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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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Ye B, Chen Z, Xie J, Xi K, Zeng X, Zhong C. Calcifying fibrous tumor of stomach: a rare case report of an upper gastrointestinal bleeding. Front Oncol 2025; 15:1512964. [PMID: 40356746 PMCID: PMC12066241 DOI: 10.3389/fonc.2025.1512964] [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: 12/09/2024] [Accepted: 03/11/2025] [Indexed: 05/15/2025] Open
Abstract
Introduction Calcifying fibrous tumor (CFT) is an uncommon benign fibrous neoplastic lesion that may manifest as singular or multiple tumors and usually occurs in children or young adults. CFT originates in the muscularis propria of the stomach and is a very rare disease. Here, we report a case of gastric CFT with upper gastrointestinal bleeding. Case information A 39-year-old male was urgently referred to our hospital with haematemesis and melena that had developed over the course of 2 hours. Enhanced abdominal CT imaging revealed a nodular lesion, measuring approximately 3.2 × 2.1 × 1.6 cm, protruding from the posterior wall of the gastric body into the gastric lumen. The lesion exhibited scattered calcifications, smooth margins, and a CT attenuation value of 50 Hounsfield units (HU). Gastroscopic ultrasonography performed in the gastroenterology department revealed a semicircular submucosal mass with signs of active bleeding. Initially, the tumor was diagnosed as a gastrointestinal stromal tumor (GIST), and surgical intervention was undertaken due to ongoing hemorrhage. Postoperative histopathological examination confirmed the diagnosis of a gastric calcifying fibrous tumor (CFT). Conclusion CFT originating from the muscularis propria of the stomach is exceptionally rare, and the case presented here mimicked a gastric submucosal tumor (SMTs),clinicians should consider this differentia diagnosis when evaluating patients with suspected cases.
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Affiliation(s)
- BaoLong Ye
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Gastrointestinal and Hernia Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - ZiWen Chen
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- Department of Gastrointestinal and Hernia Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - JunFeng Xie
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- Department of Gastrointestinal and Hernia Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - KeXing Xi
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xin Zeng
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- Department of Gastrointestinal and Hernia Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - CaiLiang Zhong
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- Department of Gastrointestinal and Hernia Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
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Rea D, Tham C, Tham TCK. Endoscopic calabash technique for gastric mesenchymal tumours: A low hanging fruit or a novel endoscopic technique? World J Gastrointest Endosc 2025; 17:101676. [PMID: 39989851 PMCID: PMC11843036 DOI: 10.4253/wjge.v17.i2.101676] [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: 09/24/2024] [Revised: 01/21/2025] [Accepted: 02/06/2025] [Indexed: 02/13/2025] Open
Abstract
The term subepithelial lesions encompasses a wide array of pathology of which numerous benign and malignant pathologies are grouped. A subset of these lesions are termed gastric mesenchymal tumours of which some have innate malignant potential. Currently there is various guidance on the recommended approach to the investigation and management of these lesions and there exists multiple methods of resection. Lin et al have developed and proposed a new method of resection of these gastric mesenchymal tumours within the field of endoscopy, a procedure they have termed endoscopic calabash ligation and resection. This editorial aims to outlay the current landscape for gastric mesenchymal tumours with regards to the various guidelines and resection techniques while comparing Lin et al's new technique to those that are already established in the field of endoscopy. Advancements in endoscopy that maintain or improve patient outcomes compared to the gold standard approach are exciting developments. Lin et al's study suggests that their technique is comparable in regard to patient outcomes while simultaneously being more efficient in its use of hospital resources including procedural time. Whilst the data and analysis proposed in the study is promising, there are areas that need to be addressed before advocating the procedure for widespread use. However, with further studies and analysis this may be foreseeable in the future.
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Affiliation(s)
- David Rea
- Department of Medical Office, Wagga Wagga Base Hospital, Wagga Wagga 2650, New South Wales, Australia
| | - Caroline Tham
- Department of Medical Office, Westmead Hospital, Sydney 2145, New South Wales, Australia
| | - Tony CK Tham
- Division of Gastroenterology, Ulster Hospital, Belfast BT16 1RH, United Kingdom
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Luo X, Chen J, Fang Y, Xu Q, Jiang F, Wang G. Association between calcification and risk stratification in gastric gastrointestinal stromal tumors. Abdom Radiol (NY) 2025; 50:579-588. [PMID: 39180668 DOI: 10.1007/s00261-024-04544-w] [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: 07/20/2024] [Revised: 08/16/2024] [Accepted: 08/16/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND Risk assessment of gastric gastrointestinal stromal tumors (GISTs), particularly those with a diameter ≤ 5 cm, remains a clinical challenge. Previous research has primarily focused on tumor size, ulceration, necrosis, and enhancement patterns, with less emphasis on the role of tumor calcification, which remains controversial regarding its correlation with malignancy risk. OBJECTIVE This study aims to explore the characteristics of calcification in gastric GISTs and its correlation with risk stratification as defined by the National Institutes of Health (NIH), to improve preoperative risk assessment for gastric GISTs ≤ 5 cm. METHODS A retrospective analysis of 385 pathologically confirmed gastric GIST patients, including 178 with small gastric GISTs (< 2 cm), was conducted. Tumors were categorized into low-risk (very low / low) and high-risk (intermediate / high) groups based on NIH criteria. Variables such as age, gender, tumor long-axis diameter, calcification rates, calcification size, the number and distribution of calcification, calcification to tumor long-axis diameter ratio were analyzed. Logistic regression was used to identify independent predictors of malignancy for gastric GISTs, with predictive values assessed via receiver operating characteristic (ROC) curves. RESULTS Significant differences were found between high-risk and low-risk groups in treatment methods, tumor long-axis diameter, the ratio of calcification to tumor long-axis, and calcification distribution (P < 0.05). Calcification rates varied across risk categories, with 23.6% in very low-risk, 31.6% in low-risk, 9.8% in intermediate-risk, and 31.7% in high-risk categories (P < 0.05). In GISTs ≤ 5 cm, both tumor long-axis diameter (OR = 3.07, 95% CI: 2.29-4.10) and calcification (OR = 0.36, 95% CI: 0.13-0.97) were independent predictors of malignancy risk (both P < 0.05). ROC curve analysis yielded areas of 0.849 for tumor long-axis diameter, 0.578 for calcification, and 0.862 for their combination. CONCLUSION The study indicates lower calcification rates in intermediate-risk gastric GISTs and higher rates in other risk categories. Additionally, tumors of different sizes exhibit two distinct calcification patterns, suggesting possible differing mechanisms of calcification in tumors. Calcification in gastric GISTs ≤ 5 cm acts as a protective factor against higher malignancy risk, and when combined with tumor long-axis diameter, significantly enhances predictive accuracy over long-axis diameter alone.
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Affiliation(s)
- Xiao Luo
- grid.469636.8Zhejiang Taizhou Hospital, Linhai, China
| | - Jinyao Chen
- grid.469636.8Zhejiang Taizhou Hospital, Linhai, China
| | - Yicheng Fang
- grid.469636.8Zhejiang Taizhou Hospital, Linhai, China
| | - Qinhui Xu
- grid.469636.8Zhejiang Taizhou Hospital, Linhai, China.
| | - Fei Jiang
- grid.469636.8Zhejiang Taizhou Hospital, Linhai, China
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Delgado-de la Mora J, Al Assaad M, Quitian S, Levine MF, Deshpande A, Sigouros M, Manohar J, Medina-Martínez JS, Sboner A, Elemento O, Jessurun J, Hissong E, Mosquera JM. Novel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors. Pathol Res Pract 2025; 266:155782. [PMID: 39708519 DOI: 10.1016/j.prp.2024.155782] [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: 12/17/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive tract. Despite multiple therapeutic advances, patients with advanced disease frequently develop resistance to tyrosine kinase inhibitors (TKIs), and therefore represent a therapeutic challenge. We employed whole genome sequencing (WGS) on three metastatic GISTs refractory to various TKIs and explored a publicly available cohort of 499 GISTs. This study sheds light on the clinical importance of alterations in cell cycle genes such as cyclin-dependent kinase 2 A (CDKN2A), and cyclin-dependent kinase 2B (CDKN2B), their frequent alteration in metastatic GISTs and their potential role in tumor progression of this neoplasm. Likewise, new structural variations were identified in cyclin-dependent kinase 12 (CDK12). Whole genome profiling of metastatic GIST provides new insights to advance precision care of the disease, focusing on new therapeutic possibilities, especially for emerging targets such as CDK12.
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Affiliation(s)
- Jesús Delgado-de la Mora
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA
| | - Majd Al Assaad
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA
| | - Stephanie Quitian
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA
| | - Max F Levine
- Isabl Inc., 175 Greenwich Street, Fl 38, New York, NY 10007, USA
| | - Aditya Deshpande
- Isabl Inc., 175 Greenwich Street, Fl 38, New York, NY 10007, USA
| | - Michael Sigouros
- Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA
| | - Jyothi Manohar
- Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA
| | | | - Andrea Sboner
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY 10021, USA
| | - Olivier Elemento
- Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY 10021, USA
| | - José Jessurun
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA
| | - Erika Hissong
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA
| | - Juan Miguel Mosquera
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA.
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Lyu HG, Witt RG, Rajkot N, Keung EZ, Torres KE, Hunt KK, Somaiah N, Lazar AJ, Roland CL, Scally CP. Patterns of Care and Outcomes of Patients with Small Gastrointestinal Stromal Tumors at a High-Volume Sarcoma Center. Ann Surg Oncol 2024; 31:9258-9264. [PMID: 39230849 DOI: 10.1245/s10434-024-16123-w] [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: 05/30/2024] [Accepted: 08/20/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND The course of subclinical gastrointestinal stromal tumors (GISTs) is variable. The management of small GISTs is not well-defined. METHODS Records of patients presenting with small GISTs with documented follow-up appointment at our institution between 2016 and 2022 were identified and reviewed. Comparative univariate analysis to compare patient and tumor characteristics and outcomes was performed. RESULTS Eighty-six patients were followed for a median of 3.7 years (range 0.1-20 years). The median size at presentation was 1.7 (range 0.1-2.5) cm. A total of 51.2% (n = 44) underwent surgery before or immediately after initial presentation for pain (18.2%), bleeding (15.9%), or patient preference (6.8%). Another 17.4% (n = 15) had delayed surgery for tumor growth (40%), patient preference (2.7%), bleeding (6.7%), or pain (6.7%). The remaining 31.4% (n = 27) of patients never underwent surgery for reasons that included no growth/stability (44.4%), concomitant cancer diagnosis/treatment (29.6%), comorbidities (14.8%), and patient preference (3.7%). Patients who underwent surveillance without intervention compared with those who had delayed surgery were older (71.1 vs. 60.8 years, p < 0.001) with multiple comorbidities or a concurrent cancer diagnosis (70.3% vs. 20%, p = 0.005). There were no differences in survival or rate of distant metastases. Average time to surgery in the delayed group was 2 (range 0.1-10.3) years, and 86% of these patients underwent surgery by 5.5 years after diagnosis. CONCLUSIONS In older patients with comorbidities or concurrent cancer diagnoses, opting out of surgery does not affect survival. Conversely, younger patients, free from significant comorbidities or other diagnoses, may consider surgery or active surveillance for up to 5 years, with comparable outcomes.
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Affiliation(s)
- Heather G Lyu
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Russell G Witt
- Division of Surgical Oncology, Department of Surgery, The University of Virginia, Charlottesville, VA, USA
| | - Nikita Rajkot
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emily Z Keung
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Keila E Torres
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kelly K Hunt
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Breast Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Neeta Somaiah
- Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Alexander J Lazar
- Department of Anatomical Pathology, Division of Pathology-Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christina L Roland
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christopher P Scally
- Department of Surgical Oncology, Division of Surgery, Sarcoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Lyu HG, Roland CL, Scally CP. ASO Author Reflections: The Optimal Timing for Resection in Patients with Small GISTs: Balancing Risks and Benefits. Ann Surg Oncol 2024; 31:9285-9286. [PMID: 39320401 DOI: 10.1245/s10434-024-16260-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 09/10/2024] [Indexed: 09/26/2024]
Affiliation(s)
- Heather G Lyu
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Christina L Roland
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christopher P Scally
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Wardelmann E, Kuntze A, Voloshin A, Elges S, Trautmann M, Hartmann W. [Gastrointestinal stromal tumors : Where do we stand?]. PATHOLOGIE (HEIDELBERG, GERMANY) 2024; 45:223-232. [PMID: 38587549 PMCID: PMC11045643 DOI: 10.1007/s00292-024-01318-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/02/2024] [Indexed: 04/09/2024]
Abstract
For more than 20 years gastrointestinal stromal tumors (GIST) have been a paradigm for a targeted treatment with tyrosine kinase inhibitors. A fundamental prerequisite for a neoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of a hereditary or syndromic predisposition must be considered because this results in consequences for the treatment and a different follow-up strategy.
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Affiliation(s)
- Eva Wardelmann
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Deutschland.
| | - Anna Kuntze
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Deutschland
| | - Artem Voloshin
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Deutschland
| | - Sandra Elges
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Deutschland
| | - Marcel Trautmann
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Deutschland
| | - Wolfgang Hartmann
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Deutschland
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Miwa S, Wu PK, Tsuchiya H. Soft Tissue Sarcomas: Treatment and Management. Cancers (Basel) 2024; 16:1042. [PMID: 38473399 DOI: 10.3390/cancers16051042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024] Open
Abstract
Due to the rarity and heterogeneity of soft tissue sarcoma (STS), investigating new treatments for this condition has been challenging [...].
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Affiliation(s)
- Shinji Miwa
- Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan
| | - Po-Kuei Wu
- Department of Orthopedics and Joint Reconstruction, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Orthopedic Department of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Therapeutical and Research Center of Musculoskeletal Tumor, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Hiroyuki Tsuchiya
- Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan
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Trembath HE, Yeh JJ, Lopez NE. Gastrointestinal Malignancy: Genetic Implications to Clinical Applications. Cancer Treat Res 2024; 192:305-418. [PMID: 39212927 DOI: 10.1007/978-3-031-61238-1_15] [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: 09/04/2024]
Abstract
Advances in molecular genetics have revolutionized our understanding of the pathogenesis, progression, and therapeutic options for treating gastrointestinal (GI) cancers. This chapter provides a comprehensive overview of the molecular landscape of GI cancers, focusing on key genetic alterations implicated in tumorigenesis across various anatomical sites including GIST, colon and rectum, and pancreas. Emphasis is placed on critical oncogenic pathways, such as mutations in tumor suppressor genes, oncogenes, chromosomal instability, microsatellite instability, and epigenetic modifications. The role of molecular biomarkers in predicting prognosis, guiding treatment decisions, and monitoring therapeutic response is discussed, highlighting the integration of genomic profiling into clinical practice. Finally, we address the evolving landscape of precision oncology in GI cancers, considering targeted therapies and immunotherapies.
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Affiliation(s)
- Hannah E Trembath
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA
| | - Jen Jen Yeh
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA
| | - Nicole E Lopez
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA.
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA.
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Li C, Wang Q, Jiang KW, Ye YJ. Hallmarks and novel insights for gastrointestinal stromal tumors: A bibliometric analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107079. [PMID: 37826966 DOI: 10.1016/j.ejso.2023.107079] [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: 08/13/2023] [Accepted: 09/13/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND Due to the increasing recognition of gastrointestinal stromal tumor (GIST), novel insights have appeared in both preclinical and clinical research and begun to reshape the field. This study aims to map the research landscape through bibliometric analysis and provide a brief overview for the future of the GIST field. METHODS We searched the Web of Science Core Collection without publication data restrictions for GISTs and performed a bibliometric analysis with CiteSpace and VOSviewer software. RESULTS In sum, 5,911 of 13,776 records were included, and these studies were published in 948 journals and written by 24,965 authors from 4,633 institutions in 100 countries. Referring to published reviews and bibliometric analysis, we classified the future trends in four groups. In epidemiological study, precise incidence and clinicopathological features in different regions and races might become potential hotspots. Novel therapy, such as drugs, modified strategies, radioligand therapy, was persistent hotspots in GIST fields, and ctDNA-guided diagnosis, monitoring, and treatment might meet future clinical needs. The debate over serosa surgery vs. mucosa surgery will remain active for a long time in GIST surgery, and function reserve surgery, biology-based surgery will play an important role in future. Moreover, rare GIST type, like NF-1-associated GIST, Carney triads and SDH mutant GIST, need more studies in pathogenesis and genetic mutation to provide appropriate treatment for this orphan GIST patients. CONCLUSIONS Potential hotspots in future GIST trends might involve epidemiology, agents, resection therapy and rare type GIST, moreover, researchers could pay more attention in these four fields.
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Affiliation(s)
- Chen Li
- Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing, 100044, China
| | - Quan Wang
- Ambulatory Surgery Center, Xijing Hospital, Air Force Military Medical University, Xi'an, 710032, China
| | - Ke-Wei Jiang
- Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing, 100044, China.
| | - Ying-Jiang Ye
- Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing, 100044, China.
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12
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Bangolo A, Fwelo P, Al-Qatish T, Bukasa-Kakamba J, Lee T, Cayago AG, Potiguara S, Nagesh VK, Kawall J, Ahmed R, Asjad Abbas M, Nursjamsi N, Lee SH, Meti S, Arana GV, Joseph CA, Mohamed A, Alencar A, Hassan HG, Aryal P, Javed A, Kalinin M, Lawal G, Khalaf IY, Mathew M, Karamthoti P, Gupta B, Weissman S. Outcomes of Patients with Gastrointestinal Stromal Tumors in the Past Decade. Med Sci (Basel) 2023; 11:54. [PMID: 37755158 PMCID: PMC10536810 DOI: 10.3390/medsci11030054] [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] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/10/2023] [Accepted: 08/25/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about their overall epidemiology, and the prognostic factors of their pathology. The current study aimed to evaluate the independent determinants of mortality in patients diagnosed with GISTs over the past decade. METHODS Our study comprised 2374 patients diagnosed with GISTs from 2000 to 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the baseline characteristics, and overall mortality (OM), as well as the cancer-specific mortality (CSM) of GISTs. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model, to determine the independent prognostic factors. RESULTS Multivariate Cox proportional hazard regression analyses of factors affecting the all-cause mortality and GIST-related mortality among US patients between 2010 and 2017 revealed a higher overall mortality in non-Hispanic Black patients (HR = 1.516, 95% CI 1.172-1.961, p = 0.002), patients aged 80+ (HR = 9.783, 95% CI 4.185-22.868, p = 0), followed by those aged 60-79 (HR = 3.408, 95% CI 1.488-7.807, p = 0.004); male patients (HR = 1.795, 95% CI 1.461-2.206, p < 0.001); patients with advanced disease with distant metastasis (HR = 3.865, 95% CI 2.977-5.019, p < 0.001), followed by cases with regional involvement via both direct extension and lymph node involvement (HR = 3.853, 95% CI 1.551-9.57, p = 0.004); and widowed patients (HR = 1.975, 95% CI 1.494-2.61, p < 0.001), followed by single patients (HR = 1.53, 95% CI 1.154-2.028, p = 0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR = 1.687, 95% CI 1.19-2.392, p = 0.003). CONCLUSION In this updated study on the outcomes of patients with GISTs, we found that non-Hispanic Black patients, male patients, and patients older than 60 years have a higher mortality with GISTs. Furthermore, patients who have received chemotherapy have a higher GIST-specific mortality, and married patients have a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing these interactions. The results of this study may help treating clinicians to identify patient populations associated with a dismal prognosis, as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival rate, we hope to encourage clinicians to involve family members of the affected patients early in the disease course, as the social support might impact the prognosis.
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Affiliation(s)
- Ayrton Bangolo
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Pierre Fwelo
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77204, USA
| | - Tha’er Al-Qatish
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - John Bukasa-Kakamba
- Division of Endocrinology, Department of Medicine, Kinshasa University Clinics, Kinshasa 7948, Democratic Republic of the Congo;
| | - Tiffany Lee
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Akira G. Cayago
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Sarah Potiguara
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Vignesh K. Nagesh
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Jessica Kawall
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Rashid Ahmed
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Muhammad Asjad Abbas
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Narissa Nursjamsi
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Stacy H. Lee
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Shagi Meti
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Georgemar V. Arana
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Chrishanti A. Joseph
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Abdifitah Mohamed
- Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Arthur Alencar
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Huzaifa G. Hassan
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Pramanu Aryal
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Aleena Javed
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Maksim Kalinin
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Gbenga Lawal
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Ibtihal Y. Khalaf
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Midhun Mathew
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Praveena Karamthoti
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
| | - Bhavna Gupta
- Division of Hematology and Oncology, Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA
| | - Simcha Weissman
- Department of Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, USA; (T.A.-Q.); (S.P.); (G.V.A.); (C.A.J.); (M.K.); (G.L.); (I.Y.K.)
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13
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Joensuu H. KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib. Cancers (Basel) 2023; 15:3879. [PMID: 37568695 PMCID: PMC10417000 DOI: 10.3390/cancers15153879] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/22/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Adjuvant imatinib improves the recurrence-free survival and overall survival (OS) of patients with gastrointestinal stromal tumors (GISTs) who have a high risk of recurrence after surgery and is now considered standard treatment. Yet, OS benefit has been demonstrated in only one randomized study, the Scandinavian Sarcoma Group XVIII/AIO trial, where patients with high-risk GISTs were allocated to either 1 year or 3 years of adjuvant imatinib. SSGXVIII/AIO is also the only randomized trial in which adjuvant imatinib duration exceeding 2 years was evaluated. In this trial, the 3-year treatment led to a 45% reduction in the risk of death during the first 10 years that followed random allocation even though some of the patients did not have GISTs at tumor histology review, had mutations now known to be imatinib-resistant or had non-localized disease at study entry. In the subgroup of patients who had KIT exon 11 deletion/indel mutation, the reduction in the risk of death was 66% in favor of the longer treatment. Proper patient selection is of crucial importance since many patients are cured with surgery. Little evidence for OS benefit is available from randomized trials for patients whose GIST harbors KIT exon 9 mutation, KIT insertion mutation, PDGFRA D842V mutation, or lacks KIT and PDGFRA mutations. Adjuvant imatinib improves OS substantially if high-risk GISTs can be identified, treatment duration is long enough, and GISTs harbor an imatinib-sensitive mutation.
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Affiliation(s)
- Heikki Joensuu
- Department of Oncology, Helsinki University Hospital and University of Helsinki, 00029 Helsinki, Finland
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14
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Unk M, Jezeršek Novaković B, Novaković S. Molecular Mechanisms of Gastrointestinal Stromal Tumors and Their Impact on Systemic Therapy Decision. Cancers (Basel) 2023; 15:1498. [PMID: 36900287 PMCID: PMC10001062 DOI: 10.3390/cancers15051498] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/08/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that mostly derive from Cajal cell precursors. They are by far the most common soft tissue sarcomas. Clinically, they present as gastrointestinal malignancies, most often with bleeding, pain, or intestinal obstruction. They are identified using characteristic immunohistochemical staining for CD117 and DOG1. Improved understanding of the molecular biology of these tumors and identification of oncogenic drivers have altered the systemic treatment of primarily disseminated disease, which is becoming increasingly complex. Gain-of-function mutations in KIT or PDGFRA genes represent the driving mutations in more than 90% of all GISTs. These patients exhibit good responses to targeted therapy with tyrosine kinase inhibitors (TKIs). Gastrointestinal stromal tumors lacking the KIT/PDGFRA mutations, however, represent distinct clinico-pathological entities with diverse molecular mechanisms of oncogenesis. In these patients, therapy with TKIs is hardly ever as effective as for KIT/PDGFRA-mutated GISTs. This review provides an outline of current diagnostics aimed at identifying clinically relevant driver alterations and a comprehensive summary of current treatments with targeted therapies for patients with GISTs in both adjuvant and metastatic settings. The role of molecular testing and the selection of the optimal targeted therapy according to the identified oncogenic driver are reviewed and some future directions are proposed.
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Affiliation(s)
- Mojca Unk
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
- Division of Medical Oncology, Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia
| | - Barbara Jezeršek Novaković
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
- Division of Medical Oncology, Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia
| | - Srdjan Novaković
- Department of Molecular Diagnostics, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
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15
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Chiu PWY, Yip HC, Chan SM, Ng SKK, Teoh AYB, Ng EKW. Endoscopic full-thickness resection (EFTR) compared to submucosal tunnel endoscopic resection (STER) for treatment of gastric gastrointestinal stromal tumors. Endosc Int Open 2023; 11:E179-E186. [PMID: 36845271 PMCID: PMC9949978 DOI: 10.1055/a-1972-3409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022] Open
Abstract
Background and study aims Submucosal tunnel endoscopic resection (STER) is being increasingly performed for treatment of gastric gastrointestinal stromal tumor (GIST), while STER has been limited by close dissection within tunnel and risking breach of tumor capsule. Endoscopic full-thickness resection (EFTR) allows resection of GIST with margins to prevent recurrence. This study aimed to compare EFTR against STER for treatment of gastric GIST. Patients and methods We retrospectively reviewed clinical outcomes of patients with gastric GIST who received either STER or EFTR. Patients with gastric GISTs < than 4 cm were included. Clinical outcomes including baseline demographics, perioperative and oncological outcomes were compared between the two groups. Results From 2013 to 2019, 46 patients with gastric GISTs were treated with endoscopic resection, 26 received EFTR and 20 received STER. Most of the GISTs were in the proximal stomach. There was no difference in operative time (94.9 vs 84.9 mins; P = 0.401), while endoscopic suturing was applied more for closure after EFTR ( P < 0.0001). Patients after STER had earlier resumption of diet and shorter hospital stay while there was no difference in adverse event rate between two groups. The en-bloc resection rate for EFTR was significantly higher than for STER (100 % vs 80 %; P = 0.029), while there was no difference in the local recurrence. Conclusions This study demonstrated that although patients who received EFTR had longer hospital stays and slower resumption of diet compared to those who underwent STER, EFTR achieved a significantly higher rate of en-bloc resection compared to STER for treatment of gastric GIST.
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Affiliation(s)
- Philip Wai Yan Chiu
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
| | - Hon Chi Yip
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
| | - Shannon Melissa Chan
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
| | - Stephen Ka Kei Ng
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
| | - Anthony Yuen Bun Teoh
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
| | - Enders Kwok Wai Ng
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
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16
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Hornick JL, Webster F, Dei Tos AP, Hemmings C, Miettinen M, Oda Y, Raut CP, Rubin BP, Von Mehren M, Wardelmann E, Fletcher CDM. Dataset for reporting of gastrointestinal stromal tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2023; 82:376-384. [PMID: 36073677 DOI: 10.1111/his.14791] [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: 07/17/2022] [Revised: 09/04/2022] [Accepted: 09/05/2022] [Indexed: 01/20/2023]
Abstract
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and are among the most frequent sarcomas. Accurate diagnosis, classification, and reporting are critical for prognostication and patient management, including selection of appropriate targeted therapy. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of GIST. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major international pathology and cancer organizations. An international expert panel consisting of pathologists, a surgical oncologist, and a medical oncologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were subspecialized soft tissue tumour experts and affiliated with tertiary referral centres. Commentary was provided for each data item to explain its clinical relevance and the rationale for selection as a core or noncore element. Following international public consultation, the datasets, which include synoptic reporting guides, were finalized and ratified, and published on the ICCR website. These first international datasets for GIST are intended to promote high-quality, standardised pathology reporting. Their widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will ultimately help to improve the management of patients with GIST. All the ICCR datasets, including these on GIST, are freely available worldwide on the ICCR website (www.iccr-cancer.org/datasets).
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Affiliation(s)
- Jason L Hornick
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Fleur Webster
- International Collaboration on Cancer Reporting, Sydney, NSW, Australia
| | - Angelo Paolo Dei Tos
- Department of Pathology, Azienda Ospedaliera Universitaria di Padova, Padova, Italy.,Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | - Chris Hemmings
- Department of Anatomic Pathology, Canterbury Health Laboratories, Christchurch, New Zealand.,Department of Pathology and Biomedical Science, Christchurch Clinical School, University of Otago School of Medicine, Christchurch, New Zealand
| | - Markku Miettinen
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, Bethesda, MD, USA
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Chandrajit P Raut
- Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.,Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Brian P Rubin
- Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Margaret Von Mehren
- Department of Hematology and Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Eva Wardelmann
- Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany
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17
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Peng MS, Zeng HT, Zhang ZL, Chen ZM, Long T, Wang LS, Xu ZL. Efficacy and safety of endoscopic "calabash" ligation and resection for small gastric stromal tumors originating from the muscularis propria. Cancer Med 2022; 12:6825-6841. [PMID: 36510478 PMCID: PMC10067037 DOI: 10.1002/cam4.5471] [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: 05/29/2022] [Revised: 09/26/2022] [Accepted: 11/13/2022] [Indexed: 12/15/2022] Open
Abstract
AIM We compared endoscopic "calabash" ligation and resection (ECLR) and endoscopic submucosal excision (ESE) in treating endophytic gastric stromal tumors (GSTs) ≤15 mm in diameter originating from the muscularis propria. METHODS We performed a retrospective study and included patients who visited our hospital for removal of small endophytic GSTs (diameter ≤ 15 mm) confirmed by postoperative pathological reports between February 2019 and December 2020. Patients were assigned to the study (received ECLR) or control (accepted ESE) groups, and their medical records were reviewed. Age, sex, GST size, resection outcomes, procedure measurements, lengths of hospital stays, medical expenses, intraoperative and postoperative complications, and follow-up outcomes were documented and compared between the two groups. Propensity score matching was used to avoid retrospective biases. RESULTS A total of 277 patients were included in the analysis, with 135 in the study group and 142 in the control group. After propensity score matching, 119 cases in each group were finally included in the study. Compared to the control group, the study group had significantly shorter procedure durations and lengths of hospital stays, as well as reduced medical expenses. Compared to the control group, the study group also had significantly lower incidence rates of intraoperative stomach perforation, postoperative intraperitoneal infection, and postoperative electrocoagulation syndrome, as well as a lower intensity of postoperative pain. There were no significant differences in the other measurements between the two groups. CONCLUSION ECLR is an effective and safe procedure for treating patients with endophytic GSTs ≤15 mm in diameter originating from the muscularis propria.
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Affiliation(s)
- Min-Si Peng
- The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong Province, China
| | - Hao-Tian Zeng
- The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong Province, China
| | - Zhu-Liang Zhang
- The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong Province, China
| | - Ze-Ming Chen
- The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong Province, China
| | - Ting Long
- Department of Pathology The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong Province, China
| | - Zheng-Lei Xu
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong Province, China
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18
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Guo J, Ge Q, Yang F, Wang S, Ge N, Liu X, Shi J, Fusaroli P, Liu Y, Sun S. Small Gastric Stromal Tumors: An Underestimated Risk. Cancers (Basel) 2022; 14:6008. [PMID: 36497489 PMCID: PMC9740305 DOI: 10.3390/cancers14236008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 12/03/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Small gastrointestinal stromal tumors (GISTs) are defined as tumors less than 2 cm in diameter, which are often found incidentally during gastroscopy. There is controversy regarding the management of small GISTs, and a certain percentage of small GISTs become malignant during follow-up. Previous studies which used Sanger targeted sequencing have shown that the mutation rate of small GISTs is significantly lower than that of large tumors. The aim of this study was to investigate the overall mutational profile of small GISTs, including those of wild-type tumors, using whole-exome sequencing (WES) and Sanger sequencing. METHODS Thirty-six paired small GIST specimens, which were resected by endoscopy, were analyzed by WES. Somatic mutations identified by WES were confirmed by Sanger sequencing. Sanger sequencing was performed in an additional 38 small gastric stromal tumor samples for examining hotspot mutations in KIT, PDGFRA, and BRAF. RESULTS Somatic C-KIT/PDGFRA mutations accounted for 81% of the mutations, including three novel mutation sites in C-KIT at exon 11, across the entire small gastric stromal tumor cohort (n = 74). In addition, 15% of small GISTs harbored previously undescribed BRAF-V600E hotspot mutations. No significant correlation was observed among the genotype, pathological features, and clinical classification. CONCLUSIONS Our data revealed a high overall mutation rate (~96%) in small GISTs, indicating that genetic alterations are common events in early GIST generation. We also identified a high frequency of oncogenic BRAF-V600E mutations (15%) in small GISTs, which has not been previously reported.
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Affiliation(s)
- Jintao Guo
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Qichao Ge
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Innovative Research Center for Integrated Cancer Omics, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Fan Yang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Sheng Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Nan Ge
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Xiang Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Jing Shi
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Pietro Fusaroli
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40126 Imola, Italy
| | - Yang Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Innovative Research Center for Integrated Cancer Omics, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Siyu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
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19
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Wong SJ, Wang HP, Shun CT, Chen CC, Han ML, Chen JH, Huang CT, Cheng TY. Tissue diagnosis necessary for small endoscopic ultrasound-suspected gastric gastrointestinal stromal tumors 2 cm or less in size: A prospective study focusing on the endoscopic incisional biopsy. J Gastroenterol Hepatol 2022; 37:1588-1595. [PMID: 35502128 DOI: 10.1111/jgh.15876] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/05/2022] [Accepted: 04/22/2022] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM The small endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs), gastric subepithelial tumors at the muscularis propria layer on EUS, are detected frequently. Bite-on-bite forceps biopsy and EUS-guided tissue sampling yield variable results. This study aimed to analyze clinicopathologic features of the small EUS-suspected gastric GISTs 2 cm or less in size and to evaluate the efficacy and safety of the endoscopic incisional biopsy (EIB) for these small tumors. METHODS This prospective study investigated 70 patients with small EUS-suspected gastric GISTs 2 cm or less in size in two stages. Firstly, 30 patients were recruited for the efficacy and safety evaluation of the EIB. Secondly, 40 patients were randomly assigned to receive either EIB or the bite-on-bite biopsy for comparison of the diagnostic yield, procedure time, and adverse event rate. RESULTS Combining two study stages, leiomyoma (74%) was diagnosed histologically to outnumber GIST (26%) with a diagnostic rate of 94% for patients receiving EIB. KIT exon 11 mutations (50%) and PDGFRA exon 12 mutations (16%) were detected in the small gastric GISTs. In the direct comparison, the diagnostic yield of EIB and the bite-on-bite biopsy was 85% and 50%, respectively (P = 0.018). There was no statistically significant difference of the mean procedure time or adverse event rate between these two groups. CONCLUSIONS Leiomyoma is more common than expected among these small tumors. Tissue diagnosis with an effective and safe sampling technique, such as EIB, is necessary for making further clinical decisions.
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Affiliation(s)
- Shenq-Jie Wong
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, Taiwan
| | - Hsiu-Po Wang
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Chuan Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Lun Han
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jiann-Hwa Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu-Chi Hospital, New Taipei City, Taiwan
| | - Chung-Tsui Huang
- Division of Gastroenterology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Tsu-Yao Cheng
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Laboratory Medicine, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan
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20
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Abstract
Gastrointestinal stromal tumors (GISTs) are rare malignancies of the gastrointestinal tract but are the most common sarcoma. This review covers aspects of the care of patients with GIST relevant to surgeons. In particular, management of sub-2 cm GISTs, the utility of neoadjuvant and adjuvant therapy for primary GISTs, and indications for surgery in the setting of metastatic disease are discussed.
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Affiliation(s)
- Ilaria Caturegli
- Department of Surgery, Brigham and Women's Hospital, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
| | - Chandrajit P Raut
- Department of Surgery, Brigham and Women's Hospital, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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21
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Dudzisz-Śledź M, Klimczak A, Bylina E, Rutkowski P. Treatment of Gastrointestinal Stromal Tumors (GISTs): A Focus on Younger Patients. Cancers (Basel) 2022; 14:2831. [PMID: 35740497 PMCID: PMC9221273 DOI: 10.3390/cancers14122831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 06/05/2022] [Accepted: 06/06/2022] [Indexed: 01/27/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) originate from Cajal's cells and are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs in young adults, i.e., patients before the age of 40, are rare and differ from those in older patients and GISTs in children in terms of the molecular and clinical features, including the location and type of mutations. They often harbor other molecular abnormalities than KIT and PDGFRA mutations (wild-type GISTs). The general principles of therapeutic management in young patients are the same as in the elderly. Considering some differences in molecular abnormalities, molecular testing should be the standard procedure to allow appropriate systemic therapy if needed. The optimal treatment strategy should be established by a multidisciplinary team experienced in sarcoma treatment. The impact of treatment on the quality of life and daily activities, including the impact on work, pregnancy, and fertility, in this patient population should be especially taken into consideration.
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Affiliation(s)
- Monika Dudzisz-Śledź
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland; (A.K.); (E.B.); (P.R.)
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22
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Ravegnini G, Fosso B, Ricci R, Gorini F, Turroni S, Serrano C, Pilco-Janeta DF, Zhang Q, Zanotti F, De Robertis M, Nannini M, Pantaleo MA, Hrelia P, Angelini S. Analysis of microbiome in GISTs: looking for different players in tumorigenesis and novel therapeutic options. Cancer Sci 2022; 113:2590-2599. [PMID: 35633186 PMCID: PMC9357631 DOI: 10.1111/cas.15441] [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: 01/18/2022] [Revised: 04/20/2022] [Accepted: 05/23/2022] [Indexed: 12/02/2022] Open
Abstract
Preclinical forms of gastrointestinal stromal tumor (GIST), small asymptomatic lesions, called microGIST, are detected in approximately 30% of the general population. Gastrointestinal stromal tumor driver mutation can be already detected in microGISTs, even if they do not progress into malignant cancer; these mutations are necessary, but insufficient events to foster tumor progression. Here we profiled the tissue microbiota of 60 gastrointestinal specimens in three different patient cohorts—micro, low‐risk, and high‐risk or metastatic GIST—exploring the compositional structure, predicted function, and microbial networks, with the aim of providing a complete overview of microbial ecology in GIST and its preclinical form. Comparing microGISTs and GISTs, both weighted and unweighted UniFrac and Bray–Curtis dissimilarities showed significant community‐level separation between them and a pronounced difference in Proteobacteria, Firmicutes, and Bacteroidota was observed. Through the LEfSe tool, potential microbial biomarkers associated with a specific type of lesion were identified. In particular, GIST samples were significantly enriched in the phylum Proteobacteria compared to microGISTs. Several pathways involved in sugar metabolism were also highlighted in GISTs; this was expected as cancer usually displays high aerobic glycolysis in place of oxidative phosphorylation and rise of glucose flux to promote anabolic request. Our results highlight that specific differences do exist in the tissue microbiome community between GIST and benign lesions and that microbiome restructuration can drive the carcinogenesis process.
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Affiliation(s)
- Gloria Ravegnini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Bruno Fosso
- National Research Council, Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), Bari, Italy.,Department of Biosciences, Biotechnology and Biopharmaceutics (DBBB), University of Bari "A. Moro", Bari, Italy
| | - Riccardo Ricci
- UOC di Anatomia Patologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Francesca Gorini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Cesar Serrano
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Daniel F Pilco-Janeta
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.,Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Qianqian Zhang
- UOC di Anatomia Patologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Federica Zanotti
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Mariangela De Robertis
- Department of Biosciences, Biotechnology and Biopharmaceutics (DBBB), University of Bari "A. Moro", Bari, Italy
| | - Margherita Nannini
- Department of Experimental, Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Abbondanza Pantaleo
- Department of Experimental, Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Patrizia Hrelia
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Sabrina Angelini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
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23
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Abstract
Over the past 20 years, gastrointestinal stromal tumor (GIST) has evolved into an increasingly complex clinical entity with ever more challenges. While surgical resection is the gold standard, advancements in genetic testing, therapeutic options, immunotherapy, and management of metastatic disease necessitate a comprehensive, multimodal approach for these tumors. This chapter highlights the importance of genomic testing of GIST, the use of neoadjuvant and adjuvant therapy for localized disease, surgical principles for GIST, as well as current and new approaches for addressing metastatic disease.
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24
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Deprez PH, Moons LMG, OʼToole D, Gincul R, Seicean A, Pimentel-Nunes P, Fernández-Esparrach G, Polkowski M, Vieth M, Borbath I, Moreels TG, Nieveen van Dijkum E, Blay JY, van Hooft JE. Endoscopic management of subepithelial lesions including neuroendocrine neoplasms: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2022; 54:412-429. [PMID: 35180797 DOI: 10.1055/a-1751-5742] [Citation(s) in RCA: 171] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
1: ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL.Strong recommendation, moderate quality evidence. 2: ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment.Weak recommendation, very low quality evidence. 3: ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs ≥ 20 mm in size.Strong recommendation, moderate quality evidence. 4: ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear.Strong recommendation, moderate quality evidence. 5: ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals.Weak recommendation, very low quality evidence. 6: ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach.Strong recommendation, low quality evidence. 7: ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise.Weak recommendation, very low quality evidence. 8: ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis.Weak recommendation, very low quality evidence. 9: ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised.Strong recommendation, low quality evidence. 10: For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease.Strong recommendation, low quality evidence.
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Affiliation(s)
- Pierre H Deprez
- Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Leon M G Moons
- Divisie Interne Geneeskunde en Dermatologie, Maag-, Darm- en Leverziekten, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands
| | - Dermot OʼToole
- Neuroendocrine Tumor Service, ENETS Centre of Excellence, St. Vincent's University Hospital and Department of Clinical Medicine, Trinity College Dublin, University of Dublin St. James's Hospital, Dublin, Ireland
| | - Rodica Gincul
- Service de Gastroentérologie et Endoscopie Digestive, Hôpital Privé Jean Mermoz, Lyon, France
| | - Andrada Seicean
- Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Pedro Pimentel-Nunes
- Department of Gastroenterology, Portuguese Oncology Institute of Porto; Department of Surgery and Physiology, Center for Research in Health Technologies and Information Systems (CINTESIS), Faculty of Medicine, University of Porto, Portugal
| | | | - Marcin Polkowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center for Postgraduate Medical Education, and Department of Oncological Gastroenterology, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Michael Vieth
- Institut of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Ivan Borbath
- Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Tom G Moreels
- Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Els Nieveen van Dijkum
- Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, The Netherlands
| | - Jean-Yves Blay
- Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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25
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The Diagnosis of Small Gastrointestinal Subepithelial Lesions by Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy. Diagnostics (Basel) 2022; 12:diagnostics12040810. [PMID: 35453857 PMCID: PMC9027519 DOI: 10.3390/diagnostics12040810] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/21/2022] [Accepted: 03/23/2022] [Indexed: 12/02/2022] Open
Abstract
Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.
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26
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Boyle W, Phillips A, Vella J, Williams A, Ganesan R. Gastrointestinal Stromal Tumors (GISTs) as Incidental Findings in Gynecological Surgery. Int J Gynecol Pathol 2022; 41:186-190. [PMID: 33811208 DOI: 10.1097/pgp.0000000000000787] [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: 11/27/2022]
Abstract
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that may be diagnosed incidentally as a part of intra-abdominal surgery for other diseases. This is a single center review to document the incidental finding of GIST at surgery for gynecological malignancies during a 10-yr period. Sixteen cases of incidental GISTs were identified in women ranging in age from 39 to 82 yr. GISTs presented as incidental secondary lesions in women undergoing surgery for other indications, typically primary debulking surgery for tubo-ovarian high-grade serous carcinoma. The GIST was located in the stomach wall in 9 cases. Other sites were cecum, omentum, and mesentery. Diagnosis of GIST was supported by immunohistochemistry in all cases and by molecular studies in 3 cases. Seventy-five percent of cases were micro-GISTs, measuring <2 cm in diameter and, where Miettinen and Lasota criteria could be applied, fitted into "no risk," "very low risk" or "low risk" prognostic groups. Seventy-five percent of women for whom survival data was available, showed disease-free survival at follow-up. The 2 women who died had concurrent high stage or high-grade gynecological malignancy at initial diagnosis.
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27
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Agaimy A. [Mesenchymal tumors and tumor-like lesions of the gastrointestinal tract: an overview]. DER PATHOLOGE 2022; 43:31-44. [PMID: 34919183 DOI: 10.1007/s00292-021-01040-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/15/2021] [Indexed: 06/14/2023]
Abstract
Mesenchymal tumors and tumor-like lesions of the gastrointestinal (GI) tract are uncommon. They vary from reactive tumefactive lesions and benign neoplasms to highly aggressive sarcomas. Among them, GI stromal tumors (GISTs) are most common, followed, with less frequency, by smooth muscle and neurogenic tumors. The major challenge resides in correctly identifying GISTs and providing a comprehensive report (including risk assessment and genotyping) that represents the basis for an optimized surgical-oncological treatment and/or adjuvant therapy. On the other hand, the challenge of benign lesions is to find a good name (well understandable and reproducible diagnostic term) that helps avoid diagnostic ambiguity and prognostic uncertainty so that overprognostication and overtreatment can be prevented. Moreover, several recently described genetically defined benign and malignant entities need be correctly diagnosed due to their special "targeted" therapeutic options and to further characterize their clinicopathological and biological properties in the future. These recent entities include aggressive epithelioid inflammatory myofibroblastic sarcoma (ALK-RANBP2-driven), malignant gastrointestinal neuroectodermal tumor (EWSR1-ATF1/CREB-related), NTRK-rearranged neoplasms, and, most recently, colorectal NUTM1-rearranged sarcomas. This review highlights the major clinicopathological features of gastrointestinal mesenchymal lesions in light of recent developments.
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Affiliation(s)
- Abbas Agaimy
- Pathologisches Institut, Universitätsklinikum Erlangen, Krankenhausstraße 8-10, 91054, Erlangen, Deutschland.
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28
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Pulkka OP, Viisanen L, Tynninen O, Laaksonen M, Reichardt P, Reichardt A, Eriksson M, Hall KS, Wardelmann E, Nilsson B, Sihto H, Joensuu H. Fibrinogen-like protein 2 in gastrointestinal stromal tumour. J Cell Mol Med 2022; 26:1083-1094. [PMID: 35029030 PMCID: PMC8831987 DOI: 10.1111/jcmm.17163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 12/14/2021] [Accepted: 12/17/2021] [Indexed: 11/26/2022] Open
Abstract
Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen‐like protein 2 (FGL2) is expressed either as a membrane‐associated protein or as a secreted soluble protein that has immune suppressive functions. We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The interstitial cells of Cajal, from which GISTs may originate, expressed FGL2. FGL2 expression was associated with small GIST size, low mitotic counts and low tumour‐infiltrating lymphocyte (TIL) counts. Patients whose GIST expressed FGL2 had better recurrence‐free survival than patients whose GIST lacked expression. Imatinib upregulated FGL2 in GIST cell lines, and the patients with FGL2‐negative GIST appeared to benefit most from long duration of adjuvant imatinib. We conclude that GISTs express FGL2 frequently and that FGL2 expression is associated with low TIL counts and favourable survival outcomes.
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Affiliation(s)
- Olli-Pekka Pulkka
- Laboratory of Molecular Oncology, Department of Oncology, University of Helsinki, Helsinki, Finland
| | - Leevi Viisanen
- Laboratory of Molecular Oncology, Department of Oncology, University of Helsinki, Helsinki, Finland
| | - Olli Tynninen
- Department of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | | | - Peter Reichardt
- Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin, Germany
| | - Annette Reichardt
- Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin, Germany
| | - Mikael Eriksson
- Department of Oncology, Skane University Hospital and Lund University, Lund, Sweden
| | - Kirsten Sundby Hall
- Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
| | - Eva Wardelmann
- Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany
| | - Bengt Nilsson
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Harri Sihto
- Rare Cancers Research Group, Department of Pathology, University of Helsinki, Helsinki, Finland
| | - Heikki Joensuu
- Laboratory of Molecular Oncology, Department of Oncology, University of Helsinki, Helsinki, Finland.,Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
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29
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Pillay Y. OUP accepted manuscript. J Surg Case Rep 2022; 2022:rjab637. [PMID: 35222939 PMCID: PMC8865916 DOI: 10.1093/jscr/rjab637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 12/27/2021] [Indexed: 11/13/2022] Open
Affiliation(s)
- Yagan Pillay
- Correspondence address. Department of General Surgery, University of Saskatchewan, Health Sciences Building, 107 Wiggins Rd B419, Saskatoon, Saskatchewan S7N 0W8, Canada. Tel: 1-306-9668641; E-mail:
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Senti M, Torres TA, Espinosa J, Shebrain S. Unusual Presentation of a Gastrointestinal Stromal Tumor in a Small Intestine Diverticulum. Case Rep Gastroenterol 2021; 15:667-673. [PMID: 34720825 PMCID: PMC8458927 DOI: 10.1159/000518019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 06/11/2021] [Indexed: 11/25/2022] Open
Abstract
A 50-year-old female with no significant medical history initially presented to an urgent care center with symptoms of acute onset abdominal pain, nausea, and emesis. Chest and abdominal X-ray revealed free air under the diaphragm, prompting immediate transfer to the emergency department. Continued abdominal tenderness and pain were concerning for perforated viscus. The patient was transferred to the operating room, and diagnostic laparoscopy was performed. Inflammation and contamination were discovered in the right side of the abdomen and pelvis secondary to a small bowel (SB) perforation. Segmental SB resection revealed a perforated diverticulum. Pathological examination confirmed a diagnosis of gastrointestinal stromal tumor (GIST) at the perforated segment. On postoperative day 5, the patient was discharged home, and at 30-month follow-up, the patient continued to do well. Although rare, SB diverticula are commonly false (i.e., pseudodiverticula). The concomitant presence of a GIST in a true SB diverticulum presenting with perforation has not yet been reported.
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Affiliation(s)
- Mackenna Senti
- Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA
| | - Tania A Torres
- Department of Surgery, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA
| | - Jairo Espinosa
- Department of Surgery, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA
| | - Saad Shebrain
- Department of Surgery, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA
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Szczepaniak K, Nasierowska-Guttmejer A. The occurrence of gastrointestinal stromal tumors with second malignancies - Case series of a single institution experience. Pathol Res Pract 2021; 228:153662. [PMID: 34749214 DOI: 10.1016/j.prp.2021.153662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 10/17/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GISTs) may coexist with different types of malignancies, either synchronously or metachronously. The aim of this study was to characterize the clinical and histopathological features of GIST coexisting with other neoplasms. METHODS A retrospective analysis of 76 GISTs cases diagnosed at our institution between January 2003 and March 2020 was performed. A subgroup of cases with concomitant second malignancy was selected. The clinical and pathologic records were reviewed. RESULTS 18 out of 76 patients (23.7%) with GISTs were diagnosed with the second neoplasms. In 11 cases GISTs were diagnosed metachronously to the second malignancy, whereas 7 cases of GIST were synchronous. The most common concomitant neoplasms were breast cancer and gastric cancer. The concomitant GIST were located mainly in small intestine (52.6%). 14 GISTs were classified as very low or low-risk (77.8%), 3 as moderate risk (16.7%) and 1 as high risk tumors (5.6%). CONCLUSION The coexistence of GIST with other malignancies may be more common, than it has been considered. As the most of concomitant GISTs occurs metachronously to the second malignancy, studying of this phenomenon requires a long-term follow-up.
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Affiliation(s)
- K Szczepaniak
- Department of Pathology, Central Clinical Hospital of the Ministry of Interior, Wołoska 137, 02-507 Warsaw, Poland
| | - A Nasierowska-Guttmejer
- Department of Pathology, Central Clinical Hospital of the Ministry of Interior, Wołoska 137, 02-507 Warsaw, Poland; Faculty of Medicine, Lazarski University in Warsaw, Świeradowska 43, 02-662 Warsaw, Poland.
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Wu H, Li C, Li H, Shang L, Jing HY, Liu J, Fang Z, Du FY, Liu Y, Fu MD, Jiang KW, Li LP. Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis. World J Gastroenterol 2021; 27:6128-6141. [PMID: 34629824 PMCID: PMC8476333 DOI: 10.3748/wjg.v27.i36.6128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 07/26/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines.
AIM To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs)
METHODS Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared.
RESULTS Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group (P = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, P = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups.
CONCLUSION Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.
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Affiliation(s)
- Hao Wu
- Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Chen Li
- Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing 100044, China
| | - Han Li
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Liang Shang
- Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Digestive Tumor Translational Medicine, Engineering Laboratory of Shandong Province, Shandong Provincial Hospital, Jinan 250021, Shandong Province, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, Shandong Province, China
| | - Hai-Yan Jing
- Department of Pathology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Jin Liu
- Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Zhen Fang
- Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Feng-Ying Du
- Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Yang Liu
- Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Meng-Di Fu
- Department of Clinical Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Ke-Wei Jiang
- Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing 100044, China
| | - Le-Ping Li
- Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Digestive Tumor Translational Medicine, Engineering Laboratory of Shandong Province, Shandong Provincial Hospital, Jinan 250021, Shandong Province, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, Shandong Province, China
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Sun X, Sun J, Yuan W, Gao X, Fu M, Xue A, Li H, Shu P, Fang Y, Hou Y, Shen K, Sun Y, Qin J, Qin X. Immune Cell Infiltration and the Expression of PD-1 and PD-L1 in Primary PDGFRA-Mutant Gastrointestinal Stromal Tumors. J Gastrointest Surg 2021; 25:2091-2100. [PMID: 33169322 DOI: 10.1007/s11605-020-04860-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 10/31/2020] [Indexed: 01/31/2023]
Abstract
PURPOSE To characterize the immune cell profile and expression of PD-1, PD-L1, and IDO in PDGFRA-mutant gastrointestinal stromal tumors (GISTs). METHODS The clinicopathological data of PDGFRA-mutant GIST patients who received surgical resection in Zhongshan Hospital between January 2013 and August 2019 were reviewed retrospectively. The specimens of tissue chips were detected for immune cell infiltration and the expression of PD-1, PD-L1, and IDO by immunohistochemical staining. RESULTS CD3+, CD8+, and CD68+ cells were the main infiltrating immune cells in the 42 patients included in this study. In addition, CD4+, CD56+, Foxp3+, and CD20+ cells were also observed. A higher CD8+ T cell count was associated with smaller tumor size and PDGFRA D842V mutation (P = 0.047, P = 0.005). A higher CD3+ and CD68+ cell count was associated with a higher mitotic index (P = 0.022, P = 0.006). CD4+ and CD20+ cell count was associated with tumor morphology (P = 0.002, P = 0.045). PD-1 expression was present in 37 (88%) samples. Eighteen samples were positive for PD-L1 expression, and it was higher in small vs. large tumors (P = 0.012) and epithelioid and mixed cell type vs. spindle cell type GISTs (P = 0.046). IDO expression was positive in all 42 patients. The number of CD4+ cells was significantly greater in the specimens with high IDO expression (P = 0.012). CONCLUSION There were abundant infiltrating immune cells in PDGFRA-mutant GISTs. PD-L1 expression was negatively associated with tumor size. The immunotherapy targeting PD-1/PD-L1 checkpoint and IDO may be valuable.
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Affiliation(s)
- Xiangfei Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Jianyi Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Wei Yuan
- Department of Pathology, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Xiaodong Gao
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Min Fu
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Anwei Xue
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - He Li
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Ping Shu
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Yong Fang
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Yingyong Hou
- Department of Pathology, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China.
| | - Kuntang Shen
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China.
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Jing Qin
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
| | - Xinyu Qin
- Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China
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Seifert H, Fusaroli P, Arcidiacono PG, Braden B, Herth F, Hocke M, Larghi A, Napoleon B, Rimbas M, Ungureanu BS, Săftoiu A, Sahai AV, Dietrich CF. Controversies in EUS: Do we need miniprobes? Endosc Ultrasound 2021; 10:246-269. [PMID: 34380805 PMCID: PMC8411553 DOI: 10.4103/eus-d-20-00252] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/04/2021] [Indexed: 11/04/2022] Open
Abstract
This is the fifth in a series of papers entitled "Controversies in EUS." In the current paper, we deal with high-resolution catheter probes, otherwise known as EUS miniprobes (EUS-MPs). The application of miniprobes for early carcinomas in the entire intestinal tract, for subepithelial lesions, and for findings in the bile duct and pancreatic duct as well as endobronchial use is critically discussed. Submucous lesions, especially in the colon, but also early carcinomas in special cases are considered the most important indications. The argument is illustrated by numerous examples.
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Affiliation(s)
- Hans Seifert
- Department of Gastroenterology, Evangelisches Krankenhaus, Oldenburg, Germany
- Universitatsklinik fur Innere Medizin - Gastroneterologie, Hepatologie; Klinikum Oldenburg, Germany
| | - Pietro Fusaroli
- Department of Medical and Surgical Sciences, Gastroenterology Unit, University of Bologna/Imola Hospital, Imola, Italy
| | - Paolo Giorgio Arcidiacono
- Research Center, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
| | - Barbara Braden
- Translational Gastroenterology Unit I, John Radcliffe Hospital I, Oxford, OX3 9DU, UK
| | - Felix Herth
- 2 Department of Pneumology and Critical Care Medicine, Thoraxklinik and Translational Lung Research Center (TLRCH), Member of the German Lung Research Foundation (DZL), University of Heidelberg, Heidelberg, Germany
| | - Michael Hocke
- Department of Medicine, Helios Klinikum Meiningen, Meiningen, Germany
| | - Alberto Larghi
- Digestive Endoscopy Unit, IRCCS Foundation University Hospital, Policlinico A. Gemelli, Rome, Italy
| | - Bertrand Napoleon
- 2 Digestive Endoscopy Unit, HopitalPrivé J Mermoz Ramsay Générale de Santé, Lyon, France
| | - Mihai Rimbas
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania
- Department of Internal Medicine, Carol Davila University of Medicine Bucharest, Romania
| | - Bogdan Silvio Ungureanu
- Research Center of Gastroenterology and Hepatology Craiova, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Adrian Săftoiu
- Research Center of Gastroenterology and Hepatology Craiova, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Anand V Sahai
- Center Hospitalier de l'Université de Montréal, Montreal, Canada
| | - Christoph F. Dietrich
- Department of Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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Chen ZM, Peng MS, Wang LS, Xu ZL. Efficacy and safety of endoscopic resection in treatment of small gastric stromal tumors: A state-of-the-art review. World J Gastrointest Oncol 2021; 13:462-471. [PMID: 34163567 PMCID: PMC8204354 DOI: 10.4251/wjgo.v13.i6.462] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/04/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumors can occur in any part of the gastrointestinal tract, but gastric stromal tumors (GSTs) are the most common. All GSTs have the potential to become malignant, and these can be divided into four different grades by risk from low to high: Very low risk, low risk, medium risk, and high risk. Current guidelines all recommend early complete excision of GSTs larger than 2 cm in diameter. However, it is not clear whether small GSTs (sGSTs, i.e., those smaller than 2 cm in diameter) should be treated as early as possible. The National Comprehensive Cancer Network recommends that endoscopic ultrasonography-guided (EUS-guided) fine-needle aspiration biopsy and imaging (computed tomography or magnetic-resonance imaging) be used to assess cancer risk for sGSTs detected by gastroscopy to determine treatment. When EUS indicates a higher risk of tumor, surgical resection is recommended. There are some questions on whether sGSTs also require early treatment. Many studies have shown that endoscopic treatment of GSTs with diameters of 2-5 cm is very effective. We here address whether endoscopic therapy is also suitable for sGSTs. In this paper, we try to explain three questions: (1) Does sGST require treatment? (2) Is digestive endoscopy a safe and effective means of treating sGST? and (3) When sGSTs are at different sites and depths, which endoscopic treatment method is more suitable?
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Affiliation(s)
- Ze-Ming Chen
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Min-Si Peng
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Zheng-Lei Xu
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
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Al-Share B, Alloghbi A, Al Hallak MN, Uddin H, Azmi A, Mohammad RM, Kim SH, Shields AF, Philip PA. Gastrointestinal stromal tumor: a review of current and emerging therapies. Cancer Metastasis Rev 2021; 40:625-641. [PMID: 33876372 DOI: 10.1007/s10555-021-09961-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/29/2021] [Indexed: 02/07/2023]
Abstract
Gastrointestinal stromal tumors (GIST) are rare neoplasms arising from the interstitial cell of Cajal in the gastrointestinal tract. Two thirds of GIST in adult patients have c-Kit mutation and smaller fractions have platelet derived growth factor receptor alpha (PDGFRA) mutation. Surgery is the only curative treatment for localized disease. Imatinib improves survival when used adjuvantly and in advanced disease. Several targeted therapies have also improved survival in GIST patients after progression on imatinib including sunitinib and regorafenib. Recently, United States Federal and Drug Administration (FDA) approved two new tyrosine kinase inhibitors for the treatment of heavily pretreated advanced/unresectable GIST including avapritinib (a selective inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib (a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this article, we will provide a comprehensive review of GIST including the current standard of care treatment and exploring future paradigm shifts in therapy.
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Affiliation(s)
- Bayan Al-Share
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Abdulrahman Alloghbi
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Mohammed Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Hafiz Uddin
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Asfar Azmi
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Ramzi M Mohammad
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Steve H Kim
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Anthony F Shields
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Philip A Philip
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA.
- Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI, USA.
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PDGFRA Immunohistochemistry Predicts PDGFRA Mutations in Gastrointestinal Stromal Tumors. Am J Surg Pathol 2021; 46:3-10. [PMID: 33859072 DOI: 10.1097/pas.0000000000001720] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Platelet-derived growth factor receptor A (PDGFRA) is a receptor tyrosine kinase that is activated by mutations in 10% of gastrointestinal stromal tumors (GISTs) and 55% to 70% of inflammatory fibroid polyps. PDGFRA-mutant GISTs are usually epithelioid and occur predominantly in the stomach. Succinate dehydrogenase-deficient GISTs also arise in the stomach and are usually epithelioid, as are some KIT-mutant GISTs. Recently, avapritinib was approved to treat PDGFRA D842V-mutant GISTs, which do not respond to conventional targeted therapy. Here, we evaluate the utility of PDGFRA immunohistochemistry (IHC) to predict PDGFRA mutations to direct targeted therapy. PDGFRA IHC was performed at 1:3000 and 1:10,000 dilutions on a tissue microarray containing 153 GISTs (126 KIT-mutant, 17 PDGFRA-mutant, and 10 succinate dehydrogenase-deficient). The "positive" staining threshold was defined as 50% of neoplastic cells staining at moderate intensity. PDGFRA IHC was 75.0% and 80.9% specific for PDGFRA mutations at 1:3000 and 1:10,000 dilutions, respectively, and it was 100% sensitive at both. On the basis of its higher specificity, a 1:10,000 dilution was used to stain whole-tissue sections of GISTs and other gastric tumor types. Combining tissue microarray and whole-tissue data, PDGFRA IHC was 94.4% sensitive and 81.0% specific for PDGFRA-mutant GIST among all 210 GISTs, and it was 84.1% specific among 149 GISTs with an epithelioid component. PDGFRA was positive in a subset of inflammatory fibroid polyps (15/30; 50%), monophasic synovial sarcomas (5/10; 50%), inflammatory myofibroblastic tumors (5/10; 50%), and plexiform fibromyxomas (2/8; 25%). It was negative in poorly differentiated adenocarcinoma (0/20), diffuse large B-cell lymphoma (0/10), glomus tumor (0/10), gastrointestinal neuroectodermal tumor (0/10), leiomyoma (0/10), gastric schwannoma (0/8), and gastroblastoma (0/3). Among GISTs, PDGFRA IHC is highly sensitive and moderately specific for PDGFRA-mutant tumors; it also can be positive in inflammatory fibroid polyp and some other mesenchymal tumor types. PDGFRA positivity could be used to triage epithelioid GISTs for PDGFRA sequencing to determine optimal therapy.
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Abstract
Gastrointestinal stromal tumours (GIST) have an incidence of ~1.2 per 105 individuals per year in most countries. Around 80% of GIST have varying molecular changes, predominantly mutually exclusive activating KIT or PDGFRA mutations, but other, rare subtypes also exist. Localized GIST are curable, and surgery is their standard treatment. Risk factors for relapse are tumour size, mitotic index, non-gastric site and tumour rupture. Patients with GIST with KIT or PDGFRA mutations sensitive to the tyrosine kinase inhibitor (TKI) imatinib that are at high risk of relapse have improved survival with adjuvant imatinib treatment. In advanced disease, median overall survival has improved from 18 months to >70 months since the introduction of TKIs. The role of surgery in the advanced setting remains unclear. Resistance to TKIs arise mainly from subclonal selection of cells with resistance mutations in KIT or PDGFRA when they are the primary drivers. Advanced resistant GIST respond to second-line sunitinib and third-line regorafenib, as well as to the new broad-spectrum TKI ripretinib. Rare molecular forms of GIST with alterations involving NF1, SDH genes, BRAF or NTRK genes generally show primary resistance to standard TKIs, but some respond to specific inhibitors of the activated genes. Despite major advances, many questions in both advanced and localized disease remain unanswered.
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Affiliation(s)
- Jean-Yves Blay
- Department of Medicine, Centre Leon Berard, UNICANCER & University Lyon I, Lyon, France.
| | - Yoon-Koo Kang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Toshiroo Nishida
- Surgery Department, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
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Lu X, Pang Y, Cao H, Liu X, Tu L, Shen Y, Jia X, Lee JC, Wang Y. Integrated Screens Identify CDK1 as a Therapeutic Target in Advanced Gastrointestinal Stromal Tumors. Cancer Res 2021; 81:2481-2494. [PMID: 33727226 DOI: 10.1158/0008-5472.can-20-3580] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 02/03/2021] [Accepted: 03/09/2021] [Indexed: 11/16/2022]
Abstract
Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumor (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with advanced GIST. Polyclonal emergence of KIT/PDGFRA secondary mutations is the main mechanism of imatinib progression, making it challenging to overcome KIT/PDGFRA-inhibitor resistance. It is unclear whether there are other therapeutic targets in advanced GIST. Using genome-wide transcriptomic profiling of advanced versus early-stage GIST and CRISPR knockout functional screens, we demonstrate that CDK1 is frequently highly expressed in advanced GIST but not in early-stage GIST across three patient cohorts. High expression of CDK1 was associated with malignancy in GIST. CDK1 was critically required for advanced GIST, including imatinib-resistant GIST. CDK1 ablation led to robust proliferation inhibition. A mass spectrometry-based proteomics screen further revealed that AKT is a novel substrate of CDK1 kinase in GIST. CDK1 bound AKT and regulated its phosphorylation, thereby promoting GIST proliferation and progression. Importantly, a pharmacologic inhibitor of CDK1, RO-3306, disrupted GIST cell proliferation in CDK1 highly expressed GIST but not in CDK1-negative GIST cells and nontransformed fibroblast cells. Treatment with RO-3306 reduced tumor growth in both imatinib-resistant and imatinib-sensitive GIST xenograft mouse models. Our findings suggest that CDK1 represents a druggable therapeutic target in GIST and warrants further testing in clinical trials. SIGNIFICANCE: These findings propose CDK1 as a novel cell-cycle-independent vulnerability in gastrointestinal stromal tumors, representing a new therapeutic opportunity for patients with advanced disease.
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Affiliation(s)
- Xiaojing Lu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, SINH - Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine (CAS-SMMU), Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yuzhi Pang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, SINH - Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine (CAS-SMMU), Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Hui Cao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoxiao Liu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, SINH - Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine (CAS-SMMU), Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Lin Tu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yanying Shen
- Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaona Jia
- CAS Key Laboratory of Tissue Microenvironment and Tumor, SINH - Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine (CAS-SMMU), Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Jen-Chieh Lee
- Department and Graduate Institute of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yuexiang Wang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, SINH - Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine (CAS-SMMU), Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
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Pitchumoni CS, Chaubal A, Desai G. Gastric Tumors (Other than Adenocarcinoma). GERIATRIC GASTROENTEROLOGY 2021:1881-1902. [DOI: 10.1007/978-3-030-30192-7_117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Xu L, Ma Y, Wang S, Feng J, Liu L, Wang J, Liu G, Xiu D, Fu W, Zhan S, Sun T, Gao P. Incidence of gastrointestinal stromal tumor in Chinese urban population: A national population-based study. Cancer Med 2021; 10:737-744. [PMID: 33320439 PMCID: PMC7877389 DOI: 10.1002/cam4.3644] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 11/07/2020] [Accepted: 11/24/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Information on incidence of gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumor in gastrointestinal tract, was limited in China. This study aimed to estimate the incidence of GIST in urban population from mainland China in 2016. METHODS Urban Employee Basic Medical Insurance (UEBMI) and Urban Residence Basic Medical Insurance (URBMI) in China were used. The denominator of incidence was the total person-years of insured individuals in 2016 in the database, covering approximately 0.43 billion individuals. The numerator was the number of incident GIST cases in 2016. RESULTS The crude incidence in 2016 was 0.40 per 100,000 person-years (95% CI, 0.06-1.03). Male incidence was higher than female incidence (0.44 vs. 0.36, rate ratio: 1.22, p < 0.001). The mean age at diagnosis was 55.20 years (SD = 14.26) and the incidence among those aged 50 years or older was 2.63 times (0.84 vs. 0.32, p < 0.001) higher than those aged under 50. The highest incidence was observed in East China (2.29, 95% CI: 0.46-5.54). CONCLUSIONS The incidence of GIST in mainland China was lower than Europe, North America and Korea. The mean age at diagnosis of GIST in China was younger than that of Europe and Canada. This study provides useful information to further research, policy formulating and management of GIST.
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Affiliation(s)
- Lu Xu
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Yanpeng Ma
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Shengfeng Wang
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Jingnan Feng
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Lili Liu
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Jinxi Wang
- Shanghai Songsheng Business Consulting Co. LtdBeijingChina
| | - Guozhen Liu
- Peking University Health Information Technology Co. LtdBeijingChina
| | - Dianrong Xiu
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Wei Fu
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Siyan Zhan
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
- Research Center of Clinical EpidemiologyPeking University Third HospitalBeijingChina
- Center for Intelligent Public HealthInstitute for Artificial IntelligencePeking UniversityBeijingChina
| | - Tao Sun
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Pei Gao
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
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Dembinski J, Sabbagh C, Chivot C, Le Mouel JP, Regimbeau JM. Two duodenal gastrointestinal stroma tumors: Management by minimally invasive surgery and then by conservative surgery. Asian J Endosc Surg 2020; 13:548-551. [PMID: 31880081 DOI: 10.1111/ases.12779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 10/29/2019] [Accepted: 12/01/2019] [Indexed: 11/27/2022]
Abstract
We report the case of a 48-year-old woman treated for a gastrointestinal stroma tumor of the duodenum after presenting with upper gastrointestinal bleeding. She was treated with a combination of a radiological and endoscopic approach and minimally invasive surgery. During follow-up, the patient developed a second metachronous duodenal gastrointestinal stroma tumor, distinct from a local recurrence. This tumor was treated with a conservative surgical approach.
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Affiliation(s)
- Jeanne Dembinski
- Department of Digestive Surgery, Amiens University Hospital, Amiens, France.,Simplification of Surgical Patient Care (SSPC) Clinical Research Unit, University of Picardie Jules Verne, Amiens, France
| | - Charles Sabbagh
- Department of Digestive Surgery, Amiens University Hospital, Amiens, France.,Simplification of Surgical Patient Care (SSPC) Clinical Research Unit, University of Picardie Jules Verne, Amiens, France
| | - Cyril Chivot
- Department of Radiology, Amiens University Hospital, Amiens, France
| | | | - Jean-Marc Regimbeau
- Department of Digestive Surgery, Amiens University Hospital, Amiens, France.,Simplification of Surgical Patient Care (SSPC) Clinical Research Unit, University of Picardie Jules Verne, Amiens, France
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Sakamaki K, Funasaka K, Miyahara R, Furukawa K, Yamamura T, Ohno E, Nakamura M, Kawashima H, Hirooka Y, Fujishiro M, Goto H. Low ETV1 mRNA expression is associated with recurrence in gastrointestinal stromal tumors. Sci Rep 2020; 10:14767. [PMID: 32901065 PMCID: PMC7478956 DOI: 10.1038/s41598-020-71719-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 07/22/2020] [Indexed: 12/28/2022] Open
Abstract
Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression (P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.
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Affiliation(s)
- Keiichi Sakamaki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Kohei Funasaka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
- Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
| | - Ryoji Miyahara
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan
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Ahmed M. Recent advances in the management of gastrointestinal stromal tumor. World J Clin Cases 2020; 8:3142-3155. [PMID: 32874969 PMCID: PMC7441252 DOI: 10.12998/wjcc.v8.i15.3142] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/26/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumor (GIST) is a rare but an important clinical entity seen in our clinical practice. It is the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine. Although the exact prevalence of GIST is not known, the incidence of GIST has been increasing. GISTs arise from interstitial cells of Cajal. Most of the GISTs occur due to mutation in c-kit gene or platelet derived growth factor receptor alpha gene. 15% of GISTs do not have these mutations and they are called wild-type GISTs. Almost all GISTs express KIT receptor tyrosine kinase. Histologically, GISTs look like spindle cell tumors most of the time but they can be epitheloid or mixed type. The median size of GISTs varies from 2.7 cm to 8.9 cm. Clinically, patients with small GISTs remain asymptomatic but as the GIST size increases, patients present with various symptoms depending on the location of the GIST. Most of GISTs are located in the stomach or small bowel. Diagnosis is suspected on imaging and endoscopic studies, and confirmed by tissue acquisition with immunohistochemical staining. The aggressiveness of GISTs depends on the size, mitotic index and location. Surgical resection is the treatment of choice. But various endoscopic modalities of resection are increasingly being tried. Tyrosine kinase inhibitors are extremely useful in the management of large GISTs, unresectable GISTs and metastatic GISTs. Treatment options for metastatic GISTs also include radiotherapy, chemotherapy, hepatic artery embolization, chemoembolization and radiofrequency ablation.
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Affiliation(s)
- Monjur Ahmed
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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Milanetto AC, Pacciani S, Fassan M, Pasquali C. Pancreatic Neuroendocrine Neoplasms and Gastrointestinal Stromal Tumors: A Single-Institution Experience of a Rare Association and Review of the Literature. Pancreas 2020; 49:918-923. [PMID: 32658075 DOI: 10.1097/mpa.0000000000001599] [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] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Pancreatic neuroendocrine neoplasms (pNENs) and gastrointestinal stromal tumors (GISTs) represent rare neoplasms. Nonsyndromic cases of pNENs associated with a synchronous GIST were evaluated, and a review of the literature was performed. METHODS We evaluated clinicopathologic features, postoperative outcome, and follow-up of patients operated on for nonsyndromic synchronous pNENs and GISTs in our unit (2003-2017). RESULTS Five (3.2%) of 156 patients with a pNEN had an associated GIST (3 male/2 female; average age, 67 years). They were diagnosed with a pNEN preoperatively and underwent pancreatic surgery. In 4 patients, GISTs were detected intraoperatively. Histology showed 3 G1 and 2 G2 pNENs. All GISTs were low risk (median size, 0.9 cm). Two patients were alive without disease 108 and 132 months after surgery. In the literature, 7 cases were described. They had low-risk GISTs, with a gastric location in 6 cases (median size, 2.85 cm). CONCLUSIONS Sporadic pNENs coexisting with a GIST have been demonstrated in 12 cases. This association is considered fortuitous, and its true incidence may be underestimated. Surgery should be performed on the GIST during the pancreatic surgery. The prognosis strictly depends on the pancreatic NENs.
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Affiliation(s)
- Anna Caterina Milanetto
- From the Chirurgica 1, Pancreatic and Endocrine Digestive Surgical Unit, Departments of Surgery, Oncology and Gastroenterology
| | - Sabrina Pacciani
- From the Chirurgica 1, Pancreatic and Endocrine Digestive Surgical Unit, Departments of Surgery, Oncology and Gastroenterology
| | | | - Claudio Pasquali
- From the Chirurgica 1, Pancreatic and Endocrine Digestive Surgical Unit, Departments of Surgery, Oncology and Gastroenterology
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Fisher SB, Kim SC, Kooby DA, Cardona K, Russell MC, Delman KA, Staley CA, Maithel SK. Gastrointestinal Stromal Tumors: A Single Institution Experience of 176 Surgical Patients. Am Surg 2020. [DOI: 10.1177/000313481307900707] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Large single-institution series of patients undergoing resection for gastrointestinal stromal tumors (GIST) are lacking. Clinicopathologic characteristics and postoperative outcomes were retrospectively collected and analyzed from patients undergoing resection for GIST from 2002 to 2011. One hundred seventy-six patients were identified; 156 underwent resection of primary nonmetastatic disease. KIT mutations were identified in 131 patients (84.0%). Of the 156 patients with primary disease, the most common site was the stomach (75.6%). Tumors were categorized as very low (24.4%), low (35.9%), intermediate (12.2%), high (24.4%), or unknown (3.2%) risk. Symptomatic patients more often had high risk (35.6 vs 9.8%; P < 0.0001) and larger tumors (7.3 vs 3.0 cm; P < 0.0001). Forty-seven patients (30.1%) underwent laparoscopic resection (LR). Compared with open surgery, LR was performed for smaller tumors (3.8 vs 6.2 cm; P = 0.002). Positive margin rates were similar (4.3% LR vs 10.2% open; P = 0.346). Median follow-up for the 156 patients with primary tumors was 32.9 months; mean overall survival was 120.9 months (median not reached). Of the 20 patients with metastatic GIST (excluded from above analysis), five patients (25.0%) died of disease with a median follow-up of 15.9 months. Most patients with resectable primary GIST have a favorable prognosis. The presence of symptoms directly related to GIST may be associated with a poor prognosis and is likely related to increased tumor size. Laparoscopic resection is well tolerated and does not appear to compromise outcomes in well-selected patients. Highly selected patients with metastatic disease may benefit from resection.
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Affiliation(s)
- Sarah B. Fisher
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - Steven C. Kim
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - David A. Kooby
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - Kenneth Cardona
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - Maria C. Russell
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - Keith A. Delman
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - Charles A. Staley
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
| | - Shishir K. Maithel
- Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, Georgia
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Yasuda T, Eto K, Yoshida N, Iwagami S, Hiyoshi Y, Nagai Y, Iwatsuki M, Ishimoto T, Baba Y, Miyamoto Y, Shiota T, Mikami Y, Baba H. Multiple heterochronic gastrointestinal stromal tumors in the stomach detected 6 years after resection: a case report. Surg Case Rep 2020; 6:48. [PMID: 32146688 PMCID: PMC7060937 DOI: 10.1186/s40792-020-00812-1] [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: 01/11/2020] [Accepted: 02/26/2020] [Indexed: 11/16/2022] Open
Abstract
Background To date, only a few cases of multiple GISTs with different clones in different organs have been published. However, a case of multiple GISTs with different clones occurring in a single organ has never been reported. Case presentation A 41-year-old patient underwent laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST) in 2012. The pathological findings showed high-risk characteristics for recurrence, so he received adjuvant therapy with imatinib for 3 years. In 2018, 3 years after completing the adjuvant therapy, tumor lesions at residual gastric cardia were incidentally identified by follow-up computed tomography (CT). The pathological findings of the tumor biopsy revealed gastric GIST. He underwent secondary laparoscopic partial gastrectomy and was diagnosed with high-risk GIST. Adjuvant therapy with imatinib was restarted immediately. The two gastric GISTs had the same exon 11 mutations in the c-kit gene, but they had different missense mutations. This molecular heterogeneity suggested that they were derived from different origins. Conclusion We reported a multiple heterochronic GIST in the stomach detected 6 years after resection. There may be a possibility that another heterochronic GIST will occur in the remnant stomach in the future, so close follow-up will be needed.
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Affiliation(s)
- Tadahito Yasuda
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kojiro Eto
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Naoya Yoshida
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shiro Iwagami
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Youhei Nagai
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takatsugu Ishimoto
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takuya Shiota
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshiki Mikami
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
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Gastric Gastrointestinal Stromal Tumors (GIST): a Case Series and Current State of the Art in the Workup and Treatment of This Rare Disease. J Gastrointest Cancer 2020; 50:548-555. [PMID: 29192406 DOI: 10.1007/s12029-017-0034-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Zhang D, Wang T, Liu Y, Li L, Li B, Yang X, Xiao J. Clinical features and surgical treatments of rare gastrointestinal stromal tumor spinal metastases. Br J Neurosurg 2020; 35:11-15. [PMID: 32054325 DOI: 10.1080/02688697.2020.1725438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVE To increase our knowledge of the characteristics of rare gastrointestinal stromal tumors (GISTs) spinal metastatic diseases and share our experience of dealing with these diseases. METHODS A total of 6 patients with spinal cord compression caused by GISTs spinal metastases operated in our department were identified from Oct, 2010 to Oct, 2018. The clinical and operative notes, radiographic images, and pathological reports with histochemistry of all these patients were reviewed. RESULTS Among these six, four were male. The average age was 57.2 ± 9.0 years-old. The average duration between GISTs resections and diagnosis of spinal metastases was 80.8 ± 91.9 months. Four patients died from their disease during follow-up. The average duration between operation and death was 8.5 ± 4.4 months. CONCLUSIONS Generally, patients with GISTs spinal metastatic diseases had a poor prognosis. The average survival of these patients did not exceed 12 months. Palliative treatments are recommended mainly to control symptoms.
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Affiliation(s)
- Dan Zhang
- Department of Orthopaedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
| | - Ting Wang
- Department of Orthopaedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
| | - Yujie Liu
- Department of Orthopaedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
| | - Lin Li
- Department of Orthopaedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
| | - Binbin Li
- Department of Pathology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
| | - Xinghai Yang
- Department of Orthopaedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
| | - Jianru Xiao
- Department of Orthopaedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, PR China
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Resection of the gastric submucosal tumor (G-SMT) originating from the muscularis propria layer: comparison of efficacy, patients' tolerability, and clinical outcomes between endoscopic full-thickness resection and surgical resection. Surg Endosc 2020; 34:4053-4064. [PMID: 32016516 PMCID: PMC7394934 DOI: 10.1007/s00464-019-07311-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 11/28/2019] [Indexed: 02/06/2023]
Abstract
Background and aims Endoscopic full-thickness resection (EFTR) has been increasingly applied in the treatment of gastric submucosal tumors (G-SMTs) with explorative intention. This study aimed to compare the efficacy, tolerability, and clinical outcomes of EFTR and surgical intervention for the management of muscularis propria (MP)-derived G-SMTs. Methods Between September 2011 and May 2019, the clinical records of patients with MP-derived G-SMTs undergoing EFTR at our endoscopic unit were collected. A cohort of people with primary MP-derived G-SMTs treated by surgery was matched in a 1:1 ratio to EFTR group with regard to patients’ baseline characteristics, clinicopathologic features of the tumor and the procedure date. The perioperative outcomes and follow-up data were analyzed. Results In total, 62 and 62 patients were enrolled into the surgery and EFTR group, respectively, with median follow-up of 786 days. The size of G-SMTs (with ulceration) ranged from 10 to 90 mm. For patients with tumor smaller than 30 mm, surgery and EFTR group presented comparable procedural success rate (both were 100%), en bloc resection rate (100% vs. 94.7%), tumor capsule rupture rate (0% vs. 5.3%), and pathological R0 resection rate (both were 100%). EFTR had a statistically significant advantage over surgery for estimated blood loss (3.12 ± 5.20 vs. 46.97 ± 60.73 ml, p ≤ 0.001), discrepancy between the pre- and postprocedural hemoglobin level (5.18 ± 5.43 vs. 9.84 ± 8.25 g/L, p = 0.005), bowel function restoration [1 (0–5) vs. 3 (1–5) days, p ≤ 0.001], and hospital cost (28,617.09 ± 6720.78 vs. 33,963.10 ± 13,454.52 Yuan, p = 0.033). The patients with tumor larger than 30 mm showed roughly the same outcomes after comparison analysis of the two groups. However, the clinical data revealed lower en bloc resection rate (75.0% vs. 100%, p = 0.022) and higher tumor capsule rupture rate (25.0% vs. 0%, p = 0.022) for EFTR when compared to surgery. The procedure time, duration of postprocedural fasting and antibiotics usage, and hospital stay of the two groups were equivalent. The occurrence rate of adverse events within postoperative day 7 were 74.2% and 72.6% after EFTR and surgery, respectively (p = 1.000). No complications occurred during the follow-up. Conclusion For treatment of MP-derived G-SMTs (with or without ulceration), our study showed the feasibility and safety of EFTR, which also provided better results in terms of procedural blood loss, the postoperative bowel function restoration and cost-effectiveness when compared to surgery, whereas the surgery was superior in en bloc resection rate for G-SMTs larger than 30 mm. The postprocedural clinical outcomes seemed to be equivalent in these two resection methods.
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