BACKGROUND Hepatic hemangiomas can be challenging to diagnose,particularly when they present with atypical features that mimic other conditions,such as gastrointestinal stromal tumors(GISTs).This case highlights the d...BACKGROUND Hepatic hemangiomas can be challenging to diagnose,particularly when they present with atypical features that mimic other conditions,such as gastrointestinal stromal tumors(GISTs).This case highlights the diagnostic difficulties encountered when imaging subepithelial lesions,especially when conventional methods such as computed tomography(CT)and endoscopic ultrasound(EUS)are used.CASE SUMMARY A 44-year-old woman presented with intermittent abdominal distension and heartburn for three months.Her medical history included iron deficiency anemia,menorrhagia,and previous cholecystectomy.One week prior to admission,an endoscopy suggested a bulging gastric fundus,which was likely a GIST,along with chronic nonatrophic gastritis and bile reflux.CT and EUS revealed nodules in the gastric fundus,which were initially considered benign tumors with a differential diagnosis of stromal tumor or leiomyoma.During surgery,unexpected lesions were found in the liver pressing against the gastric fundus,leading to laparoscopic liver resection.Postoperative pathology confirmed the diagnosis of hepatic cavernous hemangiomas.The patient recovered well and was discharged five days later,with normal follow-up results at three months.CONCLUSION This case underscores the challenges in the preoperative diagnosis of GISTs,particularly the limitations of the use of CT and EUS for the evaluation of subepithelial lesions.While CT is the primary tool for visualizing abdominal tumors,it is difficult to detect smaller lesions and assess the layers of the gastrointestinal wall on CT.EUS is recommended for the evaluation of nodules smaller than 2 cm and is useful for distinguishing GISTs from other lesions;however,its accuracy with regard to the differential diagnosis is relatively low.In this case,the gastric distension observed on imaging led to the compression of a liver tumor against the stomach,resulting in the misinterpretation of the tumor as a gastric wall lesion.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 There are currently no relevant studies at home or abroad that combine inflammatory indicators and nomograms to predict the prognosis of gastrointestinal stromal tumor(GIST)patients after surgery.The purpos...BACKGROUND There are currently no relevant studies at home or abroad that combine inflammatory indicators and nomograms to predict the prognosis of gastrointestinal stromal tumor(GIST)patients after surgery.The purpose of this study was to investigate the predictive value of related inflammatory indicators[systemic immune-inflammation index(SII),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and monocyte/Lymphocyte ratio(MLR)]in patients undergoing GIST surgery,incorporating relevant risk factors to establish a nomogram prediction model,with the aim of better predicting the prognosis of GIST patients.AIM To explore the relationships between the SII,NLR,PLR,and MLR and postoperative recurrence in patients with GIST.METHODS This study retrospectively included patients who underwent GIST surgery from January 2014 to January 2017 and analyzed the potential relationships between the preoperative SII,NLR,PLR,and MLR and clinicopathological features.The independent risk factors influencing the prognosis of GIST patients were obtained via multivariate regression analysis,and a nomogram model based on the independent risk factors was established.RESULTS Among the 124 GIST patients included in the present study,31(25%)experienced recurrence within 5 years.Kaplan-Meier survival analysis revealed a correlation between the MLR and PLR and tumor size(P=0.016 and P=0.002,respectively).The preoperative SII,MLR,NLR,and PLR were significantly associated with recurrence-free survival(RFS)(P<0.05).The multivariate analysis results identified the PLR,MLR,and targeted therapy as independent prognostic factors for patient outcomes.CONCLUSION Preoperative MLR and PLR,which are independent risk factors for GIST recurrence,were correlated with RFS.Nomograms based on the PLR,MLR and targeted therapy can be used for clinical treatment.展开更多
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(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
BACKGROUND Endoscopic resection(ER)and laparoscopic resection(LR)have been widely used for the treatment of non-metastatic gastric gastrointestinal stromal tumors(gGISTs)(2-5 cm),but there are no selection criteria fo...BACKGROUND Endoscopic resection(ER)and laparoscopic resection(LR)have been widely used for the treatment of non-metastatic gastric gastrointestinal stromal tumors(gGISTs)(2-5 cm),but there are no selection criteria for their application.AIM To provide a reference for the development of standardized treatment strategies for gGISTs.METHODS Clinical baseline characteristics,histopathological results,and short-term and long-term outcomes of patients who treated with ER or LR for gGISTs of 2-5 cm in Taizhou Hospital of Zhejiang Province from January 2014 to August 2022 were retrospectively reviewed.Propensity score matching(PSM)was employed to achieve balance in baseline characteristics of the two groups.RESULTS Among 206 patients,135 were in the ER group and 71 in the LR group.The ER group had significantly smaller tumors[3.5 cm(3.0-4.0 cm)vs 4.2 cm(3.3-5.0 cm),P<0.001]and different tumor locations(P=0.048).After PSM,59 pairs of patients were balanced.After matching,the baseline characteristics of the ER and LR groups did not differ significantly from each other.Compared with LR,ER had faster recovery of diet(P=0.046)and fewer postoperative symptoms(P=0.040).LR achieved a higher complete resection rate(P<0.001)and shorter operation time(P<0.001).No significant differences were observed in postoperative hospital stay(P=0.478),hospital costs(P=0.469),complication rates(P>0.999),pathological features(mitosis,P=0.262;National Institutes of Health risk classification,P=0.145),recurrence rates(P=0.476),or mortality rates(P=0.611).CONCLUSION Both ER and LR are safe and effective treatments for gGISTs.ER has less postoperative pain and faster recovery,while LR has a higher rate of complete resection.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
AIM:To investigate computed tomography(CT) and magnetic resonance imaging(MRI) manifestations of rectal gastrointestinal stromal tumors(GISTs) in order to enhance the recognition of these rare tumors.METHODS:Fourteen ...AIM:To investigate computed tomography(CT) and magnetic resonance imaging(MRI) manifestations of rectal gastrointestinal stromal tumors(GISTs) in order to enhance the recognition of these rare tumors.METHODS:Fourteen patients with pathologically proven rectal GISTs were retrospectively reviewed.Patient histories were retrospectively reviewed for patient age,gender,presenting symptoms,endoscopic investigations,operation notes and pathologic slides.All tumors were evaluated for CD117,CD34 expression,and the tumors were stratified according to current criteria of the National Institutes of Health(NIH).In all cases the first pre-operation imaging findings(CT and MRI,n = 3;MRI only,n = 8;CT only,n = 3) were analyzed by two experienced radiologists by consensus,which include:tumor size,shape,CT density(hypodense,isodense and hyperdense),MRI signal intensity(hypointense,isointense and hyperintense),epicenter(intraluminal or extraluminal),margin(well-defined or ill-defined),internal component(presence of calcifications,necrosis,hemorrhage or ulceration),pattern and degree of enhancement,invasion into adjacent structures.After review of the radiologic studies,clinical and pathological findings were correlated with radiological findings.RESULTS:The patients,13 men and 1 woman,were aged 31-62 years(mean = 51.5 ± 10.7 years).The most common initial presentation was hematochezia(n = 6).The mean tumor diameter was 5.68 ± 2.64 cm(range 1.5-11.2 cm).Eight lesions were round or oval,and 6 lesions were irregular.Eleven lesions were welldefined and 3 had ill-defined margins.Ten tumors were extraluminal and 4 were intraluminal.The density and MR signal intensity of the solid component of the lesions were similar to that of muscle on unenhanced CT(n = 6) and T1-weighted images(n = 11),and hyperintense on T2-weighted MR images.Calcification was detected in 2 tumors.Following intravenous injection of contrast media,3 lesions had mild enhancement and 11 lesions had moderate enhancement.Enhancement was homogenous in 3 lesions and heterogeneous in 11.In 1 of 11 patients who underwent both CT and MRI,the tumor was homogenous on CT scan and heterogeneous on MRI.Eight patients were classified as high risk according to the modified recurrent risk classification system of NIH.CONCLUSION:Rectal GISTs usually manifest as large,well-circumscribed,exophytic masses with moderate and heterogeneous enhancement on CT and MRI.The invasion of adjacent organs,bowel obstruction and local adenopathy are uncommon.展开更多
Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority o...Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.展开更多
Molecularly targeted agents have dramatically impacted the management of several cancers. Targeting KIT has led to a new treatment paradigm in gastrointestinal stromal tumors (GISTs). KIT is a cell surface receptor wi...Molecularly targeted agents have dramatically impacted the management of several cancers. Targeting KIT has led to a new treatment paradigm in gastrointestinal stromal tumors (GISTs). KIT is a cell surface receptor with tyrosine kinases that, upon binding of its ligand, stem cell factor, activates various signaling pathways. Imatinib and sunitinib, both tyrosine kinase inhibitors directed to KIT, were approved for firstand secondline treatment of metastatic and unresectable GISTs. In this article, we will review the molecular pathogenesis of GISTs followed by a discussion of imatinib and sunitinib’s role in the treatment of GISTs. Finally, we will introduce novel therapeutic options for imatiniband sunitinib-resistant GISTs.展开更多
AIM: To evaluate the feasibility and safety of a new style of laparoscopic and endoscopic cooperative surgery (LECS), an improved method of laparoscopic intragastric surgery (LIGS) for the treatment of gastric stromal...AIM: To evaluate the feasibility and safety of a new style of laparoscopic and endoscopic cooperative surgery (LECS), an improved method of laparoscopic intragastric surgery (LIGS) for the treatment of gastric stromal tumors (GSTs). METHODS: Six patients were treated with the newstyle LECS. Surgery was performed according to the following procedures: (1) Exposing and confirming the location of the tumor with gastroscopy; (2) A laparoscopy light was placed in the cavity using the trocar at the navel, and the other two trocars penetrated both the abdominal and stomach walls; (3) With gastroscopy monitoring, the operation was carried out in the gastric lumen using laparoscopic instruments and the tumor was resected; and (4) The tumor tissue was removed orally using a gastroscopy basket, and puncture holes and perforations were sutured using titanium clips. RESULTS: Tumor size ranged from 2.0 to 4.5 cm (average 3.50 ± 0.84 cm). The operative time ranged from 60 to 130 min (average 83.33 ± 26.58 min). Blood loss was less than 20 mL and hospital stay ranged from 6 to 8 d (average 6.67 ± 0.82 d). The patients were allowed out of bed 12 h later. A stomach tube was inserted for 72 h after surgery, and a liquid diet was then taken. All cases had single tumors which were completely resected using the new-style LECS. No postoperative complications occurred. Pathology of all resected specimens showed GST: no cases of implantation or metastasis were found.CONCLUSION: New-style LECS for GSTs is a quick, optimized, fast recovery, safe and effective therapy.展开更多
AIM:To investigate primarily the prognostic value of Ki-67,as well as other parameters,in gastrointestinal stromal tumors(GISTs).METHODS:Ki-67,c-KIT,platelet-derived growth factor receptor-alpha(PDGFRα),smooth muscle...AIM:To investigate primarily the prognostic value of Ki-67,as well as other parameters,in gastrointestinal stromal tumors(GISTs).METHODS:Ki-67,c-KIT,platelet-derived growth factor receptor-alpha(PDGFRα),smooth muscle actin(SMA),CD34,S100 were stained for immunohistochemistry which was performed on formalin-fixed,paraffinembeded sections on representative block from each case.Proliferation index counted by Ki-67 antibody was calculated as a number of positive nuclear reaction over 100 cells.Immunoreactivity for c-KIT and PDGFRα was evaluated semiquantitatively(weak,intermediate,strong) and for c-KIT type of reactivity was analyzed(cytoplasmic,membrane and "dot-like" staining).Immunoreactivity for SMA,CD34 and S100 were was evaluated as positive or negative antigen expression.Pathologic parameters investigated in this study included tumor size,cell type(pure spindle,pured epitheloid mixed spindle and epitheloid),mitotic count,hemorrhage,necrosis,mucosal ulceration.Clinical data included age,gender,primary tumor location and spread of disease.χ 2 test and Student's t-test were used for comparisons of baseline characteristics.The Cox's proportional hazard model was used for univariable and multivariable analyses.Survival rates were calculated by Kaplan-Meier method and statistical significance was determined by the log-rank test.RESULTS:According to the stage of disease,there were 36 patients with localized disease,29 patients with initially localized disease but with its recurrence in the period of follow up,and finally,35 patients had metastatic disease from the very beginning of disease.Tumor originated most commonly in the stomach(41%),small intestine was the second most common location(36%).The mean size of primary tumors was 6.5 cm.The mean duration of follow-up was 60 mo.Multiple parameters were analyzed for their effect on overall survival,but no one reached statistical significance(P = 0.06).Analysis of time to progression/relapse in initially localized disease(univariate analysis),tumor size,mitotic count,Ki-67 and type of d-KIT distribution(cytoplasmic vs membrane/"dot-like") showed statistically significant correlation.In multivariate analysis in the group of patients with localized disease,there were only 2 parameters that have impact on relapse,Ki-67 and SMA(P < 0.0001 and P < 0.034,respectively).Furthermore,Ki-67 was analyzed in localized diseasevs localized with recurrence and metastatic disease.It was shown that there is a strict difference between these 2 groups of patients(median value was 2.5 for localized disease vs 10.0 for recurrent/metastatic disease,P < 0.0001).It was also shown that the cut-off value which is still statistically significant in terms of relapse on the level of 6%.The curves for survival on that cut-off level are significantly different(P < 0.04,Cox F).CONCLUSION:Ki-67 presents a significant prognostic factor for GIST recurrence which could be of great importance in evaluating malignant potential of disease.展开更多
Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal malignancies. They are rarely seen near the urinary tract. In a literature review, only one case of GIST presenting as a left adrenal tumor was reporte...Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal malignancies. They are rarely seen near the urinary tract. In a literature review, only one case of GIST presenting as a left adrenal tumor was reported. We report two documented cases of gastric GISTs mimicking left adrenal tumors which were successfully treated with pure laparoscopic adrenalectomy and wedge resection of the stomach by excising the tumor from the stomach with serial fi ring of endoscopic gastrointestinal staplers. The surgical margins were clear, and the patients recovered smoothly. No adjuvant therapy with imatinib was prescribed. During the surveillance for 9 mo and 44 mo respectively, no tumor recurrence and metastasis were documented. Laparoscopic tumor excision, when adhering to the principles of surgical oncology, seems feasible and the prognosisis favorable for such tumors.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 evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestina...AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestinal stromal tumors(GIST).METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin(CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density(IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF,Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5%positive cells. The prognosis was classified as good(patient alive without recurrence) or poor(patient with recurrence/death).RESULTS: The distribution of tumor sites among the54 analyzed samples was as follows: 27(50%) in the stomach, 20(37.1%) in the small intestine, 6(11.1%)in the colon, and 1(1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm(median: 8cm); in 12 cases(22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases(77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis(P < 0.001). The cut-off values of CD105(>1.2%) and CD31(> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis.Cases with a better prognosis showed significantly null/weak staining for VEGF(P < 0.001). Ki-67 expression of≥ 5% was strongly correlated with a worse prognosis(P< 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.展开更多
AIM:To investigate the feasibility and safety of the treatment of an upper gastrointestinal(GI) submucosal tumor with endoscopic submucosal dissection(ESD).METHODS:A total of 20 patients with esophageal and gastric su...AIM:To investigate the feasibility and safety of the treatment of an upper gastrointestinal(GI) submucosal tumor with endoscopic submucosal dissection(ESD).METHODS:A total of 20 patients with esophageal and gastric submucosal tumors emerged from the muscular layer identified by endoscopic ultrasonography were collected from January 2009 to June 2010.Extramural or dumbbell-like lesions were excluded by an enhanced computerized tomography(CT) scan.All patients had intravenous anesthesia with propofol and then underwent the ESD procedure to resect these submucosal tumors.The incision was closed by clips as much as possible to decrease complications,such as bleeding or perforation,after resection of the tumor.All the specimens were collected and evaluated by hematoxylin,eosin and immunohistochemical staining,with antibodies against CD117,CD34,desmin,α-smooth muscle actin and vimentin to identify the characteristics of the tumors.Fletch's criteria was used to evaluate the risk of gastrointestinal stromal tumors(GISTs).All patients underwent a follow-up endoscopy at 3,6 and 12 mo and CT scan at 6 and 12 mo.RESULTS:The study group consisted of 5 men and 15 women aged 45-73 years,with a mean age of 60.2 years.Three tumors were located in the esophagus,9 in the gastric corpus,4 in the gastric fundus,3 lesions in the gastric antrum and 1 in the gastric angulus.Apart from the one case in the gastric angulus which was abandoned due to being deeply located in the serosa,94.7%(18/19) achieved complete gross dissection by ESD with operation duration of 60.52±30.32 min.The average maximum diameter of tumor was 14.8±7.6 mm,with a range of 6 to 30 mm,and another lesion was ligated by an endoscopic ligator after most of the lesion was dissected.After pathological and immunohistochemical analysis,12 tumors were identified as a GI stromal tumor and 6 were leiomyoma.Mitotic count of all 12 GIST lesions was fewer than 5 per 50 HPF and all lesions were at very low(9/12,75.0%) or low risk(3/12,25.0%) according to Fletch's criteria.Procedure complications mainly included perforation and GI bleeding;perforation occurred in 1 patient and conservative treatment succeeded by a suturing clip and no post-operative GI bleeding occurred.All patients were followed up for 6.5±1.8 mo(range,3-12 mo) by endoscopy and abdominal CT.Local recurrence and metastasis did not occur in any patient.CONCLUSION:ESD shows promise as a safe and feasible technique to resect esophageal and gastric submucosal tumors and the incidence of complications was very low.Clinical studies with more subjects and longer follow-up are needed to confirm its treatment value.展开更多
AIM:To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors(EGISTs)in South Korea.METHODS:A total of 51 patients with an EGIST were identified.The clinicopathologic feature...AIM:To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors(EGISTs)in South Korea.METHODS:A total of 51 patients with an EGIST were identified.The clinicopathologic features,including sex,age,location,tumor size,histology,mitotic rate,immunohistochemical features,genetic status and survival data,were analyzed.RESULTS:The median age was 55 years(range:29-80years),and male:female ratio was 1:1.04.The most common site was in the mesentery(n=15)followed by the retroperitoneum(n=13)and omentum(n=8).The median tumor size was 9.0 cm(range:2.6-30.0cm)and the median mitotic rate was 5.0/50HPF.(1/50-185/50).KIT was analyzed in 16,which revealed 10cases with wild-type KIT and 6 cases with an exon 11mutation.Among 51 patients,31 patients had undergone surgery,and 10 had unresectable disease and had taken palliative imatinib,which resulted in 22.7 mo of progression-free survival.Of the patients who had undergone surgery,18 did not take adjuvant imatinib,and 8 of these were categorized as"high risk"according to the risk criteria.However,the relapse-free survival was not different(P=0.157)between two groups.CONCLUSION:Because the biologic behaviors of GISTs differ according to the location of the tumor,a more stratified strategy is required for managing EGISTs including incorporation of molecular features.展开更多
Most gastrointestinal stromal tumors(GISTs)are characterized by KIT or platelet-derived growth factor alpha(PDGFRA)activating mutations.However,there are still 10%-15%of GISTs lacking KIT and PDGFRA mutations,called w...Most gastrointestinal stromal tumors(GISTs)are characterized by KIT or platelet-derived growth factor alpha(PDGFRA)activating mutations.However,there are still 10%-15%of GISTs lacking KIT and PDGFRA mutations,called wild-type GISTs(WT GISTs).Among these so-called WT GISTs,a small subset is associated with succinate dehydrogenase(SDH)deficiency,known as SDH-deficient GISTs.In addition,GISTs that occur in Carney triad and Carney-Stratakis syndromerepresent specific examples of SDH-deficient GISTs.SDH-deficient GISTs locate exclusively in the stomach,showing predilection for children and young adults with female preponderance.The tumor generally pursues an indolent course and exhibits primary resistance to imatinib therapy in most cases.Loss of succinate dehydrogenase subunit B expression and overexpression of insulin-like growth factor 1 receptor(IGF1R)are common features of SDH-deficient GISTs.In WT GISTs without succinate dehydrogenase activity,upregulation of hypoxia-inducible factor 1αmay lead to increased growth signaling through IGF1R and vascular endothelial growth factor receptor(VEGFR).As a result,IGF1R and VEGFR are promising to be the novel therapeutic targets of GISTs.This review will update the current knowledge on characteristics of SDH-deficient GISTs and further discuss the possible mechanisms of tumorigenesis and clinical management of SDH-deficient GISTs.展开更多
AIM:To analyze our experience in patients with duodenal gastrointestinal stromal tumors(GIST) and review the appropriate surgical approach.METHODS:We retrospectively reviewed the medical records of all patients with d...AIM:To analyze our experience in patients with duodenal gastrointestinal stromal tumors(GIST) and review the appropriate surgical approach.METHODS:We retrospectively reviewed the medical records of all patients with duodenal GIST surgically treated at our medical institution between 2002 and 2011.Patient files,operative reports,radiological charts and pathology were analyzed.For surgical therapy open and laparoscopic wedge resections and segmental resections were performed for limited resection(LR).For extended resection pancreatoduodenectomy was performed.Age,gender,clinical symptoms of the tumor,anatomical localization,tumor size,mitotic count,type of resection resectional status,neoadjuvant therapy,adjuvant therapy,risk classification and follow-up details were investigated in this retrospective study.RESULTS:Nine patients(5 males/4 females) with a median age of 58 years were surgically treated.The median follow-up period was 45 mo(range 6-111 mo).The initial symptom in 6 of 9 patients was gastrointestinal bleeding(67%).Tumors were found in all four parts of the duodenum,but were predominantly located in the first and second part of the duodenum with each 3 of 9 patients(33%).Two patients received neoadjuvant medical treatment with 400 mg imatinib per day for 12 wk before resection.In one patient,the GIST resection was done by pancreatoduodenectomy.The 8 LRs included a segmental resection of pars 4 of the duodenum,5 wedge resections with primary closure and a wedge resection with luminal closure by Roux-Y duodeno-jejunostomy.One of these LRs was done minimally invasive;seven were done in open fashion.The median diameter of the tumors was 54 mm(14-110 mm).Using the Fletcher classification scheme,3/9(33%) tumors had high risk,1/9(11%) had intermediate risk,4/9(44%) had low risk,and 1/9(11%) had very low risk for aggressive behaviour.Seven resections showed microscopically negative transsection margins(R0),two showed positive margins(R1).No patient developed local recurrence during follow-up.The one patient who underwent pancreatoduodenectomy died due to progressive disease with hepatic metastasis but without evidence of local recurrence.Another patient died in complete remission due to cardiac disease.Seven of the nine patients are alive disease-free.CONCLUSION:In patients with duodenal GIST,limited surgical resection with microscopically negative margins,but also with microscopically positive margins,lead to very good local and systemic disease-free survival.展开更多
基金Supported by the Natural Science Foundation of Gansu Province,No.24JRRA347.
文摘BACKGROUND Hepatic hemangiomas can be challenging to diagnose,particularly when they present with atypical features that mimic other conditions,such as gastrointestinal stromal tumors(GISTs).This case highlights the diagnostic difficulties encountered when imaging subepithelial lesions,especially when conventional methods such as computed tomography(CT)and endoscopic ultrasound(EUS)are used.CASE SUMMARY A 44-year-old woman presented with intermittent abdominal distension and heartburn for three months.Her medical history included iron deficiency anemia,menorrhagia,and previous cholecystectomy.One week prior to admission,an endoscopy suggested a bulging gastric fundus,which was likely a GIST,along with chronic nonatrophic gastritis and bile reflux.CT and EUS revealed nodules in the gastric fundus,which were initially considered benign tumors with a differential diagnosis of stromal tumor or leiomyoma.During surgery,unexpected lesions were found in the liver pressing against the gastric fundus,leading to laparoscopic liver resection.Postoperative pathology confirmed the diagnosis of hepatic cavernous hemangiomas.The patient recovered well and was discharged five days later,with normal follow-up results at three months.CONCLUSION This case underscores the challenges in the preoperative diagnosis of GISTs,particularly the limitations of the use of CT and EUS for the evaluation of subepithelial lesions.While CT is the primary tool for visualizing abdominal tumors,it is difficult to detect smaller lesions and assess the layers of the gastrointestinal wall on CT.EUS is recommended for the evaluation of nodules smaller than 2 cm and is useful for distinguishing GISTs from other lesions;however,its accuracy with regard to the differential diagnosis is relatively low.In this case,the gastric distension observed on imaging led to the compression of a liver tumor against the stomach,resulting in the misinterpretation of the tumor as a gastric wall lesion.
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 Chengdu Municipal Science and Technology Program,No.2023097.
文摘BACKGROUND There are currently no relevant studies at home or abroad that combine inflammatory indicators and nomograms to predict the prognosis of gastrointestinal stromal tumor(GIST)patients after surgery.The purpose of this study was to investigate the predictive value of related inflammatory indicators[systemic immune-inflammation index(SII),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and monocyte/Lymphocyte ratio(MLR)]in patients undergoing GIST surgery,incorporating relevant risk factors to establish a nomogram prediction model,with the aim of better predicting the prognosis of GIST patients.AIM To explore the relationships between the SII,NLR,PLR,and MLR and postoperative recurrence in patients with GIST.METHODS This study retrospectively included patients who underwent GIST surgery from January 2014 to January 2017 and analyzed the potential relationships between the preoperative SII,NLR,PLR,and MLR and clinicopathological features.The independent risk factors influencing the prognosis of GIST patients were obtained via multivariate regression analysis,and a nomogram model based on the independent risk factors was established.RESULTS Among the 124 GIST patients included in the present study,31(25%)experienced recurrence within 5 years.Kaplan-Meier survival analysis revealed a correlation between the MLR and PLR and tumor size(P=0.016 and P=0.002,respectively).The preoperative SII,MLR,NLR,and PLR were significantly associated with recurrence-free survival(RFS)(P<0.05).The multivariate analysis results identified the PLR,MLR,and targeted therapy as independent prognostic factors for patient outcomes.CONCLUSION Preoperative MLR and PLR,which are independent risk factors for GIST recurrence,were correlated with RFS.Nomograms based on the PLR,MLR and targeted therapy can be used for clinical treatment.
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 The Medical Science and Technology Project of Zhejiang Province,China,No.2024KY1792The Health Science and Technology Program of Zhejiang Province,China,No.22PY101+2 种基金The Program of Taizhou Science and Technology Grant,China,No.22ywb08 and No.22ywb09The Scientific Research Fund Program of Enze Medical Center,China,No.22EZB12 and No.22EZC17The Open Fund of Key Laboratory of Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province,China,No.21SZDSYS15.
文摘BACKGROUND Endoscopic resection(ER)and laparoscopic resection(LR)have been widely used for the treatment of non-metastatic gastric gastrointestinal stromal tumors(gGISTs)(2-5 cm),but there are no selection criteria for their application.AIM To provide a reference for the development of standardized treatment strategies for gGISTs.METHODS Clinical baseline characteristics,histopathological results,and short-term and long-term outcomes of patients who treated with ER or LR for gGISTs of 2-5 cm in Taizhou Hospital of Zhejiang Province from January 2014 to August 2022 were retrospectively reviewed.Propensity score matching(PSM)was employed to achieve balance in baseline characteristics of the two groups.RESULTS Among 206 patients,135 were in the ER group and 71 in the LR group.The ER group had significantly smaller tumors[3.5 cm(3.0-4.0 cm)vs 4.2 cm(3.3-5.0 cm),P<0.001]and different tumor locations(P=0.048).After PSM,59 pairs of patients were balanced.After matching,the baseline characteristics of the ER and LR groups did not differ significantly from each other.Compared with LR,ER had faster recovery of diet(P=0.046)and fewer postoperative symptoms(P=0.040).LR achieved a higher complete resection rate(P<0.001)and shorter operation time(P<0.001).No significant differences were observed in postoperative hospital stay(P=0.478),hospital costs(P=0.469),complication rates(P>0.999),pathological features(mitosis,P=0.262;National Institutes of Health risk classification,P=0.145),recurrence rates(P=0.476),or mortality rates(P=0.611).CONCLUSION Both ER and LR are safe and effective treatments for gGISTs.ER has less postoperative pain and faster recovery,while LR has a higher rate of complete resection.
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 Key Program of Shanghai Science and Technology Commission,No.09441900500
文摘AIM:To investigate computed tomography(CT) and magnetic resonance imaging(MRI) manifestations of rectal gastrointestinal stromal tumors(GISTs) in order to enhance the recognition of these rare tumors.METHODS:Fourteen patients with pathologically proven rectal GISTs were retrospectively reviewed.Patient histories were retrospectively reviewed for patient age,gender,presenting symptoms,endoscopic investigations,operation notes and pathologic slides.All tumors were evaluated for CD117,CD34 expression,and the tumors were stratified according to current criteria of the National Institutes of Health(NIH).In all cases the first pre-operation imaging findings(CT and MRI,n = 3;MRI only,n = 8;CT only,n = 3) were analyzed by two experienced radiologists by consensus,which include:tumor size,shape,CT density(hypodense,isodense and hyperdense),MRI signal intensity(hypointense,isointense and hyperintense),epicenter(intraluminal or extraluminal),margin(well-defined or ill-defined),internal component(presence of calcifications,necrosis,hemorrhage or ulceration),pattern and degree of enhancement,invasion into adjacent structures.After review of the radiologic studies,clinical and pathological findings were correlated with radiological findings.RESULTS:The patients,13 men and 1 woman,were aged 31-62 years(mean = 51.5 ± 10.7 years).The most common initial presentation was hematochezia(n = 6).The mean tumor diameter was 5.68 ± 2.64 cm(range 1.5-11.2 cm).Eight lesions were round or oval,and 6 lesions were irregular.Eleven lesions were welldefined and 3 had ill-defined margins.Ten tumors were extraluminal and 4 were intraluminal.The density and MR signal intensity of the solid component of the lesions were similar to that of muscle on unenhanced CT(n = 6) and T1-weighted images(n = 11),and hyperintense on T2-weighted MR images.Calcification was detected in 2 tumors.Following intravenous injection of contrast media,3 lesions had mild enhancement and 11 lesions had moderate enhancement.Enhancement was homogenous in 3 lesions and heterogeneous in 11.In 1 of 11 patients who underwent both CT and MRI,the tumor was homogenous on CT scan and heterogeneous on MRI.Eight patients were classified as high risk according to the modified recurrent risk classification system of NIH.CONCLUSION:Rectal GISTs usually manifest as large,well-circumscribed,exophytic masses with moderate and heterogeneous enhancement on CT and MRI.The invasion of adjacent organs,bowel obstruction and local adenopathy are uncommon.
文摘Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.
文摘Molecularly targeted agents have dramatically impacted the management of several cancers. Targeting KIT has led to a new treatment paradigm in gastrointestinal stromal tumors (GISTs). KIT is a cell surface receptor with tyrosine kinases that, upon binding of its ligand, stem cell factor, activates various signaling pathways. Imatinib and sunitinib, both tyrosine kinase inhibitors directed to KIT, were approved for firstand secondline treatment of metastatic and unresectable GISTs. In this article, we will review the molecular pathogenesis of GISTs followed by a discussion of imatinib and sunitinib’s role in the treatment of GISTs. Finally, we will introduce novel therapeutic options for imatiniband sunitinib-resistant GISTs.
文摘AIM: To evaluate the feasibility and safety of a new style of laparoscopic and endoscopic cooperative surgery (LECS), an improved method of laparoscopic intragastric surgery (LIGS) for the treatment of gastric stromal tumors (GSTs). METHODS: Six patients were treated with the newstyle LECS. Surgery was performed according to the following procedures: (1) Exposing and confirming the location of the tumor with gastroscopy; (2) A laparoscopy light was placed in the cavity using the trocar at the navel, and the other two trocars penetrated both the abdominal and stomach walls; (3) With gastroscopy monitoring, the operation was carried out in the gastric lumen using laparoscopic instruments and the tumor was resected; and (4) The tumor tissue was removed orally using a gastroscopy basket, and puncture holes and perforations were sutured using titanium clips. RESULTS: Tumor size ranged from 2.0 to 4.5 cm (average 3.50 ± 0.84 cm). The operative time ranged from 60 to 130 min (average 83.33 ± 26.58 min). Blood loss was less than 20 mL and hospital stay ranged from 6 to 8 d (average 6.67 ± 0.82 d). The patients were allowed out of bed 12 h later. A stomach tube was inserted for 72 h after surgery, and a liquid diet was then taken. All cases had single tumors which were completely resected using the new-style LECS. No postoperative complications occurred. Pathology of all resected specimens showed GST: no cases of implantation or metastasis were found.CONCLUSION: New-style LECS for GSTs is a quick, optimized, fast recovery, safe and effective therapy.
文摘AIM:To investigate primarily the prognostic value of Ki-67,as well as other parameters,in gastrointestinal stromal tumors(GISTs).METHODS:Ki-67,c-KIT,platelet-derived growth factor receptor-alpha(PDGFRα),smooth muscle actin(SMA),CD34,S100 were stained for immunohistochemistry which was performed on formalin-fixed,paraffinembeded sections on representative block from each case.Proliferation index counted by Ki-67 antibody was calculated as a number of positive nuclear reaction over 100 cells.Immunoreactivity for c-KIT and PDGFRα was evaluated semiquantitatively(weak,intermediate,strong) and for c-KIT type of reactivity was analyzed(cytoplasmic,membrane and "dot-like" staining).Immunoreactivity for SMA,CD34 and S100 were was evaluated as positive or negative antigen expression.Pathologic parameters investigated in this study included tumor size,cell type(pure spindle,pured epitheloid mixed spindle and epitheloid),mitotic count,hemorrhage,necrosis,mucosal ulceration.Clinical data included age,gender,primary tumor location and spread of disease.χ 2 test and Student's t-test were used for comparisons of baseline characteristics.The Cox's proportional hazard model was used for univariable and multivariable analyses.Survival rates were calculated by Kaplan-Meier method and statistical significance was determined by the log-rank test.RESULTS:According to the stage of disease,there were 36 patients with localized disease,29 patients with initially localized disease but with its recurrence in the period of follow up,and finally,35 patients had metastatic disease from the very beginning of disease.Tumor originated most commonly in the stomach(41%),small intestine was the second most common location(36%).The mean size of primary tumors was 6.5 cm.The mean duration of follow-up was 60 mo.Multiple parameters were analyzed for their effect on overall survival,but no one reached statistical significance(P = 0.06).Analysis of time to progression/relapse in initially localized disease(univariate analysis),tumor size,mitotic count,Ki-67 and type of d-KIT distribution(cytoplasmic vs membrane/"dot-like") showed statistically significant correlation.In multivariate analysis in the group of patients with localized disease,there were only 2 parameters that have impact on relapse,Ki-67 and SMA(P < 0.0001 and P < 0.034,respectively).Furthermore,Ki-67 was analyzed in localized diseasevs localized with recurrence and metastatic disease.It was shown that there is a strict difference between these 2 groups of patients(median value was 2.5 for localized disease vs 10.0 for recurrent/metastatic disease,P < 0.0001).It was also shown that the cut-off value which is still statistically significant in terms of relapse on the level of 6%.The curves for survival on that cut-off level are significantly different(P < 0.04,Cox F).CONCLUSION:Ki-67 presents a significant prognostic factor for GIST recurrence which could be of great importance in evaluating malignant potential of disease.
文摘Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal malignancies. They are rarely seen near the urinary tract. In a literature review, only one case of GIST presenting as a left adrenal tumor was reported. We report two documented cases of gastric GISTs mimicking left adrenal tumors which were successfully treated with pure laparoscopic adrenalectomy and wedge resection of the stomach by excising the tumor from the stomach with serial fi ring of endoscopic gastrointestinal staplers. The surgical margins were clear, and the patients recovered smoothly. No adjuvant therapy with imatinib was prescribed. During the surveillance for 9 mo and 44 mo respectively, no tumor recurrence and metastasis were documented. Laparoscopic tumor excision, when adhering to the principles of surgical oncology, seems feasible and the prognosisis favorable for such tumors.
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 evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestinal stromal tumors(GIST).METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin(CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density(IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF,Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5%positive cells. The prognosis was classified as good(patient alive without recurrence) or poor(patient with recurrence/death).RESULTS: The distribution of tumor sites among the54 analyzed samples was as follows: 27(50%) in the stomach, 20(37.1%) in the small intestine, 6(11.1%)in the colon, and 1(1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm(median: 8cm); in 12 cases(22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases(77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis(P < 0.001). The cut-off values of CD105(>1.2%) and CD31(> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis.Cases with a better prognosis showed significantly null/weak staining for VEGF(P < 0.001). Ki-67 expression of≥ 5% was strongly correlated with a worse prognosis(P< 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.
文摘AIM:To investigate the feasibility and safety of the treatment of an upper gastrointestinal(GI) submucosal tumor with endoscopic submucosal dissection(ESD).METHODS:A total of 20 patients with esophageal and gastric submucosal tumors emerged from the muscular layer identified by endoscopic ultrasonography were collected from January 2009 to June 2010.Extramural or dumbbell-like lesions were excluded by an enhanced computerized tomography(CT) scan.All patients had intravenous anesthesia with propofol and then underwent the ESD procedure to resect these submucosal tumors.The incision was closed by clips as much as possible to decrease complications,such as bleeding or perforation,after resection of the tumor.All the specimens were collected and evaluated by hematoxylin,eosin and immunohistochemical staining,with antibodies against CD117,CD34,desmin,α-smooth muscle actin and vimentin to identify the characteristics of the tumors.Fletch's criteria was used to evaluate the risk of gastrointestinal stromal tumors(GISTs).All patients underwent a follow-up endoscopy at 3,6 and 12 mo and CT scan at 6 and 12 mo.RESULTS:The study group consisted of 5 men and 15 women aged 45-73 years,with a mean age of 60.2 years.Three tumors were located in the esophagus,9 in the gastric corpus,4 in the gastric fundus,3 lesions in the gastric antrum and 1 in the gastric angulus.Apart from the one case in the gastric angulus which was abandoned due to being deeply located in the serosa,94.7%(18/19) achieved complete gross dissection by ESD with operation duration of 60.52±30.32 min.The average maximum diameter of tumor was 14.8±7.6 mm,with a range of 6 to 30 mm,and another lesion was ligated by an endoscopic ligator after most of the lesion was dissected.After pathological and immunohistochemical analysis,12 tumors were identified as a GI stromal tumor and 6 were leiomyoma.Mitotic count of all 12 GIST lesions was fewer than 5 per 50 HPF and all lesions were at very low(9/12,75.0%) or low risk(3/12,25.0%) according to Fletch's criteria.Procedure complications mainly included perforation and GI bleeding;perforation occurred in 1 patient and conservative treatment succeeded by a suturing clip and no post-operative GI bleeding occurred.All patients were followed up for 6.5±1.8 mo(range,3-12 mo) by endoscopy and abdominal CT.Local recurrence and metastasis did not occur in any patient.CONCLUSION:ESD shows promise as a safe and feasible technique to resect esophageal and gastric submucosal tumors and the incidence of complications was very low.Clinical studies with more subjects and longer follow-up are needed to confirm its treatment value.
文摘AIM:To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors(EGISTs)in South Korea.METHODS:A total of 51 patients with an EGIST were identified.The clinicopathologic features,including sex,age,location,tumor size,histology,mitotic rate,immunohistochemical features,genetic status and survival data,were analyzed.RESULTS:The median age was 55 years(range:29-80years),and male:female ratio was 1:1.04.The most common site was in the mesentery(n=15)followed by the retroperitoneum(n=13)and omentum(n=8).The median tumor size was 9.0 cm(range:2.6-30.0cm)and the median mitotic rate was 5.0/50HPF.(1/50-185/50).KIT was analyzed in 16,which revealed 10cases with wild-type KIT and 6 cases with an exon 11mutation.Among 51 patients,31 patients had undergone surgery,and 10 had unresectable disease and had taken palliative imatinib,which resulted in 22.7 mo of progression-free survival.Of the patients who had undergone surgery,18 did not take adjuvant imatinib,and 8 of these were categorized as"high risk"according to the risk criteria.However,the relapse-free survival was not different(P=0.157)between two groups.CONCLUSION:Because the biologic behaviors of GISTs differ according to the location of the tumor,a more stratified strategy is required for managing EGISTs including incorporation of molecular features.
文摘Most gastrointestinal stromal tumors(GISTs)are characterized by KIT or platelet-derived growth factor alpha(PDGFRA)activating mutations.However,there are still 10%-15%of GISTs lacking KIT and PDGFRA mutations,called wild-type GISTs(WT GISTs).Among these so-called WT GISTs,a small subset is associated with succinate dehydrogenase(SDH)deficiency,known as SDH-deficient GISTs.In addition,GISTs that occur in Carney triad and Carney-Stratakis syndromerepresent specific examples of SDH-deficient GISTs.SDH-deficient GISTs locate exclusively in the stomach,showing predilection for children and young adults with female preponderance.The tumor generally pursues an indolent course and exhibits primary resistance to imatinib therapy in most cases.Loss of succinate dehydrogenase subunit B expression and overexpression of insulin-like growth factor 1 receptor(IGF1R)are common features of SDH-deficient GISTs.In WT GISTs without succinate dehydrogenase activity,upregulation of hypoxia-inducible factor 1αmay lead to increased growth signaling through IGF1R and vascular endothelial growth factor receptor(VEGFR).As a result,IGF1R and VEGFR are promising to be the novel therapeutic targets of GISTs.This review will update the current knowledge on characteristics of SDH-deficient GISTs and further discuss the possible mechanisms of tumorigenesis and clinical management of SDH-deficient GISTs.
文摘AIM:To analyze our experience in patients with duodenal gastrointestinal stromal tumors(GIST) and review the appropriate surgical approach.METHODS:We retrospectively reviewed the medical records of all patients with duodenal GIST surgically treated at our medical institution between 2002 and 2011.Patient files,operative reports,radiological charts and pathology were analyzed.For surgical therapy open and laparoscopic wedge resections and segmental resections were performed for limited resection(LR).For extended resection pancreatoduodenectomy was performed.Age,gender,clinical symptoms of the tumor,anatomical localization,tumor size,mitotic count,type of resection resectional status,neoadjuvant therapy,adjuvant therapy,risk classification and follow-up details were investigated in this retrospective study.RESULTS:Nine patients(5 males/4 females) with a median age of 58 years were surgically treated.The median follow-up period was 45 mo(range 6-111 mo).The initial symptom in 6 of 9 patients was gastrointestinal bleeding(67%).Tumors were found in all four parts of the duodenum,but were predominantly located in the first and second part of the duodenum with each 3 of 9 patients(33%).Two patients received neoadjuvant medical treatment with 400 mg imatinib per day for 12 wk before resection.In one patient,the GIST resection was done by pancreatoduodenectomy.The 8 LRs included a segmental resection of pars 4 of the duodenum,5 wedge resections with primary closure and a wedge resection with luminal closure by Roux-Y duodeno-jejunostomy.One of these LRs was done minimally invasive;seven were done in open fashion.The median diameter of the tumors was 54 mm(14-110 mm).Using the Fletcher classification scheme,3/9(33%) tumors had high risk,1/9(11%) had intermediate risk,4/9(44%) had low risk,and 1/9(11%) had very low risk for aggressive behaviour.Seven resections showed microscopically negative transsection margins(R0),two showed positive margins(R1).No patient developed local recurrence during follow-up.The one patient who underwent pancreatoduodenectomy died due to progressive disease with hepatic metastasis but without evidence of local recurrence.Another patient died in complete remission due to cardiac disease.Seven of the nine patients are alive disease-free.CONCLUSION:In patients with duodenal GIST,limited surgical resection with microscopically negative margins,but also with microscopically positive margins,lead to very good local and systemic disease-free survival.
