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Xiang W, Yuan W, Ren L, Huang W, Liang H, Huang J, Luan L, Xu C, Hou Y. A case of quadruple wild-type gastrointestinal stromal tumor with CDC42BPB::NTRK3 fusion and abundant lymphoid infiltration. Diagn Pathol 2025; 20:31. [PMID: 40133893 PMCID: PMC11934696 DOI: 10.1186/s13000-025-01630-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 03/12/2025] [Indexed: 03/27/2025] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The most common mutations in GISTs are those in receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor alpha (PDGFRA). GISTs without KIT or PDGFRA mutations are defined as wild-type (WT) GISTs. The molecular changes, prognosis, and treatments of WT GISTs remain uncertain. Among WT GISTs, neurotrophic tyrosine receptor kinase (NTRK) fusions have rarely been reported. We report a case of quadruple wild-type GIST harboring a novel CDC42BPB::NTRK3 fusion. In this study, we described a 66-year-old male patient with intrajejunal lesion. This case showed massive lymphocytic and plasma cell infiltration, which caused diagnostic difficulties in morphology. CDC42BPB::NTRK3 fusion was detected via next-generation sequencing (NGS), and this finding was confirmed by fluorescence in situ hybridization (FISH), which revealed NTRK3 breakage. However, the expression of the Trk protein in tumor tissue was not detected by immunohistochemistry (IHC). This finding expands the genetic spectrum of NTRK rearrangements in GISTs.
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Affiliation(s)
- Wentao Xiang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Wei Yuan
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Lei Ren
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Wen Huang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Huaiyu Liang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jie Huang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Lijuan Luan
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yingyong Hou
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
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Du X, Zang X, Zhang H, Liu L, Xu Y, Li X, Mou R, Xu H, Zhu J, Xie R. Mean platelet volume/platelet count ratio can predict the recurrence-free survival rate of patients after complete resection of gastrointestinal stromal tumors. Front Oncol 2024; 14:1465283. [PMID: 39582542 PMCID: PMC11581942 DOI: 10.3389/fonc.2024.1465283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/15/2024] [Indexed: 11/26/2024] Open
Abstract
Purpose The aim of this study is to compare mean platelet volume/platelet count ratio (PVPR) and other indicators' predictive abilities. Simultaneously, a new nomogram for predicting recurrence-free survival (RFS) after gastrointestinal stromal tumors (GISTs) R0 resection was developed. Methods From January 2010 to July 2019, 295 patients with GIST who were operated on at Harbin Medical University Cancer Hospital were retrospectively reviewed. With a 4-year RFS as the end point, using the Kaplan-Meier methods and log rank test, and then conducting Cox regression analysis, we compared and identified meaningful indicators for predicting prognosis. Finally, a nomogram was developed and validated using calibration curves. Results The receiver operating characteristic curve indicated that a cutoff point of 0.044 was the ideal threshold for PVPR, and patients were divided into a high-PVPR group (≤0.044) and a low-PVPR group (>0.044). Kaplan-Meier curves suggested that PVPR>0.044 had obvious associations with better RFS (p < 0.001). In accordance with multivariate analysis, PVPR (>0.044 vs. ≤0.044) (p = 0.005), National Institutes of Health (NIH) risk category (p < 0.001), and Ki-67 (p = 0.005) were the independent prognostic indicators of RFS. Tumor size, gastrointestinal bleeding, mitotic index, NIH risk category, CD34, and Ki-67 all exhibited an obvious correlation with PVPR (all p < 0.05). The nomogram's probability of concordance was 0.823, indicating that the nomogram predictions were well calibrated. Conclusion In GISTs, RFS can be independently predicted by PVPR. Patients with higher PVPR have better RFS. The nomogram including PVPR could be used to assist clinical treatment decision-making.
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Affiliation(s)
- Xinlian Du
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Xinxin Zang
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Hanbo Zhang
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Lijia Liu
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Ying Xu
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Xuedong Li
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Ruishu Mou
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Haitao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Jiuxin Zhu
- College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, China
| | - Rui Xie
- Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
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Jayant D, Goyal M, Thakur V, Sahu S, Babu B, Subbiah Nagaraj S, Tandup C, Behera A. Advanced and Metastatic Gastrointestinal Stromal Tumors Presenting With Surgical Emergencies Managed With Surgical Resection: A Case Series. Cureus 2024; 16:e53851. [PMID: 38465042 PMCID: PMC10924631 DOI: 10.7759/cureus.53851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2024] [Indexed: 03/12/2024] Open
Abstract
Advanced and metastatic gastrointestinal stromal tumors (GISTs) presenting with surgical emergencies are rare. Neoadjuvant imatinib being the treatment of choice for non-metastatic advanced disease with a proven role in downstaging the disease may not be feasible in patients presenting with bleeding and obstruction. We present a case series with retrospective analysis of a prospectively maintained database of patients with advanced and metastatic GISTs presenting with surgical emergencies. Clinical characteristics, imaging and endoscopic findings, surgical procedures, histological findings, and outcomes in these patients were studied. Four patients were included in this case series, with three males and one female (age range: 24-60 years). Two patients presented with melena; one with hemodynamic instability despite multiple blood transfusions underwent urgent exploratory laparotomy for bleeding gastric GIST, while the other underwent surgical exploration after careful evaluation given the recurrent, metastatic disease with a stable metabolic response on six months of imatinib. One patient with metastatic jejunal GIST who presented with an umbilical nodule and intestinal obstruction was given a trial of non-operative management for 72 hours, but due to non-resolution of obstruction, segmental jejunal en bloc resection with the dome of the urinary bladder with reconstruction and metastasectomy was needed. The patient with advanced gastric GIST who presented with gastric outlet obstruction was resuscitated, and an attempt of endoscopic naso-jejunal tube placement was tried, which failed, and exploration was needed. The mean length of hospital stay was 7.5 days. Histopathological examination confirmed GIST in all four patients with microscopic negative resection margins. All patients were started on imatinib with dose escalation to 800 mg in the patient with recurrent and metastatic disease; however, the patient with bleeding gastric GIST experienced severe adverse effects of imatinib and discontinued the drug shortly. All four patients are disease-free on follow-ups of 15 months, 48 months for the patient with advanced non-metastatic disease, and six and 24 months for the patients with metastatic disease. In the era of tyrosine kinase inhibitor (TKI) therapy for advanced and metastatic disease, upfront surgery is usually reserved for surgical emergencies only. Surgical resection, the cornerstone for the treatment of resectable GIST, may also be clinically relevant in metastatic settings, although it requires a careful and individualized approach.
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Affiliation(s)
- Divij Jayant
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Mrinal Goyal
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Vipul Thakur
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Swapnesh Sahu
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Basil Babu
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Satish Subbiah Nagaraj
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Cherring Tandup
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
| | - Arunanshu Behera
- General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, IND
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Nakatani S, Okuwaki K, Watanabe M, Imaizumi H, Iwai T, Matsumoto T, Hasegawa R, Masutani H, Kurosu T, Tamaki A, Ishizaki J, Ishizaki A, Kida M, Kusano C. Stereomicroscopic on-site evaluation in endoscopic ultrasound-guided tissue acquisition of upper gastrointestinal subepithelial lesions. Clin Endosc 2024; 57:89-95. [PMID: 37070203 PMCID: PMC10834295 DOI: 10.5946/ce.2022.288] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/14/2022] [Accepted: 11/14/2022] [Indexed: 04/19/2023] Open
Abstract
BACKGROUND/AIMS In stereomicroscopic sample isolation processing, the cutoff value (≥4 mm) of stereomicroscopically visible white cores indicates high diagnostic sensitivity. We aimed to evaluate endoscopic ultrasound-guided tissue acquisition (EUS-TA) using a simplified stereomicroscopic on-site evaluation of upper gastrointestinal subepithelial lesions (SELs). METHODS In this multicenter prospective trial, we performed EUS-TA using a 22-gauge Franseen needle in 34 participants with SELs derived from the upper gastrointestinal muscularis propria, requiring pathological diagnosis. The presence of stereomicroscopically visible white core (SVWC) in each specimen was assessed using stereomicroscopic on-site evaluation. The primary outcome was EUS-TA's diagnostic sensitivity with stereomicroscopic on-site evaluation based on the SVWC cutoff value (≥4 mm) for malignant upper gastrointestinal SELs. RESULTS The total number of punctures was 68; 61 specimens (89.7%) contained stereomicroscopically visible white cores ≥4 mm in size. The final diagnoses were gastrointestinal stromal tumor, leiomyoma, and schwannoma in 76.5%, 14.7%, and 8.8% of the cases, respectively. The sensitivity of EUS-TA with stereomicroscopic on-site evaluation based on the SVWC cutoff value for malignant SELs was 100%. The per-lesion accuracy of histological diagnosis reached the highest level (100%) at the second puncture. CONCLUSION Stereomicroscopic on-site evaluation showed high diagnostic sensitivity and could be a new method for diagnosing upper gastrointestinal SELs using EUS-TA.
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Affiliation(s)
- Seigo Nakatani
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
- Department of Gastroenterology, Isehara Kyodo Hospital, Isehara, Japan
| | - Kosuke Okuwaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Masafumi Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hiroshi Imaizumi
- Department of Gastroenterology, Japan Community Health Care Organization Sagamino Hospital, Sagamihara, Japan
| | - Tomohisa Iwai
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Takaaki Matsumoto
- Department of Gastroenterology, Isehara Kyodo Hospital, Isehara, Japan
| | - Rikiya Hasegawa
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hironori Masutani
- Department of Gastroenterology, Japan Community Health Care Organization Sagamino Hospital, Sagamihara, Japan
| | - Takahiro Kurosu
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akihiro Tamaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Junro Ishizaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Ayana Ishizaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Mitsuhiro Kida
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Chika Kusano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
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Liu J, Huang BJ, Ding FF, Tang FT, Li YM. Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature. World J Gastrointest Oncol 2023; 15:1807-1822. [PMID: 37969409 PMCID: PMC10631440 DOI: 10.4251/wjgo.v15.i10.1807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/20/2023] [Accepted: 09/14/2023] [Indexed: 10/10/2023] Open
Abstract
BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer (GC) occurring synchronously with gastrointestinal stromal tumor (GIST). CASE SUMMARY We report 19 patients with concurrent GC and GIST (17 male and 2 female, median age 62 years). GC was most often located in the lower third of the stomach. GIST was diagnosed preoperatively in four patients. GIST was most often located in the gastric body (n = 8, 42%). The most common growth pattern in GIST was extraluminal (n = 12, 63%). The positive expression rates of CD117 and CD34 in GIST were 100% and 95%, respectively. Most patients with GIST (n = 17, 89%) were very low or low risk. There was no recurrence of GIST during follow-up. The 3-year cumulative survival rate was 73.9%, and the 5-year cumulative survival rate was 59.2%. The combined analysis of this study and literature reports (47 reports, 157 patients) found that GC and GIST were usually located in the lower third (42%) and middle third (51%) of the stomach. GC was usually early (stage I: 42%), poorly differentiated (42%) intestinal-type adenocarcinoma (51%). GISTs were primarily small in diameter (median: 1.2 cm) and very low or low risk (89%). CONCLUSION Synchronous GC and GIST may not be rare. They have specific clinicopathological characteristics, and may have mutual inhibition in pathogenesis and progression.
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Affiliation(s)
- Jie Liu
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
| | - Bin-Jie Huang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
| | - Fei-Fei Ding
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
| | - Fu-Tian Tang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
| | - Yu-Min Li
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
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Qiu C, Feng YD, Yang X. MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression. Curr Med Sci 2023; 43:935-946. [PMID: 37828372 DOI: 10.1007/s11596-023-2715-8] [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: 09/15/2022] [Accepted: 05/11/2023] [Indexed: 10/14/2023]
Abstract
OBJECTIVE Gastrointestinal stromal tumors (GISTs) can rapidly proliferate through angiogenesis. Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis. This study aimed to explore the specific mechanism by which microRNA-409-5p (miR-409-5p) contributes to GIST. METHODS To identify genes potentially involved in the development and progression of GIST, the differences of miR-409-5p between tumors and adjacent tissues were first analyzed. Following this analysis, target genes were predicted. To further investigate the function of miRNA in GIST cells, two GIST cell lines (GIST-T1 and GIST882) were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA (negative control). Later, the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes. RESULTS In GISTs, there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues. It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β (HIF1β) and vascular endothelial growth factor A (VEGF-A). Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3'-UTR of Lysine-specific demethylase 4D (KDM4D) mRNA. Moreover, the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis. CONCLUSION This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.
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Affiliation(s)
- Cheng Qiu
- GI Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yong-Dong Feng
- GI Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xi Yang
- GI Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Golčić M, Jones RL, Huang P, Napolitano A. Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours. Cancers (Basel) 2023; 15:4081. [PMID: 37627109 PMCID: PMC10452236 DOI: 10.3390/cancers15164081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/28/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Surgical treatment is recommended for the majority of localised GIST, while systemic treatment is the cornerstone of management for metastatic or unresectable disease. While a three-year regimen of imatinib is the standard of care in the adjuvant setting, there is no precise recommendation for the duration of neoadjuvant treatment, where imatinib is usually given between 4 and 12 months. Continuous treatment with imatinib at a dose of 400 mg once per day is recommended for most patients with unresectable or metastatic GIST in the first line. An exception is represented by patients with tumours harbouring the imatinib-insensitive PDGFRA D842V mutation who would be better treated with avapritinib. Targeted therapies are also recommended in the presence of NTRK rearrangements and BRAF mutations, although limited data are available. While an increase in the dose of imatinib to 800 mg is an option for the second line, sunitinib is usually considered the standard of care. Similar outcomes were reported for ripretinib in patients with tumours harbouring KIT exon 11 mutation, with significantly fewer side effects. Regorafenib and ripretinib are the standards of care in the third and fourth lines, respectively. The recent development of various systemic treatment options allows for a more personalised approach based on the molecular profile of the GIST, patient characteristics, and the profile of medications' adverse events. A multidisciplinary approach is paramount since combining systemic treatment with locoregional treatment options and supportive care is vital for long-term survival.
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Affiliation(s)
- Marin Golčić
- Department of Radiotherapy and Oncology, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia
| | - Robin L. Jones
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK
| | - Paul Huang
- Division of Molecular Pathology, The Institute of Cancer Research, Sutton SM2 5NG, UK;
| | - Andrea Napolitano
- Sarcoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK
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Tzikos G, Menni AE, Krokou D, Vouchara A, Doutsini S, Karlafti E, Karakatsanis A, Ioannidis A, Panidis S, Papavramidis T, Michalopoulos A, Paramythiotis D. Gastrointestinal Stromal Tumors: Our Ten-Year Experience of a Single-Center Tertiary Hospital. J Pers Med 2023; 13:1254. [PMID: 37623504 PMCID: PMC10455766 DOI: 10.3390/jpm13081254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 07/31/2023] [Accepted: 08/11/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. They have variable clinical presentation, prognosis, and molecular characteristics. Here, we present the results of our retrospective study including patients operated on for GIST during the last decade. METHODS All the patients who underwent GIST resection during the decade 2008-2018 were included in the study. The diagnosis was based on the pathology report. All the data were collected and analyzed statistically using the Statistical Package for Social Science v25.0. Finally, after having applied the proper search terms, a comprehensive review of articles published in the Medline database was held. RESULTS Thirty-two patients (sixteen women) were included in the study with a mean age of 69.6 years old (SD = 13.9). Twenty-one patients had a GIST in the stomach, eight in the small intestine, and three had an extra GIST. Of the 29 patients contacted, 21 were alive with a mean survival time of 74.3 months (SD = 49.6 months, min: 3.0 months, max: 161.0 months), whereas eight patients passed away. Finally, 13 patients were treated with tyrosine kinase inhibitors (TKIs) of whom only one died, while 9 patients passed away from those treated with surgery alone (p = 0.031). CONCLUSIONS Our results were in concordance with the existing data in the literature. GISTs require patient-based therapeutical management depending on the histology of the tumors. Gastric tumors present a better prognosis than those localized in the intestine, while the use of TKIs has led to an improvement in patient survival rate.
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Affiliation(s)
- Georgios Tzikos
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Alexandra-Eleftheria Menni
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Despoina Krokou
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Angeliki Vouchara
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Soultana Doutsini
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Eleni Karlafti
- Emergency Department, AHEPA University General Hospital of Thessaloniki, 54636 Thessaloniki, Greece;
| | - Anestis Karakatsanis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Aristeidis Ioannidis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Stavros Panidis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Theodosios Papavramidis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Antonios Michalopoulos
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Daniel Paramythiotis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
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Du C, He Z, Li L, Ning B, Zhang B, Zhai Y, Ma Y, Han K, Wang H, Tang P, Chai N, Linghu E. Endoscopic resection for the treatment of non-gastric gastrointestinal stromal tumors: A retrospective study from a large tertiary hospital in China. Clin Res Hepatol Gastroenterol 2023; 47:102152. [PMID: 37257690 DOI: 10.1016/j.clinre.2023.102152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/14/2023] [Accepted: 05/29/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND AND AIMS Few studies on endoscopic resection (ER) for the treatment of non-gastric gastrointestinal (GI) stromal tumors (GISTs) have been conducted, and most have been case reports or case series. The aim of this study was to evaluate the effectiveness and safety of ER for non-gastric GISTs. METHODS From January 2010 to December 2022, 329 patients who were diagnosed with GISTs underwent ER. After excluding 302 patients with gastric GISTs, we retrospectively assessed the data of 27 patients with non-gastric GISTs. The main outcome measures were en bloc resection, complete resection, residual disease, recurrence, and complications. RESULTS A total of 15(55.6%) females and 12(44.4%) males with a mean age of 53.8 ± 11.0 years were assessed. There were 19 (70.4%) GISTs in the esophagus, 2 (7.4%) in the duodenum, 3 (11.1%) in the colon and 3 (11.1%) in the rectum. The median tumor size was 12.0 mm (range 4.0-35.0 mm). Most of the GISTs (20, 74.1%) were very low risk, and the remaining 7(25.9%) were low risk. Both en bloc resection and complete resection were achieved in 25(92.6%) patients. Piecemeal resection mainly resulted from a larger tumor size, an irregular shape, and an extraluminal growth pattern. No residual disease or recurrence was noted during the follow-up period. The median operation time was 23 min (range 2-125 min). After excluding the operation time of EER, the operation time was prolonged to 37 min (range 12-125 min). Only one patient experienced mild abdominal pain, leading to a complication rate of 3.7%. No severe complications requiring for surgical interventions occurred. CONCLUSION ER was an effective and safe method for non-gastric GISTs in selected cases. GISTs of a small size and regular shape with an intraluminal growth pattern require complete resection.
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Affiliation(s)
- Chen Du
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Zhengting He
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Longsong Li
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Bo Ning
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Bo Zhang
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Yaqi Zhai
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Yan Ma
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Ke Han
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Hongbin Wang
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Ping Tang
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China
| | - Ningli Chai
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China.
| | - Enqiang Linghu
- Senior Department of Gastroenterology, the First Medical Center of PLA General Hospital, Fuxing Road 28. Haidian District, Beijing 100853, China.
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10
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Alabdallah E, Al Mouallem MHDM, Al-Ghotani B, Martini N, Al-Mahasna S. Retroperitoneal extra gastrointestinal stromal tumor: A case report. Int J Surg Case Rep 2023; 108:108442. [PMID: 37392585 PMCID: PMC10382849 DOI: 10.1016/j.ijscr.2023.108442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/21/2023] [Accepted: 06/27/2023] [Indexed: 07/03/2023] Open
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors. Researchers do not know precisely what leads to GISTs, but genetic mutations play an important role. These mutations have no apparent cause. GISTs are usually asymptomatic tumors, although GI bleeding and weight loss can occur. CT is preferred for investigating potential GISTs. CASE PRESENTATION A 36-year-old unmarried Syrian female came to the hospital complaining of recurrent abdominal pain. CT revealed a large mass occupying a significant portion of the left hypochondrium and the lower part of the epigastrium. The tumor exceeded the median line to the right, pressing on the mesenteric vessels and the intestinal loops below. Immunohistochemistry results showed moderate positivity to CD117 and CD34, which were compatible with the diagnosis of GIST. The entire mass was excised. Physicians performed CT follow-ups every three months for 18 months, and no evidence of recurrence was observed. DISCUSSION Extragastrointestinal GISTs are a rare subtype of GISTs that occur outside the GI tract. GISTs previously used to be misdiagnosed as leiomyoma, leiomyosarcoma, leiomyoblastoma, and schwannoma. Treatment depends on surgery with adjuvant therapy tyrosine kinase inhibitors. Follow-up is recommended as the risk of recurrence is high. CONCLUSION We recommend that GIST, as an extremely rare tumor, should be considered in the differential diagnoses of masses that occur in the extra-intestinal region. Usually, patients need surgery with lymph node resection. However, this was not needed in our case.
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Affiliation(s)
- Ebaa Alabdallah
- Damascus University, Faculty of Medicine, Damascus, Syria; Stemosis for Scientific Research, Damascus, Syria
| | - M H D Moamen Al Mouallem
- Damascus University, Faculty of Medicine, Damascus, Syria; Stemosis for Scientific Research, Damascus, Syria
| | - Basel Al-Ghotani
- Damascus University, Faculty of Medicine, Damascus, Syria; Stemosis for Scientific Research, Damascus, Syria
| | - Nafiza Martini
- Damascus University, Faculty of Medicine, Damascus, Syria; Stemosis for Scientific Research, Damascus, Syria.
| | - Souheb Al-Mahasna
- Damascus University, Faculty of Medicine, Damascus, Syria; Stemosis for Scientific Research, Damascus, Syria
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Ni L, Liu X, Wu A, Yu C, Zou C, Xu G, Wang C, Gao X. Endoscopic full‑thickness resection with clip‑ and snare‑assisted traction for gastric submucosal tumours in the fundus: A single‑centre case series. Oncol Lett 2023; 25:151. [PMID: 36936023 PMCID: PMC10018235 DOI: 10.3892/ol.2023.13737] [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: 10/24/2022] [Accepted: 02/15/2023] [Indexed: 03/06/2023] Open
Abstract
Exposed endoscopic full-thickness resection (Eo-EFTR) has been recognized as a feasible therapy for gastrointestinal submucosal tumours (SMTs) originating deep in the muscularis propria layer; however, Eo-EFTR is difficult to perform in a retroflexed fashion in the gastric fundus. As a supportive technique, clip- and snare-assisted traction may help expose the surgical field and shorten the operation time in endoscopic resection of difficult regions. However, the application of clip- and snare-assisted traction in Eo-EFTR of SMTs in the gastric fundus is limited. Between April 2018 and December 2021, Eo-EFTR with clip- and snare-assisted traction was performed in 20 patients with SMTs in the gastric fundus at The First Affiliated Hospital of Soochow University. The relevant clinical data were collected retrospectively for all of the patients and analysed. All 20 patients underwent Eo-EFTR successfully without conversion to open surgery or severe adverse events. The en bloc resection rate and R0 resection rate were both 100%. Two patients had abdominal pain and fever after the operation, and five patients had fever, which recovered with medical therapy. No complications, such as delayed bleeding or delayed perforation, were observed. The postoperative pathology indicated that 19 cases were gastrointestinal stromal tumours and one case was leiomyoma. During the follow-up, no residual tumour, local recurrence or distant metastasis was detected by endoscopy or abdominal computed tomography. In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. However, prospective studies on a larger sample size are required to verify the effect of the clip- and snare-assisted traction in Eo-EFTR.
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Affiliation(s)
- Liujing Ni
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Xiaolin Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Airong Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Chenyan Yu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Chentao Zou
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Guoting Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Chao Wang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| | - Xin Gao
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
- Correspondence to: Dr Xin Gao, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Gusu, Suzhou, Jiangsu 215000, P.R. China, E-mail:
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Carter BM, Bronsert MR, Wilky BA, McCarter MD. Mucosal Ulceration in Gastrointestinal Stromal Tumor is an Independent Predictor of Progression-Free Survival. J Surg Res 2023; 284:221-229. [PMID: 36587482 DOI: 10.1016/j.jss.2022.11.076] [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: 12/31/2021] [Revised: 11/12/2022] [Accepted: 11/20/2022] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Known prognostic features of GISTs include tumor mitotic rate, size, and location, yet one common feature of primary GISTs for which prognostic significance is unknown, is mucosal ulceration. This study aims to investigate the significance of mucosal ulceration in GISTs. MATERIALS AND METHODS A retrospective study was conducted of 513 patients at a tertiary referral center with a suspected or documented diagnosis of primary GIST between the years of 2000 and 2020. Ulceration was confirmed by definitive documentation in the endoscopic or histopathologic report. The significance of ulceration in GIST was compared to other prognostic factors. RESULTS Of the 513 patients reviewed, 310 primary GIST patients with known ulceration and disease status were identified. Of those, 27.4% (n = 85) demonstrated mucosal ulceration. Mucosal ulceration in GISTs is associated with GI bleeding, mitotic rate, tumor size, and exon 11 mutations. After a median follow-up of 35.4 (interquartile range = 17.1-62.2) mo, patients with ulcerated GISTs experienced higher rates of tumor progression (40.0% versus 14.2%, P < 0.0001). In multivariate analysis, ulceration of GISTs was highly associated with disease progression (P < 0.0001) and progression-free survival (hazard ratio = 2.4 [1.2-4.7], P = 0.01). CONCLUSIONS Mucosal ulceration in GISTs is associated with GI bleeding, mitotic rate, tumor size, and exon 11 mutations. Overall, ulceration in GISTs is associated with elevated risk of tumor progression and is an independent prognostic factor. In multivariate analysis, ulceration in GIST remains an independent risk factor for disease progression.
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Affiliation(s)
- Brian M Carter
- University of Colorado School of Medicine, Aurora, Colorado
| | - Michael R Bronsert
- Surgical Outcomes and Applied Research (SOAR), University of Colorado, Aurora, Colorado
| | - Breelyn A Wilky
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado
| | - Martin D McCarter
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Aurora, Colorado.
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13
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Priyadharshinee G, Sahu TK, Chavadi C. Giant Fibroid Mimicking a Gastrointestinal Stromal Tumor: A Diagnostic Dilemma. Cureus 2023; 15:e35883. [PMID: 37033583 PMCID: PMC10081861 DOI: 10.7759/cureus.35883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2023] [Indexed: 03/11/2023] Open
Abstract
Uterine fibroids are the most common benign pelvic tumors in females of the reproductive age group. Usually, fibroids are confined to the uterus. Here, we report an interesting and rare case of a large 17 cm abdominopelvic mass lesion that led to a diagnostic dilemma between a mesenteric gastrointestinal stromal tumor (GIST) and a uterine fibroid. We had a 26-year-old female who underwent an ultrasound examination of the abdomen as the initial imaging modality and was found to have an abnormally large solid abdominopelvic mass lesion. For further evaluation, a contrast-enhanced CT examination of the abdomen-pelvis was done. Initially, on first look, the mass was thought to be of mesenteric origin, but on further review of images, it was found to be of gynecological origin. Intraoperatively, the solid mass was seen attached to the uterine fundus and underwent excision. Histopathological examination confirmed the mass to be a uterine fibroid. This case study describes the uncommon appearance of this tumor in a young woman, including the clinical presentation, imaging, and surgical findings.
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14
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Dirkson A, den Hollander D, Verberne S, Desar I, Husson O, van der Graaf WTA, Oosten A, Reyners AKL, Steeghs N, van Loon W, van Oortmerssen G, Gelderblom H, Kraaij W. Sample Bias in Web-Based Patient-Generated Health Data of Dutch Patients With Gastrointestinal Stromal Tumor: Survey Study. JMIR Form Res 2022; 6:e36755. [PMID: 36520526 PMCID: PMC9801270 DOI: 10.2196/36755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Increasingly, social media is being recognized as a potential resource for patient-generated health data, for example, for pharmacovigilance. Although the representativeness of the web-based patient population is often noted as a concern, studies in this field are limited. OBJECTIVE This study aimed to investigate the sample bias of patient-centered social media in Dutch patients with gastrointestinal stromal tumor (GIST). METHODS A population-based survey was conducted in the Netherlands among 328 patients with GIST diagnosed 2-13 years ago to investigate their digital communication use with fellow patients. A logistic regression analysis was used to analyze clinical and demographic differences between forum users and nonusers. RESULTS Overall, 17.9% (59/328) of survey respondents reported having contact with fellow patients via social media. Moreover, 78% (46/59) of forum users made use of GIST patient forums. We found no statistically significant differences for age, sex, socioeconomic status, and time since diagnosis between forum users (n=46) and nonusers (n=273). Patient forum users did differ significantly in (self-reported) treatment phase from nonusers (P=.001). Of the 46 forum users, only 2 (4%) were cured and not being monitored; 3 (7%) were on adjuvant, curative treatment; 19 (41%) were being monitored after adjuvant treatment; and 22 (48%) were on palliative treatment. In contrast, of the 273 patients who did not use disease-specific forums to communicate with fellow patients, 56 (20.5%) were cured and not being monitored, 31 (11.3%) were on curative treatment, 139 (50.9%) were being monitored after treatment, and 42 (15.3%) were on palliative treatment. The odds of being on a patient forum were 2.8 times as high for a patient who is being monitored compared with a patient that is considered cured. The odds of being on a patient forum were 1.9 times as high for patients who were on curative (adjuvant) treatment and 10 times as high for patients who were in the palliative phase compared with patients who were considered cured. Forum users also reported a lower level of social functioning (84.8 out of 100) than nonusers (93.8 out of 100; P=.008). CONCLUSIONS Forum users showed no particular bias on the most important demographic variables of age, sex, socioeconomic status, and time since diagnosis. This may reflect the narrowing digital divide. Overrepresentation and underrepresentation of patients with GIST in different treatment phases on social media should be taken into account when sourcing patient forums for patient-generated health data. A further investigation of the sample bias in other web-based patient populations is warranted.
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Affiliation(s)
- Anne Dirkson
- Leiden Institute of Advanced Computer Science, Leiden University, Leiden, Netherlands
| | - Dide den Hollander
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Suzan Verberne
- Leiden Institute of Advanced Computer Science, Leiden University, Leiden, Netherlands
| | - Ingrid Desar
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Olga Husson
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Surgical Oncology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Winette T A van der Graaf
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Medical Oncology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Astrid Oosten
- Department of Medical Oncology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Anna K L Reyners
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Neeltje Steeghs
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Wouter van Loon
- Department of Methodology and Statistics, Leiden University, Leiden, Netherlands
| | - Gerard van Oortmerssen
- Leiden Institute of Advanced Computer Science, Leiden University, Leiden, Netherlands
- Sarcoma Patient Advocacy Global Network, Wölfersheim, Germany
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
| | - Wessel Kraaij
- Leiden Institute of Advanced Computer Science, Leiden University, Leiden, Netherlands
- The Netherlands Organisation for Applied Scientific Research, Den Haag, Netherlands
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15
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Gastrointestinal Stromal Tumors: 10-Year Experience in Cancer Center-The Ottawa Hospital (TOH). Curr Oncol 2022; 29:7148-7157. [PMID: 36290839 PMCID: PMC9600861 DOI: 10.3390/curroncol29100562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/23/2022] [Accepted: 09/26/2022] [Indexed: 01/13/2023] Open
Abstract
(1) Background: The management of gastrointestinal stromal tumors (GIST) has significantly evolved over the last two decades, with the introduction of tyrosine kinase inhibitors (TKI). We aim to report 10 years of experience of GIST management at a regional cancer center in Canada. (2) Methods: We retrospectively analyzed the records of 248 consecutive patients diagnosed with GIST between 2011 and 2021. We describe the clinical and pathological data, management, and outcome, including survival. (3) Results: The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73). At diagnosis, 83% (206) of patients had localized disease (stage I-III). According to the modified National Institutes of Health consensus criteria (NIH) for GIST, around 45% (90) had intermediate or high-risk disease. Most patients, 86% (213), underwent curative surgical resection. Forty-nine patients received adjuvant imatinib, while forty-three patients had advanced disease and received at least one line of TKI. With a median follow-up of 47 months, the 5-year recurrence-free survival (RFS) rates for very low and low risk were 100% and 94%, respectively, while those for intermediate and high risk were 84% and 51%, respectively. The 5-year overall survival (OS) rates for very low and low risk were 100% and 94%, while intermediate, high risk, and advanced were 91%, 88%, and 65%, respectively. Using the Kaplan-Meier method, there were statistically significant differences in RFS and OS between NIH risk groups, p < 0.0005. In univariate analysis, ECOG, site, mitosis, secondary malignancy, and size were predictors for OS. High mitosis and large size (>5 cm) were associated with worse RFS. (4) Conclusions: Curative surgical resection remains the gold standard management of GIST. Our results are comparable to the reported literature. Further research is needed to explore histology's role in risk stratification and initiating adjuvant TKI.
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Klangjorhor J, Pongnikorn D, Sittiju P, Phanphaisarn A, Chaiyawat P, Teeyakasem P, Kongdang P, Moonmuang S, Waisri N, Daoprasert K, Wisanuyotin T, Santong C, Sitthikong S, Tuntarattanapong P, Prechawittayakul P, Pruksakorn D. Descriptive epidemiology of soft tissue sarcomas and gastrointestinal stromal tumors in Thailand. Sci Rep 2022; 12:12824. [PMID: 35896585 PMCID: PMC9329344 DOI: 10.1038/s41598-022-15711-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 06/28/2022] [Indexed: 11/09/2022] Open
Abstract
This study aimed to analyze burden of STS and GIST in population and survival rate which represented the current situation of treatment in Thailand. The data was collected from five population-based cancer registries around the country for the period 2001 through 2015. The Segi world standard population was used to calculated age-standardized incidence rates (ASR). Standardized rate ratios (SRR) were used to compare populations. Joinpoint Trend Analysis was used to assess changes in incidence. STATA was used to examine patient survival rates. During the study period, 4080 cases of STS and 457 cases of GIST were reported. The ASR of STS and GIST was 2.14/100,000 person-years and 0.22/100,000 person-years, respectively. The most common histological types of STS were unspecified sarcoma (24.8%), leiomyosarcoma (19.0%) and liposarcoma (11.4%). The overall ASR of STS in Thailand was relatively low compared to Western countries. The five-year survival rate was 62.6% for STS and 63.4% for GIST, which was comparable to the rates reported in other countries. This is the first report of STS and GIST from PBCRs in Thailand. Based on current healthcare service, an overall survival rates of STS and GIST are comparable to those reported from others.
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Affiliation(s)
- Jeerawan Klangjorhor
- Musculoskeletal Science and Translational Research (MSTR) Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Pattaralawan Sittiju
- Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Areerak Phanphaisarn
- Musculoskeletal Science and Translational Research (MSTR) Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Parunya Chaiyawat
- Musculoskeletal Science and Translational Research (MSTR) Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pimpisa Teeyakasem
- Musculoskeletal Science and Translational Research (MSTR) Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Patiwat Kongdang
- Musculoskeletal Science and Translational Research (MSTR) Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sutpirat Moonmuang
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Narate Waisri
- Chiang Mai Cancer Registry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Taweechok Wisanuyotin
- Department of Orthopaedic, Faculty of Medicine, Khon Kaen University, Khon Kean, Thailand
| | - Chalongpon Santong
- Cancer Unit, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kean, Thailand
| | | | - Pakjai Tuntarattanapong
- Department of Orthopaedic, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Paradee Prechawittayakul
- Cancer Information Center, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Dumnoensun Pruksakorn
- Musculoskeletal Science and Translational Research (MSTR) Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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Saito H, Kotake M, Ogawa J, Hashimoto M, Sawada K, Oshima M, Hada M, Kato Y, Oyama K, Hara T, Inaki N. Laparoscopic resection of a gastrointestinal stromal tumor that recurred more than 15 years after surgery using lighted ureteral catheters: A case report. Asian J Endosc Surg 2022; 15:397-400. [PMID: 34874113 DOI: 10.1111/ases.13018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/29/2021] [Accepted: 11/15/2021] [Indexed: 11/29/2022]
Abstract
A 69-year-old woman underwent abdominoperineal resection for a gastrointestinal stromal tumor (GIST) of the rectum 15 years ago. She received adjuvant chemotherapy for 8 years. Seven years later, abdominal computed tomography revealed a soft-tissue shadow in the left lower abdomen, and fluorodeoxyglucose uptake was observed at the same site on positron emission tomography. The recurrence of GIST was suspected, and laparoscopic resection was performed. Laparoscopy showed that the tumor was located at the retroperitoneum near to the descending colon and invaded the left ovarian vessels. It also made contact with the left ureter; however, lighted ureteral catheters enabled us to identify and preserve the left ureter. An immunohistochemical examination revealed the recurrence of GIST. Recurrence may become apparent 15 years or more after GIST surgery, and, thus, a long-term follow-up is required. Lighted ureteral catheters were useful for identifying the ureter and preventing ureteral injury in a recurrent case suspected of invading the ureter.
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Affiliation(s)
- Hiroshi Saito
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Masanori Kotake
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Jyunichi Ogawa
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | | | - Koichiro Sawada
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Masahiro Oshima
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Masahiro Hada
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Yosuke Kato
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Kaeko Oyama
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Takuo Hara
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery/Breast Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
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Okuwaki K, Imaizumi H, Kida M, Masutani H, Iwai T, Watanabe M, Adachi K, Tadehara M, Hasegawa R, Nakatani S, Kurosu T, Tamaki A, Koizumi W. Usefulness of the automated multiband imaging system for EUS-FNA biopsy specimen evaluation in patients with upper gastrointestinal subepithelial lesions. Endosc Ultrasound 2022:340251. [PMID: 35313420 PMCID: PMC9526098 DOI: 10.4103/eus-d-21-00143] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background and Objectives Sample isolation processing by stereomicroscopy (SIPS) was recently introduced as an alternative to rapid on-site cytologic evaluation and showed high accuracy for use in pathologic diagnoses. SIPS is a useful, but slightly complicated procedure; therefore, a new, more straightforward method for the objective estimation of the core tissue amount required during the sampling is desirable. We evaluated the usefulness of the automated multiband imaging system (AMUS) for calculating whitish core amounts in EUS-FNA biopsy (EUS-FNAB) samples from patients with subepithelial lesions (SELs). Methods Four EUS-FNAB specimens per patient were obtained from 20 patients with upper gastrointestinal SELs. The correlation between the whitish core amount calculated by AMUS, length of the manually measured whitish cores (stereomicroscopically visible white core [SVWC]), and sample suitability for pathologic evaluation were analyzed. Results We identified 13 patients with gastrointestinal stromal tumors, five with leiomyomas, one with a schwannoma, and one with an ectopic pancreas. The histological diagnostic accuracy was 100%, median SVWC length was 9 mm, and median whitish core area, calculated using AMUS, was 10 mm2. SVWC length correlated with whitish core amount (ρ = 0.81, P < 0.01) and adequacy score (ρ = 0.54, P < 0.01). Whitish core amount correlated with adequacy score (ρ = 0.54, P < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.83 (P < 0.01; cutoff ≥4 mm2, sensitivity 98.4%). Conclusions AMUS, a simple on-site verification instrument, is an alternative to SIPS for determining the appropriate SEL tissue sampling quantity with high diagnostic accuracy.
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Affiliation(s)
- Kosuke Okuwaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hiroshi Imaizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Mitsuhiro Kida
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hironori Masutani
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Tomohisa Iwai
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Masafumi Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Kai Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Masayoshi Tadehara
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Rikiya Hasegawa
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Seigo Nakatani
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Takahiro Kurosu
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Akihiro Tamaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Wasaburo Koizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
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19
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Du C, Chai N, Linghu E, Li H, Zhai Y, Li L, Tang X, Wang H, Tang P. Clinical outcomes of endoscopic resection for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria: a 7-year experience from a large tertiary center in China. Surg Endosc 2022; 36:1544-1553. [PMID: 33742273 DOI: 10.1007/s00464-021-08443-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/05/2021] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIMS Few studies have evaluated the value of endoscopic resection (ER) for the treatment of gastric gastrointestinal (GI) stromal tumors (GISTs) originating from the muscularis propria (MP) in a large population, and no studies have evaluated risk factors for piecemeal resection. This study aimed to evaluate the efficacy and safety of ER for gastric GISTs in a real-world setting and to explore factors associated with piecemeal resection. METHODS From January 2013 to December 2019, 185 patients with gastric GISTs originating from the MP were assessed. Clinicopathological and endoscopic data were collected and analyzed. Baseline characteristics of the en bloc resection and piecemeal resection groups were compared to evaluate predictive factors for piecemeal resection. RESULTS There were 71 males and 114 females with a mean age of 57.0 ± 9.7 years. The mean size of GISTs was 15 mm (range 4-65 mm). A total of 123 were very low risk, 52 were low risk, and ten were moderate risk. In this study, 103 GISTs were treated with endoscopic submucosal excavation (ESE), 68 GISTs were treated with endoscopic full-thickness resection (EFR), and 14 GISTs were treated with submucosal tunneling ER (STER). Either en bloc resection or complete resection was achieved in 160 (86.5%) patients. No recurrence was noted during follow-up. Only five patients experienced minor complications, with a complication rate of 2.7%. Multivariate analysis demonstrated that size (odds ratio [OR] 1.060, 95% confidence interval [CI] 1.004-1.118; P = 0.035) and shape (OR 5.434, 95% CI 1.638-18.027; P = 0.006) were independent predictors of piecemeal resection. CONCLUSION ER was effective and safe for the treatment of gastric GISTs originating from the MP. Piecemeal resection did not seem to affect the efficacy of ER, and no recurrence was noted during follow-up. Large size and irregular shape are risk factors related to piecemeal resection of ER.
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Affiliation(s)
- Chen Du
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Ningli Chai
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Enqiang Linghu
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China.
| | - Huikai Li
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Yaqi Zhai
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Longsong Li
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Xiaowei Tang
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Hongbin Wang
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
| | - Ping Tang
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Haidian District, No. 28 of Fuxing Road, Beijing, 100853, China
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20
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Cherouaqi Y, Belabbes FZ, Delsa H, Nadi A, Rouibaa F. Massive Digestive Hemorrhagia Revealing a Gastro-Intestinal Stromal Tumor of the Jejunum. Cureus 2021; 13:e17316. [PMID: 34567868 PMCID: PMC8451536 DOI: 10.7759/cureus.17316] [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] [Accepted: 08/19/2021] [Indexed: 11/05/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from Cajal cells located in different sites of the digestive system. They may occur in the entire gastrointestinal tract. They are diagnosed on the basis of the identification of c-kit-positive cells. We report a case of a stromal tumor of the jejunum revealed by a massive digestive hemorrhagia. Surgical resection is the basis of the treatment of GISTs. Imatinib, a tyrosine kinase inhibitor, is a beneficial treatment after surgical resection of high-risk GISTs.
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Affiliation(s)
- Yasmine Cherouaqi
- Gastroenterology and Proctology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Fatima Zahra Belabbes
- Gastroenterology and Proctology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Hanane Delsa
- Gastroenterology and Proctology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Anass Nadi
- Gastroenterology and Proctology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
| | - Fedoua Rouibaa
- Gastroenterology and Proctology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS) Cheikh Khalifa International University Hospital, Casablanca, MAR
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21
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Mendel D, Syed T, Lippman HR, Davis B. Gastrointestinal Stromal Tumor (GIST) in Long-Standing Crohn's Disease on Anti-TNF Therapy. J Gastrointest Cancer 2021; 52:332-335. [PMID: 32592037 DOI: 10.1007/s12029-020-00442-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- David Mendel
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Taseen Syed
- Division of Gastroenterology, Hepatology & Nutrition, Virginia Commonwealth University, Richmond, VA, USA.
- Division of Gastroenterology, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA.
| | - H Robert Lippman
- Department of Pathology, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA
| | - Brian Davis
- Division of Gastroenterology, Hepatology & Nutrition, Virginia Commonwealth University, Richmond, VA, USA
- Division of Gastroenterology, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA
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22
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Inoue M, Shishida M, Watanabe A, Kajikawa R, Kajiwara R, Sawada H, Ohmori I, Miyamoto K, Ikeda M, Toyota K, Sadamoto S, Takahashi T. A liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor. Clin J Gastroenterol 2021; 14:1464-1469. [PMID: 34117599 DOI: 10.1007/s12328-021-01464-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 06/08/2021] [Indexed: 12/21/2022]
Abstract
Duodenal gastrointestinal stromal tumors (dGISTs) are rare, and a lack of consensus exists regarding their treatment, particularly for recurrent disease. We herein report a rare case of liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor. A 45-year-old woman revealed positive fecal occult blood. Upper gastrointestinal endoscopy revealed a submucosal duodenal tumor with ulceration and oozing on the apex. Endoscopic ultrasound showed a hypoechoic mass originating in the submucosa. Contrast-enhanced abdominal computed tomography (CT) revealed a 30-mm hyper-vascular tumor in the duodenal bulb. The patient underwent partial resection of the duodenal bulb with distal gastrectomy, followed by Roux-en-Y reconstruction. Histopathological evaluation revealed a tumor comprised of spindle-shaped cells including 5 mitotic figures per 50 high-power fields. Immunohistochemical evaluation indicated that the tumor cells were positive for c-Kit and CD34 expression. The tumor was diagnosed as low-risk dGIST. Postoperative follow-up was continued, and 7 years later, CT revealed a 39-mm enhanced tumor in liver segment 4. The tumor was diagnosed as a metastatic liver tumor, and the patient underwent S4 partial hepatectomy. As a result of histological and immunohistochemical analysis, the tumor was diagnosed as a liver metastasis from dGIST. The patient has been receiving oral imatinib 400 mg daily and remains free of disease 5 years after her last surgery. Low-risk dGIST can metastasize relatively long after surgery. However, an excellent long-term prognosis may be achieved by combining complete resection and imatinib therapy in patients with recurrent liver metastases.
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Affiliation(s)
- Masashi Inoue
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan.
| | - Masayuki Shishida
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Atsuhiro Watanabe
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Ryujiro Kajikawa
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Ryotaro Kajiwara
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Hiroyuki Sawada
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Ichiro Ohmori
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Kazuaki Miyamoto
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Masahiro Ikeda
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Kazuhiro Toyota
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Seiji Sadamoto
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Tadateru Takahashi
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, 513 Jike, Saijo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan.,Department of Gastrointestinal and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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23
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Watanabe M, Okuwaki K, Kida M, Tadehara M, Adachi K, Masutani H, Tamaki A, Imaizumi H, Iwai T, Yamauchi H, Kaneko T, Hasegawa R, Kurosu T, Koizumi W. Histopathological comparison of aspiration and biopsy needles in endoscopic ultrasound-guided tissue acquisition in patients with subepithelial lesions. Diagn Cytopathol 2021; 49:856-863. [PMID: 33885229 DOI: 10.1002/dc.24757] [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: 12/24/2020] [Revised: 04/12/2021] [Accepted: 04/13/2021] [Indexed: 11/05/2022]
Abstract
BACKGROUND Information on whether a fine-needle biopsy (FNB) needle can improve histopathological specimen quality or the amount of core tissue collected in the diagnosis of subepithelial lesions (SELs) remains insufficient. In this study, we aimed to compare the procedure outcomes and adequacy of histopathological specimens of fine-needle aspiration (FNA) and FNB needles in endoscopic ultrasound-guided tissue acquisition (EUS-TA) using sample isolation processing by stereomicroscopy (SIPS) in patients with SELs. METHODS We performed a retrospective comparison of SEL cases registered in two previously conducted prospective studies. Of 61 cases, we identified 56 cases of SELs that involved the muscularis propria layer. Of these, 27 patients who underwent EUS-TA using a 22-gauge FNA needle between July 2016 and December 2017, and 29 patients who underwent the procedure using a 22-gauge FNB needle between March 2018 and January 2019 were included in the FNA and FNB group, respectively. RESULTS Patient background characteristics did not differ between the groups. The technical success rate was 100% in both groups. The median adequacy score was significantly higher in the FNB group than in the FNA group (P < .01). The histological diagnosis showed no significant difference in the accuracy rate between the groups. CONCLUSIONS In EUS-TA using the SIPS procedure to target SELs derived from the muscularis propria layer, FNB needles collect more core tissues and significantly improve histopathological specimen quality compared with FNA needles. When combined with SIPS, a high tissue diagnosis rate may be obtained regardless of the type of puncture needle used.
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Affiliation(s)
- Masafumi Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Kosuke Okuwaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Mitsuhiro Kida
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Masayoshi Tadehara
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Kai Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hironori Masutani
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Akihiro Tamaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hiroshi Imaizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Tomohisa Iwai
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hiroshi Yamauchi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Toru Kaneko
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Rikiya Hasegawa
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Takahiro Kurosu
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Wasaburo Koizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
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24
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Al-Share B, Alloghbi A, Al Hallak MN, Uddin H, Azmi A, Mohammad RM, Kim SH, Shields AF, Philip PA. Gastrointestinal stromal tumor: a review of current and emerging therapies. Cancer Metastasis Rev 2021; 40:625-641. [PMID: 33876372 DOI: 10.1007/s10555-021-09961-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/29/2021] [Indexed: 02/07/2023]
Abstract
Gastrointestinal stromal tumors (GIST) are rare neoplasms arising from the interstitial cell of Cajal in the gastrointestinal tract. Two thirds of GIST in adult patients have c-Kit mutation and smaller fractions have platelet derived growth factor receptor alpha (PDGFRA) mutation. Surgery is the only curative treatment for localized disease. Imatinib improves survival when used adjuvantly and in advanced disease. Several targeted therapies have also improved survival in GIST patients after progression on imatinib including sunitinib and regorafenib. Recently, United States Federal and Drug Administration (FDA) approved two new tyrosine kinase inhibitors for the treatment of heavily pretreated advanced/unresectable GIST including avapritinib (a selective inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib (a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this article, we will provide a comprehensive review of GIST including the current standard of care treatment and exploring future paradigm shifts in therapy.
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Affiliation(s)
- Bayan Al-Share
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Abdulrahman Alloghbi
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Mohammed Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Hafiz Uddin
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Asfar Azmi
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Ramzi M Mohammad
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Steve H Kim
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Anthony F Shields
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Philip A Philip
- Department of Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA.
- Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI, USA.
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25
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Pilco-Janeta DF, García-Valverde A, Gomez-Peregrina D, Serrano C. Emerging drugs for the treatment of gastrointestinal stromal tumors. Expert Opin Emerg Drugs 2021; 26:53-62. [PMID: 33645383 DOI: 10.1080/14728214.2021.1896704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Oncogenic activation of KIT or PDGFRA receptor tyrosine kinases is the crucial event in gastrointestinal stromal tumor (GIST) biology. Seminal works during the past two decades have underscored, first, the continuous relevance of KIT/PDGFRA oncogenic signaling after progression to targeted inhibition; second, the heterogeneity of KIT/PDGFRA acquired mutations, that cannot be efficiently suppressed by any given tyrosine kinase inhibitor (TKI); and third, the presence of specific mutants highly resistant to all approved therapies. AREAS COVERED This review discusses treatment options in advanced/metastatic GIST, including a detailed dissection of ripretinib and avapritinib, the two novel small molecule inhibitors approved by the Food and Drug Administration in 2020. EXPERT OPINION The three only therapeutic options since 2012 for metastatic GIST patients were imatinib, sunitinib, and regorafenib. Although imatinib was highly effective in treatment-naïve GIST, the benefit of second- and third-line sunitinib and regorafenib was modest, thus emphasizing the medical need for new treatment options. Ripretinib, a switch control inhibitor with broad anti-KIT/PDGFRA activity, has been approved as ≥4th line in GIST after progression to all standard therapies. Avapritinib, a type I TKI highly specific against the multi-resistant PDGFRA D842V mutation, is approved in this specific subset of GIST patients.
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Affiliation(s)
- Daniel F Pilco-Janeta
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, Barcelona, Spain
| | - Alfonso García-Valverde
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, Barcelona, Spain
| | - David Gomez-Peregrina
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, Barcelona, Spain
| | - César Serrano
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, Barcelona, Spain.,Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
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26
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Gómez-Peregrina D, García-Valverde A, Pilco-Janeta D, Serrano C. Liquid Biopsy in Gastrointestinal Stromal Tumors: Ready for Prime Time? Curr Treat Options Oncol 2021; 22:32. [PMID: 33641024 DOI: 10.1007/s11864-021-00832-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2021] [Indexed: 02/07/2023]
Abstract
OPINION STATEMENT Gastrointestinal stromal tumor (GIST) constitutes a paradigm for clinically effective targeted inhibition of oncogenic driver mutations. Therefore, GIST has emerged as a compelling clinical and biological model to study oncogene addiction and to validate preclinical concepts for drug response and drug resistance. Oncogenic activation of KIT or PDGFRA receptor tyrosine kinases is the essential drivers of GIST progression throughout all stages of the disease. Interestingly, KIT/PDGFRA genotype predicts the response to first-line imatinib and to all tyrosine kinase inhibitors (TKIs) approved or in investigation after imatinib failure. Considering that TKIs are effective only against a subset of KIT or PDGFRA resistance mutations, close monitoring of tumor dynamics with non-invasive methods such as liquid biopsy emerges as a necessary step forward in the field. Liquid biopsy, in contrast to solid tumor biopsy, aims to characterize tumors irrespective of heterogeneity. Although there are several components in the peripheral blood, most recent studies have been focused on circulating tumor (ct)DNA, due to the technological feasibility, the stability of DNA itself and DNA alterations, and the therapeutic development in precision oncology largely based on the identification of genetic driver mutations. In the present review, we systematically dissect the current wealth of data of ctDNA in GIST. To do so, a critical understanding of the promises and limitations of the current technologies will be followed by an exposition of the knowledge gathered with such studies in GIST. Collectively, our goal is to establish clear premises that can be used as the foundations to build future studies towards the clinical implementation of ctDNA evaluation in GIST patients.
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Affiliation(s)
- David Gómez-Peregrina
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, C/ Natzaret 115-117, 08035, Barcelona, Spain
| | - Alfonso García-Valverde
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, C/ Natzaret 115-117, 08035, Barcelona, Spain
| | - Daniel Pilco-Janeta
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, C/ Natzaret 115-117, 08035, Barcelona, Spain
| | - César Serrano
- Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Campus, C/ Natzaret 115-117, 08035, Barcelona, Spain. .,Department of Medical Oncology, Vall d'Hebron University Hospital, P/Vall d'Hebron 119, 08035, Barcelona, Spain.
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27
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Ye S, Sharipova D, Kozinova M, Klug L, D'Souza J, Belinsky MG, Johnson KJ, Einarson MB, Devarajan K, Zhou Y, Litwin S, Heinrich MC, DeMatteo R, von Mehren M, Duncan JS, Rink L. Identification of Wee1 as a target in combination with avapritinib for gastrointestinal stromal tumor treatment. JCI Insight 2021; 6:143474. [PMID: 33320833 PMCID: PMC7934848 DOI: 10.1172/jci.insight.143474] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/09/2020] [Indexed: 12/12/2022] Open
Abstract
Management of gastrointestinal stromal tumors (GISTs) has been revolutionized by the identification of activating mutations in KIT and PDGFRA and clinical application of RTK inhibitors in advanced disease. Stratification of GISTs into molecularly defined subsets provides insight into clinical behavior and response to approved targeted therapies. Although these RTK inhibitors are effective in most GISTs, resistance remains a significant clinical problem. Development of effective treatment strategies for refractory GISTs requires identification of novel targets to provide additional therapeutic options. Global kinome profiling has the potential to identify critical signaling networks and reveal protein kinases essential in GISTs. Using multiplexed inhibitor beads and mass spectrometry, we explored the majority of the kinome in GIST specimens from the 3 most common molecular subtypes (KIT mutant, PDGFRA mutant, and succinate dehydrogenase deficient) to identify kinase targets. Kinome profiling with loss-of-function assays identified an important role for G2/M tyrosine kinase, Wee1, in GIST cell survival. In vitro and in vivo studies revealed significant efficacy of MK-1775 (Wee1 inhibitor) in combination with avapritinib in KIT mutant and PDGFRA mutant GIST cell lines as well as notable efficacy of MK-1775 as a monotherapy in the engineered PDGFRA mutant line. These studies provide strong preclinical justification for the use of MK-1775 in GIST.
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Affiliation(s)
- Shuai Ye
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Dinara Sharipova
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Marya Kozinova
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.,Pirogov Russian National Research Medical University, Moscow, Russia
| | - Lilli Klug
- Portland VA Health Care System and OHSU Knight Cancer Institute, Portland, Oregon, USA
| | - Jimson D'Souza
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Martin G Belinsky
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | | | - Margret B Einarson
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Karthik Devarajan
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Yan Zhou
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Samuel Litwin
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Michael C Heinrich
- Portland VA Health Care System and OHSU Knight Cancer Institute, Portland, Oregon, USA
| | - Ronald DeMatteo
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Margaret von Mehren
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | | | - Lori Rink
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
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Xu L, Ma Y, Wang S, Feng J, Liu L, Wang J, Liu G, Xiu D, Fu W, Zhan S, Sun T, Gao P. Incidence of gastrointestinal stromal tumor in Chinese urban population: A national population-based study. Cancer Med 2021; 10:737-744. [PMID: 33320439 PMCID: PMC7877389 DOI: 10.1002/cam4.3644] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 11/07/2020] [Accepted: 11/24/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Information on incidence of gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumor in gastrointestinal tract, was limited in China. This study aimed to estimate the incidence of GIST in urban population from mainland China in 2016. METHODS Urban Employee Basic Medical Insurance (UEBMI) and Urban Residence Basic Medical Insurance (URBMI) in China were used. The denominator of incidence was the total person-years of insured individuals in 2016 in the database, covering approximately 0.43 billion individuals. The numerator was the number of incident GIST cases in 2016. RESULTS The crude incidence in 2016 was 0.40 per 100,000 person-years (95% CI, 0.06-1.03). Male incidence was higher than female incidence (0.44 vs. 0.36, rate ratio: 1.22, p < 0.001). The mean age at diagnosis was 55.20 years (SD = 14.26) and the incidence among those aged 50 years or older was 2.63 times (0.84 vs. 0.32, p < 0.001) higher than those aged under 50. The highest incidence was observed in East China (2.29, 95% CI: 0.46-5.54). CONCLUSIONS The incidence of GIST in mainland China was lower than Europe, North America and Korea. The mean age at diagnosis of GIST in China was younger than that of Europe and Canada. This study provides useful information to further research, policy formulating and management of GIST.
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Affiliation(s)
- Lu Xu
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Yanpeng Ma
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Shengfeng Wang
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Jingnan Feng
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Lili Liu
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
| | - Jinxi Wang
- Shanghai Songsheng Business Consulting Co. LtdBeijingChina
| | - Guozhen Liu
- Peking University Health Information Technology Co. LtdBeijingChina
| | - Dianrong Xiu
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Wei Fu
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Siyan Zhan
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
- Research Center of Clinical EpidemiologyPeking University Third HospitalBeijingChina
- Center for Intelligent Public HealthInstitute for Artificial IntelligencePeking UniversityBeijingChina
| | - Tao Sun
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Pei Gao
- Department of Epidemiology and BiostatisticsSchool of Public HealthPeking UniversityBeijingChina
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Bennett M, Lomboy J. Get the GIST: A Case Study of Detection and Treatment of Gastrointestinal Stromal Tumors. Cureus 2020; 12:e11952. [PMID: 33425531 PMCID: PMC7788054 DOI: 10.7759/cureus.11952] [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] [Indexed: 12/03/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that can occur anywhere in the GI tract. There are roughly 4,000 to 6,000 cases diagnosed in the United States annually. GISTs are often asymptomatic early on and can evade detection, occasionally resulting in malignancy. Due to their insidious growth and location, it is suspected that they are more common than currently reported. It is important to know how difficult it is to identify a GIST and the various methods to treat it in a patient. Our case presents a 62-year-old male with incidental findings of multiple GISTs during workup for kidney stones. The patient was fortunate that these tumors were detected before developing into a greater health concern and this case highlights the insidious nature with which they develop.
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Gastrointestinal Stromal Tumours (GIST): Indian Experience of Rare Malignancy. Indian J Surg Oncol 2020; 11:348-354. [PMID: 33013109 DOI: 10.1007/s13193-020-01095-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 05/07/2020] [Indexed: 10/24/2022] Open
Abstract
GISTs are rare tumours of the GI tract arising from the intestinal cells of Cajal. Though various risk stratification systems have been proposed, none has been universally accepted. We audited the survival and recurrence patterns in our patients and evaluated clinicopathological features to identify prognostic factors affecting survival. We conducted a retrospective analysis of patients treated at our hospital from 1999 to 2012. Patient variables, clinicopathological factors and treatment variables were collected. Sixty-three patients were evaluated and treated at our institute of which 38 were non-metastatic. The most common site of origin was the stomach. On univariate analysis, presence of metastasis, male gender, high mitotic rate, non-gastric primary and epithelioid histology were significantly associated with poor overall survival. Tumour size > 10 cm, mitotic rate > 10/50 hpf and presence of necrosis significantly affected disease-free survival for non-metastatic patients. Multivariate analysis showed higher mitotic rate and non-gastric primary to correlate with worse outcome. In our experience, a high mitotic rate and non-gastric primary independently predicted a poor prognosis in GIST.
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Bai X, Zhou W, Li Y, Lin G. Transanal endoscopic microsurgery with alternative neoadjuvant imatinib for localized rectal gastrointestinal stromal tumor: a single center experience with long-term surveillance. Surg Endosc 2020; 35:3607-3617. [PMID: 32968924 DOI: 10.1007/s00464-020-07837-5] [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: 01/03/2020] [Accepted: 07/22/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Transanal endoscopic microsurgery (TEM) is widely used in the treatment of local rectal lesions and helps avoid radical surgery. This study evaluated the management and outcome in a long-term followed cohort of patients with localized rectal GIST underwent TEM with alternative neodajuvant imatinib (nIM). METHODS A retrospective cohort study was undertaken of patients identified from a case database at Department of General Surgery, Peking Union Medical College Hospital (PUMCH) over a continuous period, from January 2006 to December 2017. RESULTS Over 12 years, 42 patients presented with a primary rectal GIST in PUMCH. Median age was 49 (range 27-77) years. Neoadjuvant imatinib (nIM) therapy was used in 16 patients, significantly reducing mean tumor size from 4.41 to 2.46 cm (p < 0.001) and mitotic index (p = 0.041). All of these patients underwent TEM with no tumor rupture, nIM therapy enabled sphincter-preserving surgery to be undertaken in 16 (16/42) patients who would otherwise have required abdominoperineal resection or pelvic exenteration for tumor clearance and all patients (42/42) achieve R0 resection and negative margin. Imatinib was also used as postoperative adjuvant treatment in 15 patients with high-risk GIST. Median follow-up was 77 (range 14-144) and overall survival is 100%. In 42 patients, Local recurrence (LR) occurred in 3 of 42 patients and 1 of 42 patients developed distant metastasis (DM) in 112 months after TEM. In the univariate analysis, mitotic index (p = 0.028), NIH risk categories (p = 0.047) were predictive feature of local relapse. CONCLUSION The application of nIM significantly decreased tumor size in large localized rectal GIST, which permitted TEM to preserve sphincter. The TEM procedure with alternative neoadjuvant imatinib therapy is a practicable treatment for patients with rectal GIST to preserve anus and have satisfied anal function.
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Affiliation(s)
- Xueshan Bai
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
| | - Yunhao Li
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
| | - Guole Lin
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.
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Amirnasr A, Sleijfer S, Wiemer EAC. Non-Coding RNAs, a Novel Paradigm for the Management of Gastrointestinal Stromal Tumors. Int J Mol Sci 2020; 21:6975. [PMID: 32972022 PMCID: PMC7555847 DOI: 10.3390/ijms21186975] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 09/14/2020] [Accepted: 09/16/2020] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies found in the gastrointestinal tract. At a molecular level, most GISTs are characterized by gain-of-function mutations in V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (KIT) and Platelet Derived Growth Factor Receptor Alpha (PDGFRA), leading to constitutive activated signaling through these receptor tyrosine kinases, which drive GIST pathogenesis. In addition to surgery, treatment with the tyrosine kinase inhibitor imatinib forms the mainstay of GIST treatment, particularly in the advanced setting. Nevertheless, the majority of GISTs develop imatinib resistance. Biomarkers that indicate metastasis, drug resistance and disease progression early on could be of great clinical value. Likewise, novel treatment strategies that overcome resistance mechanisms are equally needed. Non-coding RNAs, particularly microRNAs, can be employed as diagnostic, prognostic or predictive biomarkers and have therapeutic potential. Here we review which non-coding RNAs are deregulated in GISTs, whether they can be linked to specific clinicopathological features and discuss how they can be used to improve the clinical management of GISTs.
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Affiliation(s)
| | | | - Erik A. C. Wiemer
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands; (A.A.); (S.S.)
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Ahmed M. Recent advances in the management of gastrointestinal stromal tumor. World J Clin Cases 2020; 8:3142-3155. [PMID: 32874969 PMCID: PMC7441252 DOI: 10.12998/wjcc.v8.i15.3142] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/26/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumor (GIST) is a rare but an important clinical entity seen in our clinical practice. It is the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine. Although the exact prevalence of GIST is not known, the incidence of GIST has been increasing. GISTs arise from interstitial cells of Cajal. Most of the GISTs occur due to mutation in c-kit gene or platelet derived growth factor receptor alpha gene. 15% of GISTs do not have these mutations and they are called wild-type GISTs. Almost all GISTs express KIT receptor tyrosine kinase. Histologically, GISTs look like spindle cell tumors most of the time but they can be epitheloid or mixed type. The median size of GISTs varies from 2.7 cm to 8.9 cm. Clinically, patients with small GISTs remain asymptomatic but as the GIST size increases, patients present with various symptoms depending on the location of the GIST. Most of GISTs are located in the stomach or small bowel. Diagnosis is suspected on imaging and endoscopic studies, and confirmed by tissue acquisition with immunohistochemical staining. The aggressiveness of GISTs depends on the size, mitotic index and location. Surgical resection is the treatment of choice. But various endoscopic modalities of resection are increasingly being tried. Tyrosine kinase inhibitors are extremely useful in the management of large GISTs, unresectable GISTs and metastatic GISTs. Treatment options for metastatic GISTs also include radiotherapy, chemotherapy, hepatic artery embolization, chemoembolization and radiofrequency ablation.
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Affiliation(s)
- Monjur Ahmed
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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Dziadkowiec KN, Stawinski P, Sánchez-Luna SA, Katz A. Gastrointestinal Stromal Tumor (GIST) Causing Obscure Gastrointestinal Bleeding: An Uncommon Way of Diagnosing An Uncommon Disease. Cureus 2020; 12:e9558. [PMID: 32905491 PMCID: PMC7470664 DOI: 10.7759/cureus.9558] [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: 07/21/2020] [Accepted: 08/04/2020] [Indexed: 12/05/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are neoplasms that arise from the wall of the gastrointestinal tract or, rarely, from other intra-abdominal tissues. They are the most common mesenchymal tumors of the gastrointestinal tract and they should be considered in the differential diagnosis of obscure gastrointestinal bleeding. Computed tomography angiogram (CTA) can be utilized as an alternative imaging study when endoscopic and colonoscopy results are non-diagnostic. We report a case of a 59-year-old woman who presented with recurrent episodes of obscure overt gastrointestinal bleeding secondary to a gastrointestinal stromal tumor (GIST).
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Affiliation(s)
| | - Peter Stawinski
- Internal Medicine, University of Miami, John F. Kennedy Regional Campus, Atlantis, USA
| | - Sergio A Sánchez-Luna
- Center for Advanced Therapeutic Endoscopy / Division of Gastroenterology, Hepatology & Nutrition, Allegheny Health Network / Allegheny Center for Digestive Health, Pittsburgh, USA
| | - Aviv Katz
- Gastroenterology and Hepatology, John F. Kennedy Medical Center, Atlantis, USA
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Cuccaro F, Burgio Lo Monaco MG, Rashid I, Bisceglia L, Caputo E, Melcarne A, Palma F, Tanzarella M, Cozzi E, Coviello V. Population-based incidence of gastrointestinal stromal tumors in Puglia. TUMORI JOURNAL 2020; 107:39-45. [PMID: 32539634 DOI: 10.1177/0300891620931944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION This study presents the incidence of gastrointestinal stromal tumors (GISTs) in an Italian region of over 4 million inhabitants monitored for 10 years and is the largest incidence study of this type of cancer conducted so far in Italy. METHODS In order to ensure the registration of all GISTs, including those with nonmalignant behavior, a cancer list was integrated with the cases found through an ad hoc data mining process that covered all the pathologic reports of Puglia. Case distributions by sex, age groups, site, and prognostic groups according to Miettinem and Lasota classification and crude and age-standardized incidence rates were produced. RESULTS In the 10-year period 2006 to 2015, 708 cases of GIST were recorded in Puglia. The average crude incidence rate was 1.7 per 100,000 person-years and the age-standardized incidence rate, using 2013 European standard population, was 1.8 per 100,000 person-years (95% confidence interval [CI], 1.6-1.9). Incidence was higher in men than in women: crude incidence rate was 2.0 per 100,000 person-years and age-standardized incidence rate 2.2 per 100,000 person-years (95% CI, 2.0-2.4) in men and 1.5 per 100,000 person-years and 1.4 per 100,000 person-years (95% CI, 1.2-1.6) in women. DISCUSSION Our incidence rates are comparable with those of other international studies and they are located in the medium to high end of the range. The comparisons are affected by a different capacity of the cancer registries to intercept and record GISTs with nonmalignant behavior. Distribution of cases for sex, age groups, sites, and prognostic risk groups are consistent with previous results.
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Affiliation(s)
- Francesco Cuccaro
- Cancer Registry of the Local Health Unit of Barletta-Andria-Trani, section of the Puglia Cancer Registry, Barletta, Italy
| | | | - Ivan Rashid
- Coordination Center of the Puglia Cancer Registry, Regional Strategic Agency for Health and Social of Puglia, Bari, Italy
| | - Lucia Bisceglia
- Coordination Center of the Puglia Cancer Registry, Regional Strategic Agency for Health and Social of Puglia, Bari, Italy
| | - Enrico Caputo
- Cancer Registry of the Local Health Unit of Bari, section of the Puglia Cancer Registry, Bari, Italy
| | - Anna Melcarne
- Cancer Registry of the Local Health Unit of Lecce, section of the Puglia Cancer Registry, Lecce, Italy
| | - Fernando Palma
- Cancer Registry of the Local Health Unit of Foggia, section of the Puglia Cancer Registry, Foggia, Italy
| | - Margherita Tanzarella
- Cancer Registry of the Local Health Unit of Taranto, section of the Puglia Cancer Registry, Taranto, Italy
| | - Emma Cozzi
- Cancer Registry of the Local Health Unit of Brindisi, section of the Puglia Cancer Registry, Brindisi, Italy
| | - Vincenzo Coviello
- Cancer Registry of the Local Health Unit of Barletta-Andria-Trani, section of the Puglia Cancer Registry, Barletta, Italy
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Optimal Endoscopic Resection Technique for Selected Gastric GISTs. The Endoscopic Suturing System Combined with ESD-a New Alternative? J Clin Med 2020; 9:jcm9061776. [PMID: 32521691 PMCID: PMC7355980 DOI: 10.3390/jcm9061776] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/24/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Background and Study Aim: In terms of therapeutic management, gastrointestinal stromal tumors (GISTs) seem to be the most difficult group of subepithelial gastrointestinal lesions (SELs). Despite various treatment option, choice of optimal management remains a dilemma in daily practice. Our aim was to evaluate a new hybrid resection technique of gastric GISTs type III as a modality of endoscopic full-thickness resection. Methods: Three males and one female (mean age of 68) were qualified for the procedure. Endoscopic full-thickness resections consisted of the endoscopic resection combined with suturing by Apollo OverStitch System. The main inclusion criterium was a complete diagnosis of GISTs (computed tomography (CT), endoscopic ultrasound (EUS), fine-needle biopsy (FNB)) with the evaluation of the tumor features, especially, the location in the gastric wall. All of the tumors were type III with a diameter between 20–40 mm. The lesions were located in the corpus (1), antrum (1) and between gastric body and fundus (2). All procedures were performed in 2019. Results: The technical and therapeutic success rate was 100% and the mean resection time 107.5 min. Neither intra- nor postprocedural complications were observed. In all four cases, R0 resection was achieved. Histopathologic assessment confirmed GIST with <5mitose/50HPF in all of the tumors, with very low risk. Conclusion: Based on our outcomes, endoscopic resection combined with the sewing by Apollo OverStitch of gastric GISTs type III, with the diameter between 20–40 mm, seems to be an effective therapeutic option with a good safety profile, however further studies with a larger treatment group are needed.
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Karstens KF, Bellon E, Polonski A, Wolters-Eisfeld G, Melling N, Reeh M, Izbicki JR, Tachezy M. Expression and serum levels of the neural cell adhesion molecule L1-like protein (CHL1) in gastrointestinal stroma tumors (GIST) and its prognostic power. Oncotarget 2020; 11:1131-1140. [PMID: 32284790 PMCID: PMC7138165 DOI: 10.18632/oncotarget.27525] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 03/03/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Diagnosis of gastrointestinal stroma tumors (GIST) is based on the histological evaluation of tissue specimens. Reliable systemic biomarkers are lacking. We investigated the local expression of the neural cell adhesion molecule L1-like protein (CHL1) in GIST and determined whether soluble CHL1 proteoforms could serve as systemic biomarkers. MATERIAL AND METHODS Expression of CHL1 was analyzed in primary tumor specimens and metastases. 58 GIST specimens were immunohistochemically stained for CHL1 on a tissue microarray (TMA). Systemic CHL1 levels were measured in sera derived from 102 GIST patients and 91 healthy controls by ELISA. Results were statistically correlated with clinicopathological parameters. RESULTS CHL1 expression was detected in GIST specimens. Reduced tissue expression was significantly associated with advanced UICC stages (p = 0.036) and unfavorable tumor localization (p = 0.001). CHL1 serum levels are significantly elevated in GIST patients (p < 0.010). Elevated CHL1 levels were significantly associated with larger tumors (p = 0.023), advanced UICC stage (p = 0.021), and an increased Fletcher score (p = 0.041). Moreover, patients with a higher CHL1 serum levels displayed a significantly shortened recurrence free survival independent of other clinicopathological variables. CONCLUSION Local CHL1 expression and serum CHL1 levels show a reverse prognostic behavior, highlighting the relevance of proteolytic shedding of the molecule. The results of the study indicate a potential role of serum CHL1 as a diagnostic and prognostic marker in GIST.
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Affiliation(s)
- Karl-Frederick Karstens
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Eugen Bellon
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Adam Polonski
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Gerrit Wolters-Eisfeld
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Nathaniel Melling
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Jakob R Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
| | - Michael Tachezy
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany
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Gastric Gastrointestinal Stromal Tumors (GIST): a Case Series and Current State of the Art in the Workup and Treatment of This Rare Disease. J Gastrointest Cancer 2020; 50:548-555. [PMID: 29192406 DOI: 10.1007/s12029-017-0034-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Wang PC, Wu PS. A retrospective cohort study of 304 patients with gastrointestinal stromal tumors in mackay memorial hospital. JOURNAL OF CANCER RESEARCH AND PRACTICE 2020. [DOI: 10.4103/jcrp.jcrp_10_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Harris PS, Romano J, Russ KB, Shoreibah MG, Baig KRKK. Gastrointestinal Stromal Tumor: GIST Another Duodenal Ulcer. Ochsner J 2020; 20:236-238. [PMID: 32612484 PMCID: PMC7310177 DOI: 10.31486/toj.18.0167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: Gastrointestinal stromal tumors (GISTs), although exceedingly rare, are the most common mesenchymal tumors in the gastrointestinal (GI) tract. GISTs are often asymptomatic; approximately 10% are found incidentally on imaging or endoscopy for other indications, although GI bleeding, intestinal obstruction, and perforation can occur. We present a case of upper GI bleeding from a duodenal GIST. Proton-pump inhibitor (PPI) therapy resulted in complete endoscopic ulcer healing, yet a discrete mass lesion was identified on endoscopic ultrasound (EUS). Case Report: A 70-year-old female presented with upper GI bleeding, and a duodenal ulcer was identified with esophagogastroduodenoscopy (EGD). Computed tomography (CT) scan of the abdomen and pelvis showed duodenal bulb thickening without clear mass. The ulcer was treated with 1:10,000 concentration epinephrine, injected in 4 quadrants around the ulcer base. The patient's GI bleeding resolved, and she was discharged with a referral for outpatient EUS follow-up. One month later, EUS showed resolution of the ulcer after PPI therapy but also showed a lesion consistent with GIST that was confirmed by cytologic analysis. The patient was started on imatinib therapy and had no further bleeding. Conclusion: Initial EGD and CT findings could have easily been attributed to duodenal peptic ulcer disease for which follow-up endoscopy is not routinely recommended given the low risk of malignancy. However, because of the high index of suspicion on the part of the referring physicians, duodenal GIST was diagnosed. This case extends the spectrum of the presentation, evaluation, and diagnosis of GISTs and stresses the importance of keeping this rare disease on the provider's differential, even after routine workup shows no findings of tumor.
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Affiliation(s)
- Patrick S. Harris
- Tinsley Harrison Internal Medicine Residency, University of Alabama at Birmingham, Birmingham, AL
| | - John Romano
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC
| | - Kirk B. Russ
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL
| | - Mohamed G. Shoreibah
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL
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Doi T, Kurokawa Y, Sawaki A, Komatsu Y, Ozaka M, Takahashi T, Naito Y, Ohkubo S, Nishida T. Efficacy and safety of TAS-116, an oral inhibitor of heat shock protein 90, in patients with metastatic or unresectable gastrointestinal stromal tumour refractory to imatinib, sunitinib and regorafenib: a phase II, single-arm trial. Eur J Cancer 2019; 121:29-39. [PMID: 31536852 DOI: 10.1016/j.ejca.2019.08.009] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 08/08/2019] [Accepted: 08/14/2019] [Indexed: 12/31/2022]
Abstract
AIM We evaluated the efficacy and safety of TAS-116, a novel class of an orally active selective inhibitor of heat shock protein 90, in patients with advanced gastrointestinal stromal tumour (GIST) after failure of three or more lines of standard treatment with imatinib, sunitinib and regorafenib. METHODS In this single-arm phase II study, patients received 160 mg/day oral TAS-116 for five consecutive days, followed by a 2-day rest. The primary end-point was centrally assessed progression-free survival (PFS). The secondary end-points were objective response rate, disease control rate, overall survival (OS), metabolic response rate, safety, pharmacokinetics and pharmacogenomics. RESULTS Forty-one patients were enrolled in Japan, and 40 patients underwent efficacy and safety evaluation. At the cut-off date, the median PFS was 4.4 months (95% confidence interval [CI], 2.8-6.0) and 12-week progression-free rate was 73.4% (95% CI, 58.1-88.7). Thirty-four patients (85.0%) had stable disease for ≥ 6 weeks. The median OS was 11.5 months (95% CI, 7.0-not reached). All patients experienced at least one treatment-related adverse event (AE), including diarrhoea (80.0%), decreased appetite (45.0%) and increase in blood creatinine level (42.5%). Grade ≥3 AEs and treatment-related grade ≥3 AEs occurred in 23 (57.5%) and 21 (52.5%) patients, respectively. All AEs resolved after dose modification, and no TAS-116-related AEs led to treatment discontinuation. CONCLUSION TAS-116 showed significant activity in advanced GIST refractory to standard treatment. Further development of TAS-116 is warranted. TRIAL REGISTRATION JapicCTI-163182.
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Affiliation(s)
| | | | - Akira Sawaki
- Fujita Health University Hospital, Nagoya, Japan
| | | | - Masato Ozaka
- The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | | | - Yoichi Naito
- National Cancer Center Hospital East, Chiba, Japan
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Kobayashi M, Inaguma S, Raffeld M, Kato H, Suzuki S, Wakasugi T, Mitsui A, Kuwabara Y, Lasota J, Ikeda H, Miettinen M, Takahashi S. Epithelioid variant of gastrointestinal stromal tumor harboring PDGFRA mutation and MLH1 gene alteration: A case report. Pathol Int 2019; 69:541-546. [PMID: 31273885 DOI: 10.1111/pin.12830] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 05/28/2019] [Indexed: 12/12/2022]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most important and common mesenchymal tumors of the gastrointestinal tract, especially in the stomach. GISTs are usually driven by activating mutations in either KIT or PDGFRA genes. It is known that activating gene mutations predicts, to a certain extent, not only the morphology of the tumor cells but also a response to treatment with tyrosine kinase inhibitors. Here, we present a case of an epithelioid variant of GIST harboring PDGFRA and MLH1 gene alterations in the stomach of a 55-year-old Japanese woman. The tumor of 98 mm with multiple cysts showed exophytic growth from the gastric fundus. Histopathologically, it consisted of scattered medium-sized epithelioid tumor cells in a loose myxoid background. Based on c-kit and DOG-1 immunoreactivity and a PDGFRA mutation (p.Trp559_Arg560del), the tumor was diagnosed as an epithelioid variant GIST. Interestingly, it had a gene alteration (p.Met524Ile) in the MLH1 gene of unknown pathogenicity. It was assigned to Group 3a (low risk for malignant behavior). After surgery, the patient has been on imatinib therapy and disease-free for 10 months.
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Affiliation(s)
- Mizuho Kobayashi
- Department of Pathology, Nagoya City West Medical Center, Nagoya, Japan.,Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Shingo Inaguma
- Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Mark Raffeld
- Laboratory of Pathology, National Cancer Institute, Bethesda, USA
| | - Hiroyuki Kato
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Shugo Suzuki
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Takehiro Wakasugi
- Gastrointestinal Surgery, Nagoya City West Medical Center, Nagoya, Japan
| | - Akira Mitsui
- Gastrointestinal Surgery, Nagoya City West Medical Center, Nagoya, Japan
| | - Yoshiyuki Kuwabara
- Gastrointestinal Surgery, Nagoya City West Medical Center, Nagoya, Japan
| | - Jerzy Lasota
- Laboratory of Pathology, National Cancer Institute, Bethesda, USA
| | - Hiroshi Ikeda
- Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Markku Miettinen
- Laboratory of Pathology, National Cancer Institute, Bethesda, USA
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
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Mara D, Sylla M, Ly S, Soumana ID, Alami B, Maâroufi M, Maazaz K, Lamrani YA. [Multiple gastrointestinal stromal masses in the small bowel detected in a patient with peritonitis]. Pan Afr Med J 2019; 33:102. [PMID: 31489080 PMCID: PMC6711688 DOI: 10.11604/pamj.2019.33.102.17240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 10/07/2018] [Indexed: 11/22/2022] Open
Abstract
We here report a case of multiple gastrointestinal stromal tumors (GIST) in the small bowel detected in a patient with peritonitis. The peculiarity of this case study is the intraoperative detection of multifocal small bowel tumor masses, suggesting gastrointestinal stromal tumors on postoperative CT scan. Tumor couldn't be suspected clinically on the basis of peritonitis.
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Affiliation(s)
- Dondo Mara
- Service de Radiologie, CHU Hassan II Fès, Maroc
| | - Moussa Sylla
- Service de Chirurgie Viscérale, CHU Hassan II Fès, Maroc
| | - Seydou Ly
- Service de Radiologie, CHU Hassan II Fès, Maroc
| | | | - Badr Alami
- Service de Radiologie, CHU Hassan II Fès, Maroc
| | | | - Khalid Maazaz
- Service de Chirurgie Viscérale, CHU Hassan II Fès, Maroc
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Laurent M, Brahmi M, Dufresne A, Meeus P, Karanian M, Ray-Coquard I, Blay JY. Adjuvant therapy with imatinib in gastrointestinal stromal tumors (GISTs)-review and perspectives. Transl Gastroenterol Hepatol 2019; 4:24. [PMID: 31143845 DOI: 10.21037/tgh.2019.03.07] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 03/19/2019] [Indexed: 12/21/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal (GI) tract. Most of them (>75%) are driven by an oncogenic initiating event involving activating mutations of the genes encoding for tyrosine kinase, KIT or platelet derived growth factor receptor alpha (PDGFRA). Efficacy of the tyrosine kinase Inhibitor imatinib is now well established for advanced disease. For localized GISTs, 3 years treatment is the recommended adjuvant therapy for high risk patients. Whether a longer duration and selection of patients for this adjuvant therapy in localized GISTs remains is not yet established (PERSIST-5 study). Similarly, it will be important to further refine the definition of the population of GIST patients at high risk of relapse including molecular criteria (Annals of Oncology, ESMO guidelines 2018). This review aims to describe current knowledges on the issue of adjuvant therapy of primary GISTs in view of available results.
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Affiliation(s)
- Marie Laurent
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | - Mehdi Brahmi
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | - Armelle Dufresne
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | - Pierre Meeus
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | - Marie Karanian
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | | | - Jean-Yves Blay
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
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Large incidental gastrointestinal stromal tumors in a patient presenting with acutely symptomatic nephrolithiasis: A case report. Radiol Case Rep 2019; 14:555-560. [PMID: 30847013 PMCID: PMC6393756 DOI: 10.1016/j.radcr.2019.02.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 02/04/2019] [Accepted: 02/08/2019] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms, representing approximately 1%-2% of all primary gastrointestinal malignancies. Incidental GISTs are often less than 1 cm when discovered and have been reported predominantly in obese patients undergoing surgery for other medical indications. We present the rare case of a large incidental GIST in a nonobese patient with acutely symptomatic nephrolithiasis. Large GISTs may be treated with neoadjuvant imatinib mesylate to reduce tumor size prior to surgery, though some tumors may experience little change in size despite effective treatment. Treatment response for GISTs can be monitored via imaging studies, such as computed tomography or magnetic resonance imaging, but computed tomography is generally preferred over magnetic resonance imaging.
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Zhu L, Khan S, Hui Y, Zhao J, Li B, Ma S, Guo J, Chen X, Wang B. Treatment recommendations for small gastric gastrointestinal stromal tumors: positive endoscopic resection. Scand J Gastroenterol 2019; 54:297-302. [PMID: 30907165 DOI: 10.1080/00365521.2019.1578405] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Objectives: To evaluate the safety and efficacy of endoscopic resection and discuss the treatment strategy of small gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. Material and methods: The data of 713 patients, who underwent endoscopic submucosal dissection (ESD) for gastric submucosal tumors (SMTs), were retrospectively analyzed. We investigated the clinicopathological features and analyzed the risk potential of small gastric GISTs, and documented therapeutic and follow-up outcomes. We also compared the follow-up results between operated patients and 58 patients who were suspected of small gastric GISTs and underwent regular surveillance under endoscopic ultrasound (EUS) in the same period. Results: GISTs were the most common gastric SMTs (289 cases, 40.5%), of which small GISTs were found in 250 cases. The mitotic index was less than 5 in all cases. However, 122 out of 250 cases (48.8%) had adverse factors under EUS, which were related to tumor size (p < .01). ESD was successfully performed in all patients, and no serious complication or perioperative death occurred. The follow-up period for 42.07 ± 22.49 months revealed improvement of symptoms in 80.2% patients and showed no recurrence or metastasis. Of the 58 patients selected for EUS surveillance, 48 (82.8%) presented with gastrointestinal symptoms and 41 out of 48 (85.4%) were not relieved during follow-up and 16 (27.6%) with severe psychological problems. Conclusions: ESD is a safe and effective treatment for small GISTs, which helps to confirm the diagnosis, improve symptoms and reduce the psychological pressure. Thus, we recommend endoscopic resection is a good option for small gastric GISTs once diagnosed.
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Affiliation(s)
- Lanping Zhu
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Samiullah Khan
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Yangyang Hui
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Jingwen Zhao
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Bianxia Li
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Shuang Ma
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Junyi Guo
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Xin Chen
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Bangmao Wang
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
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Iwatsuki M, Harada K, Iwagami S, Eto K, Ishimoto T, Baba Y, Yoshida N, Ajani JA, Baba H. Neoadjuvant and adjuvant therapy for gastrointestinal stromal tumors. Ann Gastroenterol Surg 2019; 3:43-49. [PMID: 30697609 PMCID: PMC6345649 DOI: 10.1002/ags3.12211] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/05/2018] [Accepted: 08/23/2018] [Indexed: 12/15/2022] Open
Abstract
Gastrointestinal stromal tumors (GIST) are rare and mesenchymal in origin with a yearly incidence of 10-15 cases per million people. If it is technically resectable, surgical resection is the mainstay of therapy regardless of tumor location,. Although complete (R0) resection can be achieved in up to 85% of patients with primary disease, approximately 50% of patients experience recurrence or metastases within 5 years of primary resection. Moreover, prior to 2000, the prognosis of patients with advanced, inoperable GIST was poor because the molecular mechanism had not sufficiently been elucidated, thus effective therapy was lacking. The tyrosine kinase inhibitor imatinib, which selectively inhibits tyrosine kinase KIT, has shown substantial clinical benefit for patients with GIST. In clinical trials, imatinib treatment resulted in response rates of 40%-55% and longer progression-free survival for patients with a KIT-positive unresectable or metastatic GIST. Furthermore, recent clinical trials have shown that giving imatinib after curative resection for high-risk cases prolonged recurrence-free survival and overall survival in an adjuvant setting. Several clinical trials of imatinib treatment in a neoadjuvant setting are ongoing; however, in clinical settings, there are problems to resolve, such as optimal agents, duration of administration, and postoperative management. In this review, we discuss the application of surgical options, combined with adjuvant/neoadjuvant or perioperative imatinib treatment and their potential impact on survival for patients with primary, recurrent, or metastatic GIST.
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Affiliation(s)
- Masaaki Iwatsuki
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
| | - Kazuto Harada
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
| | - Shiro Iwagami
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Kojiro Eto
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Takatsugu Ishimoto
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Yoshifumi Baba
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Naoya Yoshida
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Jaffer A. Ajani
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
| | - Hideo Baba
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
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Our Experience Regarding the Association Between Gastrointestinal Stromal Tumor and Bariatric Surgery: a Response to a Letter “Gastrointestinal Stromal Tumor After Laparoscopic Sleeve Gastrectomy: Be Awake Before, During, and After a Bariatric Procedure”. Obes Surg 2018; 29:642-644. [DOI: 10.1007/s11695-018-03645-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Åhlén J, Karlsson F, Wejde J, Nilsson IL, Larsson C, Bränström R. Wide Surgical Margin Improves the Outcome for Patients with Gastrointestinal Stromal Tumors (GISTs). World J Surg 2018; 42:2512-2521. [PMID: 29435627 PMCID: PMC6060789 DOI: 10.1007/s00268-018-4498-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Surgical resection is still the main treatment for gastrointestinal stromal tumor (GIST), and R0 excision, regardless of surgical margins, is considered sufficient. Methods A cohort of 79 consecutive GIST cases treated at the Karolinska University Hospital, who were without metastasis at diagnosis and who had not received any pre-or postoperative treatment with tyrosine kinase inhibitors, was included. Surgical margins were evaluated at the time of surgery and classified as wide, marginal or intralesional. Time to local/peritoneal recurrence, distant metastasis, and survival were recorded. Cox regression analysis was used to investigate the association between surgical margin, and recurrence and survival. Results Local/peritoneal recurrence was diagnosed in 2/39 cases with wide margins, in 7/22 cases with marginal margins, and in 13/18 cases with intralesional surgery. Compared to wide margins this gives a hazard ratio of 6.8 (confidence interval 1.4–32.7) for marginal margins and 13.5 (3–61) for intralesional margins. In multivariate analysis, adjusting for size, site, and mitotic index, surgical margin remained an independent significant predictor of risk for recurrence. When classifying patients according to R0/R1 surgery, patients with R0 surgery showed longer time to peritoneal recurrence and better recurrence-free and disease-specific survival as compared to those with R1 resection. However, when excluding patients operated with wide surgical margin, no significant difference was observed. Conclusion Wide surgical margins are of significant prognostic importance, supporting the strategy of en bloc resection with good margin and careful handling of the tumor to avoid damaging the peritoneal surface in surgical resection of GIST. Electronic supplementary material The online version of this article (10.1007/s00268-018-4498-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jan Åhlén
- Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, P9:03, 171 76, Stockholm, Sweden.
| | - Fredrik Karlsson
- Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, P9:03, 171 76, Stockholm, Sweden
| | - Johan Wejde
- Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Inga-Lena Nilsson
- Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, P9:03, 171 76, Stockholm, Sweden
| | - Catharina Larsson
- Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Robert Bränström
- Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, P9:03, 171 76, Stockholm, Sweden.
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Arellano-López P, Solalinde-Vargas R, Guzmán-Mejía J, González-Pérez L, Zamora-García A. Gastrointestinal stromal tumor of the stomach. Case report. REVISTA MÉDICA DEL HOSPITAL GENERAL DE MÉXICO 2018. [DOI: 10.1016/j.hgmx.2016.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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