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Zou FW, Tang YF, Li X, Liu C, Wu C, Zhang LY. circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway. Sci Rep 2024; 14:22004. [PMID: 39317735 PMCID: PMC11422497 DOI: 10.1038/s41598-024-73393-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 09/17/2024] [Indexed: 09/26/2024] Open
Abstract
Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development and progression of various tumors. The aim of this study was to investigate the effects of circ_SMA4 in Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in GISTs. The effect of circ_SMA4 on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_SMA4/miR-494-3p/ KIT axis. The results revealed that circ_SMA4 was significantly upregulated in GISTs, and exhibited high diagnostic efficiency with an AUC of 0.9824 (P < 0.01). circ_SMA4 promoted cell proliferation, invasion, migration, while inhibiting apoptosis in GISTs cells, both in vitro and in vivo. Silencing circ_SMA4 partially inhibited GISTs malignant progression. Additionally, circ_SMA4 acted as a competing endogenous RNA (ceRNA) by targeting miR-494-3p, and KIT was identified as a functional gene for miR-494-3p in GISTs. Furthermore, the results confirmed that circ_SMA4/miR-494-3p/ KIT axis plays a role in activating the JAK/STAT signaling pathway in GISTs. Therefore, for the first time, we have identified and emphasized that circ_SMA4 is significantly upregulated and plays an oncogenic role in GISTs by sponging miR-494-3p to activate the KIT/JAK/STAT pathway. These findings underscore circ_SMA4 may serve as a novel diagnostic biomarker and therapeutic target for GISTs.
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Affiliation(s)
- Fang-Wen Zou
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China
| | - Yi-Fang Tang
- Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China
| | - Xiaojing Li
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China
| | - Cong Liu
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China
| | - Chenhao Wu
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China
| | - Lei-Yi Zhang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China.
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Han S, Song M, Wang J, Huang Y, Li Z, Yang A, Sui C, Zhang Z, Qiao J, Yang J. Intelligent identification system of gastric stromal tumors based on blood biopsy indicators. BMC Med Inform Decis Mak 2023; 23:214. [PMID: 37833709 PMCID: PMC10576280 DOI: 10.1186/s12911-023-02324-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 10/03/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND The most prevalent mesenchymal-derived gastrointestinal cancers are gastric stromal tumors (GSTs), which have the highest incidence (60-70%) of all gastrointestinal stromal tumors (GISTs). However, simple and effective diagnostic and screening methods for GST remain a great challenge at home and abroad. This study aimed to build a GST early warning system based on a combination of machine learning algorithms and routine blood, biochemical and tumour marker indicators. METHODS In total, 697 complete samples were collected from four hospitals in Gansu Province, including 42 blood indicators from 318 pretreatment GST patients, 180 samples of gastric polyps and 199 healthy individuals. In this study, three algorithms, gradient boosting machine (GBM), random forest (RF), and logistic regression (LR), were chosen to build GST prediction models for comparison. The performance and stability of the models were evaluated using two different validation techniques: 5-fold cross-validation and external validation. The DeLong test assesses significant differences in AUC values by comparing different ROC curves, the variance and covariance of the AUC value. RESULTS The AUC values of both the GBM and RF models were higher than those of the LR model, and this difference was statistically significant (P < 0.05). The GBM model was considered to be the optimal model, as a larger area was enclosed by the ROC curve, and the axes indicated robust model classification performance according to the accepted model discriminant. Finally, the integration of 8 top-ranked blood indices was proven to be able to distinguish GST from gastric polyps and healthy people with sensitivity, specificity and area under the curve of 0.941, 0.807 and 0.951 for the cross-validation set, respectively. CONCLUSION The GBM demonstrated powerful classification performance and was able to rapidly distinguish GST patients from gastric polyps and healthy individuals. This identification system not only provides an innovative strategy for the diagnosis of GST but also enables the exploration of hidden associations between blood parameters and GST for subsequent studies on the prevention and disease surveillance management of GST. The GST discrimination system is available online for free testing of doctors and high-risk groups at https://jzlyc.gsyy.cn/bear/mobile/index.html .
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Affiliation(s)
- Shangjun Han
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Meijuan Song
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Jiarui Wang
- Department of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yalong Huang
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Zuxi Li
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Aijia Yang
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Changsheng Sui
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Zeping Zhang
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Jiling Qiao
- Department of the First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, People's Republic of China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China
| | - Jing Yang
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, People's Republic of China.
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3
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Belabbes FZ, Ibork S, Oqbani K, Bensaad A. Hypovolemic Shock Revealing a Gastrointestinal Stromal Tumor. Cureus 2023; 15:e37315. [PMID: 37181997 PMCID: PMC10167093 DOI: 10.7759/cureus.37315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2023] [Indexed: 05/16/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare neoplasms that originate in the gastrointestinal tract. Due to the nonspecific symptoms, they are often underdiagnosed. Patients typically present with abdominal pain, weight loss, asthenia, or a sensation of a "ball in the stomach." Hypovolemic shock is a rare mode of presentation. The biopsy is often inconclusive, and immunohistochemistry plays a crucial role in diagnosis. Surgery is the treatment of choice for stromal tumors with hemorrhage. Here, we present two cases of patients admitted in critical condition with hypovolemic shock. Laboratory results revealed profound anemia. Upper gastrointestinal exploration demonstrated a tumor in both cases, with normal biopsy findings in one case. However, after partial gastrectomy, pathology results revealed GIST with an immunohistochemistry profile in favor. The mode of presentation in our cases is notable, as hypovolemic shock without apparent external bleeding is an unusual presentation. Therefore, physicians should consider GIST a possible diagnosis when presented with a patient in hypovolemic shock, even without externalized bleeding.
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Affiliation(s)
- Fatima Zahra Belabbes
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Safa Ibork
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Kenza Oqbani
- Pathology, Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Ahmed Bensaad
- General Surgery, Mohammed VI University of Sciences and Health (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
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4
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Syamprasad NP, Madje N, Bachannagari J, Jannu AK, Jain S, Tene K, Shantanu PA, Naidu V, Chella N. Niclosamide nanocrystal for enhanced in-vivo efficacy against gastrointestinal stromal tumor via regulating EGFR/STAT-3/DR-4 axis. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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5
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The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth. Cancer Gene Ther 2023; 30:245-255. [PMID: 36241703 DOI: 10.1038/s41417-022-00539-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/30/2022] [Accepted: 09/12/2022] [Indexed: 11/08/2022]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mostly unknown. Previously, we found that the adaptor molecule SH3BP2 was involved in GIST cell survival, likely due to the co-regulation of the expression of KIT and Microphthalmia-associated transcription factor (MITF). Remarkably, MITF reconstitution restored KIT expression levels in SH3BP2 silenced cells and restored cell viability. This study aimed to analyze MITF as a novel driver of KIT transforming program in GIST. Firstly, MITF isoforms were characterized in GIST cell lines and GIST patients' samples. MITF silencing decreases cell viability and increases apoptosis in GIST cell lines irrespective of the type of KIT primary or secondary mutation. Additionally, MITF silencing leads to cell cycle arrest and impaired tumor growth in vivo. Interestingly, MITF silencing also affects ETV1 expression, a linage survival factor in GIST that promotes tumorigenesis and is directly regulated by KIT signaling. Altogether, these results point to MITF as a key target of KIT/PDGFRA oncogenic signaling for GIST survival and tumor growth.
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6
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Proaño-Pérez E, Serrano-Candelas E, Mancia C, Navinés-Ferrer A, Guerrero M, Martin M. SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors. Cancers (Basel) 2022; 14:cancers14246198. [PMID: 36551682 PMCID: PMC9777313 DOI: 10.3390/cancers14246198] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/05/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation.
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Affiliation(s)
- Elizabeth Proaño-Pérez
- Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Faculty of Health Sciences, Technical University of Ambato, Ambato 180105, Ecuador
| | - Eva Serrano-Candelas
- Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Cindy Mancia
- Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
| | - Arnau Navinés-Ferrer
- Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Mario Guerrero
- Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
| | - Margarita Martin
- Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Correspondence:
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Beji H, Bouassida M, Mroua B, Belfkih H, M'farrej MK, Touinsi H. Extra-gastrointestinal stromal tumor of the pancreas: A case report. Int J Surg Case Rep 2022; 98:107581. [PMID: 36057252 PMCID: PMC9482973 DOI: 10.1016/j.ijscr.2022.107581] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/28/2022] [Accepted: 08/28/2022] [Indexed: 02/07/2023] Open
Abstract
Introduction Presentation of case Clinical discussion Conclusion
Pancreatic EGIST is extremely rare. There are no specific clinical and radiologic findings. Surgical resection is the cornerstone of the treatment. Whenever possible, enucleation is sufficient.
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8
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Uzunoglu H, Tosun Y, Akinci O, Baris B. Gastrointestinal stromal tumors of the stomach: A 10-year experience of a single-center. Niger J Clin Pract 2021; 24:1785-1792. [PMID: 34889786 DOI: 10.4103/njcp.njcp_558_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Gastrointestinal tract stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract (GIS). GISTs may cause significant morbidity and mortality rates. Aim In this study, it was aimed to evaluate 10 years of gastric GIST cases followed in our hospital, and to analyze the prognostic factors. Subjects and Methods In this single-center retrospective study, a total of 64 patients who were operated between May 2010 and May 2020 due to gastric GIST tumor were reviewed. Clinical and pathological features, risk classifications, overall survival (OS) and disease-free survival (DFS) were evaluated. Results According to the risk classification, 18.8% of the patients were in the high-risk group. The overall 5-year OS and DFS rates were 85.7%. The mean OS of the patients was 47.9 SD36.2 months, and the duration of DFS was 45.5 months. Patients with a 5-year OS rate above 5 cm in diameter (P = 0.024), with a mitotic index above 5/50 high power field (HPF) (P = 0.038), and those with a high-risk group (P = 0.011) were significantly lower than the other group. In the correlation analysis, it was found that tumor diameter correlated significantly with OS (P = 0.034; r = -0.317). Tumor diameter and mitotic index were found to be inversely correlated with DFS duration (P = 0.004; r = -0.425 and P = 0.035; r = -0.316, respectively). Conclusion Our findings showed that in gastric GIST cases, as the primary tumor diameter and mitotic index increase, correlate with survival rates and the mean overall and disease-free survival times decrease.
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Affiliation(s)
- H Uzunoglu
- Department of General Surgery, Kartal Dr Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Y Tosun
- Department of General Surgery, Kartal Dr Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - O Akinci
- Department of General Surgery, Kartal Dr Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - B Baris
- Department of General Surgery, Kartal Dr Lütfi Kırdar City Hospital, Istanbul, Turkey
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Piachas A, Tooulias A, Tsoulfas G. Primary gastrointestinal stromal tumor of the left hepatic lobe: a case report and a review of the literature. J Surg Case Rep 2021; 2021:rjab572. [PMID: 34987760 PMCID: PMC8702343 DOI: 10.1093/jscr/rjab572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/22/2021] [Indexed: 11/24/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) can arise from any site of the gastrointestinal tract. These tumors are known to originate from the interstitial cells of Cajal, located in the gastrointestinal mesenchyme. In the case presented, a 37-year-old Caucasian male was admitted to our Surgery department with 2-month history of mild abdominal pain, early satiety and flatulence. The computed tomography revealed a huge mass in the left hepatic lobe consisting of both spindle and epithelial cells. Immunohistochemistry revealed strong CD117 positivity expression. Only a few other cases of liver GIST have been reported in the literature.
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Affiliation(s)
- Athanasios Piachas
- Division of Transplant Surgery, Aristotle University of Thessaloniki, Ippokratio General Hospital, Thessaloniki, Greece
| | - Andreas Tooulias
- Department of Surgery, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece
| | - Georgios Tsoulfas
- Division of Transplant Surgery, Aristotle University of Thessaloniki, Ippokratio General Hospital, Thessaloniki, Greece
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10
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Addley S, Alazzam M, Johnson C, Soleymani Majd H. Rectovaginal extragastrointestinal stromal tumour (EGIST): an additional entity to be considered in the differential diagnosis of tumours of the rectovaginal septum. BMJ Case Rep 2021; 14:14/3/e237669. [PMID: 33685909 PMCID: PMC7942270 DOI: 10.1136/bcr-2020-237669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Gastrointestinal stromal tumours (GISTs) are rare - and rectovaginal extragastrointestinal stromal tumours (RV-EGISTs) even rarer. We share a case of RV-EGIST, complemented by high-quality radiological and surgical images. A review of current literature pertaining to RV-EGIST is also included. Our case report highlights the diagnostic challenge presented by extragastrointestinal stromal tumours. Differentiated from overlapping pathologies only by targeted application of immunohistopathology and cytogenetics, the inclusion of RV-EGIST in the differential diagnosis of a rectovaginal tumour is essential to making this correct diagnosis. Primary surgery is the treatment of choice for RV-EGIST if complete cytoreduction can be achieved, combined with adjuvant tyrosine kinase inhibitor (TKI) therapy for those with high-risk features to further reduce rates of future recurrence.
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Affiliation(s)
- Susan Addley
- Department of Gynaecology Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
| | - Moiad Alazzam
- Department of Gynaecology Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
| | - Catherine Johnson
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
| | - Hooman Soleymani Majd
- Department of Gynaecology Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
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Ramaswamy A, Chaudhari V, Bhargava P, Bhandare M, Kumar R, Shrikhande SV, Ostwal V. Gastrointestinal Stromal Tumor – An Overview. Indian J Med Paediatr Oncol 2020. [DOI: 10.4103/ijmpo.ijmpo_45_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
AbstractGastrointestinal stromal tumors (GISTs) are rare tumors but are most common mesenchymal tumors of the digestive tract. They are commonly seen in the stomach (60%) and small intestine (30%). GISTs are likely derived from the interstitial cells of Cajal or their stem cell precursors. They are best characterized by computerized tomography and have a specific staining pattern on immunohistochemistry, i.e., C-Kit and DOG-1. The treatment of GIST is based on the risk assessment for relapse, and patients with localized GIST require resection with or without adjuvant imatinib mesylate (IM). Advanced unresectable tumors are usually treated with IM, with a number of further options available for patients post progression on IM. There is an increasing emphasis on identifying C-Kit and platelet-derived growth factor receptor alpha mutations in all patients with GIST, as these are driver mutations with current and future therapeutic implications.
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Affiliation(s)
- Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Vikram Chaudhari
- GI and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Manish Bhandare
- GI and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rajiv Kumar
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shailesh v Shrikhande
- GI and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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12
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Priya V, Kumari N, Krishnani N. Morphological Correlates of KIT and PDGFRA Genotypes in Gastrointestinal Stromal Tumour. Turk Patoloji Derg 2020; 36:116-125. [PMID: 31538651 PMCID: PMC10511256 DOI: 10.5146/tjpath.2019.01470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 09/10/2019] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The aim of the study was to study the clinicopathological and immunohistochemical features of gastrointestinal stromal tumours and correlation with KIT/PDGFRA mutations. MATERIAL AND METHOD Eighty consecutive resected cases were genotyped for KIT exons 11, 9, 13, 17 and PDGFRA exons 18, 14, 12 and correlated with histomorphology by nonparametric tests. RESULTS Forty-seven cases (58.8%) were in the high-risk group. Males had higher rates of KIT exon 11 and PDGFRA exon 18 mutations than females (p=0.03). KIT and PDGFRA mutation frequencies were lower (58.8%) than western data showing KIT exon 11 mutation in 63.8%, KIT exon 9 mutation in 19% and PDGFRA exon 18 mutation in 17% of the cases. Extragastrointestinal stromal tumours (n=6) showed 100% mutation. KIT exon 11 deletion was associated with gastric location (60%) (p=0.04), spindle cells (63.3%), and high-risk stratification (66.6%) (p=0.01) while KIT exon 9 mutation was common in small intestine (66.7%) (p=0.04), in higher risk groups (66.7%) (p=0.01) and 75% of codon 502-503 duplications (p=0.03). PDGFRA 18 mutation was common in males (p=0.03), in gastric location (62.5%) (p=0.04), in cases showing mild to moderate atypia (62.5%) (p=0.01) and lower risk stratification (62.5%) (p=0.01). KIT/PDGFRA mutations were significantly associated with gender (p=0.03), location (p=0.04), nuclear atypia (p=0.01) and risk stratification (p=0.01). CONCLUSION Morphological features and anatomic location may be useful in deciding molecular testing strategy, particularly in resource-limited settings, when a plethora of targetable mutations are present. An algorithm may be derived for genotyping with KIT exon 11 and PDGFRA exon 18 heading the list of targetable mutations. This approach may reduce financial burden on patients as well as workload on hospital staff.
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Affiliation(s)
- Valli Priya
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Niraj Kumari
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Narendra Krishnani
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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13
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Reichardt P, Schlemmer M, Delgado Perez JR, Papai Z, Prausova J, Melichar B, Fumagalli E, Barone C, Bauer S, Pustowka A, Crippa S, Castellana R, Quiering C, Le Cesne A. Safety of Imatinib Mesylate in a Multicenter Expanded Access Program in Adult Patients with Gastrointestinal Stromal Tumors in the Adjuvant Setting. Oncol Res Treat 2019; 42:629-635. [PMID: 31550719 DOI: 10.1159/000502749] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 08/14/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors most often caused by activating mutations of the KIT gene. KIT tyrosine kinase inhibitors provide targeted therapy for the underlying genetic mutation, and adjuvant therapy is indicated for patients who are at significant risk of relapse following GIST resection. This is a report of the safety of imatinib in patients with GIST in the adjuvant setting in an expanded access program. METHODS In this multicenter, open-label, single-arm trial, safety was assessed based on the frequency of adverse events (AEs). RESULTS Three hundred patients were treated and analyzed; 40 patients discontinued treatment. Median overall exposure during the program was 181 days (range 9-420); most patients (260/300 treated) completed the study. Six patients had disease recurrence, 4 of whom discontinued. In line with previously published reports, the most frequent AEs were nausea, diarrhea, and periorbital edema. The AEs were mild to moderate in most cases (76%). CONCLUSIONS These findings are in agreement with the known safety profile of imatinib and confirm the safety of imatinib at 400 mg/day in the adjuvant setting. The incidence of severe AEs was low.
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Affiliation(s)
- Peter Reichardt
- Department of Oncology and Palliative Care, Sarcoma Center Berlin-Brandenburg, Helios Klinikum Berlin-Buch, Berlin, Germany
| | - Marcus Schlemmer
- Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany,
| | - Juan R Delgado Perez
- Department of Medical Oncology, University Hospital Virgen de las Nieves, Granada, Spain
| | - Zsuzsanna Papai
- Department of Oncology, Medical Centre, Hungarian Defense Forces, Budapest, Hungary
| | - Jana Prausova
- Department of Oncology, University Hospital Motol, 2nd Faculty of Medicine, Charles University, Prague, Czechia
| | - Bohuslav Melichar
- Department of Oncology, Palacky University Medical School and Teaching Hospital Olomouc, Olomouc, Czechia
| | - Elena Fumagalli
- Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Carlo Barone
- Division of Medical Oncology, University Hospital A. Gemelli, Rome, Italy
| | - Sebastian Bauer
- Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University Hospital, University of Duisburg-Essen, Essen, Germany
| | | | | | | | | | - Axel Le Cesne
- Department of Medical Oncology, Gustave Roussy Institute of Oncology, Villejuif, France
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Lee H, Gachabayov M, Dong X, Bergamaschi R. Robotic transabdominal excision of pelvic gastrointestinal stromal tumour - a video vignette. Colorectal Dis 2019; 21:1099. [PMID: 31066200 DOI: 10.1111/codi.14681] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 04/12/2019] [Indexed: 01/03/2023]
Affiliation(s)
- H Lee
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York, USA
| | - M Gachabayov
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York, USA
| | - X Dong
- Section of Surgical Oncology, Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York, USA
| | - R Bergamaschi
- Section of Colorectal Surgery, Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, New York, USA
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Ma XB, Liu LJ, Niu Q, Shang BY, Li YY, Liu CX. Multiple intestinal stromal tumors in a young patient with acute gastrointestinal hemorrhage: A case report and literature review. Shijie Huaren Xiaohua Zazhi 2019; 27:972-976. [DOI: 10.11569/wcjd.v27.i15.972] [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] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute small intestinal bleeding in clinical diagnosis and treatment is not specific, and the diagnosis of small intestinal bleeding is still a major clinical challenge because of its high mobility, tortuosity, and difficulty in endoscopic examination.
CASE SUMMARY This case is a young patient with multiple stromal tumors of the small intestine complicated with acute massive hemorrhage of the digestive tract. After correction of shock, abdominal computed tomography (CT) and emergency enteroscopy were performed, followed by multi-disciplinary team discussion to develop a reasonable and standardized treatment plan and subsequent therapy to save the patient¡¯s life and maximize the benefits of the patient.
CONCLUSION Small intestinal stromal tumor has an insidious onset and lacks specific clinical manifestations. According to the characteristics of this disease, B-mode ultrasound, CT, magnetic resonance imaging, digital subtraction angiography, gastrointestinal endoscopy, capsule endoscopy, and other examinations should be used to make a preoperative diagnosis and conduct accurate clinical staging. Multidisciplinary discussion is helpful to develop standardized treatment options to improve the prognosis of patients.
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Affiliation(s)
- Xing-Bin Ma
- Department of Gastroenterology, Binzhou Medical College Affiliated Hospital, Binzhou 256603, Shandong Province, China
| | - Li-Juan Liu
- Department of Gastroenterology, Binzhou Medical College Affiliated Hospital, Binzhou 256603, Shandong Province, China
| | - Qiong Niu
- Department of Gastroenterology, Binzhou Medical College Affiliated Hospital, Binzhou 256603, Shandong Province, China
| | - Bing-Ying Shang
- Department of Gastroenterology, Binzhou Medical College Affiliated Hospital, Binzhou 256603, Shandong Province, China
| | - Yang-Yang Li
- Department of Pathology, Binzhou Medical College Affiliated Hospital, Binzhou 256603, Shandong Province, China
| | - Cheng-Xia Liu
- Department of Gastroenterology, Binzhou Medical College Affiliated Hospital, Binzhou 256603, Shandong Province, China
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Gastrointestinal Stromal Tumor: Genotype Frequency and Prognostic Relevance. Appl Immunohistochem Mol Morphol 2019; 26:153-160. [PMID: 27258566 DOI: 10.1097/pai.0000000000000395] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Genotyping has an important role in the prognosis and prediction of response to tyrosine kinase inhibitor therapy. KIT exon 11 deletions serve as an adverse prognostic marker. Gastrointestinal stromal tumor (GIST) genotype has been described in developed countries; however, data from India are lacking. The aim of this study was to determine the genotype frequency and its prognostic relevance. MATERIALS AND METHODS Eighty consecutive cases of resected GIST were evaluated for histologic and immunohistochemical findings. Mutation analysis for exons 9, 11, 13, and 17 of KIT and 12 and 18 of PDGFRA was carried out by PCR-Sanger sequencing. Genotypes were correlated with risk groups, recurrence, and imatinib therapy. RESULTS Forty-seven of 80 cases (58.7%) showed mutations, including 30 cases (37.5%) in KIT exon 11, 9 cases (11.2%) in KIT exon 9, and 8 cases (10%) in PDGFRA exon 18. Codon 557-558 deletion was present in 15 cases. D842E was the most common in PDGFRA, with similar histologic features as D842V. KIT exon 11 deletion had higher mitotic rate, larger tumor size, high-risk stratification, and lower recurrence-free survival. Recurrences were seen in 12 (16.4%) patients. Nine patients (75%) with recurrence were on imatinib therapy. CONCLUSIONS GIST genotype frequency is lower in Indians. KIT exon 11 deletion is associated with poor prognosis compared with wild-type and other missense mutations. D842E is a common PDGFRA mutation in Indian patients. Patients with a wild genotype are not suitable candidates for imatinib therapy. Genotyping can serve as an important prognostic marker.
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Krishnamurthy G, Singh H, Sharma V, Savlania A, Vasishta RK. Therapeutic Challenges in the Management of Bleeding Duodenal Gastrointestinal Stromal Tumor: a Case Report and Review of Literature. J Gastrointest Cancer 2019; 50:170-174. [PMID: 30628032 DOI: 10.1007/s12029-018-00197-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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18
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Nie Y, Sun W, Xiao Z, Ye S. Complete response to sunitinib for more than three years in a patient with a jejunum gastrointestinal stromal tumor: A case report. Medicine (Baltimore) 2019; 98:e14060. [PMID: 30653116 PMCID: PMC6370167 DOI: 10.1097/md.0000000000014060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
RATIONALE Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is characterized by KIT mutations. Patientsresistant to 1st-line imatinib therapy are usually given sunitinib assecond-line treatment, which provides a median progression-free survival of 8 to 12 months. We report the 1st case of metastatic jejunum GIST with a KIT exon 11 deletion that showed complete response (CR) to sunitinib for more than 3 years. PATIENT CONCERNS A 34-year-old man with advanced jejunum GIST was surgically treated upon initial diagnosis, and was histologically found to carry a high recurrence risk. Genetic testing revealed a KIT exon 11 deletion, and adjuvant therapy with imatinib was administered. The imatinib dose was escalated following recurrence in the abdomen, but the mass continued to grow. DIAGNOSIS He was diagnosed with abdominal recurrence of GIST based on his medical history and histopathological results. INTERVENTION Second-line sunitinib therapy was given. OUTCOMES The mass disappeared, and CR was seen following 7 months of sunitinib therapy; this CR was sustained for more than 45 months. LESSONS In cases of metastatic jejunum GIST with a KIT exon 11 deletion, sunitinib as second-line therapy can be used to achieve CR for more than 3 years.
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Affiliation(s)
- Yanli Nie
- Department of Gastrointestinal Medical Oncology, The Hubei Cancer Hospital, Huazhong University of Science and Technology
| | - Wenjia Sun
- Department of Pathology, The Hubei Cancer Hospital, Huazhong University of Science and Technology
| | - Zhihua Xiao
- Department of Gastrointestinal Medical Oncology, The Hubei Cancer Hospital, Huazhong University of Science and Technology
| | - Shengwei Ye
- Department of Gastrointestinal Surgical Oncology, The Hubei Cancer Hospital, Huazhong University of Science and Technology, Wuhan, China
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Xue F, Liu Z, Xu J, Xu X, Chen X, Tian F. Neferine inhibits growth and migration of gastrointestinal stromal tumor cell line GIST-T1 by up-regulation of miR-449a. Biomed Pharmacother 2018; 109:1951-1959. [PMID: 30551450 DOI: 10.1016/j.biopha.2018.11.029] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 10/30/2018] [Accepted: 11/06/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Gastrointestinal stromal tumor (GIST) threatens the health of middle-aged and older people with high recurrence rate and low survival rate. In this study, Neferin (Nef) was hoped to control growth and migration of GIST cell line GIST-T1. METHODS Cell viability, proliferation, apoptosis, and migration were determined by cell counting kit-8 (CCK-8) assay, bromodeoxyuridine (BrdU) assay, Annexin V-FITC/PI double staining method, and Transwell assay, respectively. The expression level of miR-449a was determined by qRT-PCR. Cell transfection was conducted to alter the expression level of miR-449a. Protein expression levels of key factors involved in cell cycle, cell apoptosis, cell migration, PI3K/AKT pathway and Notch pathways were analyzed by western boltting. RESULTS Nef significantly inhibited GIST-T1 cell viability, proliferation, migration, but promoted cell apoptosis. The expression level of miR-449a was up-regulated in GIST-T1 cells after Nef treatment. Suppression of miR-449a reversed the Nef-induced GIST-T1 cell proliferation and migration inhibition, as well as cell apoptosis. Importantly, Nef inactivated PI3K/AKT and Notch pathways in GIST-T1 cells by up-regulating miR-449a. Inhibitors of PI3K/AKT and Notch pathways notably reversed the effects of Nef + miR-449a inhibitor on GIST-T1 cell proliferation, apoptosis and migration. Besides, Nef also suppressed human gastric cancer SGC7901 cell migration and induced cell apoptosis. CONCLUSION Nef suppressed growth and migration of GIST-T1 cells possibly via up-regulation of miR-449a and then inactivation of PI3K/AKT and Notch pathways.
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Affiliation(s)
- Fangxi Xue
- Department of Gastroenterology, Linyi Central Hospital, Linyi, 276400, China
| | - Zhaoxia Liu
- Department of Gastroenterology, Linyi Central Hospital, Linyi, 276400, China
| | - Jian Xu
- Department of Gastroenterology, Linyi Central Hospital, Linyi, 276400, China
| | - Xiaoguang Xu
- Department of Gastroenterology, Linyi Central Hospital, Linyi, 276400, China
| | - Xingtian Chen
- Department of Gastroenterology, Linyi Central Hospital, Linyi, 276400, China
| | - Feng Tian
- Department of Gastroenterology, Linyi Central Hospital, Linyi, 276400, China.
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Amoruso M, Papagni V, Picciariello A, Pinto VL, D'Abbicco D, Margari A. Intestinal occlusion by stenotic neuroendocrine tumours of left colon and concomitant association with small bowel gastrointestinal stromal tumours: A case report. Int J Surg Case Rep 2018; 53:182-185. [PMID: 30408742 PMCID: PMC6222084 DOI: 10.1016/j.ijscr.2018.10.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Revised: 09/29/2018] [Accepted: 10/14/2018] [Indexed: 12/30/2022] Open
Abstract
Gastrointestinal stromal tumours (GIST) and Neuroendocrine tumours (NET) of the gastroenteropancreatic tract are rare neoplasms. Treatment for colonic NETs was similar to colonic adenocarcinoma, with segmental resection and lymphadenectomy. The associationof GIST and NET is difficult to suspect Serum CgA remains the most important biochemical marker in the diagnostics, monitoring, and establishing the prognosis in colorectal NETs. Early diagnosis of concomitant tumors such as GIST and NET will guarantee a better outcome of patients. Introduction The association between Gastrointestinal Stromal Tumours (GIST) and Neuroendocrine Tumours (NET) is very rare. These tumours have various clinical expressions and sometimes are asymptomatic. Synchronous NETs and GISTs have been already described in literature in few case reports. On the other hand, there is no mention of concomitant presence of discending colon NEC-G3 and small intestinal GIST. Presentation of case: we presented a case of a patient with clinical evidence of intestinal occlusion and radiological and intraoperative aspects of an adenocarcinoma of the left colon with a single metastasis on small bowel. The pathology analysis of the tumour showed a stenotic left colon NEC-G3 and a small bowel GIST. Discussion In this case report GIST was surgically treated as a small bowel ripetitive lesion and NET as a left colon adenocarcinoma. These tumours may have a similar presentation in terms of symptoms, endoscopic findings and imaging results. Conclusion Concomitant NEC and GIST is rare but it is important to investigate patients before surgery in order to distinguish these from other tumours because of the different prognosis.
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Affiliation(s)
- M Amoruso
- Dept of Emergency and Organ Transplantation, General Surgery Unit "G. Marinaccio", University "Aldo Moro" of Bari, Bari, Italy.
| | - V Papagni
- Dept of Emergency and Organ Transplantation, General Surgery Unit "G. Marinaccio", University "Aldo Moro" of Bari, Bari, Italy
| | - A Picciariello
- Dept of Emergency and Organ Transplantation, General Surgery Unit "G. Marinaccio", University "Aldo Moro" of Bari, Bari, Italy
| | - V L Pinto
- Dept of Emergency and Organ Transplantation, General Surgery Unit "G. Marinaccio", University "Aldo Moro" of Bari, Bari, Italy
| | - D D'Abbicco
- Dept of Emergency and Organ Transplantation, General Surgery Unit "G. Marinaccio", University "Aldo Moro" of Bari, Bari, Italy
| | - A Margari
- Dept of Emergency and Organ Transplantation, General Surgery Unit "G. Marinaccio", University "Aldo Moro" of Bari, Bari, Italy
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Valdes-Peregrina E, Hernández-González M, de León-Pacheco O, Mendoza-Ramírez S. Extra-gastrointestinal stromal tumour. Report of primary tumour in the omentum. REVISTA MÉDICA DEL HOSPITAL GENERAL DE MÉXICO 2018. [DOI: 10.1016/j.hgmx.2016.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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22
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Importance of Early Diagnosis of Gastrointestinal Stromal Tumors of the Stomach: Our 5-Year, Single-Center Experience. Int Surg 2018. [DOI: 10.9738/intsurg-d-17-00076.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective:
The aim of this study was to investigate clinicopathologic characteristics, diagnosis, treatment, and prognosis of patients who underwent surgery with a diagnosis of a gastrointestinal stromal tumor (GIST) of the stomach.
Methods:
In this single center study, the data of a total of 42 patients diagnosed with a GIST of the stomach in our center between 2010 and 2015 were retrospectively analyzed. The mean age was 60.6 years, with a male-to-female ratio of 1.47/1. Patients presented with various complaints (21 patients had stomach pain,14 patients were asymptomatic, 3 patients had hemorrhage, 2 patients had heartburn and acidity,1 patient had intumescence,1 patient had nausea and vomiting), and all patients underwent surgery. The initial diagnosis was made with endoscopy in 19 patients, with computed tomography in 21 patients, and with magnetic resonance imaging in 2 patients. Local excision or wedge resection was performed in 27 patients, whereas subtotal gastrectomy was performed in 15 patients.
Results:
The mean tumor diameter was 5.66 cm. Pathologically, 25 patients had very low, 5 patients had low, 6 patients had moderate, and 6 patients had high-grade malignancy. The patients with moderate- to high-grade malignancy received imatinib. Liver metastasis occurred in 2 patients. The mean follow-up was 33 months. The mean disease-free survival time was 31.72 months, and the mean disease-specific (n = 2) survival time was 31.25 months. All patients including metastatic ones were still alive.
Conclusions:
Our study results show that frequent use of imaging studies and increased use of endoscopic scans for various reasons may increase the rate of incidentally detected gastric stromal tumors. High rates of disease-free survival can be achieved in GIST patients who are in the low-risk group due to the early diagnosis.
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Song S, Ren W, Wang Y, Zhang S, Zhang S, Liu F, Cai Q, Xu G, Zou X, Wang L. Tumor rupture of gastric gastrointestinal stromal tumors during endoscopic resection: a risk factor for peritoneal metastasis? Endosc Int Open 2018; 6:E950-E956. [PMID: 30083583 PMCID: PMC6070373 DOI: 10.1055/a-0619-4803] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Accepted: 03/14/2018] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Up to the present time, complete surgical excision has been the standard treatment for primary GISTs greater than 2 cm. It is well known that tumor rupture during surgery is an independent risk factor for peritoneal metastasis; however, it is not known whether the risk of peritoneal metastasis increases in cases where the tumor is ruptured during endoscopic resection. PATIENTS AND METHODS A total of 195 patients treated for GIST between January 2014 and December 2016 in our hospital were enrolled in this study. They were divided into two groups according to whether the tumor was ruptured during endoscopic resection. The rate of peritoneal metastasis in patients in the two groups who also suffered perforation was investigated from the follow-up results. RESULTS Approximately 55.4 % of all patients were female and the average age of the study group was 59.0 ± 10.3 years. Of the 195 patients, the tumors in 27 were ruptured and the remaining 168 patients underwent en bloc resection. There was no statistically significant difference in gender or age between the two groups. The median tumor size (maximum diameter) in all patients was 1.5 cm (0.3 - 5.0 cm): 2.5 cm (0.8 - 5.0 cm) and 1.4 cm (0.3 - 4.0 cm) in the tumor rupture group and en bloc resection group, respectively ( P < 0.001). Most of the tumors were located in the gastric fundus. At a median follow-up of 18.7 ± 10.2 months, neither tumor recurrence (liver metastasis, peritoneal metastasis, local recurrence) nor mortality related to GISTs were detected. CONCLUSIONS Tumor rupture during endoscopic resection of gastric GISTs may not be a risk factor for peritoneal metastasis.
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Affiliation(s)
- Shiyi Song
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Wei Ren
- Department of Geriatrics, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Yi Wang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Shu Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Song Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Fei Liu
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Qiang Cai
- Digestive Diseases, Emory University, Atlanta, GA, USA
| | - Guifang Xu
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Lei Wang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China,Corresponding author Lei Wang Department of GastroenterologyThe Affiliated Drum Tower Hospital of Nanjing University, Medical SchoolNo. 321Zhongshan RoadNanjingJiangsu 210008China+86-138-51579216
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Prause M, Niedermoser S, Schirrmacher R, Wängler C, Wängler B. Synthetic approaches towards [18F]fluoro-DOG1, a potential radiotracer for the imaging of gastrointestinal stromal tumors. Tetrahedron Lett 2018. [DOI: 10.1016/j.tetlet.2018.07.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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25
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Aghdassi A, Christoph A, Dombrowski F, Döring P, Barth C, Christoph J, Lerch MM, Simon P. Gastrointestinal Stromal Tumors: Clinical Symptoms, Location, Metastasis Formation, and Associated Malignancies in a Single Center Retrospective Study. Dig Dis 2018; 36:337-345. [PMID: 29870973 DOI: 10.1159/000489556] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 04/18/2018] [Indexed: 02/02/2023]
Abstract
BACKGROUND AND AIMS Gastrointestinal stromal tumors (GISTs) are rare malignancies but the most common mesenchymal tumors of the digestive tract. Recent advances in diagnostic imaging and an increasing incidence will confront us more frequently with stromal tumors. This single center study aimed to characterize GIST patients in terms of tumor location, clinical presentation, metastasis formation, as well as associated secondary malignancies. METHODS In a retrospective study, 104 patients with a histologically confirmed diagnosis of GIST, collected between 1993 and 2011, were characterized for several clinical features. RESULTS The most common GIST location was the stomach (67.6%) followed by the small intestine (16.2%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most frequently reported symptoms whereas about one-third of patients remained clinically asymptomatic (31.6%); 14.4% of patients had either synchronous or metachronous metastases and there was a significant prevalence also in the low risk group. The proportion of secondary malignant associated neoplasms was 31% in our GIST cohort, among which gastrointestinal, genitourinary tumors, and breast cancer were the most prevalent. CONCLUSION There was a considerable risk for metastasis formation and the development of secondary neoplasias that should encourage discussion about the appropriate surveillance strategy after surgery for GIST.
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Affiliation(s)
- Ali Aghdassi
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Agnes Christoph
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Frank Dombrowski
- Institute of Pathology, University Medicine Greifswald, Greifswald, Germany
| | - Paula Döring
- Institute of Pathology, University Medicine Greifswald, Greifswald, Germany
| | | | - Jan Christoph
- Chair of Medical Informatics, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Peter Simon
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
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Badri M, Chabaane M, Gader G, Bahri K, Zammel I. Cerebellar metastasis of gastrointestinal stromal tumor: A case report and review of the literature. Int J Surg Case Rep 2017; 42:165-168. [PMID: 29248834 PMCID: PMC5985257 DOI: 10.1016/j.ijscr.2017.12.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 12/03/2017] [Accepted: 12/04/2017] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Intracranial metastases of gastro intestinal tumors are very rare. To the best of our knowledge only few cases were reported on the literature. CASE DESCRIPTION We describe the case of 66-year-old male that presented with headache and vomiting. Physical examination found a kinetic cerebellar syndrome. Brain CT scan and MRI showed a right cerebellar tumor. Sub-occipital craniotomy was performed and the tumor was completely resected. Surgical outcomes were marked by the occurrence of an abdominal pain two days after brain surgery. Peritonitis was diagnosed and the patient underwent surgery. Per-operatively, a hemorrhagic tumor perforating the intestines was found and resected. Pathologic examination of the cerebral tumor's resection piece and the intestinal resection piece concluded to a metastasis of a stromal gastro-intestinal tumor. DISCUSSION Gastro-intestinal stromal tumors are frequent neoplasms, but intracranial metastases of these neoplasms are extremely rare. Abdominal symptomatology frequently reveals the pathology. However, extra digestive symptoms may in rare cases disclose intestinal tumors. Intracranial metastases of gastro-intestinal stromal tumors are generally solitary mainly supratentorial. Infratentorial metastases are very uncommon. Management of gastro-intestinal stromal tumors is based on surgical removal of the tumor. Adjuvant treatment consisting on chemotherapy and radiotherapy is subject of debate. CONCLUSIONS Gastro-intestinal stromal tumors are frequent neoplasms with a high metastasizing potential on liver and peritoneum. Brain metastases are extremely rare and the prognosis is worse when they are present. Surgery remains the main treatment for the primitive and the secondary lesions.
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Affiliation(s)
- Mohamed Badri
- El Manar-Tunis University, Faculty of medicine of Tunis, Burns and Trauma Center, Department of Neurosurgery, Ben Arous, Tunisia.
| | - Mohamed Chabaane
- El Manar-Tunis University, Faculty of medicine of Tunis, Burns and Trauma Center, Department of Neurosurgery, Ben Arous, Tunisia.
| | - Ghassen Gader
- El Manar-Tunis University, Faculty of medicine of Tunis, Burns and Trauma Center, Department of Neurosurgery, Ben Arous, Tunisia.
| | - Kamel Bahri
- El Manar-Tunis University, Faculty of medicine of Tunis, Burns and Trauma Center, Department of Neurosurgery, Ben Arous, Tunisia.
| | - Ihsen Zammel
- El Manar-Tunis University, Faculty of medicine of Tunis, Burns and Trauma Center, Department of Neurosurgery, Ben Arous, Tunisia.
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Synthesis, in vitro and in vivo evaluation of 18F-fluoronorimatinib as radiotracer for Imatinib-sensitive gastrointestinal stromal tumors. Nucl Med Biol 2017; 57:1-11. [PMID: 29175467 DOI: 10.1016/j.nucmedbio.2017.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 11/03/2017] [Accepted: 11/15/2017] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GIST) have a wide range of mutations, but can mostly be treated with Imatinib, until eventually resistance towards this tyrosine kinase inhibitor is acquired. Early and non-invasive determination of the sensitivity of the tumor and its metastases towards Imatinib by positron emission tomography (PET) would be beneficial for therapy planning and monitoring. METHODS We developed a synthesis strategy towards the precursor molecule, performed the 18F-synthesis and in the following evaluated the radioligand in vitro regarding its lipophilicity, stability and biological activity (KIT binding properties) as well as its in vivo properties in GIST tumor-bearing mice. RESULTS [18F]fluoronorimatinib could be obtained in an overall radiochemical yield of 22.2±3.3% within 90min. The radioligand showed high GIST cell uptake and was able to distinguish between Imatinib-sensitive and resistant tumor cell lines (GIST-T1, GIST882, GIST430) in vitro. Further biological evaluations of the ligand towards 9 different GIST-relevant KIT mutations showed comparable binding affinities compared to the structural lead Norimatinib (65nM vs. 53nM for wt-KIT). The in vivo evaluation of the newly developed radioligand showed tumor-to-background-ratios comparable to previously described, similar radiotracers. CONCLUSIONS Thus, [18F]fluoronorimatinib is able to distinguish between Imatinib-resistant and sensitive KIT mutations. Although no improvement of in vivo tumor-to-background ratios could be achieved compared to formerly described radioligands, the hepatic uptake could be considerably reduced, being advantageous for the imaging of GIST. Advances in knowledge and implications for patient care: We were able to show that it is possible to significantly reduce the unfavorably high hepatic uptake of small-molecule radioligands applicable for GIST PET imaging. This work can thus be the basis for further work intending to develop a PET-radioligand for Imatinib-dependent GIST imaging.
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Ghith A, Ismail NS, Youssef K, Abouzid KA. Medicinal Attributes of Thienopyrimidine Based Scaffold Targeting Tyrosine Kinases and Their Potential Anticancer Activities. Arch Pharm (Weinheim) 2017; 350. [DOI: 10.1002/ardp.201700242] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 08/14/2017] [Accepted: 09/05/2017] [Indexed: 01/02/2023]
Affiliation(s)
- Amna Ghith
- Faculty of Pharmaceutical Sciences and Pharmaceutical Industries; Department of Pharmaceutical Chemistry; Future University in Egypt; Cairo Egypt
| | - Nasser S.M. Ismail
- Faculty of Pharmaceutical Sciences and Pharmaceutical Industries; Department of Pharmaceutical Chemistry; Future University in Egypt; Cairo Egypt
| | - Khairia Youssef
- Faculty of Pharmaceutical Sciences and Pharmaceutical Industries; Department of Pharmaceutical Chemistry; Future University in Egypt; Cairo Egypt
| | - Khaled A.M. Abouzid
- Faculty of Pharmacy; Department of Pharmaceutical Chemistry; Ain Shams University; Abbassia, Cairo Egypt
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Lu Y, Mao F, Li X, Zheng X, Wang M, Xu Q, Zhu J, Li J. Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs). J Med Chem 2017; 60:5099-5119. [DOI: 10.1021/acs.jmedchem.7b00468] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Yanli Lu
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Fei Mao
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Xiaokang Li
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Xinyu Zheng
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Manjiong Wang
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Qing Xu
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Jin Zhu
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Jian Li
- Shanghai Key Laboratory
of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
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Cybułka B, Golański M, Rapeła J, Wach A. Elective Surgery of Umbilical Hernia as a First Clinical Manifestation of a Gastrointestinal Stromal Tumor (Gist) - Case Report. POLISH JOURNAL OF SURGERY 2017; 88:221-5. [PMID: 27648625 DOI: 10.1515/pjs-2016-0056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Indexed: 11/15/2022]
Abstract
Gastrointestinal stromal tumor is a rare pathology. GISTs account for 0.3-1% of all tumors of the gastrointestinal tract. At the same time, this type of cancer is the most common, malignant, non-epithelial tumor of the gastrointestinal tube. Over 90% of GISTs are found in the stomach and small intestine. This cancer usually develops without characteristic clinical symptoms and is diagnosed incidentally. This clinical situation, in which the first symptom of a GIST-pattern tumor includes a fully-symptomatic, non-complicated umbilical hernia, is an unprecedented anomaly. This work presents a case report of a 77-year old female patient undergoing elective surgery, in which the contents of the hernial sac included a stromal tumor. Disseminated, multi-focal progression of the disease was found intraoperatively. Postoperative histopathology and immunohistochemistry revealed a gastrointestinal stromal tumor GIST of the spindle cell type, showing a CD-117, CD-34, SMA expression with possible starting point in the small intestine.
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Massani M, Capovilla G, Ruffolo C, Bassi N. Gastrointestinal stromal tumour (GIST) presenting as a strangulated inguinal hernia with small bowel obstruction. BMJ Case Rep 2017; 2017:bcr-2016-217273. [PMID: 28104721 DOI: 10.1136/bcr-2016-217273] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Gastrointestinal stromal tumours (GISTs) can arise everywhere along the gastrointestinal (GI) tract. Their presentation in unusual locations should always be taken into account. A 74-year-old man referred to the emergency department for small bowel obstruction caused by an incarcerated inguinal hernia. A CT scan showed a mesenchymal tumour originating from the herniated bowel loop and a mass in the ascending colon. Laparoscopic resection of the mass and laparoscopic right hemicolectomy were performed. The histology showed a ruptured GIST arising from the herniated small bowel and a high-grade dysplasia villous adenoma of the right colon. GISTs can present with symptoms spanning from vague abdominal discomfort to surgical urgencies. Strangulated hernia is an extremely rare presentation, with only two cases described in the literature. A safe surgical approach was obtained with laparoscopy, maintaining surgical radicality. The ileal localisation and the pseudocapsule rupture were the main risk factors on prognostic stratification.
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Affiliation(s)
- Marco Massani
- Regional Center for HPB Surgery, Regional Hospital of Treviso, Treviso, Italy
| | - Giovanni Capovilla
- Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Cesare Ruffolo
- Regional Center for HPB Surgery, Regional Hospital of Treviso, Treviso, Italy
| | - Nicolò Bassi
- Regional Center for HPB Surgery, Regional Hospital of Treviso, Treviso, Italy.,Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
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Arabadzhieva E, Yonkov A, Bonev S, Bulanov D, Taneva I, Vlahova A, Dikov T, Dimitrova V. A rare case with synchronous gastric gastrointestinal stromal tumor, pancreatic neuroendocrine tumor, and uterine leiomyoma. World J Surg Oncol 2016; 14:287. [PMID: 27846844 PMCID: PMC5111233 DOI: 10.1186/s12957-016-1051-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 11/07/2016] [Indexed: 12/17/2022] Open
Abstract
Background Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they comprise less than 1% of all gastrointestinal tumors. Neuroendocrine tumors (NET) of the gastro-enteropancreatic system are also rare, representing about 2% of all gastrointestinal neoplasms. Pancreatic localization of NET is extremely uncommon—these tumors are only 1–5% of all pancreatic cancers. Case presentation We describe an unusual case with triple tumor localization—a gastric tumor, a formation in the pancreas, which involves the retroperitoneal space, and a uterine leiomyoma. The exact diagnosis was confirmed with immunohistochemical study after surgical treatment of the patient. Distal pancreatic resection, splenectomy, partial gastrectomy, omentectomy, and hysterectomy were performed. The histological examination proved an epithelioid type of gastric GIST. Immunostaining showed focal positive expression of c-kit and no mitotic figures per 50 HPF. Histology of the pancreatic and retroperitoneal formation proved a well-differentiated NET with origin from the islets of Langerhans. The immunohistochemical study demonstrated co-expression of chromogranin A and synaptophysin. Conclusions This is the fourth case published so far of a patient with synchronous pancreatic NET and gastric GIST. The main objective of the study is to present a unique case because we have not found any reports for coexistence of the described three types of neoplasm, as in our patient, and we hope that it will be valuable in the future investigations about the genesis, diagnosis, and treatment of these types of tumors.
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Affiliation(s)
- Elena Arabadzhieva
- Department of General and Hepato-pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, 1 Georgi Sofiiski Str, 1431, Sofia, Bulgaria. .,Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria.
| | - Atanas Yonkov
- Department of General and Hepato-pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, 1 Georgi Sofiiski Str, 1431, Sofia, Bulgaria.,Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria
| | - Sasho Bonev
- Department of General and Hepato-pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, 1 Georgi Sofiiski Str, 1431, Sofia, Bulgaria.,Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria
| | - Dimitar Bulanov
- Department of General and Hepato-pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, 1 Georgi Sofiiski Str, 1431, Sofia, Bulgaria.,Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria
| | - Ivanka Taneva
- Department of General and Hepato-pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, 1 Georgi Sofiiski Str, 1431, Sofia, Bulgaria.,Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria
| | - Alexandrina Vlahova
- Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria.,Department of General and Clinical Pathology, 2 Zdrave Str, 1431, Sofia, Bulgaria
| | - Tihomir Dikov
- Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria.,Department of General and Clinical Pathology, 2 Zdrave Str, 1431, Sofia, Bulgaria
| | - Violeta Dimitrova
- Department of General and Hepato-pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, 1 Georgi Sofiiski Str, 1431, Sofia, Bulgaria.,Medical University-Sofia, 15 Acad. I. E. Geshov Bul, 1431, Sofia, Bulgaria
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Kissova M, Maga G, Crespan E. The human tyrosine kinase Kit and its gatekeeper mutant T670I, show different kinetic properties: Implications for drug design. Bioorg Med Chem 2016; 24:4555-4562. [PMID: 27527414 DOI: 10.1016/j.bmc.2016.07.059] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Revised: 07/22/2016] [Accepted: 07/26/2016] [Indexed: 12/31/2022]
Abstract
The tyrosine kinase Kit, a receptor for Stem Cell Factor, is involved, among others, in processes associated to cell survival, proliferation and migration. Upon physiological conditions, the activity of Kit is tightly regulated. However, primary mutations that lead to its constitutive activation are the causal oncogenic driver of gastrointestinal stromal tumours (GISTs). GISTs are known to be refractory to conventional therapies but the introduction of Imatinib, a selective inhibitor of tyrosine kinases Abl and Kit, significantly ameliorated the treatment options of GISTs patients. However, the acquisition of secondary mutations renders Kit resistant towards all available drugs. Mutation involving gatekeeper residues (such as V654a and T670I) influence both the structure and the catalytic activity of the enzyme. Therefore, detailed knowledge of the enzymatic properties of the mutant forms, in comparison with the wild type enzyme, is an important pre-requisite for the rational development of specific inhibitors. In this paper we report a thorough kinetic analysis of the reaction catalyzed by the Kit kinase and its gatekeeper mutated form T670I. Our results revealed the different mechanisms of action of these two enzymes and may open a new avenue for the future design of specific Kit inhibitors.
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Affiliation(s)
- Miroslava Kissova
- Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, 27100 Pavia, Italy
| | - Giovanni Maga
- Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, 27100 Pavia, Italy.
| | - Emmanuele Crespan
- Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, 27100 Pavia, Italy.
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Mastoraki A, Toliaki E, Chrisovergi E, Mastoraki S, Papanikolaou IS, Danias N, Smyrniotis V, Arkadopoulos N. Metastatic Liver Disease Associated with Gastrointestinal Stromal Tumors: Controversies in Diagnostic and Therapeutic Approach. J Gastrointest Cancer 2016; 46:237-42. [PMID: 26163021 DOI: 10.1007/s12029-015-9748-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal lesions of the GI tract. They are considered to originate from neoplastic transformation of either the intestinal pacemaker cells of Cajal or the precursor pluripotential stem cells. The genetic basis of GIST growth is an activating mutation of two receptor tyrosine kinases. Recent epidemiologic studies demonstrate that the GIST prevalence is approximately 20/1000000/year. Although GISTs develop in every part of the GI tract, stomach remains the most common localization. About 80 % of the patients experience tumor recurrence or hepatic metastasis after radical resection. GIST liver metastases are usually multiple, large in diameter, and localized in both lobes. In addition, GISTs are usually completely asymptomatic, discovered incidentally. Symptoms are not typical and depend on the location, size, and aggressiveness of the tumor. DISCUSSION Diagnostic evaluation is based on imaging techniques, such as computed tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound. Despite recent research on the therapeutic strategies against GISTs, surgical resection appears the only potentially curative approach. For the advanced metastatic disease, imatinib, a tyrosine kinase inhibitor, has been proposed neoadjuvantly with the surgery performed after the adequate reduction of tumor burden. The aim of this review was to evaluate the results of surgical treatment for metastatic GIST with special reference to the extent of its histological spread and to present the recent literature in order to provide an update on the current concepts of advanced surgical management of this entity.
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Affiliation(s)
- Aikaterini Mastoraki
- 4th Department of Surgery, Medical School, ATTIKON University Hospital, Athens University, 1 Rimini str, 12462, Chaidari, Athens, Greece,
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Wang Y, Peng J, Huang J. Giant and high-risk gastrointestinal stromal tumor in the abdomino-pelvic cavity: A case report. Oncol Lett 2016; 11:2035-2038. [PMID: 26998117 PMCID: PMC4774456 DOI: 10.3892/ol.2016.4196] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2015] [Accepted: 12/14/2015] [Indexed: 12/13/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are benign mesenchymal tumors of the gastrointestinal tract. The clinical presentations of patients with GIST are variable and may be non-specific. The current study reports the case of a 66-year-old man that presented with a gradual enlargement of the abdomen, emaciation, hyperhidrosis and frequent and urgent micturition. A computed tomography (CT) scan of the abdomen revealed a large, heterogeneous, low density mass that occupied the entire abdomino-pelvic cavity. Magnetic resonance imaging (MRI) identified a high signal intensity on the T2 weighted image and an intermediate signal intensity on the T1 weighted image. A contrast enhanced CT scan and MRI demonstrated the uptake of contrast material. A biopsy revealed that the tumor was composed of spindle cells, and immunohistochemical analysis identified the presence of mast/stem cell growth factor receptors. Together, these results lead to a diagnosis of GIST. The clinical findings, imaging modalities and pathological studies suggested that the GIST was a large and high-risk tumor located in the abdomino-pelvic cavity. The final surgical results confirmed these findings. Following conservative treatment with imatnib (400 mg, daily) for 6 months, the tumor became smaller and was suitable for surgery, which the patient received in December 2014. The final surgery confirmed the high-risk GIST. Subsequent to the surgery, the patient was recommended to continue the use of imatnib with regular CT or MRI reexaminations every 3 months, which are planned to continue for 3 years.
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Affiliation(s)
- Yujiao Wang
- Department of Radiology, Clinical Medical College of Yangtze University, Jingzhou, Hubei 434025, P.R. China
| | - Jie Peng
- Department of Radiology, Clinical Medical College of Yangtze University, Jingzhou, Hubei 434025, P.R. China
| | - Jinbai Huang
- Department of Radiology, Clinical Medical College of Yangtze University, Jingzhou, Hubei 434025, P.R. China
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Li YQ, Song J, Liu ZX, Xie DY, Jiang T, Wei GH, Ma HC, Wang JX, Jin ML. Xanthogranulomatous Cholecystitis and Misdiagnosis Analysis. Chin Med J (Engl) 2016; 128:1700-2. [PMID: 26063379 PMCID: PMC4733744 DOI: 10.4103/0366-6999.158384] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
| | | | - Zheng-Xin Liu
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
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Get the GIST? An overview of gastrointestinal stromal tumours. Ir J Med Sci 2016; 185:319-26. [DOI: 10.1007/s11845-016-1410-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 01/15/2016] [Indexed: 12/15/2022]
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Ravez S, Arsenlis S, Barczyk A, Dupont A, Frédérick R, Hesse S, Kirsch G, Depreux P, Goossens L. Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors. Bioorg Med Chem 2015; 23:7340-7. [DOI: 10.1016/j.bmc.2015.10.035] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 10/22/2015] [Accepted: 10/23/2015] [Indexed: 11/15/2022]
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Stemate A, Filimon AM, Tomescu M, Negreanu L. Colon capsule endoscopy leading to gastrointestinal stromal tumor (GIST) diagnosis after colonoscopy failure. BMC Res Notes 2015; 8:558. [PMID: 26458989 PMCID: PMC4603919 DOI: 10.1186/s13104-015-1444-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2014] [Accepted: 09/11/2015] [Indexed: 11/12/2022] Open
Abstract
Background Gastrointestinal stromal tumors are a subtype of mesenchymal tumors. In recent years a significant progress was made in their diagnosis and treatment which led to significant improvement of their prognosis. Endoscopy remains one of the main diagnostic methods. In the rare instance of colonoscopy failure, different approaches are available: different endoscope, computed tomography colonography, capsule endoscopy, use of an enteroscope. Case presentation We present the case of a 75-year-old Caucasian man admitted for abdominal pain, diarrhea and weight loss. Two colonoscopy attempts failed in a different center and a decision to use colon capsule endoscopy was made. This exam revealed a submucosal mass located in the sigmoid colon. Surgery was performed and a local invading gastrointestinal stromal tumor was removed. This is the first image of a colonic gastrointestinal stromal tumor seen on capsule endoscopy. Conclusion Colon capsule is a useful diagnostic tool in selected patients after colonoscopy failure or contraindication.
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Affiliation(s)
- A Stemate
- Internal Medicine 2-Gastroenterology Department, University Hospital, Carol Davila University of Medicine Bucharest, 169, Splaiul Independentei Street, Sector 5, Bucharest, Romania.
| | - A M Filimon
- Vascular Surgery Department, University Hospital, Carol Davila University of Medicine Bucharest, V Babes National Institute of Pathology, Bucharest, Romania.
| | - M Tomescu
- General Surgery Department, University Hospital, Carol Davila University of Medicine Bucharest, Bucharest, Romania.
| | - L Negreanu
- Internal Medicine 2-Gastroenterology Department, University Hospital, Carol Davila University of Medicine Bucharest, 169, Splaiul Independentei Street, Sector 5, Bucharest, Romania.
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Arabadzhieva E, Yonkov A, Bonev S, Bulanov D, Taneva I, Ivanova V, Dimitrova V. A rare combination between familial multiple lipomatosis and extragastrointestinal stromal tumor. Int J Surg Case Rep 2015; 14:117-20. [PMID: 26263450 PMCID: PMC4573610 DOI: 10.1016/j.ijscr.2015.07.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Revised: 07/20/2015] [Accepted: 07/25/2015] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Rarely, GISTs can be located in mesentery, retroperitoneal space, omentum or pancreas. In these cases, the neoplasm is defined as "extra-gastrointestinal stromal tumors" (EGISTs). PRESENTATION OF CASE We reported a case of a 63-year-old male patient diagnosed by computer tomography with large intraabdominal tumor with vague origin, postoperatively determined as an EGIST. The diagnosis was confirmed by immunohistochemical study. The patient had multiple, subcutaneous, painless lipomas localized in the arms, forearms, thighs, abdomen and thorax. Because of the family history and the clinical presentation the disease was determined as familial multiple lipomatosis (FML). We performed radical tumor resection with distal pancreatectomy and splenectomy, and abdominoplasty, removing redundant skin and underlying subcutaneous fat tissue with multiple lipomas. DISCUSSION FML is a rare hereditary benign disease. On the other hand, only few cases with familial GIST have been reported. In cases with extensive abdominal involvement, the primary origin of EGIST may be impossible to determine so the differential diagnosis is very difficult. CONCLUSION Although we could not prove correlation between the observed diseases, they are extremely rare and their combination is unusual which makes the presented case valuable and interesting.
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Affiliation(s)
- Elena Arabadzhieva
- Department of General and Hepato-Pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, Medical University-Sofia, 1 G.Sofiiski Str., 1431 Sofia, Bulgaria.
| | - Atanas Yonkov
- Department of General and Hepato-Pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, Medical University-Sofia, 1 G.Sofiiski Str., 1431 Sofia, Bulgaria
| | - Sasho Bonev
- Department of General and Hepato-Pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, Medical University-Sofia, 1 G.Sofiiski Str., 1431 Sofia, Bulgaria
| | - Dimitar Bulanov
- Department of General and Hepato-Pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, Medical University-Sofia, 1 G.Sofiiski Str., 1431 Sofia, Bulgaria
| | - Ivanka Taneva
- Department of General and Hepato-Pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, Medical University-Sofia, 1 G.Sofiiski Str., 1431 Sofia, Bulgaria
| | - Vesela Ivanova
- Department of General and Clinical Pathology, Medical University-Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria
| | - Violeta Dimitrova
- Department of General and Hepato-Pancreatic Surgery, University Hospital "Alexandrovska"-Sofia, Medical University-Sofia, 1 G.Sofiiski Str., 1431 Sofia, Bulgaria
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Guerin A, Sasane M, Gauthier G, Keir CH, Zhdavana M, Wu EQ. The economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who have received adjuvant imatinib therapy. J Med Econ 2015; 18:241-8. [PMID: 25422992 DOI: 10.3111/13696998.2014.991787] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To estimate the economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who received imatinib adjuvant therapy. METHODS Data from the MarketScan and PharmMetrics databases between January 2000 and March 2013 were extracted. Patients who had received at least one diagnosis of GIST, had undergone a primary surgery for GIST, and had received at least one prescription for imatinib were included in the analysis. An algorithm was applied to identify those who had a subsequent GIST recurrence. Patients who experienced a recurrence and those who did not have a recurrence were compared for differences in healthcare utilization measures and healthcare costs within 6 months after the recurrence, while adjusting for potential confounding factors. RESULTS A total of 540 patients with primary resectable GIST who received imatinib adjuvant therapy were identified, including 444 (82.2%) patients who did not experience GIST recurrence and 96 (17.8%) patients who did experience recurrence. Patients who experienced GIST recurrence utilized significantly more healthcare resources in all categories than patients who did not have a recurrence, including the number of hospitalizations, days of hospitalization, emergency room visits, outpatient visits, and other medical services (all p-values <0.01). The total healthcare cost was significantly higher for patients with GIST recurrence, with a difference of $4464 per patient per month (p < 0.01). Both the medical and pharmacy costs were significantly higher with adjusted differences of $3488 and $1423 per patient per month, respectively (both p-values <0.01). CONCLUSIONS Patients who had GIST recurrence after surgical resection incurred significantly more healthcare resource utilization and greater healthcare costs within 6 months after the recurrence than patients who did not have recurrence. These findings suggest that GIST recurrence is associated with a substantial economic burden.
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Kim IH, Kwak SG, Chae HD. Prognostic Factors of Patients with Gastric Gastrointestinal Stromal Tumor after Curative Resection: A Retrospective Analysis of 406 Consecutive Cases in a Multicenter Study. Eur Surg Res 2015; 55:12-23. [PMID: 25766570 DOI: 10.1159/000375234] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 01/13/2015] [Indexed: 11/19/2022]
Abstract
BACKGROUND/PURPOSE Gastric gastrointestinal stromal tumors (GISTs) have a highly variable clinical course, and recurrent disease sometimes develops despite curative surgery. This study was undertaken to investigate the surgical role in treating gastric GISTs and evaluate the clinicopathological features of a large series of patients who underwent curative resection for gastric GISTs to clarify which features were independent prognostic factors. METHODS The clinicopathological data of 406 patients with gastric GISTs who underwent curative resection at 4 university hospitals in Daegu, South Korea, from March 1998 to March 2012 were reviewed. All cases were confirmed as gastric GISTs by immunohistochemical staining, in which CD117 or CD34 was positive. Clinical follow-up was performed periodically, and disease-free survival rates were retrospectively investigated using the medical records. RESULTS The mean follow-up period was 42.9 months (range: 2-166). There were 11 recurrent patients (2.7%). Due to the small number of recurrences, age, sex and location were controlled using propensity score matching before performing any statistical analysis. Tumor size, mitotic count, NIH classification, and cellularity were judged to be independent prognostic factors for recurrence by univariate analysis. In a multivariate analysis, tumor size and mitotic count were significantly and independently related to recurrence, and tumor size was determined to be the most important prognostic factor for recurrence after curative resection (hazard ratio: 1.204; p < 0.01). CONCLUSIONS The results of this multicenter study demonstrate that disease-free survival rates are good. Tumor size was disclosed as the most important factor for recurrence in gastric GIST patients who underwent radical resection.
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Affiliation(s)
- In-Hwan Kim
- Department of Surgery, School of Medicine, Catholic University of Daegu, Daegu, South Korea
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Sapalidis K, Panteli N, Strati TM, Anastasiadis I, Kanellos I. Surgical management of gastrointestinal stromal tumors: a single centre's experience. Hippokratia 2015; 19:73-75. [PMID: 26435652 PMCID: PMC4574592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) represent 85% of all mesenchymal neoplasms that affect the gastrointestinal track. Aim of this study is to report a case series of 18 GISTs treated surgically in a single centre and to discuss the diagnostic and therapeutic issues regarding these tumors. CASE SERIES A retrospective search of the unit's medical records from 2002 to 2014 was carried out, to collect all cases diagnosed and treated for GISTs. Demographics and clinical features was obtained for all relevant cases. RESULTS Eighteen cases (18) of GIST were identified. Eleven tumors were located in the stomach, 3 tumors in the duodenum and 4 tumors in the jejunum. The mean age at diagnosis was 62.5 (range 42-81) years, while the male to female ratio was 1.57/1 (11 males/7 females). Patients presented with a variety of symptoms and all underwent surgery. The 5-year-survival rate of these patients was 50%. CONCLUSION Due to non-specific presentation of GISTs, initial diagnosis of these tumors may be delayed. High clinical suspicion and knowledge of their characteristics are essentials in order to achieve an early diagnosis and lead patients to surgery as soon as possible. Hippokratia 2015, 19 (1): 73-75.
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Affiliation(s)
- K Sapalidis
- 3 Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - N Panteli
- 3 Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - T M Strati
- 3 Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - I Anastasiadis
- 3 Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - I Kanellos
- 3 Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Gastrointestinal stromal tumor in a newborn diagnosed in prenatal period: a case report and review of literature. J Pediatr Hematol Oncol 2014; 36:649-52. [PMID: 24276044 DOI: 10.1097/mph.0b013e3182a8f73f] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Only 1.5% to 2% of all GISTs are observed in children and adolescents. Most of the pediatric cases are between 10 and 18 years of age, with a median age of 13 years. GIST is extremely rare in the newborn period. We could find only 5 reports on the neonatal cases. Herein, we have reported a case with abdominal tumor that was identified by prenatal ultrasonography and magnetic resonance imaging, and diagnosed as GIST on the seventh day of life. We have also reviewed the neonatal GIST cases reported in the English literature.
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Yuval JB, Almogy G, Doviner V, Bala M. Diagnostic and therapeutic approach to obscure gastrointestinal bleeding in a patient with a jejunal gastrointestinal stromal tumor: a case report. BMC Res Notes 2014; 7:695. [PMID: 25287119 PMCID: PMC4197232 DOI: 10.1186/1756-0500-7-695] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 08/05/2014] [Indexed: 12/02/2022] Open
Abstract
Background Gastrointestinal stromal tumors of the alimentary tract may present with severe bleeding. Localization and treatment of obscure gastrointestinal bleeding is challenging in cases of negative bi-directional endoscopy. Case presentation A previously healthy 64-year-old Caucasian female presented with clinical signs of active gastrointestinal bleeding. Esophagogastroduodenoscopy was normal, and colonoscopy revealed passage of blood from the small bowel. Computerized tomography angiography demonstrated a hypervascular lesion with active extravasation located in the jejunum. Angiography of the superior mesenteric artery revealed a focal hypervascular mass in the jejunum, and super selective distal coil embolization of the feeding vessel was performed. When the patient was taken for laparoscopic exploration, a 2.5 cm tumor arising from the anti-mesenteric border of the proximal jejunum was identified and resected with primary anastomosis. Pathological results demonstrated a gastrointestinal stromal tumor with a low proliferation index of 1%. Small erosions in the adjacent mucosa confirmed the locus of bleeding. Conclusions Computerized tomography is a useful tool for initial diagnosis of submucosal alimentary tumors in patients with obscure but clinically overt gastrointestinal bleeding. Selective angiography, following positive computerized tomography findings, is an important modality to allow both localization and hemostasis in actively bleeding small bowel tumors, but the procedure carries the risk of bowel necrosis. Complete surgical resection remains the mainstay for treatment of gastrointestinal stromal tumors.
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Affiliation(s)
| | | | | | - Miklosh Bala
- Department of General Surgery, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel.
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A Pancreatic Head Tumor Arising as a Duodenal GIST: A Case Report and Review of the Literature. Case Rep Med 2014; 2014:420295. [PMID: 25295063 PMCID: PMC4176913 DOI: 10.1155/2014/420295] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Revised: 05/04/2014] [Accepted: 07/02/2014] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract that originate from the intestinal cells of Cajal (ICC) (Fletcher et al., 2002). Only a few cases have been described with extragastrointestinal stromal tumors (Kim et al., 2012; Soufi et al., 2013; Meng et al., 2011). They are often diagnosed as a pancreatic head tumor as they are very difficult to relate to the duodenum with CT, MRI, or ultrasound. We present a case of a sixty-four-year-old woman who presented with abdominal pain and cardialgia for a follow-up examination after breast cancer surgery. On laparotomy there was a 3 × 5 cm hypervascular mass arising from the pancreatic head with macroscopically no attachment to the duodenum. The patient underwent pancreatoduodenectomy (PD) modified after Traverso-Longmire, histopathology proved a duodenal GIST. This case proves that duodenal GISTs can grow invasively into the pancreas and appear as solid pancreas head tumor; therefore, these tumors should be included into differential diagnosis.
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TAKEUCHI H, KOIKE H, FUJITA T, TSUJINO H, IWAMOTO Y. Sunitinib treatment for multiple brain metastases from jejunal gastrointestinal stromal tumor: case report. Neurol Med Chir (Tokyo) 2014; 54. [PMID: 24257497 PMCID: PMC4533502 DOI: 10.2176/nmc.cr.2012-0426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare malignant tumors and only a few reported cases of brain metastases can be found. Introduction of a new molecular targeted agent, imatinib mesylate in the last decade has dramatically changed the treatment strategy and prognosis. However, imatinib is usually ineffective for brain metastasis from GISTs. The authors present the case of multiple brain metastases from jejunal GIST. The brain metastasis in the right prefrontal gyrus was detected 20 months after resection of the primary lesion when left hemiparesis began although the patient was on imatinib. Then the patient began taking sunitinib instead of imatinib, and the lesion shrunk and the symptom improved. However, after the dose reduction due to side effects, a new brain metastasis was found and this time, stereotactic radiation was effectively done. Sunitinib is one of the promising receptor tyrosine kinase inhibitors used for metastatic renal cell carcinomas or imatinib-refractory GISTs. Sunitinib is thought to penetrate blood-brain barrier, and recent reports indicate effectiveness to brain metastasis. To the authors' knowledge, this is the first report of brain metastases from jejunal GIST responding to sunitinib therapy.
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Affiliation(s)
- Hayato TAKEUCHI
- Department of Neurosurgery, Yamashiro Public Hospital, Kizugawa, Kyoto,Address reprint requests to: Hayato Takeuchi, MD, PhD, Department of Neurosurgery, Saiseikai Kyoto Hospital, 8, Minamihirao, Imazato, Nagaokakyo, Kyoto 617-0814, Japan. e-mail:
| | - Hiroshi KOIKE
- Department of Surgery, Yamashiro Public Hospital, Kizugawa, Kyoto
| | - Tomoaki FUJITA
- Department of Neurosurgery, Yamashiro Public Hospital, Kizugawa, Kyoto
| | - Hitoshi TSUJINO
- Department of Neurosurgery, Yamashiro Public Hospital, Kizugawa, Kyoto
| | - Yoshihiro IWAMOTO
- Department of Neurosurgery, Yamashiro Public Hospital, Kizugawa, Kyoto
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Cameron S, Gieselmann M, Blaschke M, Ramadori G, Füzesi L. Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST). INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2014; 7:3563-3579. [PMID: 25120735 PMCID: PMC4128970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Accepted: 06/09/2014] [Indexed: 06/03/2023]
Abstract
We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene-expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% ± 7.1, vs. 26.7% ± 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% ± 2.1) and metastases (4.6% ± 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% ± 2.3 vs. 2.2% ± 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% ± 0.9 in the primary, and 2.4 ± 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% ± 0.7 in the primary and 1.8% ± 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% ± 7.4 vs. 18.2% ± 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% ± 1.8 vs. 4.4% ± 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1α (MIP-1α/CCL3) and the pro-angiogenic growth-related oncoprotein 1 (Gro-α/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites.
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Affiliation(s)
- Silke Cameron
- Clinic of Gastroenterology and Endocrinology, Georg-August UniversityGöttingen, Germany
| | - Marieke Gieselmann
- Clinic of Gastroenterology and Endocrinology, Georg-August UniversityGöttingen, Germany
| | - Martina Blaschke
- Clinic of Gastroenterology and Endocrinology, Georg-August UniversityGöttingen, Germany
| | - Giuliano Ramadori
- Clinic of Gastroenterology and Endocrinology, Georg-August UniversityGöttingen, Germany
| | - Laszlo Füzesi
- Institute of Pathology, Georg-August UniversityGöttingen, Germany
- Current address: Pius HospitalOldenburg, Germany
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Kakati DD, Weber FH. An unusual familial, recurrent neoplasm. Gastroenterology 2014; 146:e11-2. [PMID: 24786560 DOI: 10.1053/j.gastro.2014.01.065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Revised: 01/07/2014] [Accepted: 01/17/2014] [Indexed: 12/02/2022]
Affiliation(s)
- Donny D Kakati
- Department of Internal Medicine, University of Alabama Birmingham, Birmingham, Alabama
| | - Frederick H Weber
- Division of Gastroenterology and Hepatology, University of Alabama Birmingham, Birmingham, Alabama
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Beltrame V, Gruppo M, Pastorelli D, Pizzi S, Merigliano S, Sperti C. Extra-gastrointestinal stromal tumor of the pancreas: case report and review of the literature. World J Surg Oncol 2014; 12:105. [PMID: 24755359 PMCID: PMC4000617 DOI: 10.1186/1477-7819-12-105] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 04/07/2014] [Indexed: 02/08/2023] Open
Abstract
Primary extra-gastrointestinal stromal tumor (EGISTs) arising in the pancreas is extremely rare: only 20 cases have previously been reported in the English literature from 2000 to 2013. We reported a case of EGIST of the pancreas in a 69-year-old woman who presented with abdominal pain and with a solid, heterogeneously enhancing neoplasm in the uncinate process of the pancreas, revealed preoperatively by an abdominal computed tomography scan. A diagnosis of neuroendocrine tumor was suggested. Positron emission tomography with 68Ga-DOTATOC did not show pathological accumulation of the tracer in the pancreas. The patient underwent enucleation, under ultrasonic guidance, of the pancreatic tumor that emerged to the surface of the pancreas. Histopathology and immunohistochemical examination confirmed the final diagnosis of EGIST of the pancreas (CD117+), with one mitosis per 50 high-power fields. Although rarely, GIST can involve the pancreas as a primary site, and this tumor should be considered in the differential diagnosis of pancreatic neoplasms.
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Affiliation(s)
| | | | | | | | | | - Cosimo Sperti
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Giustiniani 2, 35128, Padua, Italy.
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