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1. Kuroiwa M, Hiwatari M, Hirato J, Suzuki N, Tsuchida Y, Shimada A, Shitara T, Taki T, Hayashi Y: Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year-old girl with a unique mutation of PDGFRA. J Pediatr Surg; 2005 Nov;40(11):1798-801
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year-old girl with a unique mutation of PDGFRA.
  • A 12-year-old girl presented with a large abdominal tumor.
  • At surgery, a huge pedunculated extraluminal tumor was found arising from the greater curvature of the stomach and invading the surrounding structures, and there were also a submucosal tumor measuring 5 x 4 x 4 cm and multiple intramural nodules beside the main tumor.
  • A diagnosis of gastrointestinal stromal tumor (GIST) was made.
  • The huge size of the tumor (3.6 kg in weight and 36 x 25 x 25 cm in diameter), the invasion of the surrounding structures, and the increased mitotic figures indicated the GIST had malignant potential.
  • Sequence analysis of the polymerase chain reaction product of RNAs from the tumor cells revealed a novel platelet-derived growth factor receptor alpha (PDGFRA) mutation, which would exhibit biologic consequences similar to those of the c-kit mutation.
  • The patient underwent a 3-month course of imatinib mesylate as adjuvant chemotherapy because of the possible risk for tumor recurrence.
  • Only 9 cases of GIST have been reported in children, and a review of those cases revealed GISTs in children would be associated with a better prognosis than in adults and that one third of pediatric GISTs presented with intestinal obstruction in the newborn period.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Gastrointestinal Stromal Tumors / drug therapy. Gastrointestinal Stromal Tumors / genetics. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Receptor, Platelet-Derived Growth Factor alpha / genetics
  • [MeSH-minor] Benzamides. Chemotherapy, Adjuvant. Child. Female. Humans. Imatinib Mesylate. Mutation. Prognosis

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  • (PMID = 16291174.001).
  • [ISSN] 1531-5037
  • [Journal-full-title] Journal of pediatric surgery
  • [ISO-abbreviation] J. Pediatr. Surg.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Receptor, Platelet-Derived Growth Factor alpha
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2. Ki SS, Jeong JM, Kim SH, Jeong SH, Lee JH, Han CJ, Kim YC, Lee JO, Hong YJ: A case of neurotoxicity following 5-fluorouracil-based chemotherapy. Korean J Intern Med; 2002 Mar;17(1):73-7
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  • [Title] A case of neurotoxicity following 5-fluorouracil-based chemotherapy.
  • We report a case of 5-FU neurotoxicity with organic brain syndrome and progression to multifocal leukoencephalopathy in a 44-year-old male patient having malignant gastrointestinal stromal tumor.
  • 5-FU-induced neurotoxicity should, therefore, be considered as an important differential diagnosis in cancer patients with neurological abnormality and history of chemotherapy.
  • [MeSH-minor] Adult. Electroencephalography. Gastrointestinal Neoplasms / drug therapy. Humans. Leukoencephalopathy, Progressive Multifocal / diagnosis. Leukoencephalopathy, Progressive Multifocal / etiology. Magnetic Resonance Imaging. Male

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  • (PMID = 12014219.001).
  • [ISSN] 1226-3303
  • [Journal-full-title] The Korean journal of internal medicine
  • [ISO-abbreviation] Korean J. Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] U3P01618RT / Fluorouracil
  • [Other-IDs] NLM/ PMC4531646
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3. Wellmann K, Gohla G, Wenk H: [Malignant gastrointestinal stromal tumor (GIST) of the papilla vateri. A rare tumor entity]. Chirurg; 2004 Feb;75(2):196-9
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  • [Title] [Malignant gastrointestinal stromal tumor (GIST) of the papilla vateri. A rare tumor entity].
  • [Transliterated title] Maligner gastrointestinaler Stromatumor (GIST) der Papilla vateri. Eine seltene Tumorentität.
  • We present the case report of a 68-year-old female patient who had a malignant gastrointestinal stromal tumor of the papilla of Vater.
  • The postoperative course was without complications and neither chemotherapy nor other adjunct treatment was necessary.
  • Because of heterogeneity, the different localization, and in this case the rare localization, surgery of gastrointestinal stromal tumors is difficult.
  • However, we adhered to oncological and therapeutic standards of surgery for papillary carcinoma.
  • However, until now there has been no case report of gastrointestinal stromal tumor of the papilla of Vater in the literature.
  • [MeSH-major] Ampulla of Vater / surgery. Common Bile Duct Neoplasms / surgery. Neoplasms, Complex and Mixed / surgery. Sarcoma / surgery. Stromal Cells
  • [MeSH-minor] Aged. Female. Humans. Pancreaticoduodenectomy. Prognosis. Tomography, X-Ray Computed

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  • (PMID = 14991183.001).
  • [ISSN] 0009-4722
  • [Journal-full-title] Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen
  • [ISO-abbreviation] Chirurg
  • [Language] ger
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
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4. Bümming P, Andersson J, Meis-Kindblom JM, Klingenstierna H, Engström K, Stierner U, Wängberg B, Jansson S, Ahlman H, Kindblom LG, Nilsson B: Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br J Cancer; 2003 Aug 4;89(3):460-4
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  • [Title] Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
  • Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis.
  • Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment.
  • However, surgery is usually inadequate for the treatment of malignant GIST.
  • Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST.
  • In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly.
  • The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene.
  • Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity.
  • The value of neoadjuvant imatinib treatment was illustrated in one case.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Gastrointestinal Neoplasms / drug therapy. Piperazines / pharmacology. Pyrimidines / pharmacology. Stromal Cells / pathology
  • [MeSH-minor] Adult. Aged. Benzamides. Chemotherapy, Adjuvant. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Neoadjuvant Therapy. Palliative Care. Prognosis. Proto-Oncogene Proteins c-kit / genetics. Risk Factors. Treatment Outcome

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  • (PMID = 12888812.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
  • [Other-IDs] NLM/ PMC2394385
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5. Bucher P, Villiger P, Egger JF, Buhler LH, Morel P: Management of gastrointestinal stromal tumors: from diagnosis to treatment. Swiss Med Wkly; 2004 Mar 20;134(11-12):145-53
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  • [Title] Management of gastrointestinal stromal tumors: from diagnosis to treatment.
  • Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the digestive tract.
  • Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas or leiomyosarcomas, are today classified as GIST on the basis of molecular and immunohistological features.
  • They originate from gastrointestinal pacemaker cells and are characterised by over-expression of the tyrosine kinase receptor KIT.
  • Overall 5-year survival after surgical resection of GIST is approximately 60%.
  • However, these tumours span a wide clinical spectrum from benign to highly malignant.
  • Prognostic factors have recently been identified for GIST and include tumour size, mitotic rate and other minor factors.
  • At present, surgery is the standard treatment for primary resectable GIST.
  • Benign GIST have an excellent prognosis after primary surgical treatment, with over 90% 5-year survival.
  • While recurrent or malignant GIST, which are resistant to radiotherapy and chemotherapy, had until recently an extremely poor prognosis even after surgical resection, with median survival of 12 months.
  • The development of a tyrosine kinase inhibitor has changed the management of unresectable malignant cases.
  • This new tyrosine kinase inhibitor, imatinib mesylate, which inhibits the c-kit receptor, has proved highly effective against GIST and has improved survival in metastatic GIST.
  • This paper reviews the literature and our experience of GIST, including: diagnosis, pathology, treatment and prognosis.
  • [MeSH-major] Gastrointestinal Neoplasms
  • [MeSH-minor] Algorithms. Antineoplastic Agents. Benzamides. Humans. Imatinib Mesylate. Immunohistochemistry. Lymphatic Metastasis. Neoplasm Invasiveness. Piperazines / therapeutic use. Prognosis. Protein-Tyrosine Kinases / antagonists & inhibitors. Proto-Oncogene Proteins c-kit / genetics. Pyrimidines / therapeutic use. Stromal Cells / pathology. Treatment Outcome

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  • (PMID = 15106018.001).
  • [ISSN] 1424-7860
  • [Journal-full-title] Swiss medical weekly
  • [ISO-abbreviation] Swiss Med Wkly
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
  • [Number-of-references] 84
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6. Plaat BE, Hollema H, Molenaar WM, Torn Broers GH, Pijpe J, Mastik MF, Hoekstra HJ, van den Berg E, Scheper RJ, van der Graaf WT: Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol; 2000 Sep 15;18(18):3211-20
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  • [Title] Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins.
  • PURPOSE: Several studies have reported clinical behavior and chemotherapy resistance in leiomyosarcomas, but these studies did not differentiate between soft tissue leiomyosarcomas (LMS) and malignant gastrointestinal stromal tumors (GIST).
  • The aim of the present study was to compare LMS and GIST with respect to clinical outcome and MDR parameters.
  • PATIENTS AND METHODS: Clinical outcome was evaluated in 29 patients with a primary deep-seated LMS and 26 patients with a primary malignant GIST.
  • Paraffin-embedded material, available for 26 patients with LMS and 25 with GIST, was used for immunohistochemical detection of P-gp, MRP(1), LRP, and c-kit.
  • RESULTS: Mean overall survival (OS) was 72 months for LMS patients and 31 months for GIST patients (P: <.05).
  • Metastases occurred in 16 (59%) of 27 assessable LMS patients and in 10 (56%) of 18 assessable GIST patients.
  • LMS predominantly metastasized to the lungs (14 of 16 patients), whereas GIST tended to spread to the liver (five of 10 patients) and the abdominal cavity (three of 10 patients; P: <.001).
  • P-gp and MRP(1) expression was more pronounced in GIST than in LMS (P: <.05): the mean percentage of P-gp expressing cells was 13.4% in patients with LMS and 38.4% in patients with GIST, and the mean percentage MRP(1) expressing cells was 13.3% in patients with LMS and 35.4% in patients with GIST.
  • LRP expression did not differ between LMS and GIST. c-kit was expressed in 5% of the LMS patients and in 68% of the GIST patients.
  • CONCLUSION: LMS patients have a better survival than GIST patients, and the metastatic pattern is different.
  • Expression of MDR proteins in LMS is less pronounced than in GIST.
  • [MeSH-major] ATP-Binding Cassette Transporters / biosynthesis. ATP-Binding Cassette, Sub-Family B, Member 1 / biosynthesis. Drug Resistance, Multiple / physiology. Gastrointestinal Neoplasms / metabolism. Leiomyosarcoma / metabolism. Neoplasm Proteins / biosynthesis. Soft Tissue Neoplasms / metabolism. Vault Ribonucleoprotein Particles / biosynthesis
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Drug Resistance, Neoplasm. Female. Gene Expression. Humans. Male. Middle Aged. Multidrug Resistance-Associated Proteins. Proto-Oncogene Proteins c-kit / biosynthesis. Stromal Cells / metabolism. Stromal Cells / pathology. Survival Analysis. Treatment Outcome

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  • (PMID = 10986053.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / ATP-Binding Cassette Transporters; 0 / ATP-Binding Cassette, Sub-Family B, Member 1; 0 / Multidrug Resistance-Associated Proteins; 0 / Neoplasm Proteins; 0 / Vault Ribonucleoprotein Particles; 0 / major vault protein; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
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7. Takashima M, Igaki N, Matsuda T, Ohyama M, Kanda S, Tamada F, Goto T: Malignant gastrointestinal stromal tumor of the small intestine complicated with pulmonary tuberculosis during treatment with imatinib mesylate. Intern Med; 2005 Feb;44(2):114-9
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  • [Title] Malignant gastrointestinal stromal tumor of the small intestine complicated with pulmonary tuberculosis during treatment with imatinib mesylate.
  • We describe a patient who had a metastatic gastrointestinal stromal tumor (GIST) after previous failed extensive therapy, including multiple surgeries and hepatic artery embolization.
  • Within a few months of starting administration of imatinib mesylate, the patient exhibited a clinical response with grade 3 neutropenia, when pulmonary tuberculosis developed.
  • It is unclear whether or not pulmonary tuberculosis may be induced by imatinib mesylate treatment, but caution is warranted in immunocompromised GIST patients.
  • This is the first report of tuberculosis associated with neutropenia during imatinib mesylate treatment.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Gastrointestinal Stromal Tumors / complications. Jejunal Neoplasms / complications. Leiomyosarcoma / complications. Piperazines / adverse effects. Pyrimidines / adverse effects. Tuberculosis, Pulmonary / complications
  • [MeSH-minor] Administration, Oral. Antitubercular Agents / therapeutic use. Benzamides. Combined Modality Therapy. Digestive System Surgical Procedures. Fatal Outcome. Humans. Imatinib Mesylate. Laparotomy. Liver Neoplasms / diagnosis. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Male. Middle Aged. Neutropenia / chemically induced. Neutropenia / complications. Tomography, X-Ray Computed

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  • (PMID = 15750270.001).
  • [ISSN] 0918-2918
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antitubercular Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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8. Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G: Management of malignant gastrointestinal stromal tumours. Lancet Oncol; 2002 Nov;3(11):655-64
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Management of malignant gastrointestinal stromal tumours.
  • Gastrointestinal stromal tumours (GISTs) are the most common form of mesenchymal tumour of the gastrointestinal tract.
  • Making a distinction between an indolent and a malignant GIST is unreliable with conventional histopathological techniques.
  • The presence of metastases at the time of diagnosis confirms malignancy, but all GISTs should be regarded as having malignant potential.
  • KIT activation seems to be an early tumour-promoting event in pathogenesis.
  • Commonly, malignant GISTs show high-level primary resistance to conventional chemotherapy.
  • Most patients with advanced malignant GISTs achieve clinical benefit and significant antitumour responses with imatinib mesylate.
  • Responses have been durable, and most patients tolerate the drug well at clinically effective doses.
  • Imatinib mesylate is the first effective systemic therapy for advanced GIST.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Gastrointestinal Neoplasms / drug therapy. Mesoderm / pathology. Piperazines / pharmacology. Pyrimidines / pharmacology. Sarcoma / drug therapy
  • [MeSH-minor] Benzamides. Biomarkers, Tumor. Combined Modality Therapy. Diagnosis, Differential. Humans. Imatinib Mesylate. Immunohistochemistry. Oncogene Proteins / analysis. Oncogene Proteins / biosynthesis. Prognosis. Proto-Oncogene Proteins c-kit. Radiotherapy, Adjuvant

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  • (PMID = 12424067.001).
  • [ISSN] 1470-2045
  • [Journal-full-title] The Lancet. Oncology
  • [ISO-abbreviation] Lancet Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Biomarkers, Tumor; 0 / Oncogene Proteins; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
  • [Number-of-references] 80
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9. Castillo-Sang M, Mancho S, Tsang AW, Gociman B, Almaroof B, Ahmed MY: A malignant omental extra-gastrointestinal stromal tumor on a young man: a case report and review of the literature. World J Surg Oncol; 2008;6:50
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  • [Title] A malignant omental extra-gastrointestinal stromal tumor on a young man: a case report and review of the literature.
  • BACKGROUND: Gastrointestinal stromal tumors (GIST) are uncommon intra-abdominal tumors.
  • Furthermore, these extra-gastrointestinal tumors (EGIST) tend to be more common in patients greater than 50 years of age.
  • An abdominal pelvic computerized tomography imaging demonstrated an intra-abdominal mass of 22 cm, without invasion of adjacent viscera or liver lesions.
  • Pathology results demonstrated a malignant gastrointestinal stromal tumor with positive CD117 (c-kit) staining, and negative margins of resection, and no continuity of tumor with the sigmoid colon.
  • Due to the malignant and aggressive nature of this patient's tumor, he was started on STI-571 as adjuvant chemotherapy.
  • CONCLUSION: Stromal tumors of an extra-gastrointestinal origin are rare.
  • Young patients who present with an extra-gastrointestinal stromal tumor (EGIST), who have complete resection with negative margins, have a good prognosis.
  • There is little data to support the role of STI-571 in adjuvant or neoadjuvant therapy after curative resection.
  • [MeSH-major] Gastrointestinal Stromal Tumors / pathology. Omentum. Peritoneal Neoplasms / pathology
  • [MeSH-minor] Adult. Antigens, CD34 / analysis. Benzamides. Humans. Imatinib Mesylate. Male. Piperazines / therapeutic use. Proto-Oncogene Proteins c-kit / analysis. Pyrimidines / therapeutic use

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  • (PMID = 18479530.001).
  • [ISSN] 1477-7819
  • [Journal-full-title] World journal of surgical oncology
  • [ISO-abbreviation] World J Surg Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
  • [Other-IDs] NLM/ PMC2409333
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10. Eisenberg BL: Combined-modality strategy for gastrointestinal stromal tumors. Semin Oncol; 2006 Dec;33(6 Suppl 11):S75-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Combined-modality strategy for gastrointestinal stromal tumors.
  • Gastrointestinal stromal tumor (GIST) is the most common nonepithelial tumor of the gastrointestinal tract.
  • Clinical trials of imatinib for metastatic GIST have shown either partial response or long-duration stable disease in 82% of patients.
  • Trials addressing the efficacy of adjuvant imatinib following resection for high-risk primary GIST are awaiting results.
  • The neoadjuvant preoperative use of imatinib to provide pharmacologic debulking and long-term disease control is also nearing completion in a clinical trial.
  • This trial has the potential of addressing whether the combination of surgery and imatinib can enhance organ sparing, decrease drug resistance, and prolong disease-free and overall survival.
  • The continued study of combining surgery and a target-specific agent for malignant GIST will be a valuable reference for future strategies combining surgery and targeted treatment in other solid tumors.
  • [MeSH-major] Gastrointestinal Stromal Tumors / therapy
  • [MeSH-minor] Combined Modality Therapy. Humans

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  • (PMID = 17178293.001).
  • [ISSN] 0093-7754
  • [Journal-full-title] Seminars in oncology
  • [ISO-abbreviation] Semin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 20
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11. Siewert E, Tietze L, Maintz C, Geier A, Dietrich CG, Matern S, Gartung C: [Gastrointestinal stromal tumors: a broad clinical spectrum from incidental -discovery to acute gastrointestinal bleeding]. Z Gastroenterol; 2004 Mar;42(3):233-42
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Gastrointestinal stromal tumors: a broad clinical spectrum from incidental -discovery to acute gastrointestinal bleeding].
  • [Transliterated title] Gastrointestinale Stromatumoren (GIST): variable klinische Manifestationen vom Zufallsbefund bis zur akuten gastrointestinalen Blutung.
  • Three cases of gastrointestinal stromal tumors (GIST) are reported as typical examples of the broad clinical spectrum in which these rare tumors can be detected.
  • The first case describes an 82-year-old patient with a hemorrhagic shock due to upper gastrointestinal bleeding from a GIST of the stomach.
  • GIST most frequently present with either gastrointestinal bleeding, abdominal pain or a detectable mass on physical examination or by ultrasound imaging.
  • Clinically asymptomatic tumor growth also occurs as demonstrated by the second case of a 44-year-old -woman with an incidental finding of GIST during surgery of the esophagus.
  • The cases are used to discuss the consequences for therapy and prognosis resulting from the heterogeneity of this tumor entity; the relevant immunohistochemical markers used to distinguish between various tumor subtypes of gastrointestinal mesenchymal tumors (GIMT) are listed.
  • Since gastrointestinal stromal tumors (GIST) represent the most common subgroup of GIMT, we focus on the clinicopathological prognostic factors of GIST.
  • The third case of a 40-year-old patient with a malignant GIST recurrence after surgery and exhibiting secondary resistance after one year of successful therapy with the receptor tyrosine kinase inhibitor imatinib (Gleevec), antagonizing pathogenetically relevant constitutive c-KIT activation, illustrates the potential and limitations of the only effective drug treatment for advanced GIST.
  • [MeSH-major] Abdominal Pain / etiology. Cardia. Esophageal Neoplasms / diagnosis. Gastrointestinal Hemorrhage / etiology. Neoplasms, Connective Tissue / diagnosis. Stomach Neoplasms / diagnosis
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Agents / therapeutic use. Benzamides. Biomarkers, Tumor / analysis. Chemotherapy, Adjuvant. Combined Modality Therapy. Diagnosis, Differential. Dose-Response Relationship, Drug. Drug Resistance, Neoplasm. Esophagectomy. Female. Gastrectomy. Gastric Mucosa / pathology. Gastroscopy. Humans. Imatinib Mesylate. Incidental Findings. Male. Neoplasm Recurrence, Local / diagnosis. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / pathology. Neoplasm Recurrence, Local / surgery. Piperazines / therapeutic use. Polyps / diagnosis. Polyps / drug therapy. Polyps / pathology. Polyps / surgery. Prognosis. Proto-Oncogene Proteins c-kit / analysis. Pyrimidines / therapeutic use. Receptor Protein-Tyrosine Kinases / antagonists & inhibitors. Shock, Hemorrhagic / etiology. Stromal Cells / pathology. Tomography, X-Ray Computed. Treatment Outcome


12. Ng EK, Wong SK, Mok TS, Chan WY, Chung SC: Imatinib (STI-571) heals a gastrocutaneous fistula resulting from a malignant gastric stromal tumor. Gastric Cancer; 2003;6(2):122-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Imatinib (STI-571) heals a gastrocutaneous fistula resulting from a malignant gastric stromal tumor.
  • The management of inoperable giant malignant gastrointestinal stromal tumor (GIST) of the stomach sed to be a formidable task.
  • We report our success with the use of STI-571 in treating a patient with huge GIST of the stomach complicated by gastrocutaneous fistula after an unsuccessful laparotomy.
  • The patient was a 49-year-old man who presented to our center with a painful epigastric mass in December 2001.
  • Endoscopy, biopsy, and magnetic resonance scan confirmed that it was a malignant stromal tumor arising from the gastric fundus.
  • Laparotomy with an intention to resect the tumor was performed in view of the obstructing symptoms.
  • However, massive bleeding was encountered during dissection of the tumor and gastrectomy was abandoned.
  • Follow-up computed tonography (CT) scan 3 months later confirmed significant tumor reduction, and the patient has experienced no side effects from the treatment
  • [MeSH-major] Cutaneous Fistula / drug therapy. Cutaneous Fistula / etiology. Gastric Fistula / drug therapy. Gastric Fistula / etiology. Piperazines / therapeutic use. Pyrazoles / therapeutic use. Pyrimidines / therapeutic use. Stomach Neoplasms / drug therapy
  • [MeSH-minor] Benzamides. Humans. Imatinib Mesylate. Laparotomy. Magnetic Resonance Imaging. Male. Middle Aged. Postoperative Complications / drug therapy. Postoperative Complications / etiology. Tomography, X-Ray Computed

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  • (PMID = 12884857.001).
  • [ISSN] 1436-3291
  • [Journal-full-title] Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
  • [ISO-abbreviation] Gastric Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / 4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; 0 / Benzamides; 0 / Piperazines; 0 / Pyrazoles; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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13. Ulusan S, Koç Z, Kayaselçuk F: Imaging characteristics of liver metastasis from gastrointestinal stromal tumor before and after imatinib mesylate treatment. Turk J Gastroenterol; 2008 Jun;19(2):129-32
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  • [Title] Imaging characteristics of liver metastasis from gastrointestinal stromal tumor before and after imatinib mesylate treatment.
  • Our objective was to show the unusual imaging characteristics of cystic liver metastases from a malignant gastrointestinal stromal tumor before and after treatment with imatinib mesylate.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Gastrointestinal Stromal Tumors / pathology. Gastrointestinal Stromal Tumors / ultrasonography. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Aged. Benzamides. Colon / pathology. Fatal Outcome. Humans. Imatinib Mesylate. Intestinal Neoplasms / drug therapy. Intestinal Neoplasms / ultrasonography. Intestine, Small / pathology. Liver / drug effects. Liver / pathology. Liver / ultrasonography. Male. Neoplasm Invasiveness. Stomach / pathology. Stomach Neoplasms / drug therapy. Stomach Neoplasms / ultrasonography

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  • (PMID = 19110671.001).
  • [ISSN] 2148-5607
  • [Journal-full-title] The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology
  • [ISO-abbreviation] Turk J Gastroenterol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Turkey
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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14. Demetri GD: Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). Eur J Cancer; 2002 Sep;38 Suppl 5:S52-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571).
  • Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract.
  • The concept of GIST and the definition of GIST pathology have evolved greatly over the past 5 years.
  • GIST has been shown to share immunohistochemical, ultrastructural and histogenic similarities with the interstitial cells of Cajal.
  • Both GIST and the interstitial cells of Cajal express KIT, the receptor tyrosine kinase that is the protein product of the c-kit proto-oncogene.
  • Sequencing of c-kit complementary DNA from human GIST cells has demonstrated a high frequency of mutations that lead to constitutive activation of the KIT tyrosine kinase in the absence of stimulation by its physiologic ligand (stem cell factor).
  • Historically, malignant GIST has been highly refractory to conventional cytotoxic therapy.
  • Signal transduction inhibition as cancer therapy was first tested successfully with imatinib mesylate (formerly known as STI571), a selective small-molecule tyrosine kinase inhibitor, with the initial target being blockade of Bcr-Abl, the oncogene with tyrosine kinase activity responsible for the pathogenesis of chronic myelogenous leukemia (CML).
  • Imatinib was subsequently shown to block activity of the KIT tyrosine kinase as well, and in laboratory studies this led to apoptotic death of GIST cells.
  • The first GIST patient to receive imatinib exhibited dramatic benefit despite far-advanced metastatic disease that was previously refractory to all chemotherapy.
  • Subsequently, multicenter clinical trials have been performed to assess the safety, efficacy and biologic activity of imatinib in patients with advanced GIST.
  • The results from these studies have established imatinib as an effective new therapeutic alternative for the majority of patients with advanced GIST, a solid tumor for which no prior chemotherapy has ever shown antitumor efficacy.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Enzyme Inhibitors / therapeutic use. Gastrointestinal Neoplasms / drug therapy. Neoplasms, Connective Tissue / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Stromal Cells
  • [MeSH-minor] Benzamides. Drug Resistance, Neoplasm. Humans. Imatinib Mesylate. Neoplasm Proteins / antagonists & inhibitors. Neoplasm Recurrence, Local / prevention & control. Protein-Tyrosine Kinases / antagonists & inhibitors. Proto-Oncogene Proteins c-kit. Receptor Protein-Tyrosine Kinases. Tomography, Emission-Computed

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  • (PMID = 12528773.001).
  • [ISSN] 0959-8049
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Neoplasm Proteins; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; EC 2.7.10.1 / Receptor Protein-Tyrosine Kinases
  • [Number-of-references] 28
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15. Catani M, De Milito R, Simi M: [New orientations in the management of advanced, metastatic gastrointestinal stromal tumors (GIST): combination of surgery and systemic therapy with imatinib in a case of primary gastric location]. Chir Ital; 2005 Jan-Feb;57(1):127-33
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  • [Title] [New orientations in the management of advanced, metastatic gastrointestinal stromal tumors (GIST): combination of surgery and systemic therapy with imatinib in a case of primary gastric location].
  • [Transliterated title] Nuovi orientamenti nella cura dei tumori stromali gastroenterici (GIST) avanzati e metastatici: trattamento combinato intervento chirurgico-terapia sistemica con imatinib in un caso a localizzazione primitiva gastrica.
  • Gastrointestinal stromal tumours (GIST) are rare neoplasms originating from connective tissue in the digestive tract with an incidence of less than 1% and account for most non-epithelial primitive digestive tumours.
  • Metastasis diagnosed at the time of disease discovery confirms GIST malignancy.
  • Kit protein, a trans-membrane tyrosine kinase receptor of staminal cells, is characteristically expressed by GIST.
  • Most GIST have a mutation in the kit proto-oncogene.
  • Resistance to conventional chemotherapy is commonly shown by malignant GIST.
  • Most patients with advanced malignant GIST achieve clinical benefit with imatinib mesilate, an orally administered selective inhibitor of the tyrosine kinase receptor.
  • We treated a 43-year-old male patient suffering from a gastric GIST diagnosed during a surgical emergency operation for peritonitis caused by gastric perforation.
  • At the time of the first operation the patient had lost 10 kg body weight over the previous months and was seriously cachectic.
  • Considering the action mechanism of imatinib and the extent of the lesion we decided to perform a total gastrectomy procedure.
  • At the time of the operation the stomach seemed to have a modified volume and shape: it appeared to be divided into two sacs, the larger and deeper of which was the original gastric cavity, while the superficial, smaller one seemed to be a protrusion of the organ.
  • The stomach was indistinguishable from the spleen, the transverse colon and the distal pancreatic tract.
  • The patient was discharged on postoperative day 8 and commenced imatinib therapy 30 days after the operation with 4 tablets per day.
  • One year after the operation the outcome appears to be lasting and the patient has tolerated the drug treatment well.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Gastrectomy. Gastrointestinal Stromal Tumors / therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Stomach Neoplasms / therapy
  • [MeSH-minor] Adult. Benzamides. Humans. Imatinib Mesylate. Male. Treatment Outcome

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  • (PMID = 15832750.001).
  • [ISSN] 0009-4773
  • [Journal-full-title] Chirurgia italiana
  • [ISO-abbreviation] Chir Ital
  • [Language] ita
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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16. Goldstein D, Tan BS, Rossleigh M, Haindl W, Walker B, Dixon J: Gastrointestinal stromal tumours: correlation of F-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment response--an AGITG study. Oncology; 2005;69(4):326-32
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Gastrointestinal stromal tumours: correlation of F-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment response--an AGITG study.
  • BACKGROUND: Malignant gastrointestinal stromal tumours (GISTs) are a rare subset of aggressive mesenchymal tumours specific to the gastrointestinal system.
  • The aim of this analysis was to report on our experience of the utility of coincidence positron emission tomography (co-PET) based on an 18F-FDG gamma camera in assessing treatment response to imatinib using CT as the comparator and the final clinical outcome as the end point.
  • All patients had biopsy-proven malignant GIST and were on treatment with the targeted pharmacotherapeutic agent imatinib.
  • The majority of the patients were receiving treatment as part of the randomized trial of the European Organization for Research and Treatment of Cancer, the Australian Gastrointestinal Trials Group and the Italian Sarcoma Group, comparing 400 with 800 mg (400 mg b.i.d.).
  • The monitoring of tumour response was achieved by serial CT measurements according to the RECIST criteria.
  • RESULTS: A total of 18 patients were recruited into the study, with a total of 74 lesions.
  • CONCLUSION: 18F-FDG co-PET is a useful modality to monitor treatment response to imatinib in patients with malignant GIST.
  • Although there is a relatively reduced sensitivity when compared with CT for the detection of lesions especially in the liver, co-PET changes in several instances precede the changes on CT scanning.
  • This modality has the potential to influence clinical decision making and should be considered as part of the standard care of patients on imatinib.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Fluorodeoxyglucose F18. Gastrointestinal Stromal Tumors / drug therapy. Gastrointestinal Stromal Tumors / pathology. Piperazines / therapeutic use. Positron-Emission Tomography. Pyrimidines / therapeutic use. Tomography, X-Ray Computed
  • [MeSH-minor] Benzamides. Gamma Cameras. Humans. Imatinib Mesylate. Radiopharmaceuticals. Treatment Outcome

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  • [Copyright] Copyright (c) 2005 S. Karger AG, Basel.
  • (PMID = 16293972.001).
  • [ISSN] 0030-2414
  • [Journal-full-title] Oncology
  • [ISO-abbreviation] Oncology
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 0 / Radiopharmaceuticals; 0Z5B2CJX4D / Fluorodeoxyglucose F18; 8A1O1M485B / Imatinib Mesylate
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17. Chen TW, Liu HD, Shyu RY, Yu JC, Shih ML, Chang TM, Hsieh CB: Giant malignant gastrointestinal stromal tumors: recurrence and effects of treatment with STI-571. World J Gastroenterol; 2005 Jan 14;11(2):260-3
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  • [Title] Giant malignant gastrointestinal stromal tumors: recurrence and effects of treatment with STI-571.
  • AIM: Malignant gastrointestinal stromal tumors (GISTs) are rare.
  • Tumors larger than 10 cm tend to recur earlier: the larger the volume of the tumor, the worse the prognosis.
  • We hypothesized that treatment with imatinib mesylate (Gleevec; STI-571), a c-kit tyrosine kinase inhibitor, as palliative therapy would prolong the survival of patients with recurrent giant malignant GISTs after resection.
  • After that time, 9 patients received this drug.
  • The factors of age, sex, tumor location, histological surgical margin, and STI-571, tumor size changes and drug side effects were reviewed.
  • We compared the survival rate to determine the prognostic factors and the effects of STI-571 on patients with recurrent malignant gastrointestinal stromal tumor.
  • A negative surgical margin and palliative treatment with STI-571 were significant prognostic variables (Log-rank test, P<0.05).
  • Age, sex and tumor location were not significant prognostic variables.
  • The use of STI-571 gave a significant tumor shrinkage (6/9) rate in patients with giant GIST recurrence after resection.
  • Achieving a tumor-free surgical margin is still the best primary treatment for patients with such tumors.
  • If STI-571 is used immediately when the surgical margin is positive and the tumor recurs after resection, then the prognosis of patients with giant GISTs can be improved.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Gastrointestinal Neoplasms / drug therapy. Gastrointestinal Neoplasms / pathology. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Benzamides. Female. Follow-Up Studies. Humans. Imatinib Mesylate. Male. Middle Aged. Recurrence. Retrospective Studies. Stromal Cells / pathology. Survival Analysis. Time Factors

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  • (PMID = 15633227.001).
  • [ISSN] 1007-9327
  • [Journal-full-title] World journal of gastroenterology
  • [ISO-abbreviation] World J. Gastroenterol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Other-IDs] NLM/ PMC4205413
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18. Elliott DD, Fanning CV, Caraway NP: The utility of fine-needle aspiration in the diagnosis of gastrointestinal stromal tumors: a cytomorphologic and immunohistochemical analysis with emphasis on malignant tumors. Cancer; 2006 Feb 25;108(1):49-55
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  • [Title] The utility of fine-needle aspiration in the diagnosis of gastrointestinal stromal tumors: a cytomorphologic and immunohistochemical analysis with emphasis on malignant tumors.
  • BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the tubular gut and mesentery.
  • Fine-needle aspiration biopsy (FNAB) currently is a useful tool in the diagnosis of GIST because of various mutations of the KIT protooncogene that are recognized as characteristic of these tumors.
  • Despite such advances, the malignant potential of GIST remains variable, and few studies have reported their findings in patients with malignant GIST.
  • Therefore, in the current study, the authors have reported their experience with FNAB as a diagnostic tool in one of the largest series of malignant GISTs and have analyzed the cytomorphologic features of the tumors relative to their clinical behavior to determine which, if any, cytologic features are indicators of malignancy.
  • METHODS: All patients with histologically confirmed GIST who were diagnosed by image-guided FNAB and confirmed with positive CD117 staining from 1998 to 2003 were included in the study.
  • For study purposes, the patients were divided into two groups: Group A included all patients with malignant tumors, defined as those with metastatic disease or recurrent disease after adequate surgery with or without chemotherapy; Group B included all other patients.
  • RESULTS: In total, 26 tumors from 23 patients (8 males and 15 females) with a mean age of 60.9 years were available for review.
  • Twenty-one tumors were unequivocally malignant and were placed into Group A; the remaining 5 tumors were placed into Group B.
  • None of the cytologic features that were evaluated could distinguish reliably between benign tumors and malignant tumors, as expected.
  • However, on cytologic examination, all tumors that demonstrated mitoses (n = 7 tumors) and/or pretreatment necrosis (n = 3 tumors) were identified as malignant.
  • CONCLUSIONS: FNAB remains a reliable method for the diagnosis of GIST.
  • Immunohistochemical staining of cytologic material with CD117 has been reliable in establishing this diagnosis by FNAB, provided adequate tissue is procured.
  • In the current study, the presence of necrosis or mitoses in cytologic specimens was correlated with a diagnosis of malignant GIST.
  • [MeSH-major] Biopsy, Fine-Needle. Gastrointestinal Stromal Tumors / diagnosis

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  • [Copyright] (c) 2005 American Cancer Society.
  • (PMID = 16130141.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
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19. Miyake M, Takeda Y, Hasuike Y, Kashiwazaki M, Mishima H, Ikenaga M, Mano M, Takada Y, Hirota S, Tsujinaka T: [A case of metastatic gastrointestinal stromal tumor developing a resistance to STI571 (imatinib mesylate)]. Gan To Kagaku Ryoho; 2004 Oct;31(11):1791-4
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [A case of metastatic gastrointestinal stromal tumor developing a resistance to STI571 (imatinib mesylate)].
  • Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract characterized by the expression of a receptor that activates tyrosine kinase called c-kit.
  • Since malignant GISTs are resistant to conventional radiation therapy and chemotherapy, recurrent or malignant GIST has an extremely poor prognosis even after surgical resection.
  • The development of a tyrosine kinase inhibitor, STI571 (imatinib mesylate, Glivec, Gleevec), which inhibits the BCR-ABL, PDGF-R alpha and c-kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastatic disease.
  • We report a patient with GIST and diffused peritoneal metastases, whose tumor initially responded to STI571 and eventually became resistant.
  • A 45-year-old woman underwent partial jejunostomy on September 3, 1998, under a diagnosis of submucosal tumor of the jejunum.
  • Pathological examination of the primary tumor revealed a strong c-kit expression and GIST was diagnosed.
  • A treatment with STI571 (400 mg/day) was initiated on October 15, 2001, and she was free from peritoneal masses for 8 months after the fourth operation.
  • However, the patient herself suspended the STI571 therapy for one month and multiple peritoneal metastases developed.
  • Although the treatment with STI571 was restarted at 400 mg/day, the peritoneal masses did not respond this time.
  • Her tumors showed mutations in exons 9 or 11 of KIT, which had longer event-free and overall survival times than those tumors that had mutations of exons 13 or 17.
  • After the interruption of the treatment, an additional point mutation arose in exon 13 that caused a resistance to STI571.
  • Currently STI571 is the first-line therapy for non-resectable GISTs, but a single-agent therapy often leads to tumor resistance.
  • It is our hope that we will be able to design an alternative treatment to overcome such resistance.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Gastrointestinal Stromal Tumors / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Benzamides. Drug Resistance, Neoplasm. Exons / genetics. Female. Humans. Imatinib Mesylate. Middle Aged. Peritoneal Neoplasms / secondary. Protein-Tyrosine Kinases / analysis. Protein-Tyrosine Kinases / antagonists & inhibitors

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  • (PMID = 15553717.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases
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