BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abd...BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity,the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors.CASE SUMMARY The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days.Upon physical examination,the patient had flat and tough abdomen with mild pressing pain at lower abdomen,no obvious abdominal mass was touchable,and shifting dullness was positive.Positron emission tomography-computed tomography(CT)showed that in his peritoneal cavity,there were multiple nodules of various sizes,seroperitoneum,multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules.Plain CT scanning at epigastrium/hypogastrium/pelvic cavity+enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity,peritoneum and right groin.Tumor marker of carbohydrate antigen 125 was 808 U/mL,diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia,and postoperative pathological examination confirmed EGIST.Imatinib was administered with better therapeutic effect.CONCLUSION Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation,and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.展开更多
BACKGROUND Gastrointestinal stromal tumors(GIST)are prevalent neoplasm originating from the gastrointestinal mesenchyme.Approximately 50%of GIST patients experience tumor recurrence within 5 years.Thus,there is a pres...BACKGROUND Gastrointestinal stromal tumors(GIST)are prevalent neoplasm originating from the gastrointestinal mesenchyme.Approximately 50%of GIST patients experience tumor recurrence within 5 years.Thus,there is a pressing need to accurately evaluate risk stratification preoperatively.AIM To assess the application of a deep learning model(DLM)combined with computed tomography features for predicting risk stratification of GISTs.METHODS Preoperative contrast-enhanced computed tomography(CECT)images of 551 GIST patients were retrospectively analyzed.All image features were independently analyzed by two radiologists.Quantitative parameters were statistically analyzed to identify significant predictors of high-risk malignancy.Patients were randomly assigned to the training(n=386)and validation cohorts(n=165).A DLM and a combined DLM were established for predicting the GIST risk stratification using convolutional neural network and subsequently evaluated in the validation cohort.RESULTS Among the analyzed CECT image features,tumor size,ulceration,and enlarged feeding vessels were identified as significant risk predictors(P<0.05).In DLM,the overall area under the receiver operating characteristic curve(AUROC)was 0.88,with the accuracy(ACC)and AUROCs for each stratification being 87%and 0.96 for low-risk,79%and 0.74 for intermediate-risk,and 84%and 0.90 for high-risk,respectively.The overall ACC and AUROC were 84%and 0.94 in the combined model.The ACC and AUROCs for each risk stratification were 92%and 0.97 for low-risk,87%and 0.83 for intermediate-risk,and 90%and 0.96 for high-risk,respectively.Differences in AUROCs for each risk stratification between the two models were significant(P<0.05).CONCLUSION A combined DLM with satisfactory performance for preoperatively predicting GIST stratifications was developed using routine computed tomography data,demonstrating superiority compared to DLM.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The reg...BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.展开更多
Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-der...Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.展开更多
BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 ...BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.展开更多
BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication...BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use.Here,we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.CASE SUMMARY A 66-year-old male with metastatic GIST was admitted because of reduced consciousness.Imatinib was administered as the first-line systemic therapy.He experienced repeated episodes of peritonitis due to tumor perforation,and surgery was performed.Progressive disease was confirmed based on increased liver metastasis,and sunitinib was initiated as a salvage treatment.However,23 d after the third course of sunitinib,he presented to the emergency room with an episode of altered consciousness and behavioral changes.Based on the patient clinical history and examination findings,sunitinib-induced encephalopathy was suspected.Sunitinib was discontinued,and the patient was treated for hyperammonemia.The patient had a normal level of consciousness four days later,and the serum ammonia level gradually decreased.No further neurological symptoms were reported in subsequent follow-ups.CONCLUSION TKI-induced hyperammonemic encephalopathy is potentially life-threatening.Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.展开更多
BACKGROUND Computed tomography(CT)imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors(GISTs).AIM To determine the multi-slice CT imaging features for predicting risk str...BACKGROUND Computed tomography(CT)imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors(GISTs).AIM To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs.METHODS The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed.All patients had received dynamic contrast-enhanced CT(CECT)followed by surgical resection.According to the modified National Institutes of Health criteria,147 lesions were classified into the low malignant potential group(very low and low risk;101 lesions)and high malignant potential group(medium and high-risk;46 lesions).The association between malignant potential and CT characteristic features(including tumor location,size,growth pattern,contour,ulceration,cystic degeneration or necrosis,calcification within the tumor,lymphadenopathy,enhancement patterns,unenhanced CT and CECT attenuation value,and enhancement degree)was analyzed using univariate analysis.Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential.The receiver operating curve(ROC)was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification.RESULTS There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs.Univariate analysis showed no significant differences in age,gender,tumor location,calcification,unenhanced CT and CECT attenuation values,and enhancement degree between the two groups(P>0.05).However,a significant difference was observed in tumor size(3.14±0.94 vs 6.63±3.26 cm,P<0.001)between the low-grade and high-grade groups.The univariate analysis further revealed that CT imaging features,including tumor contours,lesion growth patterns,ulceration,cystic degeneration or necrosis,lymphadenopathy,and contrast enhancement patterns,were associated with risk stratification(P<0.05).According to binary logistic regression analysis,tumor size[P<0.001;odds ratio(OR)=26.448;95%confidence interval(CI):4.854-144.099)],contours(P=0.028;OR=7.750;95%CI:1.253-47.955),and mixed growth pattern(P=0.046;OR=4.740;95%CI:1.029-21.828)were independent predictors for risk stratification of gastric GISTs.ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919(95%CI:0.863-0.975)and 0.940(95%CI:0.893-0.986),respectively.The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm,and the sensitivity and specificity were 93.5%and 84.2%,respectively.CONCLUSION CT features,including tumor size,growth patterns,and lesion contours,were predictors of malignant potential for primary gastric GISTs.展开更多
BACKGROUND The use of endoscopic surgery for treating gastrointestinal stromal tumors(GISTs)between 2 and 5 cm remains controversial considering the potential risk of metastasis and recurrence.Also,surgeons are facing...BACKGROUND The use of endoscopic surgery for treating gastrointestinal stromal tumors(GISTs)between 2 and 5 cm remains controversial considering the potential risk of metastasis and recurrence.Also,surgeons are facing great difficulties and challenges in assessing the malignant potential of 2-5 cm gastric GISTs.AIM To develop and evaluate computerized tomography(CT)-based radiomics for predicting the malignant potential of primary 2-5 cm gastric GISTs.METHODS A total of 103 patients with pathologically confirmed gastric GISTs between 2 and 5 cm were enrolled.The malignant potential was categorized into low grade and high grade according to postoperative pathology results.Preoperative CT images were reviewed by two radiologists.A radiological model was constructed by CT findings and clinical characteristics using logistic regression.Radiomic features were extracted from preoperative contrast-enhanced CT images in the arterial phase.The XGboost method was used to construct a radiomics model for the prediction of malignant potential.Nomogram was established by combing the radiomics score with CT findings.All of the models were developed in a training group(n=69)and evaluated in a test group(n=34).RESULTS The area under the curve(AUC)value of the radiological,radiomics,and nomogram models was 0.753(95%confidence interval[CI]:0.597-0.909),0.919(95%CI:0.828-1.000),and 0.916(95%CI:0.801-1.000)in the training group vs 0.642(95%CI:0.379-0.870),0.881(95%CI:0.772-0.990),and 0.894(95%CI:0.773-1.000)in the test group,respectively.The AUC of the nomogram model was significantly larger than that of the radiological model in both the training group(Z=2.795,P=0.0052)and test group(Z=2.785,P=0.0054).The decision curve of analysis showed that the nomogram model produced increased benefit across the entire risk threshold range.CONCLUSION Radiomics may be an effective tool to predict the malignant potential of 2-5 cm gastric GISTs and assist preoperative clinical decision making.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are dr...Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.展开更多
AIM To determine the feasibility,safety,and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors(GISTs)based on favorable or unfavorable location.METHODS Our hospital database inclu...AIM To determine the feasibility,safety,and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors(GISTs)based on favorable or unfavorable location.METHODS Our hospital database included 207 patients who underwent laparoscopic removal of gastric GISTs from January 2004 to September 2015.Patient demographics,clinical presentation,surgery,histopathology,postoperative course,and oncological outcomes were reviewed and analyzed.RESULTS Gastric GIST in favorable locations was present in81/207(39.1%)cases,and in unfavorable locations in 126/207(60.9%)cases.Overall mean tumor size was 3.28±1.82 cm.No conversions occurred,and complete R0 resection was achieved in 207(100%)cases.There were three incidences of iatrogenic tumor rupture.The feasibility and safety of laparoscopic surgery were comparable in both groups with no statistical difference between unfavorable and favorable location groups,respectively:for operative time:83.86±44.41 vs 80.77±36.46 min,P=0.627;conversion rate:0%vs 0%;estimated blood loss:27.74±45.2vs 29.59±41.18 m L,P=0.780;tumor rupture during surgery:0.90%vs 2.82%,P=0.322;or postoperative complications:3.74%vs 7.04%,P=0.325.The follow-up period recurrence rate was 1.89%with no significant differences between the two groups(3.03%vs 0%,P=0.447).Overall 5-year survival rate was98.76%and survival rates were similar between the two groups:98.99%vs 98.39%,P=0.623(unfavorable vs favorable,respectively).CONCLUSION The laparoscopic approach for gastric GISTs is safe and feasible with well-accepted oncological surgical outcomes.Strategies for laparoscopic resection should be selected according to the location and size of the tumor.Laparoscopic treatment of gastric GISTs in unfavorable locations should not be restricted in gastrointestinal centers.展开更多
AIM:To report our experience of gastrointestinal stromal tumors (GISTs) during the last 29 years. METHODS:Thirty two cases of GIST referred to our Institution from the 1st January 1981 to the 10th June 2010 were revie...AIM:To report our experience of gastrointestinal stromal tumors (GISTs) during the last 29 years. METHODS:Thirty two cases of GIST referred to our Institution from the 1st January 1981 to the 10th June 2010 were reviewed. Metastases,recurrence and survival data were collected in relation to age,history,clinical presentation,location,size,resection margins and cellular features. RESULTS:Mean age was 63.7 years (range,40-90) and incidence was slightly higher in males (56%). R0 resection was performed in 90.7% of cases,R1 in 6.2% (2 cases) and R2 in 3.1% (one case). Using Fletcher's classification 8/32 (25%) had high risk,9/32 (28%) intermediate and 15/32 (47%) low risk tumors. Follow-up varied from 1 mo to 29 years,with a median of 8 years; overall survival was 75% (24/32),disease-free survival was 72% and tumor-related mortality was 9.3%. Three patients with high risk GIST were treated with imatinib mesylate:one developed a recurrence after 36 mo,and 2 are free from disease at 41 mo. CONCLUSION:Surgical treatment remains the gold standard therapy for resectable GISTs. Pathological and biological features of the neoplasm represent the most important factors predicting the prognosis.展开更多
AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohi...AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.展开更多
AIM: To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography (DSA) for bleeding small bowel gastrointestinal stromal tumors (GISTs).
Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract and are thought to arise from precursors of the interstitial cells of Cajal.GISTs can arise anywhere in the...Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract and are thought to arise from precursors of the interstitial cells of Cajal.GISTs can arise anywhere in the GI tract,but most commonly originate from the stomach and small intestine.The majority of GISTs occur as a result of activating mutations in two receptor protein tyrosine kinases:KIT and/or platelet-derived growth factor receptor-α.Mutational analyses allow for predicting patient prognosis and treatment response.Clinical presentations can vary from no symptoms,typical in the case of small incidentally found tumors,to GI bleeding,abdominal discomfort,and ulcer-related symptoms when the tumor is enlarged.Imaging plays a critical role in the diagnosis and management of these tumors with multiphasic computed tomography serving as the imaging modality of choice.Magnetic resonance imaging and positron emission tomography-computed tomography can serve as imaging adjuncts in lesion characterization,especially with liver metastases,and subsequent staging and assessment for treatment response or recurrence.Surgical resection is the preferred management for small GISTs,while tyrosine kinase inhibitors−imatinib mesylate and sunitinib malate−serve as crucial molecular-targeted therapies for locally advanced and metastatic GISTs.This review article highlights the clinical presentation,pathology and molecular cytogenetics,imaging features,and current management of GISTs.展开更多
AIM： To review clinical and pathologic features of Gastrointestinal strornal tumors （GISTs） occurring synchronously with other primary gastrointestinal neoplasms. METHODS： 28 patients with primary GIST were treate...AIM： To review clinical and pathologic features of Gastrointestinal strornal tumors （GISTs） occurring synchronously with other primary gastrointestinal neoplasms. METHODS： 28 patients with primary GIST were treated at our institution between 1989 and 2005. Clinical and pathologic records were reviewed. RESULTS： The gastrointestinal stromal tumor occurred simultaneously with other primary GI malignancies in 14% of all patients with GIST. The synchronous stromal tumors were located in the stomach and were incidentally found during the operation. The coexistent neoplasms were colon adenocarcinoma, gastric cancer （2 cases） and gastric lymphoma. CONCLUSION： The synchronous occurrence of GISTs and other gastrointestinal malignancies is more common than it has been considered. The development of gastrointestinal stromal tumors and other neoplasms may involve the same carcinogenic agents.展开更多
AIM:To perform a meta-analysis to derive a more precise estimation of imatinib treatment for different genotypes of gastrointestinal stromal tumors(GIST).METHODS:Studies were identified by searching PubMed and Embase....AIM:To perform a meta-analysis to derive a more precise estimation of imatinib treatment for different genotypes of gastrointestinal stromal tumors(GIST).METHODS:Studies were identified by searching PubMed and Embase.Inclusive criteria were patients with exon 9-mutant,exon 11-mutant or wide type(WT) GIST,receiving chemotherapy of imatinib for clinical trial,and efficacy evaluation was cumulative response (CR)including complete response and partial response.The odds ratios(OR)for CR in stem cell factor receptor (KIT)mutation patients vs WT genotype patients,KIT exon 11-mutant genotype patients vs KIT exon 9-mutant genotype patients and KIT exon 9-mutant genotype patients vs WT genotype patients were calculated with 95%confidence interval(CI)for each study as an estimation of the efficacy of imatinib.RESULTS:Five studies including 927 patients were involved in this meta-analysis.The overall OR(KIT group vs WT group)was 3.34(95%CI:2.30-4.86,P <0.00001,P heterogeneity=0.04).The overall OR in KIT exon 11 group vs KIT exon 9 group was 3.29(95%CI: 2.17-5.00,P<0.00001,P heterogeneity=0.33).The overall OR in KIT exon 9 group vs WT group was 1.23(95% CI:0.73-2.10,P=0.44,P heterogeneity=0.42).CONCLUSION:Most patients with different genotypes of GIST and KIT exon 11-mutant will benefit from the individualized treatment of imatinib.展开更多
Gastrointestinal stromal tumors(GISTs)are uncommon neoplasms of the gastrointestinal tract with peculiar clinical,genetic,and imaging characteristics.Preoperative knowledge of risk stratification and mutational status...Gastrointestinal stromal tumors(GISTs)are uncommon neoplasms of the gastrointestinal tract with peculiar clinical,genetic,and imaging characteristics.Preoperative knowledge of risk stratification and mutational status is crucial to guide the appropriate patients’treatment.Predicting the clinical behavior and biological aggressiveness of GISTs based on conventional computed tomography(CT)and magnetic resonance imaging(MRI)evaluation is challenging,unless the lesions have already metastasized at the time of diagnosis.Radiomics is emerging as a promising tool for the quantification of lesion heterogeneity on radiological images,extracting additional data that cannot be assessed by visual analysis.Radiomics applications have been explored for the differential diagnosis of GISTs from other gastrointestinal neoplasms,risk stratification and prediction of prognosis after surgical resection,and evaluation of mutational status in GISTs.The published researches on GISTs radiomics have obtained excellent performance of derived radiomics models on CT and MRI.However,lack of standardization and differences in study methodology challenge the application of radiomics in clinical practice.The purpose of this review is to describe the new advances of radiomics applied to CT and MRI for the evaluation of gastrointestinal stromal tumors,discuss the potential clinical applications that may impact patients’management,report limitations of current radiomics studies,and future directions.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST,which eventually develops into recurrence and acquired drug resistance.Therefore,it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs.CC chemokine receptor type 8(CCR8)protein participates in regulation of immune responses.Recent studies on CCR8 in nonsmall cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis.AIM To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs.METHODS Tissue samples were used for the tissue microarrays construction.The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression.Next,Kaplan–Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data,and the potential prognostic value of CCR8 was evaluated by Cox regression analysis.Finally,a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database.RESULTS CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm.Among 125 tissue samples,74 had CCR8 high expression and 51 had low or negative expression.Statistical analyses suggested CCR8 was significantly correlated with tumor size,mitotic index,AFIP-Miettinen risk classification and tumor location.Kaplan–Meier and multivariate analyses showed that patients with low or negative CCR8 expression,mitotic index<5/high-power fields(HPF)and tumor diameter<5 cm had a better prognosis.Based on the STRING database,CCR8 was significantly enriched in biological processes such as tumor immunity,T lymphocyte chemotaxis,migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks.CONCLUSION CCR8 is a prognostic biomarker for malignant potential of GISTs,with high expression correlated with malignancy and poor prognosis.展开更多
文摘BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity,the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors.CASE SUMMARY The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days.Upon physical examination,the patient had flat and tough abdomen with mild pressing pain at lower abdomen,no obvious abdominal mass was touchable,and shifting dullness was positive.Positron emission tomography-computed tomography(CT)showed that in his peritoneal cavity,there were multiple nodules of various sizes,seroperitoneum,multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules.Plain CT scanning at epigastrium/hypogastrium/pelvic cavity+enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity,peritoneum and right groin.Tumor marker of carbohydrate antigen 125 was 808 U/mL,diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia,and postoperative pathological examination confirmed EGIST.Imatinib was administered with better therapeutic effect.CONCLUSION Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation,and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.
基金National Natural Science Foundation of China,No.82160842Clinical Research Project of Research Fund of Gansu Provincial Hospital,No.23GSSYD-17General Program of the Joint Scientific Research Fund,No.23JRRA1521.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.
基金Supported by The Chinese National Key Research and Development Project,No.2021YFC2500400 and No.2021YFC2500402Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009A.
文摘BACKGROUND Gastrointestinal stromal tumors(GIST)are prevalent neoplasm originating from the gastrointestinal mesenchyme.Approximately 50%of GIST patients experience tumor recurrence within 5 years.Thus,there is a pressing need to accurately evaluate risk stratification preoperatively.AIM To assess the application of a deep learning model(DLM)combined with computed tomography features for predicting risk stratification of GISTs.METHODS Preoperative contrast-enhanced computed tomography(CECT)images of 551 GIST patients were retrospectively analyzed.All image features were independently analyzed by two radiologists.Quantitative parameters were statistically analyzed to identify significant predictors of high-risk malignancy.Patients were randomly assigned to the training(n=386)and validation cohorts(n=165).A DLM and a combined DLM were established for predicting the GIST risk stratification using convolutional neural network and subsequently evaluated in the validation cohort.RESULTS Among the analyzed CECT image features,tumor size,ulceration,and enlarged feeding vessels were identified as significant risk predictors(P<0.05).In DLM,the overall area under the receiver operating characteristic curve(AUROC)was 0.88,with the accuracy(ACC)and AUROCs for each stratification being 87%and 0.96 for low-risk,79%and 0.74 for intermediate-risk,and 84%and 0.90 for high-risk,respectively.The overall ACC and AUROC were 84%and 0.94 in the combined model.The ACC and AUROCs for each risk stratification were 92%and 0.97 for low-risk,87%and 0.83 for intermediate-risk,and 90%and 0.96 for high-risk,respectively.Differences in AUROCs for each risk stratification between the two models were significant(P<0.05).CONCLUSION A combined DLM with satisfactory performance for preoperatively predicting GIST stratifications was developed using routine computed tomography data,demonstrating superiority compared to DLM.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.
基金supported by Quzhou City Jiang District Life Oasis Public Welfare Service Center,Health and Health Development Promotion Project(Oncology Research Special Project,no:BJHA-CRP-027).
文摘Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.
基金Supported by Clinical Research Fund Project of Zhejiang Medical Association,China,No.2021ZYC-A173.
文摘BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.
文摘BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use.Here,we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.CASE SUMMARY A 66-year-old male with metastatic GIST was admitted because of reduced consciousness.Imatinib was administered as the first-line systemic therapy.He experienced repeated episodes of peritonitis due to tumor perforation,and surgery was performed.Progressive disease was confirmed based on increased liver metastasis,and sunitinib was initiated as a salvage treatment.However,23 d after the third course of sunitinib,he presented to the emergency room with an episode of altered consciousness and behavioral changes.Based on the patient clinical history and examination findings,sunitinib-induced encephalopathy was suspected.Sunitinib was discontinued,and the patient was treated for hyperammonemia.The patient had a normal level of consciousness four days later,and the serum ammonia level gradually decreased.No further neurological symptoms were reported in subsequent follow-ups.CONCLUSION TKI-induced hyperammonemic encephalopathy is potentially life-threatening.Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.
基金Supported by the Roentgen Imaging Research Project of Beijing Kangmeng Charitable Foundation,No.SD-202008-017.
文摘BACKGROUND Computed tomography(CT)imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors(GISTs).AIM To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs.METHODS The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed.All patients had received dynamic contrast-enhanced CT(CECT)followed by surgical resection.According to the modified National Institutes of Health criteria,147 lesions were classified into the low malignant potential group(very low and low risk;101 lesions)and high malignant potential group(medium and high-risk;46 lesions).The association between malignant potential and CT characteristic features(including tumor location,size,growth pattern,contour,ulceration,cystic degeneration or necrosis,calcification within the tumor,lymphadenopathy,enhancement patterns,unenhanced CT and CECT attenuation value,and enhancement degree)was analyzed using univariate analysis.Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential.The receiver operating curve(ROC)was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification.RESULTS There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs.Univariate analysis showed no significant differences in age,gender,tumor location,calcification,unenhanced CT and CECT attenuation values,and enhancement degree between the two groups(P>0.05).However,a significant difference was observed in tumor size(3.14±0.94 vs 6.63±3.26 cm,P<0.001)between the low-grade and high-grade groups.The univariate analysis further revealed that CT imaging features,including tumor contours,lesion growth patterns,ulceration,cystic degeneration or necrosis,lymphadenopathy,and contrast enhancement patterns,were associated with risk stratification(P<0.05).According to binary logistic regression analysis,tumor size[P<0.001;odds ratio(OR)=26.448;95%confidence interval(CI):4.854-144.099)],contours(P=0.028;OR=7.750;95%CI:1.253-47.955),and mixed growth pattern(P=0.046;OR=4.740;95%CI:1.029-21.828)were independent predictors for risk stratification of gastric GISTs.ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919(95%CI:0.863-0.975)and 0.940(95%CI:0.893-0.986),respectively.The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm,and the sensitivity and specificity were 93.5%and 84.2%,respectively.CONCLUSION CT features,including tumor size,growth patterns,and lesion contours,were predictors of malignant potential for primary gastric GISTs.
基金Supported by Beijing Hospitals Authority Ascent Plan,No.20191103Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support,No.ZYLX201803+1 种基金Beijing Natural Science Foundation,No.Z180001 and No.Z200015PKU-Baidu Fund,No.2020BD027.
文摘BACKGROUND The use of endoscopic surgery for treating gastrointestinal stromal tumors(GISTs)between 2 and 5 cm remains controversial considering the potential risk of metastasis and recurrence.Also,surgeons are facing great difficulties and challenges in assessing the malignant potential of 2-5 cm gastric GISTs.AIM To develop and evaluate computerized tomography(CT)-based radiomics for predicting the malignant potential of primary 2-5 cm gastric GISTs.METHODS A total of 103 patients with pathologically confirmed gastric GISTs between 2 and 5 cm were enrolled.The malignant potential was categorized into low grade and high grade according to postoperative pathology results.Preoperative CT images were reviewed by two radiologists.A radiological model was constructed by CT findings and clinical characteristics using logistic regression.Radiomic features were extracted from preoperative contrast-enhanced CT images in the arterial phase.The XGboost method was used to construct a radiomics model for the prediction of malignant potential.Nomogram was established by combing the radiomics score with CT findings.All of the models were developed in a training group(n=69)and evaluated in a test group(n=34).RESULTS The area under the curve(AUC)value of the radiological,radiomics,and nomogram models was 0.753(95%confidence interval[CI]:0.597-0.909),0.919(95%CI:0.828-1.000),and 0.916(95%CI:0.801-1.000)in the training group vs 0.642(95%CI:0.379-0.870),0.881(95%CI:0.772-0.990),and 0.894(95%CI:0.773-1.000)in the test group,respectively.The AUC of the nomogram model was significantly larger than that of the radiological model in both the training group(Z=2.795,P=0.0052)and test group(Z=2.785,P=0.0054).The decision curve of analysis showed that the nomogram model produced increased benefit across the entire risk threshold range.CONCLUSION Radiomics may be an effective tool to predict the malignant potential of 2-5 cm gastric GISTs and assist preoperative clinical decision making.
文摘Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.
文摘AIM To determine the feasibility,safety,and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors(GISTs)based on favorable or unfavorable location.METHODS Our hospital database included 207 patients who underwent laparoscopic removal of gastric GISTs from January 2004 to September 2015.Patient demographics,clinical presentation,surgery,histopathology,postoperative course,and oncological outcomes were reviewed and analyzed.RESULTS Gastric GIST in favorable locations was present in81/207(39.1%)cases,and in unfavorable locations in 126/207(60.9%)cases.Overall mean tumor size was 3.28±1.82 cm.No conversions occurred,and complete R0 resection was achieved in 207(100%)cases.There were three incidences of iatrogenic tumor rupture.The feasibility and safety of laparoscopic surgery were comparable in both groups with no statistical difference between unfavorable and favorable location groups,respectively:for operative time:83.86±44.41 vs 80.77±36.46 min,P=0.627;conversion rate:0%vs 0%;estimated blood loss:27.74±45.2vs 29.59±41.18 m L,P=0.780;tumor rupture during surgery:0.90%vs 2.82%,P=0.322;or postoperative complications:3.74%vs 7.04%,P=0.325.The follow-up period recurrence rate was 1.89%with no significant differences between the two groups(3.03%vs 0%,P=0.447).Overall 5-year survival rate was98.76%and survival rates were similar between the two groups:98.99%vs 98.39%,P=0.623(unfavorable vs favorable,respectively).CONCLUSION The laparoscopic approach for gastric GISTs is safe and feasible with well-accepted oncological surgical outcomes.Strategies for laparoscopic resection should be selected according to the location and size of the tumor.Laparoscopic treatment of gastric GISTs in unfavorable locations should not be restricted in gastrointestinal centers.
文摘AIM:To report our experience of gastrointestinal stromal tumors (GISTs) during the last 29 years. METHODS:Thirty two cases of GIST referred to our Institution from the 1st January 1981 to the 10th June 2010 were reviewed. Metastases,recurrence and survival data were collected in relation to age,history,clinical presentation,location,size,resection margins and cellular features. RESULTS:Mean age was 63.7 years (range,40-90) and incidence was slightly higher in males (56%). R0 resection was performed in 90.7% of cases,R1 in 6.2% (2 cases) and R2 in 3.1% (one case). Using Fletcher's classification 8/32 (25%) had high risk,9/32 (28%) intermediate and 15/32 (47%) low risk tumors. Follow-up varied from 1 mo to 29 years,with a median of 8 years; overall survival was 75% (24/32),disease-free survival was 72% and tumor-related mortality was 9.3%. Three patients with high risk GIST were treated with imatinib mesylate:one developed a recurrence after 36 mo,and 2 are free from disease at 41 mo. CONCLUSION:Surgical treatment remains the gold standard therapy for resectable GISTs. Pathological and biological features of the neoplasm represent the most important factors predicting the prognosis.
文摘AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.
文摘AIM: To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography (DSA) for bleeding small bowel gastrointestinal stromal tumors (GISTs).
文摘Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract and are thought to arise from precursors of the interstitial cells of Cajal.GISTs can arise anywhere in the GI tract,but most commonly originate from the stomach and small intestine.The majority of GISTs occur as a result of activating mutations in two receptor protein tyrosine kinases:KIT and/or platelet-derived growth factor receptor-α.Mutational analyses allow for predicting patient prognosis and treatment response.Clinical presentations can vary from no symptoms,typical in the case of small incidentally found tumors,to GI bleeding,abdominal discomfort,and ulcer-related symptoms when the tumor is enlarged.Imaging plays a critical role in the diagnosis and management of these tumors with multiphasic computed tomography serving as the imaging modality of choice.Magnetic resonance imaging and positron emission tomography-computed tomography can serve as imaging adjuncts in lesion characterization,especially with liver metastases,and subsequent staging and assessment for treatment response or recurrence.Surgical resection is the preferred management for small GISTs,while tyrosine kinase inhibitors−imatinib mesylate and sunitinib malate−serve as crucial molecular-targeted therapies for locally advanced and metastatic GISTs.This review article highlights the clinical presentation,pathology and molecular cytogenetics,imaging features,and current management of GISTs.
文摘AIM： To review clinical and pathologic features of Gastrointestinal strornal tumors （GISTs） occurring synchronously with other primary gastrointestinal neoplasms. METHODS： 28 patients with primary GIST were treated at our institution between 1989 and 2005. Clinical and pathologic records were reviewed. RESULTS： The gastrointestinal stromal tumor occurred simultaneously with other primary GI malignancies in 14% of all patients with GIST. The synchronous stromal tumors were located in the stomach and were incidentally found during the operation. The coexistent neoplasms were colon adenocarcinoma, gastric cancer （2 cases） and gastric lymphoma. CONCLUSION： The synchronous occurrence of GISTs and other gastrointestinal malignancies is more common than it has been considered. The development of gastrointestinal stromal tumors and other neoplasms may involve the same carcinogenic agents.
文摘AIM:To perform a meta-analysis to derive a more precise estimation of imatinib treatment for different genotypes of gastrointestinal stromal tumors(GIST).METHODS:Studies were identified by searching PubMed and Embase.Inclusive criteria were patients with exon 9-mutant,exon 11-mutant or wide type(WT) GIST,receiving chemotherapy of imatinib for clinical trial,and efficacy evaluation was cumulative response (CR)including complete response and partial response.The odds ratios(OR)for CR in stem cell factor receptor (KIT)mutation patients vs WT genotype patients,KIT exon 11-mutant genotype patients vs KIT exon 9-mutant genotype patients and KIT exon 9-mutant genotype patients vs WT genotype patients were calculated with 95%confidence interval(CI)for each study as an estimation of the efficacy of imatinib.RESULTS:Five studies including 927 patients were involved in this meta-analysis.The overall OR(KIT group vs WT group)was 3.34(95%CI:2.30-4.86,P <0.00001,P heterogeneity=0.04).The overall OR in KIT exon 11 group vs KIT exon 9 group was 3.29(95%CI: 2.17-5.00,P<0.00001,P heterogeneity=0.33).The overall OR in KIT exon 9 group vs WT group was 1.23(95% CI:0.73-2.10,P=0.44,P heterogeneity=0.42).CONCLUSION:Most patients with different genotypes of GIST and KIT exon 11-mutant will benefit from the individualized treatment of imatinib.
文摘Gastrointestinal stromal tumors(GISTs)are uncommon neoplasms of the gastrointestinal tract with peculiar clinical,genetic,and imaging characteristics.Preoperative knowledge of risk stratification and mutational status is crucial to guide the appropriate patients’treatment.Predicting the clinical behavior and biological aggressiveness of GISTs based on conventional computed tomography(CT)and magnetic resonance imaging(MRI)evaluation is challenging,unless the lesions have already metastasized at the time of diagnosis.Radiomics is emerging as a promising tool for the quantification of lesion heterogeneity on radiological images,extracting additional data that cannot be assessed by visual analysis.Radiomics applications have been explored for the differential diagnosis of GISTs from other gastrointestinal neoplasms,risk stratification and prediction of prognosis after surgical resection,and evaluation of mutational status in GISTs.The published researches on GISTs radiomics have obtained excellent performance of derived radiomics models on CT and MRI.However,lack of standardization and differences in study methodology challenge the application of radiomics in clinical practice.The purpose of this review is to describe the new advances of radiomics applied to CT and MRI for the evaluation of gastrointestinal stromal tumors,discuss the potential clinical applications that may impact patients’management,report limitations of current radiomics studies,and future directions.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST,which eventually develops into recurrence and acquired drug resistance.Therefore,it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs.CC chemokine receptor type 8(CCR8)protein participates in regulation of immune responses.Recent studies on CCR8 in nonsmall cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis.AIM To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs.METHODS Tissue samples were used for the tissue microarrays construction.The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression.Next,Kaplan–Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data,and the potential prognostic value of CCR8 was evaluated by Cox regression analysis.Finally,a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database.RESULTS CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm.Among 125 tissue samples,74 had CCR8 high expression and 51 had low or negative expression.Statistical analyses suggested CCR8 was significantly correlated with tumor size,mitotic index,AFIP-Miettinen risk classification and tumor location.Kaplan–Meier and multivariate analyses showed that patients with low or negative CCR8 expression,mitotic index<5/high-power fields(HPF)and tumor diameter<5 cm had a better prognosis.Based on the STRING database,CCR8 was significantly enriched in biological processes such as tumor immunity,T lymphocyte chemotaxis,migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks.CONCLUSION CCR8 is a prognostic biomarker for malignant potential of GISTs,with high expression correlated with malignancy and poor prognosis.
