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Abraham FO, McPherson T, Blackshear L, Liu Y, Gillespie T, Sundar P, Patel V, Orr J, Chawla S, Keilin SA, Willingham FF. Overall survival and margin status in resected gastric stromal tumors. IGIE 2025; 4:48-60. [DOI: 10.1016/j.igie.2025.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/14/2025]
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Rea D, Tham C, Tham TCK. Endoscopic calabash technique for gastric mesenchymal tumours: A low hanging fruit or a novel endoscopic technique? World J Gastrointest Endosc 2025; 17:101676. [PMID: 39989851 PMCID: PMC11843036 DOI: 10.4253/wjge.v17.i2.101676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 01/21/2025] [Accepted: 02/06/2025] [Indexed: 02/13/2025] Open
Abstract
The term subepithelial lesions encompasses a wide array of pathology of which numerous benign and malignant pathologies are grouped. A subset of these lesions are termed gastric mesenchymal tumours of which some have innate malignant potential. Currently there is various guidance on the recommended approach to the investigation and management of these lesions and there exists multiple methods of resection. Lin et al have developed and proposed a new method of resection of these gastric mesenchymal tumours within the field of endoscopy, a procedure they have termed endoscopic calabash ligation and resection. This editorial aims to outlay the current landscape for gastric mesenchymal tumours with regards to the various guidelines and resection techniques while comparing Lin et al's new technique to those that are already established in the field of endoscopy. Advancements in endoscopy that maintain or improve patient outcomes compared to the gold standard approach are exciting developments. Lin et al's study suggests that their technique is comparable in regard to patient outcomes while simultaneously being more efficient in its use of hospital resources including procedural time. Whilst the data and analysis proposed in the study is promising, there are areas that need to be addressed before advocating the procedure for widespread use. However, with further studies and analysis this may be foreseeable in the future.
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Affiliation(s)
- David Rea
- Department of Medical Office, Wagga Wagga Base Hospital, Wagga Wagga 2650, New South Wales, Australia
| | - Caroline Tham
- Department of Medical Office, Westmead Hospital, Sydney 2145, New South Wales, Australia
| | - Tony CK Tham
- Division of Gastroenterology, Ulster Hospital, Belfast BT16 1RH, United Kingdom
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Meyer M, Ota H, Messiou C, Benson C, Henzler T, Mattonen SA, Marin D, Bartsch A, Schoenberg SO, Riedel RF, Hohenberger P. Prospective evaluation of quantitative response parameter in patients with Gastrointestinal Stroma Tumor undergoing tyrosine kinase inhibitor therapy-Impact on clinical outcome. Int J Cancer 2024; 155:2047-2057. [PMID: 39023303 DOI: 10.1002/ijc.35094] [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: 01/10/2024] [Revised: 05/18/2024] [Accepted: 06/04/2024] [Indexed: 07/20/2024]
Abstract
The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment (HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.
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Affiliation(s)
- Mathias Meyer
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim-Heidelberg University, Mannheim, Germany
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Hideki Ota
- Department of Diagnostic Radiology, Tohoku University Hospital, Miyagi, Japan
| | - Christina Messiou
- Department of Radiology, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | | | - Thomas Henzler
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim-Heidelberg University, Mannheim, Germany
| | - Sarah A Mattonen
- Department of Medical Biophysics, Western University, London, Canada
| | - Daniele Marin
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Anna Bartsch
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim-Heidelberg University, Mannheim, Germany
- Department of Orthopedics and Traumatology, University Hospital Basel, Basel, Switzerland
| | - Stefan O Schoenberg
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim-Heidelberg University, Mannheim, Germany
| | - Richard F Riedel
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA
| | - Peter Hohenberger
- Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
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Huang X, Chen L, Liu L, Chen H, Gong Z, Lyu J, Li Y, Jiang Q, Zeng X, Zhang P, Zhou H. Untargeted metabolomics analysis reveals the potential mechanism of imatinib-induced skin rash in patients with gastrointestinal stromal tumor. Int Immunopharmacol 2024; 140:112728. [PMID: 39098227 DOI: 10.1016/j.intimp.2024.112728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/09/2024] [Accepted: 07/17/2024] [Indexed: 08/06/2024]
Abstract
Imatinib-induced skin rash poses a significant challenge for patients with gastrointestinal stromal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. However, the underlying mechanism of imatinib-induced skin rashes in gastrointestinal stromal tumor patients remains unclear. A total of 51 patients (27 with rash and 24 without rash) were enrolled in our study. Blood samples were collected concomitantly with the onset of clinical manifestations of rashes, and simultaneously collecting clinical relevant information. The imatinib concentration and untargeted metabolomics were performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. There were no significant differences in age, gender, imatinib concentration and white blood cells count between the rash group and the control group. However, the rash group exhibited a higher eosinophil count (P<0.05) and lower lymphocyte count (P<0.05) compared to the control group. Untargeted metabolomics analysis found that 105 metabolites were significantly differentially abundant. The univariate analysis highlighted erucamide, linoleoylcarnitine, and valine betaine as potential predictive markers (AUC≥0.80). Further enriched pathway analysis revealed primary metabolic pathways, including sphingolipid signaling pathway, sphingolipid metabolism, cysteine and methionine metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, and biosynthesis of amino acids. These findings suggest that the selected differential metabolites could serve as a foundation for the prediction and management of imatinib-induced skin rash in gastrointestinal stromal tumor patients.
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Affiliation(s)
- Xiao Huang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, China
| | - Linhua Chen
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, China
| | - Li Liu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, China
| | - Hefen Chen
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zhujun Gong
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Jianbo Lyu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yao Li
- Department of Gastrointestinal Surgery, Department of Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Qi Jiang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xiangyu Zeng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Hong Zhou
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, China.
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Beecroft JR, Brar S, Feng X, Hamilton T, Han-Lee C, Henning JW, Josephy PD, Khalili K, Ko YJ, Lemieux C, Liu DM, MacDonald DB, Noujaim J, Pollett A, Salawu A, Saleh R, Smrke A, Warren BE, Zbuk K, Razak AA. Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada. Ther Adv Med Oncol 2024; 16:17588359241266179. [PMID: 39386314 PMCID: PMC11461906 DOI: 10.1177/17588359241266179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/18/2024] [Indexed: 10/12/2024] Open
Abstract
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.
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Affiliation(s)
- J. Robert Beecroft
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Toronto, ON, Canada
| | - Savtaj Brar
- Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Xiaolan Feng
- Division of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada
| | - Trevor Hamilton
- Department of Surgery, BC Cancer, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Cheng Han-Lee
- Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB, Canada
| | - Jan-Willem Henning
- Department of Oncology, Tom Baker Cancer Centre, Cuming School of Medicine, University of Calgary, Calgary, AB, Canada
| | | | - Korosh Khalili
- Department of Medical Imaging, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Yoo-Joung Ko
- Department of Medicine, St. Michael’s Hospital, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Christopher Lemieux
- Division of Hematology and Medical Oncology, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec City, QC, Canada
| | - David M. Liu
- Department of Radiology, University of British Columbia, School of Biomedical Engineering, Vancouver, BC, Canada
- Department of Interventional Radiology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - D. Blair MacDonald
- Department of Medical Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Jonathan Noujaim
- Division of Medical Oncology, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, QC, Canada
| | - Aaron Pollett
- Pathology and Laboratory Medicine, Division of Diagnostic Medical Genetics, Mount Sinai Hospital, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Abdulazeez Salawu
- Division of Medical Oncology, Princess Margaret Cancer Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Ramy Saleh
- Division of Medical Oncology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alannah Smrke
- Division of Medical Oncology, BC Cancer, University of British Columbia, Vancouver, BC, Canada
| | - Blair E. Warren
- Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
| | - Kevin Zbuk
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Albiruni Abdul Razak
- Division of Medical Oncology, Princess Margaret Cancer Centre, Mount Sinai Hospital, University of Toronto, 610 University Ave., Toronto, ON M2G 2M9, Canada
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Doi T, Yamamoto N, Ohkubo S. Pimitespib for the treatment of advanced gastrointestinal stromal tumors and other tumors. Future Oncol 2024; 20:507-519. [PMID: 38050698 DOI: 10.2217/fon-2022-1172] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2023] Open
Abstract
Pimitespib (TAS-116) is the first heat shock protein 90 (HSP90) inhibitor approved in Japan, and it is indicated for the treatment of gastrointestinal stromal tumors (GIST) that have progressed after treatment with imatinib, sunitinib and regorafenib. This review describes the preclinical and clinical research with pimitespib, including its mechanism of action, pharmacokinetics, clinical antitumour activity and safety. In a phase III study, pimitespib significantly prolonged progression-free survival compared with placebo (median 2.8 vs 1.4 months; hazard ratio 0.51; 95% CI 0.30-0.87; p = 0.006). Common treatment-related adverse events were diarrhoea, decreased appetite, increase in serum creatinine, malaise, nausea and eye disorders. The efficacy and safety of pimitespib are being investigated in other tumour types and in combination with other anticancer therapies.
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Affiliation(s)
- Toshihiko Doi
- Department of Experimental Therapeutics, National Cancer Centre Hospital East, Kashiwa, Japan
| | - Noboru Yamamoto
- Department of Experimental Therapeutics, National Cancer Centre Hospital, Tokyo, Japan
| | - Shuichi Ohkubo
- Discovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd, Tsukuba, Ibaraki, Japan
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Yorke J, Brenu SG, Awoonor-Williams R, Tabiri S, Seidu AS, Yamoah FA, Akpaloo J, Der EM, Adjei E, Okyere I, Ihekanandu KK, Bonsu EBO, Kyei I, Mensah S, Adinku MO, Yorke DA, Agyapong AO, Aitpillah FSK, Agyei MK, Oppong-Nkrumah NA, Annan KD, Ellis TAF, Danso P, Buckman TA, Acheampong E. A gist on an obscure neoplasm in Ghana: gastrointestinal stromal tumours. BMC Res Notes 2023; 16:318. [PMID: 37932827 PMCID: PMC10629135 DOI: 10.1186/s13104-023-06593-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 10/24/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND Gastrointestinal Stromal Tumour is a rare but potentially curable tumour of the gastrointestinal tract accounting for up to 1% of all gastrointestinal tumours. The discovery of Imatinib mesylate, a novel tyrosine kinase inhibitor has improved the chances even for unresectable, recurrent, or metastatic diseases. METHODS This study sought to document the clinical and pathological characteristics of GISTs from two tertiary hospitals in Ghana that have undergone immunohistochemistry confirmation between 2014 and 2021. RESULTS The median age of the subjects was 50 years with most of them (28.0%) being above 61 years. There were more females than males (64.0% vs. 36.0%). Abdominal mass and abdominal pain made up the majority of the clinical presentations. The majority of the subjects had partial gastrectomy (32.0%) which was followed by wedge resection (28.0%). Appendectomy and sleeve gastrectomy were the least performed procedures (8% each). Four of the 25 patients (16.0%) had resections of involved contiguous organs done with splenectomy being the most common procedure. The majority of GISTs were found in the stomach (68.0%) followed by the appendix (12.0%) and small bowel (12.0%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most reported symptoms. Free resection margins were observed in 84.0% of the subjects and only 3/25 (12.0%) experienced tumour recurrence. CONCLUSION GIST is a potentially curable tumour that once was obscure but currently gaining popularity. Surgical resection offers the hope of a cure for localized disease while targeted therapies is a viable option for recurrent, metastatic, or unresectable tumours.
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Affiliation(s)
- Joseph Yorke
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | | | - Stephen Tabiri
- Department of Surgery, School of Medical Sciences, University of Development Studies, Tamale, Ghana
| | | | | | - Joseph Akpaloo
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | - Ernest Adjei
- Directorate of Pathology, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Isaac Okyere
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | | | - Ishmael Kyei
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Samuel Mensah
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Michael Ofoe Adinku
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | | | - Francis Somiah-Kwaw Aitpillah
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Martin Kofi Agyei
- Directorate of Internal Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | | | | | - Patrick Danso
- Directorate of Surgery, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Tonnies Abeku Buckman
- Department of Medical Laboratory Science, KAAF University College, Fetteh-Kakraba, Gomoa East District, Gomoa-East, Ghana.
| | - Emmanuel Acheampong
- Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
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Yamashina T, Shimatani M, Matsumoto H, Orino M, Kano M, Kasai T, Saito N, Horitani S, Mitsuyama T, Sumimoto K, Takeo M, Yuba T, Naganuma M. Perforation-free removal of gastric gastrointestinal stromal tumors: Endoscopic inversion and strangulation of muscle layer and resection (EISMR). Endosc Int Open 2023; 11:E800-E804. [PMID: 37664786 PMCID: PMC10473888 DOI: 10.1055/a-2112-5210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 06/15/2023] [Indexed: 09/05/2023] Open
Abstract
Endoscopic resection for GIST has become more widespread in recent years because it is less invasive than surgery. However, when endoscopic resection is performed, a full-layer resection of the gastric wall is often necessary, and extensive suturing is required if perforation occurs, which is a technically challenging procedure. Recently, we reported a new method called endoscopic inversion and strangulation of the muscle layer and resection (EISMR), which consists of endoscopically inverting the muscle layer into the gastric lumen and strangulating the muscle layer with a detachable snare, followed by resection. The study comprised five consecutive patients with gastric GIST ≤50 mm in diameter who underwent EISMR procedures. The main outcomes of the study were en bloc resection rate, R0 resection rate, procedure time, and complications. The results showed that all five patients successfully underwent complete resection without perforation, and the en bloc resection and R0 resection rates were 100%. The median procedure time was 93 min (range, 58-120 min), and there were no major complications. We concluded that EISMR would be a safe and effective technique for endoscopic resection of gastric GISTs and may be an alternative to surgery or endoscopic submucosal dissection.
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Affiliation(s)
- Takeshi Yamashina
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Masaaki Shimatani
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Hironao Matsumoto
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Masahiro Orino
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Masataka Kano
- Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Takeshi Kasai
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Natsuko Saito
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Shunsuke Horitani
- Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Toshiyuki Mitsuyama
- Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Kimi Sumimoto
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Masahiro Takeo
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Takafumi Yuba
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Moriguchi, Japan
| | - Makoto Naganuma
- Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
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Naito Y, Nishida T, Doi T. Current status of and future prospects for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Gastric Cancer 2023; 26:339-351. [PMID: 36913072 PMCID: PMC10115693 DOI: 10.1007/s10120-023-01381-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/02/2023] [Indexed: 03/14/2023]
Abstract
Gastrointestinal stromal tumours (GISTs) are soft-tissue sarcomas of the gastrointestinal tract. Surgery is the standard treatment for localised disease, but the risk of relapse and progression to more advanced disease is substantial. Following the discovery of the molecular mechanisms underlying GISTs, targeted therapies for advanced GIST were developed, with the first being the tyrosine kinase inhibitor (TKI) imatinib. Imatinib is recommended in international guidelines as first-line therapy to reduce the risk of GIST relapse in high-risk patients, and for locally advanced, inoperable and metastatic disease. Unfortunately, imatinib resistance frequently occurs and, therefore, second-line (sunitinib) and third-line (regorafenib) TKIs have been developed. Treatment options are limited for patients with GIST that has progressed despite these therapies. A number of other TKIs for advanced/metastatic GIST have been approved in some countries. Ripretinib is approved as fourth-line treatment of GIST and avapritinib is approved for GIST harbouring specific genetic mutations, while larotrectinib and entrectinib are approved for solid tumours (including GIST) with specific genetic mutations. In Japan, pimitespib, a heat shock protein 90 (HSP90) inhibitor, is now available as a fourth-line therapy for GIST. Clinical studies of pimitespib have indicated that it has good efficacy and tolerability, importantly not displaying the ocular toxicity of previously developed HSP90 inhibitors. Additional approaches for advanced GIST have been investigated, including alternative uses of currently available TKIs (such as combination therapy), novel TKIs, antibody-drug conjugates, and immunotherapies. Given the poor prognosis of advanced GIST, the development of new therapies remains an important goal.
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Affiliation(s)
- Yoichi Naito
- Department of General Internal Medicine, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
- Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan.
- Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
| | - Toshirou Nishida
- Department of Surgery, Japan Community Health Care Organization Osaka Hospital, Osaka, Japan
- National Cancer Center Hospital, Tsukiji, Tokyo, Japan
| | - Toshihiko Doi
- Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan
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10
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Wood D, Janssen G, Aljanabi I. Extragastrointestinal stromal tumour of the transverse mesocolon mimicking giant ovarian cystic neoplasm. BMJ Case Rep 2023; 16:e253816. [PMID: 36731947 PMCID: PMC9896349 DOI: 10.1136/bcr-2022-253816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2023] [Indexed: 02/04/2023] Open
Abstract
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours which are most commonly found along the gastrointestinal tract. They are more rarely found in an extragastrointestinal location and typically present late due to only vague symptoms from mass effect. There are very few case reports of GIST arising within the transverse mesocolon. We report a case of a large cystic transverse mesocolic GIST which preoperative imaging concluded was likely of ovarian origin. This resulted in an abrupt change in the surgical management intraoperatively, but fortunately, an R0 resection was still achieved. This serves as an important lesson to keep the differential diagnosis broad when dealing with large cystic abdominal masses. The tumour was found to be KIT wild type, with a platelet-derived growth factor receptor alpha D842V mutation identified, conferring intrinsic resistance to imatinib.
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Affiliation(s)
- Douglas Wood
- General Surgery, Wellington Regional Hospital, Wellington, New Zealand
| | - Greer Janssen
- General Surgery, Wellington Regional Hospital, Wellington, New Zealand
| | - Imad Aljanabi
- General Surgery, Wellington Regional Hospital, Wellington, New Zealand
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11
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van de Wal D, Venkatesan S, Benson C, van der Graaf WTA, Johnson CD, Husson O, Sodergren SC. A patient's perspective on the side effects of tyrosine kinase inhibitors in the treatment of advanced and metastatic gastrointestinal stromal tumors. Future Oncol 2023; 19:299-314. [PMID: 37038981 DOI: 10.2217/fon-2022-0730] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2023] Open
Abstract
Aim: To provide the gastrointestinal stromal tumor patient's perspective on side effects of tyrosine kinase inhibitors and compare this with that of healthcare professionals. Materials & methods: Semi-structured interviews were conducted with 19 patients with an advanced or metastatic gastrointestinal stromal tumor, as well as six healthcare professionals, and five patients participated in a focus group. Thematic analysis was used to interpret the data. Results: Most participants (n = 29) reported gastrointestinal symptoms followed by tiredness (n = 25), edema (n = 22), muscle cramps (n = 21), skin problems (n = 21), eye problems (n = 11) and trouble sleeping (n = 10). Patients, but not healthcare professionals, reported cognitive problems or symptoms of depression. Conclusion: These results underline the importance of including the patient's perspective, as there is a gap in symptom reporting between patients and healthcare professionals.
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Affiliation(s)
- Deborah van de Wal
- Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands
| | | | - Charlotte Benson
- Sarcoma Unit, The Royal Marsden National Health Service Foundation Trust, London, SW3 6JJ, UK
| | - Winette TA van der Graaf
- Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD, Rotterdam, The Netherlands
| | - Colin D Johnson
- Cancer Sciences, University of Southampton, Southampton, SO17 1BJ, UK
| | - Olga Husson
- Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD, Rotterdam, The Netherlands
- Division of Clinical Studies, Institute of Cancer Research, London, SW3 6JB, UK
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12
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Yip HC, Teh JL, Teoh AYB, Chiu P. Pure endoscopic resection versus laparoscopic assisted procedure for upper gastrointestinal stromal tumors: Perspective from a surgical endoscopist. Dig Endosc 2023; 35:184-194. [PMID: 36318279 DOI: 10.1111/den.14463] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 10/31/2022] [Indexed: 11/27/2022]
Abstract
Management of upper gastrointestinal (UGI) tract gastrointestinal stromal tumor (GIST) has evolved significantly over the past two decades. For GIST size smaller than 5 cm, laparoscopic resection has become the current standard. To avoid postoperative gastric deformity and preserve gastric function, laparoscopic endoscopic cooperative surgery (LECS) was developed and various modifications have been reported and utilized successfully. Pure endoscopic resection techniques have also been reported at a similar period of time, which further push the boundary of incisionless surgery in managing these lesions. Both tunneling and nontunneling exposed type endoscopic full thickness resection are well described procedures for resection of small UGI GIST. In this review, a summary of these procedures is provided, and the pros and cons of each technique from the perspective of a surgical endoscopist are discussed in detail. LECS and endoscopic resection are complementary to each other. The choice of technique should be tailored to the location, morphology, and size of the target lesions, taking into account the experience of the laparoscopic surgeons and endoscopists.
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Affiliation(s)
- Hon Chi Yip
- Division of Upper Gastrointestinal and Metabolic Surgery, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Liang Teh
- Division of Upper Gastrointestinal and Metabolic Surgery, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.,National University Health System, Singapore City, Singapore
| | - Anthony Y B Teoh
- Division of Upper Gastrointestinal and Metabolic Surgery, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Philip Chiu
- Division of Upper Gastrointestinal and Metabolic Surgery, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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13
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Kanesaka T, Inoue T, Tajiri A, Fukuda H, Waki K, Shichijo S, Maekawa A, Yamamoto S, Takeuchi Y, Higashino K, Uedo N, Michida T, Tanada S, Honma K, Ishihara R. Boring biopsy with rapid on-site evaluation for gastric gastrointestinal stromal tumor: A pilot study. JGH Open 2023; 7:68-71. [PMID: 36660046 PMCID: PMC9840186 DOI: 10.1002/jgh3.12854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 11/15/2022] [Accepted: 12/04/2022] [Indexed: 12/29/2022]
Abstract
One of 4 patients (25%) and 2 of 3 patients (67%) were correctly diagnosed by conventional and hot boring biopsies, respectively. The median procedure time of conventional and hot boring biopsies was 21 (range, 13-33) and 17 (range, 16-23) min, respectively. Rapid on-site evaluation was performed totally 12 times in 7 patients. The positive and negative predictive values of rapid on-site evaluation for gastrointestinal stromal tumor were 0.5 (0.12-0.88) and 1.0 (0.42-1.00), respectively.
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Affiliation(s)
- Takashi Kanesaka
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Takahiro Inoue
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Ayaka Tajiri
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Hiromu Fukuda
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
| | - Kotaro Waki
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Satoki Shichijo
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Akira Maekawa
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Sachiko Yamamoto
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yoji Takeuchi
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Koji Higashino
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Noriya Uedo
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Tomoki Michida
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Satoshi Tanada
- Department of Diagnostic Pathology and CytologyOsaka International Cancer InstituteOsakaJapan
| | - Keiichiro Honma
- Department of Diagnostic Pathology and CytologyOsaka International Cancer InstituteOsakaJapan
| | - Ryu Ishihara
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
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14
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Yue L, Sun Y, Wang X, Hu W. Advances of endoscopic and surgical management in gastrointestinal stromal tumors. Front Surg 2023; 10:1092997. [PMID: 37123546 PMCID: PMC10130460 DOI: 10.3389/fsurg.2023.1092997] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/24/2023] [Indexed: 05/02/2023] Open
Abstract
As one of the most common mesenchymal malignancies in the digestive system, gastrointestinal stromal tumors (GISTs) occur throughout the alimentary tract with diversified oncological characteristics. With the advent of the tyrosine kinase inhibitor era, the treatment regimens of patients with GISTs have been revolutionized and GISTs have become the paradigm of multidisciplinary therapy. However, surgery resection remains recognized as the potentially curative management for the radical resection and provided with favorable oncological outcomes. The existing available surgery algorithms in clinical practice primarily incorporate open procedure, and endoscopic and laparoscopic surgery together with combined operation techniques. The performance of various surgery methods often refers to the consideration of risk evaluation of recurrence and metastases; the degree of disease progression; size, location, and growth pattern of tumor; general conditions of selected patients; and indications and safety profile of various techniques. In the present review, we summarize the fundamental principle of surgery of GISTs based on risk assessment as well as tumor size, location, and degree of progress with an emphasis on the indications, strengths, and limitations of current surgery techniques.
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Affiliation(s)
- Lei Yue
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
| | - Yingchao Sun
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
| | - Xinjie Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
| | - Weiling Hu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
- Institute of Gastroenterology, Zhejiang University (IGZJU), Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
- Correspondence: Weiling Hu
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15
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Montoya D, Call JW, Eshak J, Knox P, Luedke M, Kaur S, Rothschild S, Garland M, Scherzer NJ. Barriers to mutational testing in patients with gastrointestinal stromal tumors (GIST) – a survey of life raft group members. BMC Gastroenterol 2022; 22:455. [DOI: 10.1186/s12876-022-02548-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 10/20/2022] [Indexed: 11/16/2022] Open
Abstract
Abstract
Background
Due to the low mutational testing rate in patients with Gastrointestinal Stromal Tumors (GIST), The Life Raft Group (LRG), a non-profit organization that provides support, advocacy and conducts research for patients with GIST, analyzed various factors that may have an impact on patients’ ability to receive mutational testing.
Methods
A survey about mutational testing for patients with GIST or their caregivers, was conducted in June 2020. The survey, sent to 1004 GIST patients and caregivers through email, was promoted through social media with instructions to contact the LRG to participate. The survey was designed by the LRG Patient Registry Department. Members of the LRG, regardless of Patient Registry status, were eligible to participate.
Results
A total of 295 patients/caregivers participated in this study (response rate: 29.4%). The percentage of patients who indicated they had received mutational testing was much higher in this survey (80%) than in the general GIST community (26.7%).
Several reasons were cited for having a test, including: “My doctor ordered/suggested that I have it done” (54%); “The Life Raft Group advised/suggested I have it done” (25%); “I asked my doctor to have it done” (22%); “I had it done as part of a clinical trial” (5%); “I am not sure” (3%) and “Other” (14%). Mutational testing resulted in a treatment change in 25% of cases. Patients were able to select more than one option when completing this question resulting in a percentage greater than 100.
Conclusions
The LRG membership is voluntary and proactive; patients who join are more likely to participate in surveys and mutational testing, as well as more likely to have a GIST specialist. Mutational testing can influence understanding of a patient’s GIST and the treatment best suited to each case. These are extremely important findings, as it helps ensure that patients are on the proper treatment, which should lead to better outcomes.
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16
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Gunawardene A, Fischer J. Obscure gastrointestinal bleeding in a patient with neurofibromatosis type 1. ANZ J Surg 2022; 92:3105-3106. [PMID: 35212097 PMCID: PMC9790566 DOI: 10.1111/ans.17573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 12/30/2022]
Affiliation(s)
- Ashok Gunawardene
- Department of General SurgeryWaikato District Health BoardHamiltonNew Zealand,Department of SurgeryUniversity of AucklandAucklandNew Zealand
| | - Jesse Fischer
- Department of General SurgeryWaikato District Health BoardHamiltonNew Zealand,Department of SurgeryUniversity of AucklandAucklandNew Zealand
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17
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Blay JY, Duffaud F, George S, Maki RG, Penel N. Regorafenib for the Treatment of Sarcoma. Curr Treat Options Oncol 2022; 23:1477-1502. [PMID: 36178573 DOI: 10.1007/s11864-022-00990-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2022] [Indexed: 01/30/2023]
Abstract
OPINION STATEMENT Sarcomas are a rare group of tumors with many subtypes, conventionally classified into soft-tissue sarcomas and bone sarcomas. Chemotherapeutic regimens form the mainstay of systemic therapy but are not well defined beyond the first-line setting and clinical outcomes are variable. Tyrosine kinase inhibitors (TKIs), with a broad inhibition profile which have been shown to target tumor angiogenesis, have an established role in the treatment of sarcomas without characteristic driver alterations. One such TKI, regorafenib, has been evaluated in sarcomas and clinical data are discussed in this review. An overview of regorafenib data from five phase 2 and one phase 1b clinical trials in over 10 sarcoma subtypes (both soft-tissue and bone) in adult and pediatric patients is reviewed. Regorafenib demonstrated clinical benefit in patients with non-adipocytic soft-tissue sarcomas, osteosarcoma and Ewing sarcoma who had progressed on prior therapy. Patients with otherwise limited treatment options may therefore benefit from regorafenib therapy.
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Affiliation(s)
- Jean-Yves Blay
- Department of Medicine, Léon Bérard Center, Lyon, France.
| | - Florence Duffaud
- Medical Oncology Unit, La Timone University Hospital, Marseille, France.,Aix Marseille University (AMU), Marseille, France
| | - Suzanne George
- Dana-Farber Cancer Institute, Harvard Medical School, Cambridge, MA, USA
| | - Robert G Maki
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Nicolas Penel
- Medical Oncology Department, Oscar Lambret Cancer Center and Lille University, Lille, France
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18
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Xu JQ, Xu JX, Xu XY, Yao L, Xu MD, Chen SY, Zhong YS, Zhang YQ, Chen WF, Hu JW, Cai MY, Yao LQ, Li QL, Zhou PH. Landscape of esophageal submucosal tunneling endoscopic resection-related adverse events in a standardized lexicon: a large volume of 1701 cases. Surg Endosc 2022; 36:8112-8120. [PMID: 35467145 DOI: 10.1007/s00464-022-09241-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 04/02/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Submucosal tunneling endoscopic resection (STER) has been widely applied for esophageal submucosal tumors. This large volume study aims to provide a standard landscape of STER-related AEs for reference. METHODS 1701 patients with esophageal SMTs undergoing STER were included at Zhongshan Hospital, Fudan University. Data of clinical characteristics and adverse events were collected and analyzed in depth. Adverse events were recorded by ASGE lexicon and graded by ASGE grading/Clavien-Dindo system. Risk factors for major AEs were analyzed by univariate and multivariate logistic regression. RESULTS Three hundred and twenty (18.8%) patients with 962 cases of adverse events were observed. Accordingly, 84 (5.0%) were classified as major AEs (moderate and severe) by ASGE grading and 37 (2.2%) were classified as major AEs (grades III-V) by Clavien-Dindo grading. First 1 year operation, distance > 6 cm from incision to tumor, piecemeal resection, partially extraluminal location, mucosal injury, and operation time > 60 min were included in the risk score model for major AEs of STER, with 57.1% sensitivity and 87.5% specificity. CONCLUSIONS STER was a safe procedure for diagnosis and treatment of esophageal SMTs with a total 18.8% incidence of AEs, among which only 5.0% were major AEs requiring therapeutic measurements.
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Affiliation(s)
- Jia-Qi Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia-Xin Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiao-Yue Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lu Yao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mei-Dong Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shi-Yao Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yun-Shi Zhong
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi-Qun Zhang
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wei-Feng Chen
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian-Wei Hu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming-Yan Cai
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li-Qing Yao
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Quan-Lin Li
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Ping-Hong Zhou
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
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19
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Jaros D, Bozic B, Sebesta C. [Gastrointestinal stromal tumors (GIST)]. Wien Med Wochenschr 2022; 173:201-205. [PMID: 36155864 DOI: 10.1007/s10354-022-00965-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 08/10/2022] [Indexed: 12/01/2022]
Abstract
Gastrointestinal stromal tumors (GIST) are rare tumors with a varying malignancy potential, most frequently located in the stomach and the small intestine. The median age at diagnosis is around 65 years. Standard treatment of localized disease is complete surgical resection. A GIST is generally resistant to conventional chemotherapy. Most GISTs harbor tyrosine kinase activating mutations in either the KIT or PDGFRA proto-oncogene. The standard treatment of locally advanced and metastatic GIST with such mutations is the tyrosine kinase inhibitor imatinib. In cases of progressive disease after successive treatment with imatinib, sunitinib, and regorafenib, a fourth-line therapy with ripretinib was recently approved. Approved in 2020, avapritinib is the first effective targeted therapy for advanced stage GIST harboring an imatinib-resistant PDGFRA D842V mutation.
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Affiliation(s)
- David Jaros
- 2.Medizinische Abteilung, Klinik Donaustadt, Langobardenstr. 122, 1220, Wien, Österreich.
| | - Boris Bozic
- 2.Medizinische Abteilung, Klinik Donaustadt, Langobardenstr. 122, 1220, Wien, Österreich
| | - Christian Sebesta
- 2.Medizinische Abteilung, Klinik Donaustadt, Langobardenstr. 122, 1220, Wien, Österreich
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20
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Abdullah AD, Mohammed S, Alradhi M, Zhu X, Yang D. Laparoscopic retroperitoneal resection of the duodenal gastrointestinal stromal tumors in neurofibromatosis type 1; Case Report and literature review. Front Surg 2022; 9:939705. [PMID: 36090331 PMCID: PMC9458937 DOI: 10.3389/fsurg.2022.939705] [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: 05/09/2022] [Accepted: 08/10/2022] [Indexed: 11/13/2022] Open
Abstract
Background Neurofibromatosis type 1, also known as NF1, is a disorder that is passed down in an autosomal dominant manner. It manifests in a wide variety of tumors and affects several organ systems. It is expected that those carrying the NF1 gene will develop a rare mesenchymal tumor known as a gastrointestinal stromal tumor (GIST) more than general population. Case report This research discusses a 42-year-old female patient with NF1 who was identified with a duodenal GIST but clinically and radiographically misinterpreted as having a retroperitoneal neurofibroma. She had minimally invasive retroperitoneal laparoscopic surgery to remove the tumor and primary anastomosis of the affected duodenal wall. A spindle cell GIST was entirely excised during surgery, as indicated by the pathologist. As a consequence of dialogue at a multidisciplinary team meeting, the patient was discharged from the hospital on the fourth postoperative day and is presently undergoing regular clinical follow-up. Conclusion Anatomically problematic sites, such as the duodenal GIST in NF1 patients, can be treated safely with the laparoscopic retroperitoneal approach even when retroperitoneal neoplasia arises from the intrabdominal structure and protrudes into the retroperitoneal region.
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Affiliation(s)
- Al-Danakh Abdullah
- Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Safi Mohammed
- Department of Respiratory Diseases, Shandong Second Provincial General Hospital, Shandong University, Jinan, China
| | - Mohammed Alradhi
- Department of Urology, The Affiliated Hospital of Qingdao Binhai Univesity, Qingdao, China
| | - Xinqing Zhu
- Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, China
- Correspondence: Deyong Yang Xinqing Zhu
| | - Deyong Yang
- Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, China
- Department of Surgery, Healing Hands Clinic, Dalian, China
- Correspondence: Deyong Yang Xinqing Zhu
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21
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Goggin C, Stansfeld A, Mahalingam P, Thway K, Smith MJ, Huang P, Jones RL, Napolitano A. Ripretinib in advanced gastrointestinal stromal tumors: an overview of current evidence and drug approval. Future Oncol 2022; 18:2967-2978. [PMID: 35880452 DOI: 10.2217/fon-2022-0226] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Over the past 20 years, the management of gastrointestinal stromal tumors has acted as an important model in the advancement of molecularly targeted therapies for solid tumors. The success of imatinib has established it as a lasting therapy in the management of early-stage and advanced disease in the first-line setting. Imatinib resistance inevitably develops, resulting in the need for further lines of therapy. Ripretinib is an orally administered switch-control tyrosine kinase inhibitor, specifically developed to target both primary and secondary KIT and PDGFRα resistance mutations. Herein, the authors discuss the molecular rationale, the preclinical evidence and the clinical use of ripretinib in the treatment of gastrointestinal stromal tumors in the advanced stages of disease.
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Affiliation(s)
- Caitriona Goggin
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
| | - Anna Stansfeld
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
| | | | - Khin Thway
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.,The Institute of Cancer Research, London, SM2 5NG, UK
| | - Myles J Smith
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.,The Institute of Cancer Research, London, SM2 5NG, UK
| | - Paul Huang
- The Institute of Cancer Research, London, SM2 5NG, UK
| | - Robin L Jones
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.,The Institute of Cancer Research, London, SM2 5NG, UK
| | - Andrea Napolitano
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
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22
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Jakob J, Salameh R, Wichmann D, Charalambous N, Zygmunt AC, Kreisel I, Heinz J, Ghadimi M, Ronellenfitsch U. Needle tract seeding and abdominal recurrence following pre-treatment biopsy of gastrointestinal stromal tumors (GIST): results of a systematic review. BMC Surg 2022; 22:202. [PMID: 35597932 PMCID: PMC9124402 DOI: 10.1186/s12893-022-01648-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 05/12/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GIST) are rare abdominal tumors. Pretreatment biopsies may be used to diagnose a GIST and enable tailored treatment. Some experts are skeptical about biopsies because they fear tumor cell seeding. The objective of this study was to determine if pretreatment biopsy is associated with increased tumor recurrence. METHODS We performed a systematic literature search and included studies assessing the oncological outcome of GIST patients who underwent a pre-treatment core needle biopsy or fine needle aspiration. We assessed methodological quality with the Newcastle-Ottawa-Scale for non-randomized studies. This review was registered in the PROSPERO database (CRD42021170290). RESULTS Three non-randomized studies and eight case reports comprising 350 patients were eligible for inclusion. No prospective study designed to answer the review question was found. One case of needle tract seeding after percutaneous core needle biopsy of GIST was reported. None of the studies reported an increased rate of abdominal recurrence in patients with pretreatment biopsy. CONCLUSIONS The existing evidence does not indicate a relevant risk of needle tract seeding or abdominal recurrence after pre-treatment biopsy of GIST. Biopsy can safely be done to differentiate GIST from other tumors and to select the most appropriate treatment.
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Affiliation(s)
- Jens Jakob
- Department of Surgery, Sarcoma Unit, University Medical Center Mannheim, Th.-Kutzer-Ufer 1-3, 68163, Mannheim, Germany.
| | - Rashad Salameh
- Department of Visceral, Thoracic, Vascular and Transplant Surgery, University Hospital Dresden, Dresden, Germany
| | - David Wichmann
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Goettingen, Germany
| | - Nicos Charalambous
- Department of Visceral, Thoracic, Vascular and Transplant Surgery, University Hospital Dresden, Dresden, Germany
| | - Anne-Christine Zygmunt
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Goettingen, Germany
| | - Inga Kreisel
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Goettingen, Germany
| | - Judith Heinz
- Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany
| | - Michael Ghadimi
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Goettingen, Germany
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23
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Liu X, Yin Y, Wang X, Yang C, Wan S, Yin X, Wu T, Chen H, Xu Z, Li X, Song B, Zhang B. Gastrointestinal stromal tumors: associations between contrast-enhanced CT images and KIT exon 11 gene mutation. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1496. [PMID: 34805358 PMCID: PMC8573436 DOI: 10.21037/atm-21-3811] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/02/2021] [Indexed: 02/05/2023]
Abstract
Background Mutation screening for gastrointestinal stromal tumor (GIST) is crucial and the c kit gene (KIT) exon 11 mutation is the most common type. This study aimed to explore the associations between GIST with KIT exon 11 mutation and contrast-enhanced computed tomography (CT) images. Methods Pathologically proven GISTs with definitive genotype testing results in our hospital were retrospectively included. Abdominal contrast-enhanced CT images were analyzed. Conventional CT image features and radiomic features were recorded and extracted to build the following models: model [CT], model [radiomic + clinic] and model [CT + radiomic + clinic]. The diagnostic performances of GISTs with KIT exon 11 mutation and KIT exon 11 deletion involving codons 557–558 were evaluated. Results In total, 327 GISTs (255 with KIT exon 11 mutation, and 73 with KIT exon 11 mutation deletion involving codons 557–558) were included. Significant CT features were found for GISTs with KIT exon 11 mutation. The area under curves (AUCs) of the models for KIT exon 11 mutation were 0.7158, 0.7530, and 0.8375 in the training cohort, and 0.6777, 0.7349, and 0.8105 in validation cohort, respectively. The AUCs of the models for KIT exon 11 mutation deletion involving codons 557–558 were 0.7155, 8621, and 0.8691 in the training cohort, and 0.7099, 0.8355, and 0.8488 in the validation cohort, respectively. The model [CT + radiomic + clinic] demonstrated the highest AUCs for prediction of KIT exon 11 mutation and those with deletion involving codons 557–558 (P<0.05), respectively. The model [radiomic + clinic] showed higher diagnostic performance than model [CT] significantly. Conclusions Our results demonstrated the associations between GIST with KIT exon 11 mutation and contrast-enhanced CT images. We found combing conventional image analysis and texture analysis is a useful tool to distinguish GIST with KIT exon 11 mutation. CT radiogenomics exhibited good application potential in predict the KIT exon 11 mutation of GIST.
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Affiliation(s)
- Xijiao Liu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaozhou Wang
- Department of Radiology, Meishan People's Hospital, Meishan, China
| | - Caiwei Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Shang Wan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Tingfan Wu
- Clinical Education Team, GE Healthcare China, Shanghai, China
| | - Huijiao Chen
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhongming Xu
- Department of Radiology, Meishan People's Hospital, Meishan, China
| | - Xin Li
- Global Research, GE Healthcare China, Shanghai, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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Dual-Energy CT Vital Iodine Tumor Burden for Response Assessment in Patients With Metastatic GIST Undergoing TKI Therapy: Comparison to Standard CT and FDG PET/CT Criteria. AJR Am J Roentgenol 2021; 218:659-669. [PMID: 34668385 DOI: 10.2214/ajr.21.26636] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background: CT-based criteria for assessing gastroinstestinal stromal tumor (GIST) response to tyroskine kinase inhibitor (TKI) therapy are limited partly because tumor attenuation is influenced by treatment-related changes including hemorrhage and calcification. Iodine concentration may be less impacted by such changes. Objective: To determine whether DECT vital iodine tumor burden (TB) provides improved differentiation between responders and non-responders in patients with metastatic GIST undergoing TKI therapy compared to established CT and PET/CT criteria. Methods: An anthropomorphic phantom with spherical inserts mimicking GIST lesions of varying iodine concentrations and having non-enhancing central necrotic cores underwent DECT to determine a threshold iodine concentration. Forty patients (median age 57 years; 25 women, 15 men) treated with TKI for metaststic GIST were retrospectively evaluated. Patients underwent baseline and follow-up DECT and FDG PET/CT. Response assessment was performed using RECIST 1.1, modified Choi (mChoi), vascular tumor burden (VTB), DECT vital iodine TB, and European Organization for Research and Treatment of Cancer (EORTC PET) criteria. DECT vital iodine TB used the same percentage changes as RECIST 1.1 response categories. Progression-free survival (PFS) was compared between responders and non-responders for each response criteria using Cox proportional hazard ratios and Harrell's c-indices. Results: The phantom experiment identified a 0.5 mg/mL threshold to differentiate vital from non-vital tissue. Using DECT vital iodine TB, median PFS was significantly different between non-responders and responders (587 vs 167 days, respectively; p=.02). Hazard ratio for progression for DECT vital iodine TB non-responders versus responders was 6.9, versus 7.6 for EORTC PET, 3.3 for VTB, 2.3 for RECIST 1.1, and 2.1 for mChoi. C-index was 0.74 for EORTC PET, 0.73 for DECT vital iodine TB, 0.67 for VTB, 0.61 for RECIST 1.1, and 0.58 for mChoi. C-index was significantly greater for DECT vital iodine TB than RECIST 1.1 (p=.02) and mChoi (p=.002), but not different than VTB and EORTC PET (p>.05). Conclusion: DECT vital iodine TB criteria showed comparable performance as EORTC PET and outperformed RECIST 1.1 and mChoi for response assessment of metastatic GIST under TKI therapy. Clinical Impact: DECT vital iodine TB could help guide early management decisions in patients on TKI therapy.
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Zhao Y, Feng M, Wang M, Zhang L, Li M, Huang C. CT Radiomics for the Preoperative Prediction of Ki67 Index in Gastrointestinal Stromal Tumors: A Multi-Center Study. Front Oncol 2021; 11:689136. [PMID: 34595107 PMCID: PMC8476965 DOI: 10.3389/fonc.2021.689136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 06/30/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose This study established and verified a radiomics model for the preoperative prediction of the Ki67 index of gastrointestinal stromal tumors (GISTs). Materials and Methods A total of 344 patients with GISTs from three hospitals were divided into a training set and an external validation set. The tumor region of interest was delineated based on enhanced computed-tomography (CT) images to extract radiomic features. The Boruta algorithm was used for dimensionality reduction of the features, and the random forest algorithm was used to construct the model for radiomics prediction of the Ki67 index. The receiver operating characteristic (ROC) curve was used to evaluate the model’s performance and generalization ability. Results After dimensionality reduction, a feature subset having 21 radiomics features was generated. The generated radiomics model had an the area under curve (AUC) value of 0.835 (95% confidence interval(CI): 0.761–0.908) in the training set and 0.784 (95% CI: 0.691–0.874) in the external validation cohort. Conclusion The radiomics model of this study had the potential to predict the Ki67 index of GISTs preoperatively.
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Affiliation(s)
- Yilei Zhao
- First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Meibao Feng
- First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Minhong Wang
- First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Liang Zhang
- Zhejiang Cancer Hospital, University of Chinese Academy of Sciences, Hangzhou, China
| | - Meirong Li
- First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chencui Huang
- Beijing Deepwise & League of PHD Technology Co., Ltd, Beijing, China
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26
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Yang CW, Liu XJ, Zhao L, Che F, Yin Y, Chen HJ, Zhang B, Wu M, Song B. Preoperative prediction of gastrointestinal stromal tumors with high Ki-67 proliferation index based on CT features. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1556. [PMID: 34790762 PMCID: PMC8576677 DOI: 10.21037/atm-21-4669] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/13/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND To determine whether preoperative computed tomography (CT) features can be used for the prediction of gastrointestinal stromal tumors (GISTs) with a high Ki-67 proliferation index (Ki-67 PI). METHODS A total of 198 patients with surgically and pathologically proven GISTs were retrospectively included. All GISTs were divided into a low Ki-67 PI group (<10%) and a high Ki-67 PI group (≥10%). All imaging features were blindly interpreted by two radiologists. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the predictive performance of the imaging features. RESULTS Imaging features were found to be significantly different between the low and the high Ki-67 PI groups (P<0.05). Wall thickness of necrosis showed the highest predictive ability, with an area under the curve (AUC) of 0.838 [95% confidence interval (CI): 0.627-0.957], followed by necrosis, necrosis degree, hyperenhancement of the overlying mucosa (HYOM), and long diameter (LD) (AUC >0.7, P<0.05). HYOM was the strongest predictive feature for the high Ki-67 PI GISTs group, with an odds ratio (OR) value of 30.037 (95% CI: 5.707-158.106). CONCLUSIONS Imaging features, including the presence of necrosis, high necrosis degree, thick wall of necrosis, and HYOM were significant predictive indicators for the high Ki-67 PI GISTs group.
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Affiliation(s)
- Cai-Wei Yang
- West China School of Medicine, Sichuan University, Chengdu, China
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Xi-Jiao Liu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Lian Zhao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Che
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hui-Jiao Chen
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Min Wu
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Clinic Medical Center, Dazhou Central Hospital, Dazhou, China
- Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
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Kim HJ, Park JY, Kim BJ, Kim JG, Kim HS, Park JM. Gastric Gastrointestinal Stromal Tumor with Repeated Recurrence at the Anastomosis Site in a Very Elderly Patient. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 76:206-210. [PMID: 33100316 DOI: 10.4166/kjg.2020.76.4.206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/30/2020] [Accepted: 08/16/2020] [Indexed: 11/03/2022]
Abstract
Although high-risk gastrointestinal stromal tumors (GISTs) frequently recur, even after a complete resection and imatinib therapy, local recurrence at the suture line after complete resection is rare. The present case was an 88-year-old woman who was initially diagnosed with high-risk GIST without a distant metastasis. She underwent a complete surgical resection of the lesion and received adjuvant imatinib therapy for 18 months, which was discontinued due to severe drug-induced anemia. During the follow- up, an endoscopic examination performed 40 months after the initial surgery revealed local recurrence at the anastomosis site. Although a complete surgical resection was performed, repeated local recurrence was detected 18 months later, which progressed rapidly to metastatic disease. This paper reports a case of a completely resected gastric GIST with repeated local recurrence, despite the complete surgical resections and adjuvant imatinib therapy.
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Affiliation(s)
- Hye-Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jae Yong Park
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hee Sung Kim
- Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea
| | - Joong-Min Park
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
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Gheorghe G, Bacalbasa N, Ceobanu G, Ilie M, Enache V, Constantinescu G, Bungau S, Diaconu CC. Gastrointestinal Stromal Tumors-A Mini Review. J Pers Med 2021; 11:694. [PMID: 34442339 PMCID: PMC8400825 DOI: 10.3390/jpm11080694] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 07/17/2021] [Accepted: 07/20/2021] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They are potentially malignant, and have an unpredictable evolution. The origin of these tumors is in the interstitial cells of Cajal, which are cells that are interposed between the intramural neurons and the smooth muscle cells of the digestive tract. GISTs are characterized by mutations in the gene c-Kit, but also other mutations, such as those of the platelet-derived growth factor receptor alpha. The most common locations of these tumors are the stomach and small intestine, although they can occur at any level of the digestive tract and occasionally in the omentum, mesentery and peritoneum. Most cases of GISTs are sporadic, and about 5% of cases are part of family genetic syndromes. The correct diagnosis of GIST is determined by histopathological examination and immunohistochemistry. According to histopathology, there are three main types of GISTs: spindle cell type, epithelioid type and mixed type. The therapeutic management of GIST includes surgery, endoscopic treatment and chemotherapy. The prognosis of patients with GIST varies depending on a number of factors, such as risk category, GIST stage, treatment applied and recurrence after treatment.
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Affiliation(s)
- Gina Gheorghe
- Clinical Emergency Hospital of Bucharest, Department of Gastroenterology, University of Medicine and Pharmacy “Carol Davila“, 050474 Bucharest, Romania; (G.G.); (M.I.)
| | - Nicolae Bacalbasa
- Department of Visceral Surgery, “Fundeni” Clinical Institute, University of Medicine and Pharmacy “Carol Davila“, 050474 Bucharest, Romania;
| | - Gabriela Ceobanu
- “Sfanta Maria” Clinical Hospital, Department of Internal Medicine and Rheumatology, 011172 Bucharest, Romania;
| | - Madalina Ilie
- Clinical Emergency Hospital of Bucharest, Department of Gastroenterology, University of Medicine and Pharmacy “Carol Davila“, 050474 Bucharest, Romania; (G.G.); (M.I.)
| | - Valentin Enache
- Clinical Emergency Hospital of Bucharest, Department of Anatomical Pathology, 050474 Bucharest, Romania;
| | - Gabriel Constantinescu
- Clinical Emergency Hospital of Bucharest, Department of Gastroenterology, University of Medicine and Pharmacy “Carol Davila“, 050474 Bucharest, Romania; (G.G.); (M.I.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Camelia Cristina Diaconu
- Clinical Emergency Hospital of Bucharest, Department of Internal Medicine, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania;
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Seifert H, Fusaroli P, Arcidiacono PG, Braden B, Herth F, Hocke M, Larghi A, Napoleon B, Rimbas M, Ungureanu BS, Săftoiu A, Sahai AV, Dietrich CF. Controversies in EUS: Do we need miniprobes? Endosc Ultrasound 2021; 10:246-269. [PMID: 34380805 PMCID: PMC8411553 DOI: 10.4103/eus-d-20-00252] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/04/2021] [Indexed: 11/04/2022] Open
Abstract
This is the fifth in a series of papers entitled "Controversies in EUS." In the current paper, we deal with high-resolution catheter probes, otherwise known as EUS miniprobes (EUS-MPs). The application of miniprobes for early carcinomas in the entire intestinal tract, for subepithelial lesions, and for findings in the bile duct and pancreatic duct as well as endobronchial use is critically discussed. Submucous lesions, especially in the colon, but also early carcinomas in special cases are considered the most important indications. The argument is illustrated by numerous examples.
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Affiliation(s)
- Hans Seifert
- Department of Gastroenterology, Evangelisches Krankenhaus, Oldenburg, Germany
- Universitatsklinik fur Innere Medizin - Gastroneterologie, Hepatologie; Klinikum Oldenburg, Germany
| | - Pietro Fusaroli
- Department of Medical and Surgical Sciences, Gastroenterology Unit, University of Bologna/Imola Hospital, Imola, Italy
| | - Paolo Giorgio Arcidiacono
- Research Center, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
| | - Barbara Braden
- Translational Gastroenterology Unit I, John Radcliffe Hospital I, Oxford, OX3 9DU, UK
| | - Felix Herth
- 2 Department of Pneumology and Critical Care Medicine, Thoraxklinik and Translational Lung Research Center (TLRCH), Member of the German Lung Research Foundation (DZL), University of Heidelberg, Heidelberg, Germany
| | - Michael Hocke
- Department of Medicine, Helios Klinikum Meiningen, Meiningen, Germany
| | - Alberto Larghi
- Digestive Endoscopy Unit, IRCCS Foundation University Hospital, Policlinico A. Gemelli, Rome, Italy
| | - Bertrand Napoleon
- 2 Digestive Endoscopy Unit, HopitalPrivé J Mermoz Ramsay Générale de Santé, Lyon, France
| | - Mihai Rimbas
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania
- Department of Internal Medicine, Carol Davila University of Medicine Bucharest, Romania
| | - Bogdan Silvio Ungureanu
- Research Center of Gastroenterology and Hepatology Craiova, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Adrian Săftoiu
- Research Center of Gastroenterology and Hepatology Craiova, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Anand V Sahai
- Center Hospitalier de l'Université de Montréal, Montreal, Canada
| | - Christoph F. Dietrich
- Department of Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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30
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Al-Maqrashi Z, Burney IA, Taqi KM, Al-Sawafi Y, Qureshi A, Lakhtakia R, Mehdi I, Al-Bahrani B, Kumar S, Al-Moundhri M. Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study. Sultan Qaboos Univ Med J 2021; 21:e237-e243. [PMID: 34221471 PMCID: PMC8219329 DOI: 10.18295/squmj.2021.21.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/13/2020] [Accepted: 09/09/2020] [Indexed: 11/16/2022] Open
Abstract
Objectives This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. Methods This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. Results A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. Conclusion The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.
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Affiliation(s)
| | - Ikram A Burney
- Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Kadhim M Taqi
- Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Yaqoob Al-Sawafi
- Department of General Surgery, Armed Forces Hospital, Muscat, Oman
| | - Asim Qureshi
- Department of Pathology, King's Mill Hospital, Sherwood Forest Hospitals National Health Service Foundation Trust, Mansfield, Nottinghamshire, UK.,Department of Pathology, Sultan Qaboos University Hospital, Muscat, Oman
| | - Ritu Lakhtakia
- Department of Pathology, Mohammed bin Rashid University of Medicine & Health Sciences, Dubai, United Arab Emirates
| | - Itrat Mehdi
- National Oncology Centre, Royal Hospital, Muscat, Oman
| | | | - Shiyam Kumar
- Department of Medical Oncology, Yeovil District Hospital NHS Foundation Trust, Somerset, UK
| | - Mansour Al-Moundhri
- Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
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Apte SS, Radonjic A, Wong B, Dingley B, Boulva K, Chatterjee A, Purgina B, Ramsay T, Nessim C. Preoperative imaging of gastric GISTs underestimates pathologic tumor size: A retrospective, single institution analysis. J Surg Oncol 2021; 124:49-58. [PMID: 33857332 DOI: 10.1002/jso.26494] [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] [Received: 12/22/2020] [Revised: 03/21/2021] [Accepted: 04/02/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND How well imaging size agrees with pathologic size of gastric gastrointestinal stromal tumors (GISTs) is unknown. GIST risk stratification is based on pathologic size, location, and mitotic rate. To inform decision making, the size discrepancy between imaging and pathology for gastric GISTs was investigated. METHODS Imaging and pathology reports were reviewed for 113 patients. Bland-Altman analyses and intraclass correlation (ICC) assessed agreement of imaging and pathology. Changes in clinical risk category due to size discrepancy were identified. RESULTS Computed tomography (CT) (n = 110) and endoscopic ultrasound (EUS) (n = 50) underestimated pathologic size for gastric GISTs by 0.42 cm, 95% confidence interval (CI): (0.11, 0.73), p = 0.008 and 0.54 cm, 95% CI: (0.25, 0.82), p < 0.001, respectively. ICCs were 0.94 and 0.88 for CT and EUS, respectively. For GISTs ≤ 3 cm, size underestimation was 0.24 cm for CT (n = 28), 95% CI: (0.01, 0.47), p = 0.039 and 0.56 cm for EUS (n = 26), 95% CI: (0.27, 0.84), p < 0.0001. ICCs were 0.72 and 0.55 for CT and EUS, respectively. Spearman's correlation was ≥0.84 for all groups. For GISTs ≤ 3 cm, 6/28 (21.4% p = 0.01) on CT and 7/26 (26.9% p = 0.005) on EUS upgraded risk category using pathologic size versus imaging size. No GISTs ≤ 3 cm downgraded risk categories. Size underestimation persisted for GISTs ≤ 2 cm on EUS (0.39 cm, 95% CI: [0.06, 0.72], p = 0.02, post hoc analysis). CONCLUSION Imaging, particularly EUS, underestimates gastric GIST size. Caution should be exercised using imaging alone to risk-stratify gastric GISTs, and to decide between surveillance versus surgery.
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Affiliation(s)
- Sameer S Apte
- Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.,Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
| | - Aleksandar Radonjic
- Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
| | - Boaz Wong
- Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
| | - Brittany Dingley
- Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.,Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
| | - Kerianne Boulva
- Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.,Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
| | - Avijit Chatterjee
- Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada.,Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Bibiana Purgina
- Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada.,Department of Pathology, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Timothy Ramsay
- Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
| | - Carolyn Nessim
- Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.,Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada
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Wang Q, Huang ZP, Zhu Y, Fu F, Tian L. Contribution of Interstitial Cells of Cajal to Gastrointestinal Stromal Tumor Risk. Med Sci Monit 2021; 27:e929575. [PMID: 33760802 PMCID: PMC8006562 DOI: 10.12659/msm.929575] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/17/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs), which originate from interstitial cells of Cajal (ICCs), are one of most common mesenchymal tumors of the gastrointestinal tract. This study explored the impact of ICCs and immunological markers on GIST risk. MATERIAL AND METHODS A total of 122 patients diagnosed with GISTs who underwent surgery were recruited for the study. Demographic and clinical information, including modified NIH criteria, sex, age, tumor site, and tumor size, of all patients were collected. GIST risk was assessed using the modified NIH risk classification for primary GISTs. Paraffin-embedded GIST specimens were evaluated by hematoxylin-eosin staining and ICCs immunohistochemistry. RESULTS According to the modified NIH criteria, most GIST cases (44 cases, 36.07%) were at very low risk. Females had greater incidence of high-risk GISTs (P<0.05). The mean age at GIST diagnosis was 58.69±9.90 years and had no impact on GIST risk (P>0.05). Most GISTs were located in the stomach (87 cases, 71.73%), and the size of the tumors varied (0.5-20 cm). CD117/c-kit and CD34 were specific immuno-markers for ICCs and GIST. Most patients with GIST were CD117-positive (115 cases, 94.26%), 111 cases (90.98%) were CD34-positive, and 109 cases (89.34%) were positive for both CD117/c-kit and CD34. With increasing GIST risk, CD117 (also named c-k0it) and CD34 expression levels increased, as well as the number of ICCs (all P<0.05). CONCLUSIONS ICCs have a great impact on GISTs incidence. CD117/c-kit and CD34 expression, as well ICCs levels, appear to affect GIST risk.
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Affiliation(s)
- Qi Wang
- Department of Pathology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China
| | - Zhen-peng Huang
- Guangzhou Institute of Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China
| | - Yu Zhu
- Department of Science and Education, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China
| | - Fei Fu
- Department of Pathology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China
| | - Lin Tian
- Department of Pathology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China
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Li C, Yang KL, Wang Q, Tian JH, Li Y, Gao ZD, Yang XD, Ye YJ, Jiang KW. Clinical features of multiple gastrointestinal stromal tumors: A pooling analysis combined with evidence and gap map. World J Gastroenterol 2020; 26:7550-7567. [PMID: 33384554 PMCID: PMC7754550 DOI: 10.3748/wjg.v26.i47.7550] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 11/09/2020] [Accepted: 11/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Multiple gastrointestinal stromal tumors (MGISTs) are a very rare type of gastrointestinal stromal tumor (GIST) and are usually observed in syndrome.
AIM The paper aimed to describe the clinical and oncological features of MGISTs and to offer evidence for the diagnosis and treatment.
METHODS Data of consecutive patients with MGISTs who were diagnosed at Peking University People’s Hospital (PKUPH) from 2008 to 2019 were retrospectively evaluated. Further, a literature search was conducted by retrieving data from PubMed, EMBASE, and the Cochrane library databases from inception up to November 30, 2019.
RESULTS In all, 12 patients were diagnosed with MGISTs at PKUPH, and 43 published records were ultimately included following the literature review. Combined analysis of the whole individual patient data showed that female (59.30%), young (14.45%), and syndromic GIST (63.95%) patients comprised a large proportion of the total patient population. Tumors were mainly located in the small intestine (58.92%), and both CD117 and CD34 were generally positive. After a mean 78.32-mo follow-up, the estimated median overall survival duration (11.5 years) was similar to single GISTs, but recurrence-free survival was relatively poorer.
CONCLUSION The clinical and oncological features are potentially different between MGISTs and single GIST. Further studies are needed to explore appropriate surgical approach and adjuvant therapy.
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Affiliation(s)
- Chen Li
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Ke-Lu Yang
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Quan Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Jin-Hui Tian
- Evidence Based Medicine Center, School of Basic Medical Science of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Yang Li
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Zhi-Dong Gao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Xiao-Dong Yang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Ying-Jiang Ye
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Ke-Wei Jiang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, China
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Retrospective Comparison of Endoscopic Full-Thickness Versus Laparoscopic or Surgical Resection of Small (≤ 5 cm) Gastric Gastrointestinal Stromal Tumors. J Gastrointest Surg 2020; 24:2714-2721. [PMID: 31823317 DOI: 10.1007/s11605-019-04493-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 11/24/2019] [Indexed: 02/07/2023]
Abstract
AIM AND BACKGROUND The aim of this study was to compare the efficacy and safety between endoscopic full-thickness resection (EFR) and laparoscopic or surgical resection methods for gastric gastrointestinal stromal tumor (GIST) in size of 5.0 cm or less. Gastric GISTs are common, and resection is the most effective treatment. METHOD We retrospectively reviewed 216 resections of gastric GISTs in size of up to 5.0 cm at our center from 2009 to 2017.Eligible resection cases were divided into EFR (n = 85), laparoscopic(n = 64), and surgical (n = 67) groups. The clinical records, patient demographic, symptoms, perioperative data, pathological findings, and long-term follow-up outcomes were collected and compared statistically. RESULTS No tumor rupture or recurrence occurred in the three groups. The prevalence of complications was significantly lower in EFR (5.9%) than both laparoscopic (7.8%) and surgical group (16.4%) (P < 0.01). In EFR group, the R0 resection rate (95.3%) was significantly lower than in the laparoscopic group and surgical group (100%) (P < 0.001). The hospital cost (OR = 62.79, CI: 12.954-304.363, P < 0.0001) were significantly lower in the EFR than in the laparoscopic group. The hospital cost (OR = 39.032, CI: 8.045-189.371, P < 0.0001) and post-operative diet time (OR = 2.779, CI: 1.225-6.304, P < 0.05) were also significantly lower in the EFR than in the surgical group. CONCLUSION EFR was a feasible treatment for gastric GISTs of size of ≤ 5.0 cm with an acceptable complete resection rate. In addition, EFR had significantly fewer postoperative complications, shorter length of hospital stay, and lower cost.
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Yang CW, Liu XJ, Liu SY, Wan S, Ye Z, Song B. Current and Potential Applications of Artificial Intelligence in Gastrointestinal Stromal Tumor Imaging. CONTRAST MEDIA & MOLECULAR IMAGING 2020; 2020:6058159. [PMID: 33304203 PMCID: PMC7714601 DOI: 10.1155/2020/6058159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 10/18/2020] [Accepted: 10/31/2020] [Indexed: 02/05/2023]
Abstract
The most common mesenchymal tumors are gastrointestinal stromal tumors (GISTs), which have malignant potential and can occur anywhere along the gastrointestinal system. Imaging methods are important and indispensable of GISTs in diagnosis, risk staging, therapy, and follow-up. The recommended imaging method for staging and follow-up is computed tomography (CT) according to current guidelines. Artificial intelligence (AI) applies and elaborates theses, procedures, modes, and utilization systems for simulating, enlarging, and stretching the intellectual capacity of humans. Recently, researchers have done a few studies to explore AI applications in GIST imaging. This article reviews the present AI studies in GISTs imaging, including preoperative diagnosis, risk stratification and prediction of prognosis, gene mutation, and targeted therapy response.
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Affiliation(s)
- Cai-Wei Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xi-Jiao Liu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Si-Yun Liu
- GE Healthcare (China), Beijing 100176, China
| | - Shang Wan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zheng Ye
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Cai XL, Li XY, Liang C, Xu Y, Zhang MZ, Yu WM, Li XY. Endoscopic or laparoscopic resection for small gastrointestinal stromal tumors: a cumulative meta-analysis. Chin Med J (Engl) 2020; 133:2731-2742. [PMID: 32889913 PMCID: PMC7725529 DOI: 10.1097/cm9.0000000000001069] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. METHODS The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. RESULTS A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34). CONCLUSIONS In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.
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Affiliation(s)
- Xian-Lei Cai
- Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
| | - Xue-Ying Li
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, China
| | - Chao Liang
- Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
| | - Yuan Xu
- Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
| | - Miao-Zun Zhang
- Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
| | - Wei-Ming Yu
- Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
| | - Xiu-Yang Li
- Department of Neurology of the Second Affiliated Hospital of Zhejiang University School of Medicine, Interdisciplinary Institute of Neuroscience and Technology of Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, Zhejiang 310000, China
- Department of Epidemiology & Biostatistics, Zhejiang University, Hangzhou, Zhejiang 310000, China
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Tyler R, Davies E, Tan D, Hodson J, Taniere P, Thway K, Jafri M, Almond M, Ford S, Strauss D, Hayes A, Smith M, Desai A. Tumor necrosis is significantly associated with reduced recurrence-free survival after curative resection of gastrointestinal stromal tumors. J Surg Oncol 2020; 123:432-438. [PMID: 33169386 DOI: 10.1002/jso.26294] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND OBJECTIVES The impact of tumor necrosis as a prognostic factor in gastrointestinal stromal tumor (GISTs) is still debated. The objective was to determine whether tumor necrosis is an independent risk factor for survival in patients with GISTs. METHODS Patients undergoing surgery for primary GIST from March 2003 to October 2018 at two sarcoma referral centers were retrospectively identified. Patients who received neoadjuvant imatinib were excluded. Multivariable Cox regression models were produced, to assess whether tumor necrosis was an independent predictor of either overall or recurrence-free survival. RESULTS Forty-one out of 195 (21.0%) patients had tumor necrosis. Tumor necrosis was associated with a significantly higher modified National Institute of Health risk score, with 29 out of 41 (70.7%) patients with necrosis classified as high risk, compared to 52 out of 153 (34.0%) without (p < .001). Tumor necrosis was found to be independently predictive of recurrence-free survival (hazard ratio: 5.26, 95% CI: 2.62-10.56, p < .001) on multivariable analysis. At 5 years, 44.3% of patients with necrosis had either died or developed recurrence, compared to 9.9% of those without. CONCLUSION Tumor necrosis is an independent predictor of recurrence-free survival in patients with operable GISTs. It should be routinely reported by pathologists, and used by clinicians when counseling patients and deciding on adjuvant therapy.
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Affiliation(s)
- Robert Tyler
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
| | - Emma Davies
- Sarcoma Unit, Royal Marsden Hospital, London, Chelsea, UK
| | - Dominic Tan
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, Edgbaston, UK
| | - James Hodson
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
| | - Phillipe Taniere
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
| | - Khin Thway
- Sarcoma Unit, Royal Marsden Hospital, London, Chelsea, UK
| | - Mariam Jafri
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
| | - Max Almond
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
| | - Samuel Ford
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
| | - Dirk Strauss
- Sarcoma Unit, Royal Marsden Hospital, London, Chelsea, UK
| | - Andrew Hayes
- Sarcoma Unit, Royal Marsden Hospital, London, Chelsea, UK
| | - Myles Smith
- Sarcoma Unit, Royal Marsden Hospital, London, Chelsea, UK
| | - Anant Desai
- Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Edgbaston, UK
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Lee DJW, Warner M, Shannon T, Moschilla J. Incidental finding of ileal gastrointestinal stromal tumour during prostate cancer staging with prostate-specific membrane antigen scan. J Med Imaging Radiat Oncol 2020; 65:89-91. [PMID: 33118296 DOI: 10.1111/1754-9485.13113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 09/20/2020] [Indexed: 11/27/2022]
Abstract
Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is used in managing and staging prostate cancer, but can identify other non-prostate pathology. We present the first reported case where small bowel gastrointestinal stromal tumour (GIST) has been incidentally identified on PSMA-PET scan and highlight the need for awareness of other pathology being identified on PSMA-PET/CT.
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Affiliation(s)
- Daniel Jia Wei Lee
- Department of General Surgery, Hollywood Private Hospital, Perth, Western Australia, Australia
| | - Michael Warner
- Department of General Surgery, Hollywood Private Hospital, Perth, Western Australia, Australia
| | - Thomas Shannon
- Department of Urology, Hollywood Private Hospital, Perth, Western Australia, Australia
| | - Jerry Moschilla
- Envision Medical Imaging, Perth, Western Australia, Australia
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Foo MY, Yeung BPM, Tan JTH. Laparoscopic resectional oesophago-gastroplasty: a novel technique for minimally invasive treatment of large high gastric lesser curve GIST involving gastroesophageal junction. J Surg Case Rep 2020; 2020:rjaa346. [PMID: 33072252 PMCID: PMC7546678 DOI: 10.1093/jscr/rjaa346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 08/05/2020] [Indexed: 12/01/2022] Open
Abstract
A paramount factor in selecting the operative approach for gastric gastrointestinal stromal tumours (GIST) is tumour location. Tumours located high along the lesser curve of the stomach pose a challenge in laparoscopic resection. A 56-year-old lady presented with per rectal bleeding and loss of weight. Endoscopic and radiological investigations revealed a large gastric GIST located over the lesser curve with proximal margin <1 cm from the gastroesophageal junction (GEJ). We present the steps of a novel technique for laparoscopic resectional oesophago-gastroplasty to resect large high gastric lesser curve GIST involving the GEJ.
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Affiliation(s)
- Mang Yik Foo
- Division of Upper Gastrointestinal and Bariatric Surgery, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Baldwin P M Yeung
- Division of Upper Gastrointestinal and Bariatric Surgery, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Jeremy T H Tan
- Division of Upper Gastrointestinal and Bariatric Surgery, Department of General Surgery, Sengkang General Hospital, Singapore
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Winder A, Strauss DC, Jones RL, Benson C, Messiou C, Chaudry MA, Smith MJ. Robotic surgery for gastric gastrointestinal stromal tumors: A single center case series. J Surg Oncol 2020; 122:691-698. [PMID: 32488872 DOI: 10.1002/jso.26053] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 05/06/2020] [Accepted: 05/21/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND OBJECTIVES The aim of surgical treatment of gastrointestinal stromal tumors (GIST) is a microscopically complete resection. Initial indications for laparoscopic surgery were limited to smaller tumors, in favorable locations. Over time, indications for minimal invasive surgery (MIS) have expanded, however concerns remain when considering resection of larger GISTs. Our aims were to assess the utility of robotic resection of gastric GISTs for challenging tumors. METHODS GIST resections, in this study were performed using the Intuitive Da Vinci Surgical Xi System. GIST's were considered challenging if tumor size was >50 mm at the time of surgery and/or the location of the tumor was type II, III, or IV using Privette/Al-Thanai classification. RESULTS Robotic resections were performed on 12 consecutive patients, 83% were considered challenging cases, 6 out of 12 for location and 5 out of 12 for size. Initial median tumor size on imaging was 53.7 mm, and post-imatinib was 45.8 mm. All tumors were removed with clear margins (R0) via wedge resections, with no complications. Median operative time was 192 minutes (95-250). Length of hospital stay was 2 days (2-6). CONCLUSIONS Robotic resection of gastric GIST's appears oncologically safe, and may expand the benefits of MIS to a greater cohort of complex cases.
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Affiliation(s)
- Alec Winder
- Department of Academic Surgery, Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital, London, UK
| | - Dirk C Strauss
- Department of Academic Surgery, Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital, London, UK
| | - Robin L Jones
- Department of Academic Surgery, Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital, London, UK
| | - Charlotte Benson
- Department of Academic Surgery, Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital, London, UK
| | | | - Mohammed Asif Chaudry
- Department of Oesophageal and Gastric Cancer Surgery, The Royal Marsden Hospital, London, UK
| | - Myles J Smith
- Department of Academic Surgery, Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital, London, UK
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Small Bowel Tumors – Case Series Analysis: Prognostic Factors and Survivals. Indian J Surg 2020. [DOI: 10.1007/s12262-020-02092-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Businello G, Dal Pozzo CA, Sbaraglia M, Mastracci L, Milione M, Saragoni L, Grillo F, Parente P, Remo A, Bellan E, Cappellesso R, Pennelli G, Michelotto M, Fassan M. Histopathological landscape of rare oesophageal neoplasms. World J Gastroenterol 2020; 26:3865-3888. [PMID: 32774063 PMCID: PMC7385561 DOI: 10.3748/wjg.v26.i27.3865] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 06/19/2020] [Accepted: 07/04/2020] [Indexed: 02/06/2023] Open
Abstract
The landscape of neoplastic pathology of the oesophagus is dominated by malignancies of epithelial origin, in particular by oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. However, several other histopathological variants can be distinguished, some associated with peculiar histopathological profiles and prognostic behaviours and frequently underrecognized in clinical practice. The aim of this review is to provide a comprehensive characterization of the main morphological and clinical features of these rare variants of oesophageal neoplastic lesions.
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Affiliation(s)
- Gianluca Businello
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Carlo Alberto Dal Pozzo
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Marta Sbaraglia
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Luca Mastracci
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genova, Genova 16123, Italy
| | - Massimo Milione
- Department of Pathology and Laboratory Medicine, First Pathology Division, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Luca Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
| | - Federica Grillo
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genova, Genova 16123, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo 71013, Italy
| | - Andrea Remo
- Department of Pathology, Ospedale Mater Salutis di Legnago, Legnago 37045, Italy
| | - Elena Bellan
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Rocco Cappellesso
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Gianmaria Pennelli
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Mauro Michelotto
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua 35121, Italy
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Smrke A, Gennatas S, Huang P, Jones RL. Avapritinib in the treatment of PDGFRA exon 18 mutated gastrointestinal stromal tumors. Future Oncol 2020; 16:1639-1646. [PMID: 32517495 DOI: 10.2217/fon-2020-0348] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Gastrointestinal stromal tumors (GIST) can be molecularly classified based on different subtypes including mutations in KIT and PDGFRA. Patients with PDGFRA mutations are an important subgroup that commonly arise in the stomach and are associated with a more indolent disease course. Importantly, the most common PDGFRA molecular subtype, the D842V mutation in exon 18 of the gene which alters the activation loop, is imatinib insensitive in in vitro studies. Poor responses to imatinib have been seen clinically compared with PDGFRA exon 18 non-D842V-mutated GIST. Avapritinib (BLU-285) is a potent KIT and PDGFRA-specific tyrosine kinase inhibitor which has shown >90% response rates in patients with PDGFRA exon 18 D842V-mutated GIST. Results from the Phase I trial of avapritinib have indicated that this drug should be the standard of care for patients with PDGFRA exon 18 D842V-mutated GIST.
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Affiliation(s)
- Alannah Smrke
- Sarcoma Unit, Royal Marsden Hospital, 203 Fulham Road, London, SW36JJ, UK
| | - Spyridon Gennatas
- Sarcoma Unit, Royal Marsden Hospital, 203 Fulham Road, London, SW36JJ, UK
| | - Paul Huang
- Department of Pathology, Molecular & Systems Oncology, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK
| | - Robin L Jones
- Sarcoma Unit, Royal Marsden Hospital, 203 Fulham Road, London, SW36JJ, UK.,Department of Pathology, Molecular & Systems Oncology, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK
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Ashoor AA, Barefah G. Unusual presentation of a large GIST in an extraintestinal site: a challenging diagnosis dilemma. BMJ Case Rep 2020; 13:e229839. [PMID: 32033995 PMCID: PMC7021108 DOI: 10.1136/bcr-2019-229839] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2020] [Indexed: 12/11/2022] Open
Abstract
Gastrointestinal stromal tumour (GIST) is a recent recognised tumour entity. In the past, those tumours were classified as leiomyomas, leiomyosarcomas and leiomyoblastomas, but it is now evident that GIST is a separate tumour entity and is the most common sarcoma of the gastrointestinal tract especially with advances in immunohistochemical staining techniques and improvements in microscopic structural imaging. We present a case of GIST of unusual location and presentation pattern, with an overview over current GISTs' diagnosis and management strategies. The precise incidence and tumour behaviour of rare extragastrointestinal stromal tumour (EGIST) remain to be clarified. Further research is needed in large series with long duration of follow-up and modified risk stratification assessment tailored for EGISTs.
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Affiliation(s)
- Arwa Ahmed Ashoor
- Department of Surgery, King Fahad General Hospital, Jeddah, Saudi Arabia
| | - Ghaith Barefah
- Department of Radilogy, King Fahad General Hospital, Jeddah, Saudi Arabia
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Chamberlain F, Farag S, Williams-Sharkey C, Collingwood C, Chen L, Mansukhani S, Engelmann B, Al-Muderis O, Chauhan D, Thway K, Fisher C, Jones RL, Gennatas S, Benson C. Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre. Clin Sarcoma Res 2020; 10:1. [PMID: 31911828 PMCID: PMC6942401 DOI: 10.1186/s13569-019-0123-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Accepted: 12/10/2019] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. METHODS Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. RESULTS Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8-14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2-28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3-4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. CONCLUSION Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.
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Affiliation(s)
| | - Sheima Farag
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | | | | | - Lucia Chen
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | - Sonia Mansukhani
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | - Bodil Engelmann
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | - Omar Al-Muderis
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | - Dharmisha Chauhan
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | - Khin Thway
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
- The Institute of Cancer Research, London, SW7 3RP UK
| | - Cyril Fisher
- The Institute of Cancer Research, London, SW7 3RP UK
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW UK
| | - Robin L. Jones
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
- The Institute of Cancer Research, London, SW7 3RP UK
| | - Spyridon Gennatas
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
| | - Charlotte Benson
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW6 3JJ UK
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A Huge Pelvic-Abdominal Malignant GIST Tumour in a Patient with Neurofibromatosis Type 1: Case Report and Literature Review. Case Rep Oncol Med 2020; 2020:6590307. [PMID: 31984144 PMCID: PMC6964723 DOI: 10.1155/2020/6590307] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 08/25/2019] [Accepted: 12/23/2019] [Indexed: 11/18/2022] Open
Abstract
Gastrointestinal stromal tumours are rare tumours of the gastrointestinal tract (GIT) accounting for 0.1%–3% of all gastrointestinal tumours. The most common location is the stomach (55%) followed by the small bowel (31.8%), colon (6%), other various locations (5.5%), and the oesophagus (0.7%). They may also occur in extraintestinal locations. The signs and symptoms of GIST depend on the tumour's location and size. Gastrointestinal bleeding is one of the most common symptoms. Other signs and symptoms include abdominal discomfort, pain or distention; intestinal obstruction, and weight loss. The association between the development of GISTs and neurofibromatosis 1 (NF1) has been established. NF1-associated GISTs tend to have a distinct phenotype, and the absence of KIT/PDGRFα mutations in turn has implications on further management when they do not respond well to imatinib treatment. Here, we present one of the largest GISTs reported in the literature with a total volume of 25.3 × 20 × 14 cm + 27.9 × 23 × 8 cm and an overall weight of 7.3 kg, which developed in a 43-year-old female patient with NF1 and was resected on an emergency basis due to the rapid deterioration and development of abdominal compartment syndrome. Pathology assessment showed a malignant GIST composed of spindle cells with elongated nuclei with necrosis, marked pleomorphism and numerous giant cell. The mitotic count was >15/50 HPF, Ki 67 was 80%, and the lymphovascular invasion was clear. Immunohistochemistry investigations showed that Vimentin, CD117, and DOG1 were positive, while BCL-2 and CD99 were focal positives. Pan-CK, S-100, CD34, Desmin, SMA, and HMB-45 were negatives.
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Wilding CP, Elms ML, Judson I, Tan AC, Jones RL, Huang PH. The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib. Expert Rev Anticancer Ther 2019; 19:971-991. [PMID: 31665941 PMCID: PMC6882314 DOI: 10.1080/14737140.2019.1686979] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/28/2019] [Indexed: 02/06/2023]
Abstract
Introduction: Tyrosine kinases are key mediators of intracellular signaling cascades and aberrations in these proteins have been implicated in driving oncogenesis through the dysregulation of fundamental cellular processes including proliferation, migration, and apoptosis. As such, targeting these proteins with small molecule tyrosine kinase inhibitors (TKI) has led to significant advances in the treatment of a number of cancer types.Areas covered: Soft tissue sarcomas (STS) are a heterogeneous and challenging group of rare cancers to treat, but the approval of the TKI pazopanib for the treatment of advanced STS demonstrates that this class of drugs may have broad utility against a range of different sarcoma histological subtypes. Since the approval of pazopanib, a number of other TKIs have entered clinical trials to evaluate whether their activity in STS matches the promising results seen in other solid tumors. In this article, we review the emerging role of TKIs in the evolving landscape of sarcoma treatment.Expert opinion: As our biological understanding of response and resistance of STS to TKIs advances, we anticipate that patient management will move away from a 'one size fits all' paradigm toward personalized, multi-line, and patient-specific treatment regimens where patients are treated according to the underlying biology and genetics of their specific disease.
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Affiliation(s)
| | - Mark L Elms
- Division of Molecular Pathology, The Institute of Cancer Research, London, UK
| | - Ian Judson
- Department of Medical Oncology, Sarcoma Unit, The Royal Marsden Hospital, London, UK
| | - Aik-Choon Tan
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA
| | - Robin L Jones
- Department of Medical Oncology, Sarcoma Unit, The Royal Marsden Hospital, London, UK
| | - Paul H Huang
- Division of Molecular Pathology, The Institute of Cancer Research, London, UK
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Hughes C, Radhakrishna G. Haemostatic radiotherapy for bleeding cancers of the upper gastrointestinal tract. Br J Hosp Med (Lond) 2019; 80:579-583. [DOI: 10.12968/hmed.2019.80.10.579] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Bleeding can cause significant morbidity in patients with upper gastrointestinal malignancies. Palliative radiotherapy can palliate bleeding effectively across numerous cancer sites such as the lung and rectum. The data available regarding the role in bleeding from upper gastrointestinal cancers are limited to a single meta-analysis, a phase 2 trial, eleven retrospective cohorts and two case reports, with the majority focusing on gastric cancer. From the data available radiotherapy appears to be a well-tolerated, effective haemostatic agent that should be considered in all patients with bleeding from an upper gastrointestinal malignancy. Questions remain regarding the radiobiology of haemostasis and the optimum fractionation schedule. There is no convincing evidence that protracted higher dose regimens provide additional benefit. Commonly used fractionation schedules use 1, 5 or 10 fractions. Short fractionation schedules have been used in patients with deteriorating performance status.
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Affiliation(s)
- Christopher Hughes
- ST5 Registrar, Department of Clinical Oncology, the Christie NHS Foundation Trust, Manchester M20 4BX
| | - Ganesh Radhakrishna
- Clinical Oncology Consultant, Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester
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Alessandrino F, Tirumani SH, Jagannathan JP, Ramaiya NH. Imaging surveillance of gastrointestinal stromal tumour: current recommendation by National Comprehensive Cancer Network and European Society of Medical Oncology-European Reference Network for rare adult solid cancers. Clin Radiol 2019; 74:746-755. [PMID: 31345555 DOI: 10.1016/j.crad.2019.06.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 06/24/2019] [Indexed: 12/23/2022]
Abstract
Imaging plays an active role in the surveillance of gastrointestinal stromal tumours (GISTs). Risk stratification schemes, based on size, mitotic count, and anatomical site of origin of the GIST, help in planning preoperative and postoperative imaging strategies especially in determining the frequency and duration of surveillance; however, there is no clear consensus on the optimal imaging strategies in patients with GISTs who are completely cured by surgery and patients who are at risk of recurrence. In addition, current surveillance protocols depend on the resectability of the primary tumour and presence of metastatic disease. The objective of this article is to provide a comprehensive review of the role of the different imaging methods for surveillance of GISTs, focusing on the guidelines recommended by National Comprehensive Cancer Network and European Society of Medical Oncology - European Network for Rare adult solid Cancers, and to propose practical guidelines for surveillance of GISTs for various risk categories.
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Affiliation(s)
- F Alessandrino
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
| | - S H Tirumani
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Department of Radiology, UH Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA
| | - J P Jagannathan
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - N H Ramaiya
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Department of Radiology, UH Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA
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