagnostic tool in pathology and a modality for identifying targetable alterations. However, sequencing is still a somewhat expensive and time-consuming. Here, we discuss tumor types for which (1) molecular testing is not generally indicated, (2) surrogate immunohistochemical markers have rendered molecular testing unnecessary, or (3) sequencing is important for diagnostic and therapeutic purposes. We also provide a practical framework to assist in decision-making for molecular testing of both classified and unclassified mesenchymal neoplasms, reflecting our practice in a tertiary sarcoma referral center.
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Affiliation(s)
| | - David J Papke
- Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
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Ma Y, Wang Y, Wang S, Wang H, Zhao Y, Peng C, Liu X, Yang J. Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors. Clin Exp Med 2025; 25:150. [PMID: 40347390 PMCID: PMC12065685 DOI: 10.1007/s10238-025-01667-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Accepted: 04/02/2025] [Indexed: 05/12/2025]
Abstract
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by KIT or PDGFRA mutations. Programmed cell death (PCD), including apoptosis, autophagy, and ferroptosis, plays a crucial role in GIST pathogenesis, progression, and treatment response. Non-coding RNAs (ncRNAs) have emerged as key regulators of PCD pathways, influencing GIST proliferation, metastasis, and drug resistance, particularly in response to tyrosine kinase inhibitors (TKIs) such as imatinib. Apoptosis suppression is strongly associated with poor prognosis, while autophagy contributes to tumor dormancy and TKI resistance. Ferroptosis, a novel iron-dependent cell death pathway, represents a promising therapeutic target. Recent evidence suggests that ncRNAs modulate these PCD pathways through interactions with key molecular regulators such as miR-494, miR-30a, and lncRNAs, which affect signaling networks including PI3K/AKT, MAPK, and mTOR. Furthermore, ncRNAs have mediated secondary resistance to imatinib by promoting autophagic flux and altering ferroptosis sensitivity. Understanding the molecular interplay between ncRNAs and PCD in GIST provides novel insights into disease mechanisms and offers potential therapeutic strategies to overcome drug resistance. Targeting ncRNA-mediated regulation of apoptosis, autophagy, and ferroptosis may enhance treatment efficacy and improve patient outcomes. Future research should focus on elucidating the mechanistic roles of ncRNAs in PCD pathways to develop innovative diagnostic and therapeutic approaches for GIST.
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Affiliation(s)
- Yuxuan Ma
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Yuhao Wang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Shu Wang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
| | - Haoyuan Wang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Yan Zhao
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Chaosheng Peng
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Xin Liu
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jianjun Yang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China.
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Li J, Yan Y, Jiang D, Wang X, Wang L, Liu L, Shu T, Zhou Z, Sun X. Diagnostic accuracy and influencing factors of microprobe endoscopic ultrasound for gastrointestinal subepithelial lesions: a multicenter retrospective study. BMC Gastroenterol 2025; 25:353. [PMID: 40346490 PMCID: PMC12063432 DOI: 10.1186/s12876-025-03927-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Accepted: 04/22/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Microprobe endoscopic ultrasonography (MEUS) has been widely adopted in primary hospitals due to its affordability, ease of use, and simple operation. This study aims to assess the diagnostic accuracy of MEUS in classifying gastrointestinal subepithelial lesions (SELs), identify key influencing factors, and explore strategies for improvement. METHODS A retrospective analysis was conducted on 855 patients with histopathologically confirmed SELs across five Chinese hospitals. The overall diagnostic accuracy (DA) of MEUS for SELs was calculated. Independent factors were identified using univariate and multivariate logistic regression analyses, followed by subgroup analysis. RESULTS Among 896 lesions across 31 SEL types, the overall DA was 70.31%. Non-gastrointestinal stromal tumor (GIST) and non-neuroendocrine tumor (NET) lesions, along with gastric location, were identified as risk factors for lower diagnostic accuracy, while rectal location was protective. In the subgroup analysis, gastric leiomyomas had a DA of 9.85% with 99.17% incorrectly classified as GISTs, compared to 94.78% for gastric GISTs, 84.24% for gastric NETs, and 31.2% for other lesions. Lesions with inhomogeneous echoes were 20 times more likely than those with homogeneous echoes to be diagnosed as gastric GISTs compared to gastric leiomyoma. Additionally, the inhomogeneous echo patterns of gastric GISTs were characterized by hyperechogenic spots in 93.67%, marginal halos in 18.99%, and cystic changes in 13.92%. CONCLUSION MEUS is effective for classifying SELs, although differentiating between gastric GISTs and leiomyomas remains challenging. Improved assessment of echo heterogeneity and expanded knowledge of atypical and rare cases may enhance diagnostic accuracy.
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Affiliation(s)
- Jiao Li
- Department of Gastroenterology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Qinglong street 82#, Chengdu, Sichuan, China
| | - Yongfeng Yan
- Department of Gastroenterology, The First People's Hospital of Liangshan Yi Autonomous Prefecture, Xichang, China
| | - Dandan Jiang
- Department of Gastroenterology, The Suining Central Hospital, Sunning, China
| | - Xiaoxiang Wang
- Department of Gastroenterology, The First People's Hospital of Chengdu, Chengdu, China
| | - Li Wang
- Department of Gastroenterology, Sichuan Mianyang 404 Hospital, Mianyang, China
| | - Li Liu
- Department of Gastroenterology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Qinglong street 82#, Chengdu, Sichuan, China
| | - Tao Shu
- Department of Gastroenterology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Qinglong street 82#, Chengdu, Sichuan, China
| | - Zhengkui Zhou
- Department of Gastroenterology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Qinglong street 82#, Chengdu, Sichuan, China
| | - Xiaobin Sun
- Department of Gastroenterology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Qinglong street 82#, Chengdu, Sichuan, China.
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Yeung KTD, Kumar S, Patel N, Doyle J, Strauss D, Bhogal RH. The role for pancreatic preserving surgery for duodenal (D2) gastrointestinal stromal tumours. Surg Endosc 2025; 39:3167-3172. [PMID: 40204905 DOI: 10.1007/s00464-025-11692-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 03/30/2025] [Indexed: 04/11/2025]
Abstract
INTRODUCTION A variety of surgical options are available to achieve a complete oncological resection for duodenal gastrointestinal stromal tumours (GISTs). The most common location of such tumours is the second portion (D2) of the duodenum. The key step in assessing the feasibility of localised duodenal resection is the relationship between the GIST and ampulla. We present our surgical approach and results for patients with D2 GISTs undergoing surgical resection at our tertiary oncology centre. METHODS Patients diagnosed with duodenal GIST involving D2 who underwent surgical resection at The Royal Marsden NHS Foundation Trust between March 2018 and May 2024 were included in this study. RESULTS 11 patients with D2 GISTs were included in the study. The mean age was 60 ± 11.2 years. The majority (n = 9) of patients presented with gastrointestinal haemorrhage. The locations of duodenal GIST were D1/2 (n = 1), D2 (n = 8), and D2/3 (n = 2). 9 patients received neoadjuvant Imatinib treatment. 10 patients had peri-ampullary D2 GISTs resected with pancreatic preservation. There were no anastomotic or duodenotomy leaks. One patient developed delayed gastric emptying (DGE). One patient who underwent segmental D2/3 resection and duodeno-jejunostomy developed biliary obstruction and required PTC and biliary stent. One patient who presented with biliary obstruction underwent pancreaticoduodenectomy developed a Grade A post-operative pancreatic fistula. The median study follow-up was 38 months (range 3-72 months) and at the end of the study period only one patient had developed recurrence. All patients remain disease free and under active follow-up. CONCLUSION In summary, we demonstrate that for D2 GISTs presenting without biliary obstruction, localised D2 resection should be considered, and this approach is associated with low patient morbidity and good long-term patient outcomes.
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Affiliation(s)
| | - Sacheen Kumar
- The Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, SW3 6JJ, UK
- The Institute of Cancer Research, Old Brompton Road, London, SW3 3RP, UK
| | - Nikhil Patel
- The Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, SW3 6JJ, UK
| | - Joseph Doyle
- The Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, SW3 6JJ, UK
| | - Dirk Strauss
- The Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, SW3 6JJ, UK
| | - Ricky H Bhogal
- The Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, SW3 6JJ, UK.
- The Institute of Cancer Research, Old Brompton Road, London, SW3 3RP, UK.
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Chen Y, Zhu X, Ding S, Chen M, Yang J, Deng K. Minimally invasive treatment strategies for submucosal tumors of the upper gastrointestinal tract: Advances in innovative endoscopy-based therapies. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109626. [PMID: 39874944 DOI: 10.1016/j.ejso.2025.109626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/01/2025] [Accepted: 01/18/2025] [Indexed: 01/30/2025]
Abstract
The increasing detection of submucosal tumors (SMTs) in the upper gastrointestinal tract (UGI) is due to the increased clinical use of endoscopy and imaging technology. Some of these SMTs have malignant potential and may cause clinical symptoms. Thus, it is recommended in clinical guidelines to consider resection of these SMTs. Endoscopic techniques have become widely used in the diagnosis and treatment of SMT in the UGI as compared with traditional surgery due to their advantages of minimally invasive, quick recovery, and economical cost. Recently, new endoscopic techniques and instruments have been continuously implemented, leading to revolutionary innovation in endoscopic treatments. However, the safety and efficacy of these innovative techniques remain unclear. Therefore, we have comprehensively summarized the various techniques used in the treatment of UGI tumors in recent years, evaluated the indications and effects of each technique, and compared their benefits and disadvantages. We hope that this review will provide a more comprehensive reference for clinical and endoscopic practitioners, and help them develop more individualized treatment plans for different patients. This will ultimately expand the patient population that can benefit from these innovative technologies.
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Affiliation(s)
- Yuxiang Chen
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xinrui Zhu
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Shasha Ding
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Mo Chen
- Department of Gerontology, Tibetan Chengdu Branch Hospital of West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Department of Gerontology, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, 610041, China
| | - Jinlin Yang
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Kai Deng
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Feng Y, Liu L. Clinicopathological characteristics and long-term prognosis of peritoneal and retroperitoneal gastrointestinal stromal tumors. Surg Endosc 2025; 39:2911-2924. [PMID: 40102271 PMCID: PMC12040990 DOI: 10.1007/s00464-025-11600-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 01/29/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND Peritoneal and retroperitoneal gastrointestinal stromal tumors (PRGISTs) are exceedingly uncommon, and their clinicopathological characteristics and long-term prognosis remain unreported. Therefore, our objective is to analyze these aspects of patients with PRGISTs using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS Patients diagnosed with PRGISTs and small intestine stromal tumors (SISTs) between 2000 and 2019 were included in the study. Differences between groups were compared using Chi-square tests. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate overall survival (OS) and cancer-specific survival (CSS). RESULTS A total of 3817 patients were enrolled, with 3513 diagnosed with SISTs and 304 with PRGISTs. Compared to SISTs, PRGISTs patients were older, with larger tumors, higher mitotic rates, and greater risk of lymph node (5.3%) and distant (30.6%) metastasis (P < 0.001). Multivariate analysis identified N stage and mitotic rate as risk factors for distant metastasis in PRGISTs. In comparison to SISTs, PRGISTs patients exhibited a significantly worse OS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.57-2.15, P < 0.001) and CSS (HR 2.11, 95% CI 1.73-2.58, P < 0.001). Subgroup analyses by age, sex, surgical status, chemotherapy, and marital status consistently demonstrated poorer OS and CSS for PRGISTs patients compared to SISTs patients (P < 0.05). The 1-, 3-, 5-, and 10-year OS rates for PRGISTs patients were 77.9%, 61.6%, 51.6%, and 32.8%, respectively, with corresponding CSS rates of 84.5%, 71.7%, 63.3%, and 49.0%. Multivariate Cox regression analysis identified age, race, surgical status, and mitotic rate as risk factors influencing OS, while race, surgical status, and mitotic rate were identified as risk factors affecting CSS. CONCLUSIONS In comparison to SISTs, PRGISTs patients exhibit distinct clinicopathological features and have a worse prognosis. However, surgical intervention can improve the prognosis of PRGISTs patients.
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Affiliation(s)
- Yunfu Feng
- Department of Endoscopy Center, The First People's Hospital of Kunshan, Suzhou, China
| | - Luojie Liu
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Suzhou, China.
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12
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Chen L, Lu Y, Qian J, Qiu J, Wu C, Qiao Z, Ma Y, Yu F. Clinical characteristics and prognosis of non-metastatic multiple gastrointestinal stromal tumors: a population-based study. Discov Oncol 2025; 16:643. [PMID: 40304924 PMCID: PMC12043539 DOI: 10.1007/s12672-025-02454-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 04/21/2025] [Indexed: 05/02/2025] Open
Abstract
PURPOSE Multiple gastrointestinal stromal tumors (MGISTs) are relatively rare and may exhibit distinct clinical characteristics and prognosis compared to solitary GISTs (SGISTs). The objective of this study was to investigate the clinical features and prognosis of MGISTs. MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all GIST patients diagnosed between 2010 and 2019. Multiple imputation (MI) was utilized to address missing data, while propensity score matching (PSM) was conducted to mitigate selection bias. The impact of demographic and clinical factors on overall survival (OS) was evaluated using Kaplan-Meier analyses and Cox proportional hazards models. RESULTS A total of 6241 patients were included in the study, with 4546 having SGISTs and 1695 having MGISTs. MGISTs have a higher prevalence in males, Caucasians, and elderly patients. Compared to MGISTs, the OS of SGISTs is significantly better (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.44-0.55, P < 0.001). After PSM, 3390 patients (equally distributed between the SGISTs and MGISTs groups) were matched for comparison. The OS of SGISTs is still better than that of MGISTs (HR 0.65, 95% CI 0.56-0.75, P < 0.001). Age, sex, site, surgery, marital status, mitotic rate, and chemotherapy were independent risk factors for OS in MGISTs patients. The OS of MGISTs patients who underwent surgery was significantly better than those who did not (P < 0.001). Similarly, chemotherapy-treated MGISTs patients showed improved OS compared to those who did not receive it (P = 0.045). CONCLUSIONS MGISTs have unique clinical characteristics and show worse OS compared to SGISTs. Surgical intervention and chemotherapy has the potential to ameliorate the prognosis of patients with MGISTs.
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Affiliation(s)
- Liang Chen
- Department of General Surgery, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Ye Lu
- Department of Endocrinology, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Jiawei Qian
- Department of General Surgery, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Jie Qiu
- Department of General Surgery, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Chuanfu Wu
- Department of General Surgery, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Zhenguo Qiao
- Department of Gastroenterology, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China.
| | - Yimin Ma
- Departments of Gastroenterology, Gaochun People's Hospital of Nanjing, Nanjing, China.
| | - Feng Yu
- Department of General Surgery, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China.
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13
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Sun YF, Cao XK, Wei Q, Gao YH. Potential biomarkers for the prognosis of gastrointestinal stromal tumors. World J Gastrointest Oncol 2025; 17:102831. [PMID: 40235893 PMCID: PMC11995323 DOI: 10.4251/wjgo.v17.i4.102831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/17/2025] [Accepted: 02/05/2025] [Indexed: 03/25/2025] Open
Abstract
In this editorial we comment on the article published in the recent issue of World Journal of Gastrointestinal Oncology. This study aims to explore the relationship between preoperative inflammation markers and the recurrence of gastrointestinal stromal tumors (GIST) after surgery. It is well known that the best-documented prognostic parameters for GIST are mitotic activity, tumor size and anatomical site. Besides, mutation status represents a prognostic as well as predictive factor. This study provides a new tool for postoperative recurrence risk assessment of GIST patients by establishing a line chart prediction model, which is certificated by previous research that high platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio correlated with increased tumour sizes, more advanced tumour stages and mitotic index. However, as a retrospective study, inevitable bias exists in the results; furthermore, the sample size of this study is relatively small, influencing the universality of the results. Moreover, when assessing risk rating and prognosis of GIST, some novel inflammatory makers could be taken into consideration, such as proenkephalin and SLITRK3. Overall, this study can offer an additional model for GIST prognosis and recurrence risk assessment, independent of the traditional prognostic factors of GIST.
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Affiliation(s)
- Yue-Fang Sun
- Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200000, China
| | - Xuan-Ke Cao
- Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200000, China
| | - Qing Wei
- Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200000, China
| | - Yao-Hui Gao
- Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200000, China
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Romandini D, Sobczuk P, Cicala CM, Serrano C. Next questions on gastrointestinal stromal tumors: unresolved challenges and future directions. Curr Opin Oncol 2025:00001622-990000000-00251. [PMID: 40207474 DOI: 10.1097/cco.0000000000001145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
PURPOSE OF REVIEW Despite remarkable progress in the management of gastrointestinal stromal tumors (GISTs), critical challenges persist. Key aspects such as risk stratification, the optimal duration of adjuvant therapy, and strategies to enhance the efficacy of first-line treatment remain subjects of ongoing debate. This review explores emerging concepts and innovative approaches aimed at refining patient selection and optimizing therapeutic decision-making to further improve clinical outcomes. RECENT FINDINGS Molecular and genomic parameters have the potential to enhance traditional risk models, enabling more precise stratification of high-risk patients. Innovations in artificial intelligence and liquid biopsy are emerging as powerful tools for refining predictions of recurrence and treatment response. Meanwhile, the definition and prognostic significance of tumor rupture remain pivotal challenges that influence both risk assessment and adjuvant therapy decisions. Furthermore, transcriptomic and multiomic analyses have unveiled distinct GIST subtypes with significant prognostic and therapeutic implications, paving the way for more tailored treatment strategies. SUMMARY Integrating molecular features into clinical decision making may refine risk assessment and personalize the treatment in patients with GIST. Future research should focus on validating these tools and redefine clinical trial designs to accelerate drug development for this rare disease.
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Affiliation(s)
- Davide Romandini
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO)
| | - Pawel Sobczuk
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO)
| | - Carlo M Cicala
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO)
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - César Serrano
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO)
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
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Liu Y, Chen Y, Feroze A, Fu Z. An Incidental Finding of Appendiceal Gastrointestinal Stromal Tumor with Abundant Skeinoid Fibers: A Rare Case Report with Insights from a Comprehensive Literature Review. Diagnostics (Basel) 2025; 15:924. [PMID: 40218274 PMCID: PMC11989053 DOI: 10.3390/diagnostics15070924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/29/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Background and Clinical Significance: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract but are exceedingly rare in the appendix, with only 20 cases reported in the literature. Due to their rarity, clinical behavior, histopathologic features, and management of appendiceal GISTs remain poorly understood. Case Presentation: We present the case of a 74-year-old man who underwent a right hemicolectomy for colonic adenocarcinoma, during which an incidental 1.2 cm appendiceal GIST was discovered. Histopathological examination revealed spindle cell morphology with abundant skeinoid fibers (SF), minimal mitotic activity (<1/50 HPF), and no nuclear atypia. Immunohistochemical staining confirmed positivity for CD117, DOG1, and CD34. The tumor was classified as low risk based on its size and mitotic count, and the patient remained recurrence-free at a 4-month follow-up. Conclusions: Our case expands the limited literature on appendiceal GISTs by demonstrating their histopathological and immunohistochemical features, favorable prognostic outcomes, and potential for incidental detection during surgeries for unrelated conditions. However, additional studies are needed to further elucidate their molecular characteristics and overall clinical behavior.
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Affiliation(s)
| | | | | | - Zhiyan Fu
- Department of Pathology, LSUHSC School of Medicine, New Orleans, LA 70112, USA; (Y.L.); (Y.C.); (A.F.)
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Lagopoulos VI, Gigi E, Savvakis S, Sidiropoulou M, Gkoutziotis I, Emfietzis PK. A Large Gastrointestinal Stromal Tumor under the Disguise of a Gastric Diverticulum: Report of a Case and Review of the Literature. Surg Case Rep 2025; 11:24-0133. [PMID: 40230825 PMCID: PMC11994293 DOI: 10.70352/scrj.cr.24-0133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 02/23/2025] [Indexed: 04/16/2025] Open
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GISTs) are a relatively rare clinical entity. They usually appear as solid masses in numerous locations throughout the gastrointestinal tract, varying in size and typically exhibiting extraluminal expansion along with a range of nonspecific symptoms. The exophytic growth pattern of these tumors may occasionally complicate the differential diagnosis from other medical conditions with similar clinical and imaging findings. CASE PRESENTATION We describe a case of a 46-year-old male patient who presented to the emergency department with symptoms of upper gastrointestinal tract hemorrhage. Initial endoscopic findings suggested a large gastric diverticulum. Surprisingly, further investigation with computed tomography and a second endoscopy with biopsy sampling revealed that the stomach wall outpouching was actually a disguised, oversized gastric GIST. The patient underwent a posterior wall sleeve gastrectomy en bloc with the mass, the spleen, and the tail of the pancreas and recovered uneventfully. Daily administration of imatinib as adjuvant therapy was included in the treatment plan. No recurrence was observed even up to the 4-year follow-up period. CONCLUSIONS GISTs are uncommon tumors with the ability to masquerade as gastrointestinal tract diverticula, causing diagnostic confusion. Nevertheless, high clinical suspicion combined with a thorough clinical and imaging evaluation can ultimately lead to the correct diagnosis and an appropriate treatment plan.
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Affiliation(s)
- Vasileios I Lagopoulos
- 3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Gigi
- 2nd Internal Medicine Department, Hippokration General Hospital of Thessaloniki Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stavros Savvakis
- 3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Sidiropoulou
- Computed Tomography Department, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - Ioannis Gkoutziotis
- 5th Department of Surgery, Hippokration General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Panagiotis-Konstantinos Emfietzis
- 3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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17
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Jia X, Xiao Y, Zhang H, Li J, Lv S, Zhang Y, Chai F, Feng C, Liu Y, Chen H, Ma F, Wei S, Cheng J, Zhang S, Gao Z, Hong N, Tang L, Wang Y. CT assessed morphological features can predict higher mitotic index in gastric gastrointestinal stromal tumors. Eur Radiol 2025; 35:2094-2105. [PMID: 39349725 DOI: 10.1007/s00330-024-11087-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 06/13/2024] [Accepted: 08/02/2024] [Indexed: 03/18/2025]
Abstract
OBJECTIVES To investigate the correlation of the mitotic index (MI) of 1-5 cm gastric gastrointestinal stromal tumors (gGISTs) with CT-identified morphological and first-order radiomics features, incorporating subgroup analysis based on tumor size. METHODS We enrolled 344 patients across four institutions, each pathologically diagnosed with 1-5 cm gGISTs and undergoing preoperative contrast-enhanced CT scans. Univariate and multivariate analyses were performed to investigate the independent CT morphological high-risk features of MI. Lesions were categorized into four subgroups based on their pathological LD: 1-2 cm (n = 69), 2-3 cm (n = 96), 3-4 cm (n = 107), and 4-5 cm (n = 72). CT morphological high-risk features of MI were evaluated in each subgroup. In addition, first-order radiomics features were extracted on CT images of the venous phase, and the association between these features and MI was investigated. RESULTS Tumor size (p = 0.04, odds ratio, 1.41; 95% confidence interval: 1.01-1.96) and invasive margin (p < 0.01, odds ratio, 4.55; 95% confidence interval: 1.77-11.73) emerged as independent high-risk features for MI > 5 of 1-5 cm gGISTs from multivariate analysis. In the subgroup analysis, the invasive margin was correlated with MI > 5 in 3-4 cm and 4-5 cm gGISTs (p = 0.02, p = 0.03), and potentially correlated with MI > 5 in 2-3 cm gGISTs (p = 0.07). The energy was the sole first-order radiomics feature significantly correlated with gGISTs of MI > 5, displaying a strong correlation with CT-detected tumor size (Pearson's ρ = 0.85, p < 0.01). CONCLUSIONS The invasive margin stands out as the sole independent CT morphological high-risk feature for 1-5 cm gGISTs after tumor size-based subgroup analysis, overshadowing intratumoral morphological characteristics and first-order radiomics features. KEY POINTS Question How can accurate preoperative risk stratification of gGISTs be achieved to support treatment decision-making? Findings Invasive margins may serve as a reliable marker for risk prediction in gGISTs up to 5 cm, rather than surface ulceration, irregular shape, necrosis, or heterogeneous enhancement. Clinical relevance For gGISTs measuring up to 5 cm, preoperative prediction of the metastatic risk could help select patients who could be treated by endoscopic resection, thereby avoiding overtreatment.
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Affiliation(s)
- Xiaoxuan Jia
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Youping Xiao
- Department of Radiology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Hui Zhang
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Jiazheng Li
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China
| | - Shiying Lv
- Department of Radiology, Shijiazhuang People's Hospital, Shijiazhuang, China
| | - Yinli Zhang
- Department of Pathology, Peking University People's Hospital, Beijing, China
| | - Fan Chai
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Caizhen Feng
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Yulu Liu
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Haoquan Chen
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Feiyu Ma
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Shengcai Wei
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Jin Cheng
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Sen Zhang
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Zhidong Gao
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
| | - Nan Hong
- Department of Radiology, Peking University People's Hospital, Beijing, China
| | - Lei Tang
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
| | - Yi Wang
- Department of Radiology, Peking University People's Hospital, Beijing, China.
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Stavrou N, Memos N, Filippatos C, Sergentanis TN, Zagouri F, Gavriatopoulou M, Ntanasis-Stathopoulos I. Neoadjuvant Imatinib in Recurrent/Metastatic Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis of Proportions. J Gastrointest Cancer 2025; 56:88. [PMID: 40140195 PMCID: PMC11947046 DOI: 10.1007/s12029-025-01210-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2025] [Indexed: 03/28/2025]
Abstract
INTRODUCTION Metastatic and recurrent gastrointestinal stromal tumors (GISTs) present challenging clinical management. Imatinib is the standard first-line therapy, improving survival and reducing tumor burden in the neoadjuvant use, facilitating surgical intervention. This systematic review and meta-analysis assessed the efficacy of neoadjuvant imatinib in metastatic/recurrent GISTs, highlighting its potential to enhance surgical outcomes and overall patient management. METHODS A systematic search was conducted in PubMed, Embase and Scopus (end-of-search: February 13, 2025) for records on neoadjuvant imatinib therapy in recurrent/metastatic GISTs. Pooled proportions and 95% confidence intervals were calculated with common-effect and random-effects models. Subgroup and meta-regression analysis were performed, addressing heterogeneity and examining any potential association between the factors that varied and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS The search identified 957 articles, and 14 were analyzed. The meta-analysis of proportions indicated that 2-year and 5-year PFS were 76% (95% CI 58-88%) and 43% (95% CI 17-74%), respectively, while 2-year and 5-year OS were 84% (95% CI 78-89%) and 60% (95% CI 51-68%), respectively. The pooled R0 resection rate was 82% (95% CI 64-92%), associated positively with that of radiological partial response (PR) (β = 3.92, p < 0.001). Further meta-regression analysis yielded no significant association with preoperative imatinib duration. CONCLUSION The present meta-analysis of trials and studies on metastatic or recurrent GISTs highlights key insights into post-surgery patient outcomes following neoadjuvant treatment with imatinib. Pooled effect estimates revealed promising 2-year and 5-year PFS rates of 76% and 43%, respectively, and 2-year and 5-year OS rates of 84% and 60%, respectively. Furthermore, the high pooled R0 resection rate of 82% emphasizes a substantial surgical efficacy in this population, while it was significantly correlated with successful R0 resections in patients with favorable outcomes.
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Affiliation(s)
- Niki Stavrou
- Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
| | - Nikolaos Memos
- Surgical Department, School of Medicine, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Charalampos Filippatos
- Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Flora Zagouri
- Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Ntanasis-Stathopoulos
- Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Xu EP, Qi ZP, Zhang JW, Li B, Ren Z, Cai MY, Cai SL, Lv ZT, Chen ZH, Liu JY, Zhong YS, Zhou PH, Shi Q. Endoscopic treatment outcome of oesophageal gastrointestinal stromal tumours. World J Gastroenterol 2025; 31:102393. [PMID: 40093666 PMCID: PMC11886535 DOI: 10.3748/wjg.v31.i10.102393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 01/04/2025] [Accepted: 02/08/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours (GISTs). Thus, the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs. AIM To investigate endoscopic treatment effective of oesophageal GISTs. METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection (ER) between January 2012 and January 2023 in two Hospital. Clinicopathologic, endoscopic records, and follow-up data were collected and analysed. RESULTS Thirty-one patients underwent en bloc resection and 24 (75.0%) lesions underwent R0 resection. The size of GISTs was 2.12 ± 1.88 cm. The overall complication rate was 25.0%, including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome. The mean mitotic index was 3.34 ± 5.04 (median, 1.50; range, 1.00-4.00). Eighteen (56.3%), 6 (18.8%), 2 (6.3%), and 6 (18.8%) patients were identified as very low, low, intermediate, and high risk, respectively. Three patients developed recurrence after a median follow-up of 64.69 ± 33.13 months. The 5-year overall survival rate was 100%, and the disease-free survival rate was 90.6%. CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs. Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.
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Affiliation(s)
- En-Pan Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Zhi-Peng Qi
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jia-Wei Zhang
- Endoscopy Center, Shanghai Xuhui District Central Hospital, Shanghai 200030, China
| | - Bing Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhong Ren
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ming-Yan Cai
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Shi-Lun Cai
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhen-Tao Lv
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhang-Han Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jing-Yi Liu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yun-Shi Zhong
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ping-Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Shanghai Collaborative Innovation Center of Endoscopy, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qiang Shi
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Yang C, Li K, Xiang B. Case Report: Duodenal gastrointestinal stromal tumor misdiagnosed as tumor located on the major duodenal papilla leading to fatal gastrointestinal bleeding in a child. Front Pediatr 2025; 13:1546914. [PMID: 40123671 PMCID: PMC11925956 DOI: 10.3389/fped.2025.1546914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
Background Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they are rare in children, particularly those located on the duodenum. Here, we present an interesting pediatric case involving a 13-year-old boy who experienced gastrointestinal hemorrhage, he was misdiagnosed with a tumor located on the major duodenal papilla and was ultimately confirmed to be duodenal GISTs. Case presentation A 13-year-old boy presented to a local hospital with fatigue and melena. Gastroscopy suggested a tumor located at the major duodenal papilla, and the patient was referred to our hospital for surgical evaluation. Upon further investigation and surgical exploration, the diagnosis was revised to a duodenal GIST with surface ulceration and active bleeding. The ulcer's morphology and location mimicked the appearance of the major duodenal papilla, leading to the initial diagnostic error. Conclusions Duodenal GISTs in pediatric patients often present asymptomatically but can manifest with severe complications such as fatal gastrointestinal bleeding. The tumor's morphology and location can obscure the major papilla, complicating preoperative diagnosis and influencing surgical decision-making. Comprehensive preoperative evaluation and careful intraoperative exploration are critical for accurate diagnosis and optimal management.
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Affiliation(s)
| | - Kewei Li
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Bo Xiang
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
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21
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Schneider MA, Vetter D, Gutschow CA. Management of subepithelial esophageal tumors. Innov Surg Sci 2025; 10:21-30. [PMID: 40144787 PMCID: PMC11934943 DOI: 10.1515/iss-2023-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 07/16/2024] [Indexed: 03/28/2025] Open
Abstract
Subepithelial esophageal tumors (SET) are normally benign intramural esophageal lesions of mesenchymal origin. Although rare, the incidence of SET has increased in recent decades due to the more widespread use of endoscopy and diagnostic imaging. The current review aims to provide an overview of the histopathologic spectrum and the most frequent entities including leiomyoma and gastrointestinal stromal tumor (GIST), diagnostic workup, and multidisciplinary treatment options. Staging for SET should include endoscopy, endoscopic ultrasonography (EUS), and tissue sampling. Current consensus guidelines recommend that SET suggestive of gastrointestinal stromal tumor (GIST) larger than 20 mm or lesions with high-risk stigmata should undergo tissue sampling. Most SET have an excellent long-term outcome, but malignancy may be present in certain subtypes. Asymptomatic SET without high-risk stigmata discovered incidentally usually do not require specific treatment. However, depending on the size and location of the lesion symptoms may occur. Therapeutic interventions range from endoscopic interventional resections to major surgical procedures. Enucleation via minimally invasive or robotic-assisted access remains the standard of care for most SET sub-entities.
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Affiliation(s)
- Marcel A. Schneider
- Department of Visceral and Transplant Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Diana Vetter
- Department of Visceral and Transplant Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Christian A. Gutschow
- Department of Visceral and Transplant Surgery, University Hospital Zürich, Zurich, Switzerland
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22
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Strauss G, George S. Gastrointestinal Stromal Tumors. Curr Oncol Rep 2025; 27:312-321. [PMID: 39985704 DOI: 10.1007/s11912-025-01636-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2025] [Indexed: 02/24/2025]
Abstract
PURPOSE OF REVIEW This review aims to outline the current understanding of the molecular drivers and treatment paradigms of gastrointestinal stromal tumors, with a focus on recent developments in treatment in the advanced disease setting. RECENT FINDINGS There have been recent advancements in our understanding of the molecular biology of gastrointestinal stromal tumors, including the identification of new genetic drivers and complex resistance mechanisms. We review the most recent findings in these areas, focusing on how new research insights are reshaping treatment strategies. Recent advancements in our understanding of the biology and treatment of GIST are paving the way for more personalized and effective therapeutic options. As knowledge of rare molecular subtypes, resistance mechanisms, and novel genomic techniques grows, new approaches are emerging in an effort to improve patient outcomes.
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Affiliation(s)
- Gal Strauss
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Suzanne George
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
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23
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Yan W, Yu H, Xu C, Zeng M, Wang M. The value of a nomogram model based on CT imaging features in differentiating duodenal gastrointestinal stromal tumors from pancreatic head neuroendocrine tumors. Abdom Radiol (NY) 2025; 50:1330-1341. [PMID: 39302444 DOI: 10.1007/s00261-024-04579-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/07/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024]
Abstract
OBJECTIVE To construct a nomogram model based on multi-slice spiral CT imaging features to predict and differentiate between duodenal gastrointestinal stromal tumors (GISTs) and pancreatic head neuroendocrine tumors (NENs), providing imaging evidence for clinical treatment decisions. METHODS A retrospective collection of clinical information, pathological results, and imaging data was conducted on 115 cases of duodenal GISTs and 76 cases of pancreatic head NENs confirmed by surgical pathology at Zhongshan Hospital Fudan University from November 2013 to November 2022. Comparative analysis was performed on the tumor's maximum diameter, shortest diameter, long diameter/short diameter ratio, tumor morphology, tumor border, central position of the lesion, lesion long-axis direction, the relationship between tumor and common bile duct (CBD), duodenal side ulceration of the lesion, calcification, cystic and solid proportion within the tumor, thickened feeding arteries, tumor neovascularization, distant metastasis, and CT values during plain and enhanced scans in arterial and venous phases. Statistical analysis was conducted using t-tests, Mann-Whitney U tests, and χ2 tests. Univariate and multivariate logistic regression analyses were used to identify independent predictors for differentiating duodenal GISTs from pancreatic head NENs. Based on these independent predictors, a nomogram model was constructed, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the model. The nomogram was validated using a calibration curve, and decision curve analysis was applied to assess the clinical application value of the nomogram. RESULTS There were significant differences in the duodenal GISTs group and the pancreatic head NENs group in terms of longest diameter (P < 0.001), shortest diameter (P < 0.001), plain CT value (P < 0.001), arterial phase CT value (P < 0.001), venous phase CT value (P = 0.002), lesion long-axis direction (P < 0.001), central position of the lesion (P < 0.001), the relationship between tumor and CBD(< 0.001), border (P = 0.004), calcification (P = 0.017), and distant metastasis (P = 0.018). Multivariate logistic regression analysis identified uncertain location (OR 0.040, 95% CI 0.003-0.549), near the duodenum (OR 0, 95% CI 0-0.009), with the lesion long-axis direction along the pancreas as a reference, along the duodenum (OR 0.106, 95% CI 0.010-1.156) or no significant difference (OR 4.946, 95% CI 0.453-54.017), and the relationship between tumor and CBD (OR 0.013, 95% CI 0.001-0.180), shortest diameter (OR 0.705, 95% CI 0.546-0.909), and calcification (OR 18.638, 95% CI 1.316-263.878) as independent risk factors for differentiating between duodenal GISTs and pancreatic head NENs (all P values < 0.05). The combined diagnostic model's AUC values based on central position of the lesion, calcification, lesion long axis orientation, the relationship between tumor and CBD, shortest diameter, and the joint diagnostic model were 0.937 (0.902-0.972), 0.700(0.624-0.776), 0.717(0.631-0.802), 0.559 (0.473-0.644), 0.680 (0.603-0.758), and 0.991(0.982-0.999), respectively, with a sensitivity of 97.3% and a specificity of 93.0% for the joint diagnostic model. The nomogram model's AUC value was 0.985(0.973-0.996), with a sensitivity and specificity of 94.7% and 93.9%, respectively. The calibration curve indicated good agreement between predicted and actual risks. Decision curve analysis verified the clinical application value of the nomogram. CONCLUSION The nomogram model based on CT imaging features effectively differentiates between duodenal GISTs and pancreatic head NENs, aiding in more precise clinical treatment decisions.
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Affiliation(s)
- Wenjie Yan
- The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haiyan Yu
- Weifang People's Hospital, Weifang, China
| | - Chuanfang Xu
- The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Mengshu Zeng
- Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Geriatric Medical Center, Shanghai, China
| | - Mingliang Wang
- Zhongshan Hospital, Fudan University, Shanghai, China.
- Shanghai Geriatric Medical Center, Shanghai, China.
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24
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Xu X, Zhao S, Xue L. Leiomyosarcomas of the inferior vena cava: diagnostic features on contrast-enhanced CT, ultrasonography and MRI. Front Oncol 2025; 15:1442674. [PMID: 39968070 PMCID: PMC11832406 DOI: 10.3389/fonc.2025.1442674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 01/14/2025] [Indexed: 02/20/2025] Open
Abstract
Purpose To evaluate clinical presentation and imaging characteristics of leiomyosarcomas of the inferior vena cava (IVC LMS) using contrast-enhanced CT (CECT), ultrasonography (US), magnetic resonance imaging (MRI), and to identify features that facilitate early and accurate pre-operative diagnosis. Materials and methods Our study enrolled 21 patients with pathologically confirmed IVC LMS from October 2015 to June 2022. All participants underwent CECT, and additionally, 12 participants had US examinations and 3 had MRI. Images were independently reviewed by two experienced radiologists. The clinical presentations and diagnostic characteristics were recorded. Results The study involved 16 female and 5 male patients, with an average age of 55 ± 11 years (ranging from 34 to 80 years). Common clinical symptoms included abdominal pain, back pain, leg discomfort, abdominal distension, jaundice, and the presence of an abdominal mass. On CT scans, a large, lobulated, heterogeneous mass with progressive enhancement was typically seen in 13 of the 21 patients (61.9%). Ultrasonography revealed that IVC LMS typically presented as a lobulated, heterogeneous, hypoechoic mass. Color Doppler imaging evaluated lumen obstruction in 8 of the 12 patients (66.7%), and high velocity flow signals were detected by Pulsed wave Doppler in 4 of the 12 patients (33.3%). On MRI, IVC LMS presented as a heterogeneous mass that exhibited intermediate intensity on T1-weighted images, slightly high intensity on T2-weighted images and high intensity on diffusion-weighted images. Conclusion Several diagnostic characteristics on CECT, US and MRI could aid in the diagnosis of IVC LMS. The detection of a heterogeneous mass with progressive enhancement along the inferior vena cava on CECT was strongly indicative of IVC LMS. Both CT and US are effective in accurately indicating the location of the tumor within the IVC.
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Affiliation(s)
- Xiaolin Xu
- Department of Ultrasound, Beijing GoBroad Hospital, Beijing, China
| | - Shilei Zhao
- Department of Radiology, Peking University International Hospital, Beijing, China
| | - Lifang Xue
- Department of Ultrasound, Beijing GoBroad Hospital, Beijing, China
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25
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Sutter LD, De Cock L, Wang CC, Gorgels D, Wyns K, Verbeeck K, Vanleeuw U, Douchy T, Hompes D, Jaekers J, Van Raemdonck D, Vanden Bempt I, Debiec-Rychter M, Sciot R, Wozniak A, Schöffski P. Patient-derived xenograft models of gastrointestinal stromal tumors provide a ready-to-use platform for translational research. Dis Model Mech 2025; 18:DMM052225. [PMID: 39853155 PMCID: PMC11876840 DOI: 10.1242/dmm.052225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 01/07/2025] [Indexed: 01/26/2025] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancy of the gastrointestinal tract. Most GISTs harbor mutations in oncogenes, such as KIT, and are treated with tyrosine kinase inhibitors (TKIs), such as imatinib. Most tumors develop secondary mutations, inducing drug resistance against the available TKIs, requiring novel therapies. We established a GIST patient-derived xenograft (PDX) platform of GIST that can be used for preclinical drug testing. Tumor tissue from consenting GIST patients was transplanted subcutaneously to NMRI nu/nu mice. Once tumor growth was observed, the tumor was re-transplanted to a next generation of mice. Tumors were characterized histopathologically and molecularly at every re-transplantation and compared with the original patient tumor. We transplanted 112 tumor samples from 99 GIST patients, resulting in 12 established and well-characterized GIST models with different mutations and TKI sensitivity. Three models harbor secondary KIT mutations. One model is characterized by a primary, imatinib-resistant PDGFRA exon 18 p.D842V mutation. Our established platform of well-characterized GIST PDX models, covering the most relevant driver mutations, serves as an excellent tool for preclinical drug testing and tumor biology studies.
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Affiliation(s)
- Luna De Sutter
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
- Department of Surgical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Lore De Cock
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Chao-Chi Wang
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Daniël Gorgels
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Karo Wyns
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Kimberly Verbeeck
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Ulla Vanleeuw
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Thomas Douchy
- Department of Surgical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Daphne Hompes
- Department of Surgical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Joris Jaekers
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven 3000, Belgium
| | - Dirk Van Raemdonck
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven 3000, Belgium
| | - Isabelle Vanden Bempt
- Department of Human Genetics, KU Leuven, University Hospitals Leuven, Leuven 3000, Belgium
| | - Maria Debiec-Rychter
- Department of Human Genetics, KU Leuven, University Hospitals Leuven, Leuven 3000, Belgium
| | - Raf Sciot
- Department of Pathology, University Hospitals Leuven, Leuven 3000, Belgium
| | - Agnieszka Wozniak
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
| | - Patrick Schöffski
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
- Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven 3000, Belgium
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26
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Li J, Khajoueinejad N, Sarpel U. Surgical Management of Gastric Gastrointestinal Stromal Tumors. Surg Clin North Am 2025; 105:109-124. [PMID: 39523067 DOI: 10.1016/j.suc.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Gastrointestinal stromal tumors (GISTs) are sarcomas that arise from the muscular layer of the gastrointestinal tract. The stomach is the most common location, followed by the small intestine. Surgical resection is the cornerstone of treatment; extensive margins and lymphadenectomy are not routinely required. Commonly utilized resection techniques include wedge gastrectomy, excision and closure of the gastrotomy, and anterior gastrotomy access with internal wedge resection. Tyrosine kinase inhibitors can be utilized in the neoadjuvant setting for cases where a reduction in tumor size would optimize resection, and in the adjuvant setting for high-risk tumors. In select cases, metastasectomy may improve prognosis.
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Affiliation(s)
- Judy Li
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1259, New York, NY 10029, USA
| | - Nazanin Khajoueinejad
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1259, New York, NY 10029, USA
| | - Umut Sarpel
- Division of Surgical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, East/Shapiro 3, Boston, MA 02215, USA.
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27
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Lee WY. Laparoscopic wedge resection of a descending duodenal gastrointestinal stromal tumor under endoscopic nasobiliary drainage guidance: A case report. Int J Surg Case Rep 2025; 127:110877. [PMID: 39813985 PMCID: PMC11783127 DOI: 10.1016/j.ijscr.2025.110877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/08/2025] [Accepted: 01/11/2025] [Indexed: 01/18/2025] Open
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GIST), which occur anywhere in the gastrointestinal (GI) tract, typically occur in the stomach and small intestine but rarely in the duodenum. We present a case report wherein a descending duodenal GIST was treated with a limited, minimally invasive surgery after endoscopic nasobiliary drainage (ENBD) insertion. PRESENTATION OF CASE A 67-year-old woman visited our hospital with an incidentally discovered duodenal tumor. Gastroduodenoscopy revealed a duodenal subepithelial tumor (SET) measuring approximately 2 cm in descending duodenum. Endoscopic ultrasound revealed a well-circumscribed, inhomogeneous hypoechoic lesion measuring approximately 17 × 4.6 mm, thought to arise from the muscularis layer. Computed tomography (CT) revealed an inhomogeneous enhancing mass with central necrosis, measuring approximately 2.7 cm, in the descending duodenum. Pathological findings from the bite-on-bite biopsy showed c-kit and DOG-1 positivity and CD34 and desmin negativity, leading to a GIST diagnosis. Laparoscopic wedge resection with preoperative ENBD insertion was planned due to the risk of pancreaticobiliary duct (PBD) damage during surgery because the lesion was located near the ampulla of Vater (AoV) and minor papilla. Surgery was performed using laparoscopic wedge resection without PBD injury. The patient was discharged 10 days post-surgery without complications. DISCUSSION Descending duodenal GIST is difficult to operate on with minimally invasive surgery. However, if the size is not excessive and the PBD is not involved, minimal and limited surgery is possible after ENBD insertion. CONCLUSION We report the first case of limited and minimally invasive surgery followed by ENBD insertion in a rare descending duodenal GIST.
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Affiliation(s)
- Woo Yong Lee
- Department of Surgery, Inje University Haeundae Paik Hospital, 875 Haeundae-ro, Haeundae-gu, Busan 48108, Republic of Korea.
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28
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Harutyunyan N. A Hidden Tumor: Unraveling a Gastrointestinal Stromal Tumor in a 44-Year-Old Male Patient With Epigastric Pain. Cureus 2025; 17:e78953. [PMID: 40091963 PMCID: PMC11910190 DOI: 10.7759/cureus.78953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/12/2025] [Indexed: 03/19/2025] Open
Abstract
This case report discusses a 44-year-old male who presented with recurrent epigastric pain after starting Ozempic for weight management, which persisted despite switching to Jardiance. His symptoms evolved into diarrhea and fever while vacationing in Mexico, with notable episodes of bloody stools and greasy, floaty stools upon return home. Despite normal laboratory tests and negative stool pathogen results, a CT scan revealed a mass in the gastric antrum. Subsequent endoscopy and fine-needle aspiration confirmed a gastrointestinal stromal tumor (GIST), classified as T3N0. The patient underwent laparoscopic distal gastrectomy with Billroth II gastrojejunostomy. This case underscores the challenge of diagnosing GISTs due to nonspecific gastrointestinal symptoms, emphasizing the necessity for thorough evaluation in persistent cases. The favorable prognosis associated with T3N0 classification highlights the importance of early identification and surgical intervention. Monitoring for recurrence and considering adjuvant therapy are essential in managing such tumors. This case illustrates the value of multidisciplinary care in addressing complex gastrointestinal conditions.
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Affiliation(s)
- Nika Harutyunyan
- Department of Medicine, University of California Los Angeles (UCLA) Health, Los Angeles, USA
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29
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Nigro MC, Marchetti A, Fumagalli ER, De Luca I, Bertuzzi AF, Grimaudo MS, Grignani G, D’Ambrosio L, Merlini A, Badalamenti G, Incorvaia L, Dimino A, Gasperoni S, Vincenzi B, Fanti S, Di Federico A, Campana D, Pantaleo MA, Nannini M. 18F-Fluorodeoxyglucose Uptake in PDGFRA-Mutant Gastrointestinal Stromal Tumors. JAMA Netw Open 2025; 8:e2456058. [PMID: 39853981 PMCID: PMC11762236 DOI: 10.1001/jamanetworkopen.2024.56058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 11/15/2024] [Indexed: 01/26/2025] Open
Abstract
Importance The D842V platelet-derived growth factor receptor α (PDGFRA) mutation identifies a molecular subgroup of gastrointestinal stromal tumors (GISTs), primarily resistant to standard tyrosine kinase inhibitors and with an overall more indolent behavior. Although functional imaging with 18F-fluorodeoxyglucose-labeled positron emission tomography ([18F]FDG-PET) plays a proven role in GISTs, especially in early assessment of tumor response, less is known about [18F]FDG uptake according to the GIST molecular subtypes. Objective To evaluate the degree of [18F]FDG uptake in PDGFRA-mutant GISTs and better define the role of functional imaging in this rare and peculiar subset of GISTs. Design, Setting, and Participants This multi-institutional retrospective cohort study involving 7 GIST reference centers in Italy included patients with PDGFRA-mutant GIST who underwent [18F]FDG-PET from January 1, 2000, to December 31, 2023. Data on the maximum standardized uptake value (SUVmax) of primary tumor or metastatic disease were collected. Exposure PDGFRA-mutant GIST and [18F]FDG-PET. Main Outcome and Measure The primary outcome was the degree of [18F]FDG uptake of PDGFRA-mutant GISTs, with a focus on the D842V-mutant subgroup. Secondary objectives were to assess the association between the degree of [18F]FDG uptake and main clinicopathologic features. Results A total of 71 patients with PDGFRA-mutant GISTs were included in the analysis: 37 (52.1%) in the D842V subgroup (group A) and 34 (47.9%) in the non-D842V subgroup (group B). Additionally, 70 patients with KIT exon 11-mutant GIST served as a control group (group C). For all 141 participants, the median age at diagnosis was 59 (range, 26-89) years, and 81 patients (57.4%) were male. Overall, the median SUVmax was 4.4 (IQR, 0-10.1), while the median SUVmax for group A was 0 (IQR, 0-3.2); for group B, 3.6 (IQR, 0-5.1); and for group C, 10.1 (IQR, 5.1-13.9). The median SUVmax of PDGFRA-mutant GISTs was significantly lower than the median value of KIT exon 11-mutant GISTs (0 [IQR, 0-4.3] vs 10.1 [IQR, 5.1-14.0]; P < .001). Median [18F]FDG uptake was significantly lower in the D842V subgroup compared with the non-D842V subgroup (0 [IQR, 0-3.2] vs 3.6 [IQR, 0-5.1]; P = .02). Moreover, the triad of gastric primary tumor, tumor size greater than 10 cm, and SUVmax of 5.75 or less was associated with identification of PDGFRA-mutant GISTs. Conclusions and Relevance In this cohort study of patients with PDGFRA-mutant GISTs, the D842V-mutant GISTs were associated with an overall lower [18F]FDG uptake compared with other GIST subgroups. Therefore, the role of functional imaging with [18F]FDG-PET in this subset of GISTs may be limited and should be further explored for its potential prognostic and predictive value.
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Affiliation(s)
- Maria Concetta Nigro
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Andrea Marchetti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Elena Rosa Fumagalli
- Medical Oncology Unit 2, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori, Milano, Italy
| | - Ida De Luca
- Medical Oncology Unit 2, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori, Milano, Italy
| | - Alexia Francesca Bertuzzi
- Department of Medical Oncology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Maria Susanna Grimaudo
- Department of Medical Oncology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Giovanni Grignani
- Department of Medical Oncology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino, Italy
- Candiolo Cancer Institute, Fondazione del Piemonte–IRCCS, Candiolo (Turin), Turin, Italy
| | - Lorenzo D’Ambrosio
- Department of Medical Oncology, University of Turin, Turin, Italy
- Azienda Ospedaliera Universitaria San Luigi Gonzaga University Hospital, Orbassano, Italy
| | - Alessandra Merlini
- Candiolo Cancer Institute, Fondazione del Piemonte–IRCCS, Candiolo (Turin), Turin, Italy
- Department of Medical Oncology, University of Turin, Turin, Italy
| | - Giuseppe Badalamenti
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Lorena Incorvaia
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Alessandra Dimino
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Silvia Gasperoni
- Department of Oncology, Clinical Oncology Unit, University Hospital Careggi, Firenze, Italy
| | - Bruno Vincenzi
- Department of Medical Oncology, Campus Biomedico University of Rome, Rome, Italy
| | - Stefano Fanti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Nuclear Medicine, IRCCS, Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy
| | | | - Davide Campana
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Department of Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Maria Abbondanza Pantaleo
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Department of Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Margherita Nannini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Department of Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
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Judson I, Jones RL, Wong NACS, Dileo P, Bulusu R, Smith M, Almond M. Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines. Br J Cancer 2025; 132:1-10. [PMID: 38840030 PMCID: PMC11723931 DOI: 10.1038/s41416-024-02672-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 03/21/2024] [Accepted: 03/25/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND British Sarcoma Group guidelines for the management of GIST were initially informed by those published by the European Society of Clinical Oncology. This update was written by a group of experts to includes a discussion of the highlight improvements in our knowledge of the disease and recent treatment developments. The guidelines include sections on Incidence, Aetiology, Diagnosis, including risk assessment, Treatment and Follow-up. METHODS A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Areas of uncertainty are indicated appropriately. CONCLUSION Guidelines represent a consensus view of current best clinical practice. Where appropriate, key recommendations are given and the levels of evidence and strength of recommendation gradings are those used by the European Society for Medical Oncology (ESMO).
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Affiliation(s)
- Ian Judson
- The Institute of Cancer Research, London, UK.
| | | | | | | | | | - Myles Smith
- Royal Marsden NHS Foundation Trust, London, UK
| | - Max Almond
- Birmingham University Hospitals, Birmingham, UK
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Ben Rejeb S, Aloui D, Ayari A, Chouchen A. Prognostic Significance of C-MYC and EGFR Overexpression in Gastrointestinal Stromal Tumors: An Immunohistochemical Study. Appl Immunohistochem Mol Morphol 2025; 33:43-48. [PMID: 39636317 DOI: 10.1097/pai.0000000000001235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 10/14/2024] [Indexed: 12/07/2024]
Abstract
INTRODUCTION In addition to mutations in KIT and PDGFRA, many other genetic alterations have been described in gastrointestinal stromal tumors (GISTs), including amplifications of C-MYC and EGFR, which are often associated with increased protein expression. The main of this study was to investigate the prognostic significance of C-MYC and EGFR expression in GISTs using immunohistochemistry (IHC). METHODS We collected all GIST cases over a 16-year period. These cases were tested using antibodies against C-MYC (Leica, clone EP121) and EGFR (Leica, clone 113). C-MYC staining was assessed using the H-score method for nuclear, cytoplasmic, and combined staining. For EGFR staining (either cytoplasmic or nuclear), the intensity was graded as follows: 0 (no staining), 1 (weak staining), 2 (moderate staining), and 3 (strong staining). The percentage of positive cells was evaluated using a semiquantitative approach. Statistical analysis was performed using SPSS24. RESULTS A total of 37 cases were included in our study. Nuclear expression of C-MYC was observed in 43% of the cases, with a high H-score in 43%. A statistically significant association was found between a high nuclear H-score for C-MYC and mitotic rate (P=0.046), as well as a high Ki-67 proliferation rate (P=0.046). However, no statistically significant associations were identified between the nuclear H-score of C-MYC and other clinical, pathologic, or survival data. Cytoplasmic expression of C-MYC was noted in 22% of cases, but no significant correlations were found with the clinicopathological data. EGFR staining was observed in 86% of cases, with a high score of 51%. EGFR expression was significantly associated with the mitotic index (P=0.012) and Ki-67 proliferation rate (P=0.046). CONCLUSIONS Our findings suggest that both C-MYC and EGFR may be overexpressed and/or amplified in GISTs, indicating their potential prognostic role. This could also pave the way for therapeutic strategies targeting these proteins.
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Affiliation(s)
| | | | - Asma Ayari
- Department of Pathology, Rabta's Hospital, Marsa, Tunisia
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Liang SQ, Cui YT, Hu GB, Guo HY, Chen XR, Zuo J, Qi ZR, Wang XF. Development and validation of a machine-learning model for preoperative risk of gastric gastrointestinal stromal tumors. J Gastrointest Surg 2025; 29:101864. [PMID: 39448018 DOI: 10.1016/j.gassur.2024.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) have malignant potential, and treatment varies according to risk. However, no specific protocols exist for preoperative assessment of the malignant potential of gastric GISTs (gGISTs). This study aimed to use machine learning (ML) to develop and validate clinically relevant preoperative models to predict the malignant potential of gGISTs. METHODS This study screened patients diagnosed with gGISTs at the Affiliated Hospital of North Sichuan Medical College. Moreover, this study employed the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to identify risk factors. Subsequently, an ensemble of ML models was used to determine the optimal classifier. In addition, this study used SHapley Additive exPlanations (SHAP) for tailored risk profiling. RESULTS This study included 318 patients with gGISTs. Using LASSO regression and multifactorial logistic regression, this study analyzed the training dataset, revealing that the presence of endoscopic ultrasound (EUS) high-risk features, tumor border clarity, tumor diameter, and monocyte-to-lymphocyte ratio (MLR) were significant predictors of high malignancy risk in gGIST. As determined by our ML approach, the logistic classification model demonstrated optimal performance, with area under the receiver operating characteristic curves of 0.919 for the training set and 0.925 for the test set. Furthermore, decision curve analysis confirmed the clinical relevance of the model. CONCLUSION High-risk EUS features, ill-defined tumor margins, larger tumor diameters, and elevated MLR independently predicted increased malignant potential in gGIST. This study developed logistic regression models based on these factors, which were further interpreted using the SHAP methodology. This analytical approach facilitated personalized therapeutic decision-making among diverse patient populations.
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Affiliation(s)
- Shi-Qi Liang
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yu-Tong Cui
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Guang-Bing Hu
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Hai-Yang Guo
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xin-Rui Chen
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Ji Zuo
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Zhi-Rui Qi
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xian-Fei Wang
- Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China; Digestive Endoscopy Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
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Niranjan G, Prasad P, Verma A, Kumar A. Cytological Diagnosis of Hepatic Metastasis from Rectal Gastrointestinal Stromal Tumor: A Case Report. Discoveries (Craiova) 2025; 13:e202. [PMID: 40351503 PMCID: PMC12062738 DOI: 10.15190/d.2025.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/30/2024] [Accepted: 01/01/2025] [Indexed: 05/14/2025] Open
Abstract
Gastrointestinal stromal tumours (GIST) are rare mesenchymal tumours which represent 1% to 3% of all gastrointestinal neoplasms. Rectal location of GIST is extremely rare accounting for 5% of GIST and only 0.1% of rectal tumours. They usually metastasise to the liver (65%). We hereby report a case of rectal stromal tumour with hepatic metastasis. A 55-year-old female presented with pelvic pain, associated with rectal bleeding. A thoracoabdominal computed tomography showed a large heterogeneous enhancing mass, arising from the rectum, anal canal and distal sigmoid colon measuring 12.3x8.7x7.6cm. Based on histopathological examination followed by immunohistochemistry, she was diagnosed with locally advanced rectal GIST. The tumour reduced in size after neoadjuvant-targeted treatment with imatinib. A local resection of the rectal GIST was successfully performed, and a diversion colostomy was done, later colostomy bag was attached. Following the operation, oral imatinib treatment was continued. On subsequent follow-up, her triple phase CECT whole abdomen showed multiple small well-defined peripherally enhancing hypodense liver lesions, the largest measuring 29x18mm suggestive of metastases. Ultrasound-guided fine needle aspiration from a liver lesion was reported as metastatic GIST. The patient underwent surgery, sunitinib was started and was discharged in stable condition. Thus, cytologic examination provides rapid interpretation, is a less invasive technique than open biopsy, and provides a cost-effective modality for diagnosing and managing inaccessible lesions.
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Affiliation(s)
- Gauri Niranjan
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Pallavi Prasad
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Archana Verma
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Cicala CM, Matito J, Quindos M, Gómez-Peregrina D, Romero-Lozano P, Fernández-Suárez P, Valverde C, González M, Landolfi S, Pérez-Albert P, Gros L, Vivancos A, Serrano C. Targeted Next-Generation Sequencing in Succinate Dehydrogenase-Deficient GI Stromal Tumor Identifies Actionable Alterations in the PI3K/mTOR Pathway. JCO Precis Oncol 2025; 9:e2400497. [PMID: 39787462 DOI: 10.1200/po-24-00497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/29/2024] [Accepted: 11/22/2024] [Indexed: 01/12/2025] Open
Abstract
PURPOSE Less than 5% of GI stromal tumors (GISTs) are driven by the loss of the succinate dehydrogenase (SDH) complex, resulting in a pervasive DNA hypermethylation pattern that leads to unique clinical features. Advanced SDH-deficient GISTs are usually treated with the same therapies targeting KIT and PDGFRA receptors as those used in metastatic GIST. However, these treatments display less activity in the absence of alternative therapeutic options. Therefore, it is critical to identify novel actionable alterations in SDH-deficient GIST. PATIENTS AND METHODS We performed a single-center, retrospective analysis of patients with SDH-deficient GIST together with next-generation sequencing (NGS) analysis from their respective tumor samples to identify mutations and copy number alterations and chromosomal alterations. NGS-tailored treatment was implemented whenever possible. RESULTS Seventeen tumor samples from 14 patients with SDH-deficient GIST underwent NGS. Mutational load was low, although three patients (21%) displayed molecular events in relapse samples leading to PI3K/mTOR pathway hyperactivation. mTOR inhibition with everolimus obtained a sustained tumor response in a heavily pretreated patient. Other alterations, largely present in late-stage patients, uncovered genes involved in cell cycle regulation, telomere maintenance, and DNA damage repair. Chromosomal arm-level alterations differed from the canonical cytogenetic progression in KIT/PDGFRA-mutant GIST. CONCLUSION This molecular landscape of SDH-deficient GIST uncovers novel molecular alterations, mostly in relapse and/or previously pretreated patients. The identification of genetic events leading to PI3K/mTOR dysregulation together with the remarkable activity of everolimus in one patient showcases the clinical relevance of this pathway, validates the utility of NGS in this population, and poses everolimus as a novel therapeutic alternative. Several other alterations were found at the genetic and genomic levels, underscoring novel biological processes likely involved during tumor evolution.
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Affiliation(s)
- Carlo María Cicala
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Judit Matito
- Cancer Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - María Quindos
- Medical Oncology Department, Complexo Hospitalario Universitario de A Coruña. Biomedical Research Institute (INIBIC), A Coruña, Spain
| | - David Gómez-Peregrina
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Paula Romero-Lozano
- Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Paula Fernández-Suárez
- Abdominal Imaging, Radiodiagnostic Department, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain
| | - Claudia Valverde
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Macarena González
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Stefania Landolfi
- Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Paula Pérez-Albert
- Paediatric Oncology and Hematology Department, Vall d'Hebron University Hospital, Barcelona, Spain
- Childhood Cancer and Blood Disorders Group, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Luis Gros
- Paediatric Oncology and Hematology Department, Vall d'Hebron University Hospital, Barcelona, Spain
- Childhood Cancer and Blood Disorders Group, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Ana Vivancos
- Cancer Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - César Serrano
- Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
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Liu FC, Wang CH, Chen PJ, Shih YL, Lin HH, Lin JC, Chang WK, Hsieh TY, Lin GM, Huang TY. Characteristics and prognosis of small bowel tumors: A retrospective study. World J Clin Cases 2024; 12:6696-6704. [PMID: 39650821 PMCID: PMC11514353 DOI: 10.12998/wjcc.v12.i34.6696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 09/02/2024] [Accepted: 09/25/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND Small bowel tumors (SBTs) are a heterogeneous group of difficult-to-diagnose tumors that account for 2%-5% of all gastrointestinal tumors. Single-balloon enteroscopy greatly enhances the diagnosis and treatment of SBTs. However, few epidemiological studies have been conducted in Taiwan to determine the clinical profile of SBTs. AIM To investigate the clinical characteristics, managements and prognosis of SBTs in a medical center in Taiwan. METHODS The study enrolled 51 patients aged 58.9 ± 8.8 years (range, 22-93) diagnosed with SBTs from November 2009 to July 2021. We retrospectively recorded clinical characteristics, indications, endoscopic findings, pathological results, management, and outcomes for further analysis. RESULTS A male preponderance was observed (56.8%). The most common indications were suspected small intestinal tumors (52.9%) and obscure gastrointestinal bleeding (39.2%). The most common tumor location was the ileum (41.2%). The performance of imaging studies (P = 0.004) and the types of findings (P = 0.005) differed significantly between malignant and benign SBTs. The most frequent imaging finding was a small intestinal mass (43.1%). The top three malignant tumor types were gastrointestinal stromal tumors (GISTs), adenocarcinomas, and lymphomas. Moreover, the proportions of benign and malignant tumors were 27.5% and 72.5%, respectively. The survival rates of patients with malignant tumors in the GIST and non-GIST groups differed significantly (P = 0.015). Kaplan-Meier survival analysis showed a significant difference in survival between patients in the malignant and benign groups (P = 0.04). All patients with lymphoma underwent chemotherapy (n = 7/8, 87.5%), whereas most patients with GISTs underwent surgery (n = 13/14, 92.8%). CONCLUSION Patients with GISTs have a significantly higher survival rate than those with other malignant SBTs. Therefore, a large-scale nationwide study is warranted to evaluate the population-based epidemiology of SBTs.
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Affiliation(s)
- Fang-Chen Liu
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Ching-Hsiang Wang
- Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan
| | - Peng-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Hsuan-Hwai Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Jung-Chun Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Wei-Kuo Chang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Gen-Min Lin
- Department of Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei 114, Taiwan
- Department of Medicine, Hualien Armed Forces General Hospital, Hualien 970, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan 33305, Taiwan
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Qiao Z, Zhang Z, Chen J, Yin P, Ling X, Chen W, Yang L. Influence of lymph node removal on the prognosis of high malignancy potential gastric gastrointestinal stromal tumors: Insights from population-based study. PLoS One 2024; 19:e0314504. [PMID: 39636787 PMCID: PMC11620419 DOI: 10.1371/journal.pone.0314504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024] Open
Abstract
High malignancy potential gastric gastrointestinal stromal tumors (HMP-gGISTs) generally require surgical resection. However, the necessity of lymph node removal (LR) for patients with such tumors remains unclear. Therefore, we conducted a population-based study to analyze the impact of LR on the long-term prognosis of patients with HMP-gGISTs. Patients with HMP-gGISTs were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was utilized to address potential selection bias. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses and multivariate Cox proportional hazards models. A total of 840 patients with HMP-gGISTs were included in the study, with 317 undergoing LR and 523 not undergoing LR. The prognosis for OS (P = 0.026) and CSS (P < 0.001) in the LR group was worse compared to the No-LR group. After PSM, 634 patients were matched for comparison. The results showed that the OS (P = 0.028) and CSS (P = 0.006) in the LR group remained poorer than those in the No-LR group. Subgroup analysis further indicated that patients who did not undergo LR had a better prognosis. Our findings suggest that LR may not improve the prognosis of patients with HMP-gGISTs, implying that LR may not be necessary for these patients.
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Affiliation(s)
- Zhenguo Qiao
- Department of Gastroenterology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Zhi Zhang
- Department of General Surgery, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Junjie Chen
- Department of General Surgery, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Ping Yin
- Department of Traditional Chinese Medicine, Wujiang Fifth People’s Hospital, Suzhou, China
| | - Xin Ling
- Department of Gastroenterology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Weihai Chen
- Department of Cardiology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Lingxia Yang
- Department of Gastroenterology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
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Xie Y, Duan C, Zhou X, Zhou X, Shao Q, Wang X, Zhang S, Liu F, Sun Z, Zhao R, Wang G. Different radiomics models in predicting the malignant potential of small intestinal stromal tumors. Eur J Radiol Open 2024; 13:100615. [PMID: 39659979 PMCID: PMC11629208 DOI: 10.1016/j.ejro.2024.100615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 11/08/2024] [Accepted: 11/18/2024] [Indexed: 12/12/2024] Open
Abstract
Objectives To explore the feasibility of different radiomics models for predicting the malignant potential of small intestinal stromal tumors (SISTs), and to select the best radiomics model. Methods A retrospective analysis of 140 patients with SISTs was conducted. Radiomics features were extracted from CT-enhanced images. Support vector machine (SVM), Decision tree (DT), Conditional inference trees (CIT), Random Forest (RF), K-nearest neighbors (KNN), Back-propagation neural network (BPNet), and Bayes were used to construct different radiomics models. The clinical data and CT performance were selected using univariate analysis and to construct clinical model. Nomogram model was developed by combining clinical data and radiomics features. Model performances were assessed by using the area under the receiver operator characteristic (ROC) curve (AUC). The models' clinical values were assessed by decision curve analysis (DCA). Results A total of 1132 radiomics features were extracted. Among radiomics models, SVM was better than DT, CIT, RF, KNN, BPNet, Bayes because it had the highest AUC with a significant difference (P<0.05). The AUC of the clinical model was 0.781. The AUC of the radiomics model was 0.910. The AUC of nomogram model was 0.938. Clinical models had the lowest AUC. Nomogram AUC were slightly higher than radiomics model, but the difference was not significant (P=0.48). The DCA of the nomogram model and radiomics model showed optimal clinical efficacy. Conclusions The model constructed with SVM method was the best model for predicting the malignant potential of SISTs. Radiomics model and nomogram model showed high predictive value in predicting the malignant potential of SISTs.
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Affiliation(s)
- Yuxin Xie
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Chongfeng Duan
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xuzhe Zhou
- University of western Ontario, 1151 Richmond Street, London, Ontario N6A3K7, Canada
| | - Xiaoming Zhou
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Qiulin Shao
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xin Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Shuai Zhang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Fang Liu
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Zhenbo Sun
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ruirui Zhao
- Operating room, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Gang Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
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Blay JY, Schiffler C, Bouché O, Brahmi M, Duffaud F, Toulmonde M, Landi B, Lahlou W, Pannier D, Bompas E, Bertucci F, Chaigneau L, Collard O, Pracht M, Henon C, Ray-Coquard I, Armoun K, Salas S, Spalato-Ceruso M, Adenis A, Verret B, Penel N, Moreau-Bachelard C, Italiano A, Dufresne A, Metzger S, Chabaud S, Perol D, Le Cesne A. A randomized study of 6 versus 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse. Ann Oncol 2024; 35:1157-1168. [PMID: 39241959 DOI: 10.1016/j.annonc.2024.08.2343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/22/2024] [Accepted: 08/27/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND The administration of adjuvant imatinib during 3 years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. METHODS IMADGIST (NCT02260505) was a multicenter, open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-year arm) compared with interruption (3-year arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to-treat disease-free survival. Secondary endpoints included overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, and safety. RESULTS From 24 December 2014 to 4 April 2023, 136 patients aged ≥18 years, Eastern Cooperative Oncology Group performance status ≤2, with a localized gastrointestinal stromal tumor with an R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network (NCCN) risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-year arm versus 71 to the 6-year arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients, respectively. Respectively, 52 (38%) and 71 (52%) patients had a risk of relapse of 35%-70% and >70%. With a median follow-up of 55 months (interquartile range 46-59 months) after randomization, disease-free survival was significantly superior in the 6-year arm [hazard ratio: 0.40 (0.20-0.69), P = 0.0008]. Time to imatinib resistance, survival, adverse events, and quality of life were not different in the two arms. CONCLUSIONS Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.
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Affiliation(s)
- J-Y Blay
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France.
| | - C Schiffler
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - O Bouché
- CHU & Université de Reims, Reims, France
| | - M Brahmi
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - F Duffaud
- Hôpital La Timone & Université Aix-Marseille, Marseille, France
| | | | - B Landi
- Hôpital Européen George Pompidou, Paris, France
| | - W Lahlou
- Hôpital Européen George Pompidou, Paris, France
| | - D Pannier
- Centre Oscar Lambret & Université Lille, Lille, France
| | - E Bompas
- Institut Cancérologie de l'Ouest, Nantes, France
| | - F Bertucci
- Institut Paoli-Calmette & Université Aix-Marseille, Marseille, France
| | | | - O Collard
- Hôpital Privé de la Loire, Saint-Etienne, France
| | - M Pracht
- Centre Eugene Marquis, Rennes, France
| | - C Henon
- Institut Gustave Roussy, Villejuif, France
| | - I Ray-Coquard
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - K Armoun
- CHU & Université de Reims, Reims, France
| | - S Salas
- Hôpital La Timone & Université Aix-Marseille, Marseille, France
| | | | - A Adenis
- Centre Oscar Lambret & Université Lille, Lille, France; Institut de Cancerologie de Montpellier & CLCC Val d'Aurelle, Montpellier, France
| | - B Verret
- Institut de Cancerologie de Montpellier & CLCC Val d'Aurelle, Montpellier, France
| | - N Penel
- Centre Oscar Lambret & Université Lille, Lille, France
| | | | | | - A Dufresne
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - S Metzger
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - S Chabaud
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - D Perol
- Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France
| | - A Le Cesne
- Institut Gustave Roussy, Villejuif, France
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Sun J, Li J, He Y, Kang W, Ye X. Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence. Comput Struct Biotechnol J 2024; 23:1065-1075. [PMID: 38455069 PMCID: PMC10918489 DOI: 10.1016/j.csbj.2024.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 02/19/2024] [Accepted: 02/20/2024] [Indexed: 03/09/2024] Open
Abstract
We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers-GPX4, RBM4, TPM3, PFKFB2, and PGAM5-and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.
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Affiliation(s)
| | | | - Yixuan He
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiming Kang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Ye
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Chida A, Kawasaki K, Kuramoto J, Hayashi H, Kawahara T, Makiuchi S, So E, Shimizu S, Kishimoto S, Horie S, Saito Y, Shimozaki K, Tsugaru K, Togasaki K, Hirata K, Nishihara H, Kanai Y, Kanai T, Hamamoto Y. Clinical characteristics of gastrointestinal stromal tumors with hypoglycemia. Oncol Lett 2024; 28:568. [PMID: 39390979 PMCID: PMC11465228 DOI: 10.3892/ol.2024.14701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/05/2024] [Indexed: 10/12/2024] Open
Abstract
The development of tyrosine-kinase inhibitors has improved survival rates for patients with gastrointestinal stromal tumors (GISTs). Despite the progress, not all the patients can universally receive the benefit from treatment due to the individual underlying conditions in a real-world setting. The present study focused on the well-known but understudied condition of GIST with hypoglycemia. Hypoglycemia in GIST is characterized by hypoglycemic symptoms such as dizziness, sweating and confusion. It is caused by several factors such as multiple liver metastases, drug adverse effects, postoperative complications and paraneoplastic syndrome [non-islet cell tumor hypoglycemia (NICTH)]. Comprehensive analysis of this condition has been hindered due to its rarity, and has been mostly limited to case reports. In the present study, a single-institution retrospective analysis of GIST with hypoglycemia was conducted to investigate its prevalence and prognosis, and the cause of this condition. The present study identified that the prevalence of hypoglycemic episodes of GIST was 4.1% in all patients with GIST, and recurrent hypoglycemic cases had a poor prognosis. The present study identified 1 case with recurrent hypoglycemia due to NICTH. Since NICTH is a rare hypoglycemic cause and requires further evaluation, an autopsy and genetic sequencing were performed using the available clinical materials. Through this histological and genetic investigation, the histological diversity of NICTH-GIST was revealed and insulin-like growth factor II (IGF-II) amplification was identified. Furthermore, a chronological analysis was performed using multiple resected archived samples from the same case, and revealed that diffuse IGF-II expression may have occurred in the early phase of tumor development. The present study catalogued the characteristics of GIST with hypoglycemia with a focus on NICTH-GIST.
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Affiliation(s)
- Akihiko Chida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kenta Kawasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Junko Kuramoto
- Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hideyuki Hayashi
- Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Toru Kawahara
- Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Satomi Makiuchi
- Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Eiichiro So
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Satoko Shimizu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Shotaro Kishimoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Sara Horie
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Yuki Saito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Keitaro Shimozaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kai Tsugaru
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kazuhiro Togasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Kenro Hirata
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hiroshi Nishihara
- Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Yae Kanai
- Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Yasuo Hamamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Keio Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan
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Li T, Li J, Hu Z, Lu M. An ultrasound based method for predicting the malignant potential of primary gastrointestinal stromal tumors preoperatively. Abdom Radiol (NY) 2024; 49:4189-4197. [PMID: 38849537 DOI: 10.1007/s00261-024-04341-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 06/09/2024]
Abstract
OBJECTIVE Gastrointestinal stromal tumors (GISTs) are difficult to identify the risk level accurately without surgical pathological confirmation. The purpose of our study was to propose a noninvasive prediction method for predicting the malignant potential of GISTs preoperatively by using contrast-enhanced ultrasound (CEUS) with gastric distention. METHODS We reviewed 47 GISTs who underwent CEUS from April 2017 to August 2023 retrospectively, all the lesions were certificated by pathology after surgery. The age of the patient, size of the lesion, shape, necrosis, calcification in the lesion, perfusion parameters including arrival time (AT), peak intensity (PI), time to peak (TTP), and area under the curve (AUC) of the lesion and surrounding normal tissue were analyzed. Logistic regression analyses were performed. Of the 47 GISTs, 26 were high-risk and 21 low-risk tumors respectively. RESULTS Compared with low-risk GISTs, high-risk GIST had faster AT (7.7s vs. 11.5s, p < 0.05), higher PI (15.2dB vs. 12.5dB, p < 0.05), and larger size (4.4 cm vs. 2.2 cm, p < 0.001). In multivariate logistic regression, AT, PI, and size were significant features. The corresponding regression equation In (p/(1-p)=-5.9 + 4.5 size + 4.6 PI + 4.0 AT). CONCLUSION The size, AT, and PI of the GISTs on CEUS can be used as parameters for a noninvasive risk level prediction model of GISTs. This model may help identify the different risk levels of GISTs before surgery.
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Affiliation(s)
- Tingting Li
- Department of Ultrasound, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Juan Li
- Department of Ultrasound, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - ZiYue Hu
- Department of Ultrasound, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Man Lu
- Department of Ultrasound, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
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Pan Y, Gao Y, Yang P, Yu G. Gastrointestinal stromal tumor mimicking perineurioma: A case report. Cytojournal 2024; 21:51. [PMID: 39737118 PMCID: PMC11683401 DOI: 10.25259/cytojournal_104_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 10/21/2024] [Indexed: 01/01/2025] Open
Abstract
Although gastrointestinal stromal tumor (GIST) can present with various histological characteristics, GIST mimicking perineurioma has not been previously reported. We present the case of a 47-year-old woman diagnosed with GIST after laparoscopic resection of a stomach tumor near the lesser curvature of the gastric body close to the cardia. Morphological features resembled a perineurioma. c.1504_1509 (p.A502_Y503) duplication was found in exon 9 of kinase insert domain receptor (c-KIT). This specific mutation is associated with constitutive activation of the c-KIT, which is crucial in the pathogenesis of GIST. Such unique histological characteristics broaden our understanding of the morphological diversity within GISTs and underscore the importance of considering an extended differential diagnosis when encountering atypical gastrointestinal tumors. This rare presentation may challenge conventional diagnostic criteria and could influence therapeutic strategies, emphasizing the need for comprehensive histological and molecular assessments in patient management.
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Affiliation(s)
- Yu Pan
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Yuan Gao
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Ping Yang
- Department of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Guohua Yu
- Department of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
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43
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Kim Y, Lee SH. Pathologic diagnosis and molecular features of gastrointestinal stromal tumors: a mini-review. Front Oncol 2024; 14:1487467. [PMID: 39629000 PMCID: PMC11611718 DOI: 10.3389/fonc.2024.1487467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/29/2024] [Indexed: 12/06/2024] Open
Abstract
Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal, predominantly affecting the stomach and small intestine, with rare occurrences in the duodenum, rectum, and extraintestinal sites. Histologically, GISTs can present as spindle cells, epithelioid cells, or mixed morphologies, with immunohistochemical staining revealing expression of KIT (CD117) and discovered on GIST 1 (DOG1). Approximately 80% of GISTs harbor activating mutations in KIT or platelet derived growth factor receptor α (PDGFRA), which influence their clinical behavior and treatment response. SDH-deficient GISTs, associated with syndromes such as Carney triad and Carney-Stratakis syndrome, represent a distinct subgroup with unique characteristics and management challenges. The standard treatment includes surgery and imatinib for metastatic cases; however, resistance to tyrosine kinase inhibitors remains a significant hurdle, especially in pediatric and wildtype GISTs. This highlights the need for advanced therapeutic strategies and emphasizes the importance of molecular profiling in guiding treatment decisions and improving outcomes for GIST patients.
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Affiliation(s)
| | - Sung Hak Lee
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Zhang C, Dong HK, Gao JM, Zeng QQ, Qiu JT, Wang JJ. Advances in the diagnosis and treatment of MET-variant digestive tract tumors. World J Gastrointest Oncol 2024; 16:4338-4353. [PMID: 39554732 PMCID: PMC11551650 DOI: 10.4251/wjgo.v16.i11.4338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/24/2024] [Accepted: 09/10/2024] [Indexed: 10/25/2024] Open
Abstract
The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth, survival, migration and angiogenesis, and its abnormal activation is closely related to the occurrence and development of various tumors. This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors. In terms of diagnosis, the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient, providing a reliable basis for individualized treatment. In terms of treatment, MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials. In addition, the combination of immunotherapy and MET inhibitors also demonstrated potential synergies, further improving the therapeutic effect. However, the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research. In the future, it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients. The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization, and have broad application prospects.
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Affiliation(s)
- Chen Zhang
- The First Department of Radiation Oncology, Lu’an Hospital of Traditional Chinese Medicine of Anhui Province, Lu’an 237000, Anhui Province, China
| | - Hu-Ke Dong
- The Fourth Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Jian-Ming Gao
- The First Department of Oncology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230000, Anhui Province, China
| | - Qi-Qi Zeng
- Department of Gastroenterology, Nanjing University Affiliated Gulou Hospital, Nanjing 210008, Jiangsu Province, China
| | - Jiang-Tao Qiu
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, Beijing 100084, China
| | - Jia-Jia Wang
- Ultrasound of Medicine Department, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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45
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Haller V, Reiff C, Hamacher R, Kostbade K, Kaths M, Treckmann J, Bertram S, Zaun Y, Bauer S, Falkenhorst J. Overall survival of patients with KIT-mutant metastatic GIST in the era of multiple kinase inhibitor availability. J Cancer Res Clin Oncol 2024; 150:489. [PMID: 39516299 PMCID: PMC11549121 DOI: 10.1007/s00432-024-05965-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 09/19/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE The prognosis of patients with metastatic GIST and imatinib-sensitive primary mutations has significantly improved. However, limited data are available to inform patients about outcomes across different lines of treatment. This retrospective analysis aims to evaluate patient outcomes at a large German GIST referral center over the past 15 years. PATIENTS AND METHODS Overall survival (OS) and progression-free survival (PFS) were analyzed in patients with metastatic GIST, with diagnosis of metastases between 2008 and 2021, when at least three lines of treatment were available in Germany (n = 174). RESULTS The median overall survival far exceeds historical data for patients with primary exon 11 and exon 9 mutations (median OS in palliative treatment with imatinib: 7.1 years; median OS in second-line palliative treatment with sunitinib: 2.9 years; median OS in third-line palliative treatment with regorafenib: 1.9 years). Among those patients who received palliative imatinib treatment, no significant difference in median OS survival was observed between those who had received perioperative imatinib for localized disease and those who did not. Furthermore, the location of metastases significantly impacted survival, whereas the time between the initial diagnosis and the diagnosis of metastases had no significant effect on survival. CONCLUSION In conclusion, this study provides a novel, real-world reference for survival outcomes in patients with metastatic GIST.
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Affiliation(s)
- Valerie Haller
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
| | - Carina Reiff
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
| | - Rainer Hamacher
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
| | - Karina Kostbade
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
| | - Moritz Kaths
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
- Department of Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Juergen Treckmann
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
- Department of Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Stefanie Bertram
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
- Department of Pathology, University Hospital Essen, Essen, Germany
| | - Yasmin Zaun
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
| | - Sebastian Bauer
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany.
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
| | - Johanna Falkenhorst
- Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
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Bertsimas D, Koulouras AG, Margonis GA. The R.O.A.D. to precision medicine. NPJ Digit Med 2024; 7:307. [PMID: 39489814 PMCID: PMC11532393 DOI: 10.1038/s41746-024-01291-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/06/2024] [Indexed: 11/05/2024] Open
Abstract
We propose a novel framework that addresses the deficiencies of Randomized clinical trial data subgroup analysis while it transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision medicine. Our approach counters the effects of unobserved confounding in observational data through a two-step process that adjusts predicted outcomes under treatment. These adjusted predictions train decision trees, optimizing treatment assignments for patient subgroups based on their characteristics, enabling intuitive treatment recommendations. Implementing this framework on gastrointestinal stromal tumors (GIST) data, including genetic sub-cohorts, showed that our tree recommendations outperformed current guidelines in an external cohort. Furthermore, we extended the application of this framework to RCT data from patients with extremity sarcomas. Despite initial trial indications of universal treatment necessity, our framework identified a subset of patients who may not require treatment. Once again, we successfully validated our recommendations in an external cohort.
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Affiliation(s)
- Dimitris Bertsimas
- Sloan School of Management and Operations Research Center, E62-560, Massachusetts Institute of Technology, Boston, MA, USA
| | - Angelos Georgios Koulouras
- Sloan School of Management and Operations Research Center, E62-560, Massachusetts Institute of Technology, Boston, MA, USA
| | - Georgios Antonios Margonis
- Sloan School of Management and Operations Research Center, E62-560, Massachusetts Institute of Technology, Boston, MA, USA.
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Ibrahim A, Montgomery EA. Gastrointestinal Stromal Tumors: Variants and Some Pitfalls That They Create. Adv Anat Pathol 2024; 31:354-363. [PMID: 39466697 DOI: 10.1097/pap.0000000000000463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
The diagnosis of gastrointestinal stromal tumors (GISTs) is generally straightforward using a combination of histologic evaluation and pertinent immunohistochemical staining with CD117/kit and DOG-1 (discovered on GIST) antibodies. However, this tumor can be challenging in cases with an unusual morphology, in limited biopsies, for those in uncommon sites, post-treatment, and when other neoplasms express CD117/kit and DOG-1, thereby mimicking GIST. Finding epithelioid GISTs in the stomach in younger patients should prompt testing for succinate dehydrogenase (SHD)-deficiency using immunohistochemical staining for subunit B (SDHB). However, SDH-deficient GISTs can also arise in older patients, or as part of the Carney triad or Carney-Stratakis syndrome. GISTs with PDGFRA mutations can also prove difficult if they lack kit expression. It is also important to consider morphologic and immunophenotypic changes associated with treatment, including the potential absence of kit expression, particularly in GISTs that have metastasized. Therefore, obtaining clinical information regarding prior therapy with a tyrosine kinase inhibitor (TKI) is crucial.
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Affiliation(s)
- Ammoura Ibrahim
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL
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48
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Renne SL, Cammelli M, Santori I, Tassan-Mangina M, Samà L, Ruspi L, Sicoli F, Colombo P, Terracciano LM, Quagliuolo V, Cananzi FCM. True Mitotic Count Prediction in Gastrointestinal Stromal Tumors: Bayesian Network Model and PROMETheus (Preoperative Mitosis Estimator Tool) Application Development. J Med Internet Res 2024; 26:e50023. [PMID: 39437385 PMCID: PMC11538881 DOI: 10.2196/50023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 05/14/2024] [Accepted: 07/21/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) present a complex clinical landscape, where precise preoperative risk assessment plays a pivotal role in guiding therapeutic decisions. Conventional methods for evaluating mitotic count, such as biopsy-based assessments, encounter challenges stemming from tumor heterogeneity and sampling biases, thereby underscoring the urgent need for innovative approaches to enhance prognostic accuracy. OBJECTIVE The primary objective of this study was to develop a robust and reliable computational tool, PROMETheus (Preoperative Mitosis Estimator Tool), aimed at refining patient stratification through the precise estimation of mitotic count in GISTs. METHODS Using advanced Bayesian network methodologies, we constructed a directed acyclic graph (DAG) integrating pertinent clinicopathological variables essential for accurate mitotic count prediction on the surgical specimen. Key parameters identified and incorporated into the model encompassed tumor size, location, mitotic count from biopsy specimens, surface area evaluated during biopsy, and tumor response to therapy, when applicable. Rigorous testing procedures, including prior predictive simulations, validation utilizing synthetic data sets were employed. Finally, the model was trained on a comprehensive cohort of real-world GIST cases (n=80), drawn from the repository of the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, with a total of 160 cases analyzed. RESULTS Our computational model exhibited excellent diagnostic performance on synthetic data. Different model architecture were selected based on lower deviance and robust out-of-sample predictive capabilities. Posterior predictive checks (retrodiction) further corroborated the model's accuracy. Subsequently, PROMETheus was developed. This is an intuitive tool that dynamically computes predicted mitotic count and risk assessment on surgical specimens based on tumor-specific attributes, including size, location, surface area, and biopsy-derived mitotic count, using posterior probabilities derived from the model. CONCLUSIONS The deployment of PROMETheus represents a potential advancement in preoperative risk stratification for GISTs, offering clinicians a precise and reliable means to anticipate mitotic counts on surgical specimens and a solid base to stratify patients for clinical studies. By facilitating tailored therapeutic strategies, this innovative tool is poised to revolutionize clinical decision-making paradigms, ultimately translating into improved patient outcomes and enhanced prognostic precision in the management of GISTs.
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Affiliation(s)
- Salvatore Lorenzo Renne
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Manuela Cammelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Ilaria Santori
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Marta Tassan-Mangina
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Laura Samà
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Laura Ruspi
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Federico Sicoli
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Piergiuseppe Colombo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Luigi Maria Terracciano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Department, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Vittorio Quagliuolo
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Ferdinando Carlo Maria Cananzi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Sarcoma, Melanoma and Rare Tumors Surgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy
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49
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Jemedafe N, Jan ZU, Ayegba D, Adugba A, Jan MY. Multifocal Small Bowel Gastrointestinal Stromal Tumor (GIST): A Case Report. Cureus 2024; 16:e70678. [PMID: 39493093 PMCID: PMC11528396 DOI: 10.7759/cureus.70678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2024] [Indexed: 11/05/2024] Open
Abstract
Gastrointestinal stromal tumours, also known as GIST, are a rare subset of soft tissue sarcomas. They are the most common mesenchymal neoplasms of the GI tract and can be found multifocal intra-operatively. We present a 44-year-old male patient who presented with vague upper abdominal pain of one-week duration associated with non-bilious vomiting. His CT abdomen with IV contrast revealed a non-enhancing intraperitoneal mass, which displaced the small bowel and mesentery; however, there was no obstruction or strangulation. A CT-guided biopsy was done and showed a low-grade gastrointestinal stromal tumor (GIST). Interestingly, during diagnostic laparoscopy, in addition to the large serosal ileal mass, he had multiple smaller lesions throughout the small bowel. He underwent resection of all the masses. He made an excellent recovery and was discharged home on postoperative day three. Small bowel GIST can rarely present as multiple lesions. Examination of all bowels during surgery is mandatory.
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Affiliation(s)
- Noah Jemedafe
- Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC), Muscat, OMN
| | - Zaka U Jan
- Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC), Muscat, OMN
| | - Dominic Ayegba
- Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC), Muscat, OMN
| | - Aboje Adugba
- Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC), Muscat, OMN
| | - Mohammed Y Jan
- Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC), Muscat, OMN
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Cerrah E, Çomunoğlu C. Multiple Gastrointestinal Stromal Tumors, Malignant Peripheral Nerve Sheath Tumor and Atypical Neurofibromatous Neoplasm With Uncertain Biologic Potential Developing in A Single Patient With Neurofibromatosis Type 1 Syndrome. Int J Surg Pathol 2024; 32:1415-1421. [PMID: 38303154 DOI: 10.1177/10668969241229350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Neurofibromatosis type 1 (NF1) is the most common human genetic disease. In these patients, the incidence of malignant peripheral nerve sheath tumors (MPNST) and gastrointestinal stromal tumors (GIST) is increased. A male patient in his forties with neurofibromatosis 1, presented with the coexistence of multiple GISTs located at intestinal and colonic mesentery, MPNST located at his leg and atypical neurofibromatous neoplasm with uncertain biologic potential located at colonic mesentery. By FISH, the MPNST harbored CDKN2A loss and recurred 1 year later. After reresection and radiotherapy, the patient is now disease-free without evidence of disease. Atypical neurofibromatous neoplasm with uncertain biologic potential is a newly defined entity, and it is important to discriminate it from low-grade MPNST, which requires more aggressive treatment methods. To the best of our knowledge, this is the first report describing synchronous GISTs, MPNST, and atypical neurofibromatous neoplasm with uncertain biologic potential developing in a single NF1 patient.
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Affiliation(s)
- Elif Cerrah
- Department of Pathology, Prof. Dr Cemil Taşçıoğlu Ş. Hospital, Istanbul, Turkey
| | - Cem Çomunoğlu
- Department of Pathology, Prof. Dr Cemil Taşçıoğlu Ş. Hospital, Istanbul, Turkey
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