Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of an autopsy of unusual retroperitoneal sympathetic paraganglioma (SPG) that directly invaded the duodenum and showed expansive growth mimicking a submucosal tumor. The tumor was clinically suspected to be a gastrointestinal stromal tumor (GIST) of the duodenum because of its location and extension to the retroperitoneum without catecholamine-associated symptoms. However, a small biopsy specimen of the tumor showed diffuse proliferation of large basophilic cells that were negative for C-kit and CD34, ruling out GIST and indicating an epithelial malignancy. An autopsy revealed that the tumor was mainly in the retroperitoneum, measuring 7.5 x 9.5 cm, weighing 600 g and extending into the duodenum, adjacent to the pancreas but free of the adrenal glands. On cut section, the tumor involved the entire wall of the duodenum. There were no metastases in any organs. For differential diagnosis, endocrine tumors of the duodenum or pancreas and extra-adrenal SPG were considered. The tumor cells were immunohistochemically strongly positive for chromogranin A and were surrounded by cells positive for S100 protein. The Ki67-labeling index was under 1%. The four catecholamine-synthesizing enzymes were detected in the tumor cells. We report this case of SPG with emphasis on differential diagnosis and the significance of its local invasion.
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PMID:A retroperitoneal sympathetic paraganglioma invading the duodenum and mimicking a submucosal tumor. 1843 26

Gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal neoplasm of the gastrointestinal tract. Now, there is widespread scientific and clinical interest in GIST because of identifying in principal pathogenetic defects and development of a specific molecular inhibitor of GIST. GISTs have a gain-of-function mutation in the c-kit protooncogene. Mutation results in constitutive activation of the Kit receptor tyrosine kinase, which induces malignant cell proliferation. Imatinib (gleevec) is an oral agent that selectively inhibits c-Kit, whose efficacy proves that a specific inhibitor can counteract the effects of a genetic defect responsible for cancer. Although STI571 was first applied to GIST, it has already revolutionized the treatment of patients with metastases. Now so many molecular target agents are under development in clinical trials.
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PMID:[GIST]. 1848 9

The efficacy of percutaneous cryosurgery (PCS) as a treatment strategy for unresected liver tumor was evaluated in two cases. The first patient was a 64-year-old man who was found to have multiple liver tumors after undergoing gastrectomy for gastric cancer (T3, N0, M0, Stage II). Two PCS treatments under local anesthesia decreased the size of both the treated and untreated tumors. The second patient was a 61-year-old man in whom multiple liver tumors were discovered after hepatectomy for metastases of a duodenal gastrointestinal stromal tumor, which also had been treated surgically. A third surgery was performed for mass reduction. The patient showed stable improvement after surgery, and PCS combined with administration of polysaccharide-Kureha was selected to treat the unresectable tumors. PCS was performed once a week with an overnight hospital stay. After nine PCS treatment, the remarkable reduction in the size and number of liver tumors was observed, even among non-treated tumors. The patient remains in good condition without tumors 21 months after treatment.
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PMID:Growth inhibition of unresectable tumors induced by hepatic cryoablation: report of two cases. 1850 13

Gastrointestinal stromal tumour (GIST) is the commonest mesenchymal tumour to affect the gastrointestinal tract. Appropriate management requires accurate diagnosis and the skills of a multidisciplinary team. Surgery is the only curative treatment option and should be performed whenever feasible, by experienced personnel. For patients with advanced unresectable or metastatic disease, the receptor tyrosine kinase inhibitor imatinib offers effective therapy and can provide effective palliation for the majority of patients with this disease. The background to this recent development and a guideline for the management of GIST is proposed.
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PMID:A Guideline for the Management of Gastrointestinal Stromal Tumour (GIST). 1852 37

Introduction. Adult pelvic soft tissue sarcomas are a rare group of heterogeneous malignancies. These sarcomas differ from extremity and trunk soft tissue sarcomas in presentation, characteristics and response to treatment.Methods. A retrospective analysis of patient and tumor characteristics, treatment and prognosis and prognostic factors was performed.Results. Between 1977 and 1997, a total of 33 adult patients with soft tissue sarcomas involving the pelvis but excluding uterine leiomyosarcoma were identified. Leiomyosarcomas (18), including six GIST, and rhabdomyosarcomas (eight) were the most commonly seen tumors. At first presentation, nine patients already had metastases. The mean follow-up was 52 months (1-200). Recurrences developed in 15 of the 24 cases (63%) with tumors without metastases at first presentation; in six (25%) recurrence was locally only, in nine distant metastases occurred. The nine patients with metastatic disease at first presentation died of the disease, while eight of the 24 patients with localized disease at presentation died. One patient died of an unrelated cause, four were alive with disease, and 11 patients were alive and free of disease. The only identifiable prognostic factor of disease-free interval and overall survival was histological grade.Conclusion. Soft tissue sarcomas of the pelvis appear to be associated with increased rate of metastasis at the time of diagnosis and higher rates of local recurrence. In this study, multi-modality treatment for most primary tumors did not show a significant benefit in recurrence rate, DFI and OST, when compared to single modality approach. Although the number of patients in this study is small, and different types of sarcomas were studied, the only identifiable predictor for survival was low histological grade of the tumors. The differences of this heterogeneous group of pelvic sarcomas with retroperitoneal, trunk and extremity sarcomas should be taken into consideration in the management of these sarcomas.
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PMID:Adult pelvic sarcomas: a heterogeneous collection of sarcomas? 1852 89

We report two pulmonary pleomorphic carcinoma patients both of which underwent surgical resection of solitary gastric metastases. A 69-year-old man developed anemia 5 months after right upper lobectomy for pulmonary pleomorphic carcinoma and gastric metastasis was detected endoscopically. He underwent distal gastrectomy and has survived for 5 years without any other recurrence or metastasis. Preoperative abdominal computed tomography detected a submucosal gastric tumor in a 62-year-old man with left upper lobe pleomorphic carcinoma. A gastrointestinal stromal tumor was suspected. Left upper lobectomy was performed followed by partial gastrectomy with splenectomy. The histologic diagnosis was primary pulmonary pleomorphic carcinoma with gastric metastasis. He has survived for 4 years without any other recurrence or metastasis. Resection of gastric metastasis following complete pulmonary pleomorphic carcinoma resection may be indicated if the metastasis is solitary.
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PMID:Long-term survival in two cases of resected gastric metastasis of pulmonary pleomorphic carcinoma. 1859 28

Most GIST patients develop clinical resistance to KIT/PDGFRA tyrosine kinase inhibitors (TKI). However, it is unclear whether clinical resistance results from single or multiple molecular mechanisms in each patient. KIT and PDGFRA mutations were evaluated in 53 GIST metastases obtained from 14 patients who underwent surgical debulking after progression on imatinib or sunitinib. To interrogate possible resistance mechanisms across a broad biological spectrum of GISTs, inter- and intra-lesional heterogeneity of molecular drug-resistance mechanisms were evaluated in the following: conventional KIT (CD117)-positive GISTs with KIT mutations in exon 9, 11 or 13; KIT-negative GISTs; GISTs with unusual morphology; and KIT/PDGFRA wild-type GISTs. Genomic KIT and PDGFRA mutations were characterized systematically, using complementary techniques including D-HPLC for KIT exons 9, 11-18 and PDGFRA exons 12, 14, 18, and mutation-specific PCR (V654A, D820G, N822K, Y823D). Primary KIT oncogenic mutations were found in 11/14 patients (79%). Of these, 9/11 (83%), had secondary drug-resistant KIT mutations, including six (67%) with two to five different secondary mutations in separate metastases, and three (34%) with two secondary KIT mutations in the same metastasis. The secondary mutations clustered in the KIT ATP binding pocket and kinase catalytic regions. FISH analyses revealed KIT amplicons in 2/10 metastases lacking secondary KIT mutations. This study demonstrates extensive intra- and inter-lesional heterogeneity of resistance mutations and gene amplification in patients with clinically progressing GIST. KIT kinase resistance mutations were not found in KIT/PDGFRA wild-type GISTs or in KIT-mutant GISTs showing unusual morphology and/or loss of KIT expression by IHC, indicating that resistance mechanisms are fundamentally different in these tumours. Our observations underscore the heterogeneity of clinical TKI resistance, and highlight the therapeutic challenges involved in salvaging patients after clinical progression on TKI monotherapies.
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PMID:Heterogeneity of kinase inhibitor resistance mechanisms in GIST. 1862 23

Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of gastrointestinal tract often driven by oncogenic KIT exon 11 mutations. Although deletions and substitutions are most frequent KIT exon 11 mutations, duplications and insertions have been reported as well. In contrast to duplications, which cluster in 3'KIT exon 11, insertions affect 5'KIT, particularly codon 558. Clinicopathologic profile of gastrointestinal stromal tumors with insertions in codon 558 is not known. In this study, 17 gastrointestinal stromal tumors with codon 558 insertions are reported. Fifteen (88.2%) KIT codon 558 insertions consisted of 1694_1695insTCC leading to Lys558delinsAsnPro. However, 2 variant mutants Lys558delinsAsnGln and Lys558delinsAsnAsn were also identified. Based on analysis of inserted and flanking sequences, the insertions contain inverted DNA sequences of the opposite strand. Therefore, these insertions may develop due to a DNA strand switch during replication by DNA polymerases and by the effects of several different DNA repair processes. Patient median age was 61 years, and male-to-female ratio was 1:1.8. gastrointestinal stromal tumors were diagnosed in stomach (n = 4), small intestine (n = 7), and rectum (n = 3). Three tumors were disseminated and primary location could not be established. Fourteen tumors had spindle cell morphology, and epithelioid cell features were seen in 2 intestinal and 1 disseminated gastrointestinal stromal tumor. Based on size and mitotic activity, 2 (50%) of 4 gastric and 3 (48.9%) of 7 small intestinal gastrointestinal stromal tumors had more than 50% risk of metastases according to previous studies of gastrointestinal stromal tumor prognosis. All 3 rectal gastrointestinal stromal tumors were malignant. Metastases were verified in 8 (66.7%) of 12 patients with known clinical and follow-up data. In summary, KIT codon 558 insertions are rare mutations accounting for less than 1% of all KIT mutants. Gastrointestinal stromal tumors with these mutations appear to have predilection to female patients and intestinal location. Moreover, KIT codon 558 insertions might indicate an increased risk of malignant behavior for gastric gastrointestinal stromal tumors.
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PMID:KIT codon 558 insertions in gastrointestinal stromal tumors. Analysis of 17 rare KIT mutants. 1871 19

Gastrointestinal stromal tumors (GISTs) generally arise from primary activating mutations in the KIT or PDGFRA genes that result in constitutive activation of receptor tyrosine kinase activity. Imatinib provides targeted therapy for GIST by inhibiting the KIT and PDGFR-alpha tyrosine kinases. Clinical benefit is achieved in approximately 85% of patients with unresectable or metastatic disease, with a median progression-free survival of 20 to 24 months. The mechanisms of acquired resistance to imatinib are heterogeneous, with most involving the emergence of secondary mutations in KIT exons 13, 14, or 17. In patients failing or intolerant to imatinib, the multitargeted agent sunitinib achieves durable disease control in approximately 50% of cases. Experimental treatment options beyond those currently available consist of other KIT-targeting tyrosine kinase inhibitors, such as nilotinib, or agents targeting alternative pathways, such as antiangiogenic agents, mammalian target of rapamycin, RAF kinase, and chaperone inhibitors.
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PMID:Novel approaches to imatinib- and sunitinib-resistant GIST. 1877 61

Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. One hundred one patients (54 women and 47 men) with a mean age of 64.1 years (range, 17-94 years) were surgically treated for a GIST within a 10-year period. Of these patients, 28 (28%) were affected by metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97 GIST patients (96%). In patients with high-risk GIST, the expression of p16 expression was highly predictive for poor prognosis, i.e., the development of recurrence or metastases (P = .006) and poor survival (P = .004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041). The disease-specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85% and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high-risk classification were confirmed as relevant predictors for unfavorable prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases, the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for "very high risk GIST."
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PMID:p16 expression differentiates high-risk gastrointestinal stromal tumor and predicts poor outcome. 1881 51


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