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 Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric patients.To our knowledge,this is the first report of IgG4-RD presenting as a calcifyin...BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric patients.To our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child.We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based approaches.Therefore,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary surgery.CASE SUMMARY The patient suffered from epigastric pain for several days.Panendoscopy and computed tomography scan revealed a submucosal tumor.Differential diagnoses included GIST,leiomyoma,teratoma,and mucinous adenocarcinoma.However,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease.CONCLUSION We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical 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
BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic...BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.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
Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors arising in the digest tract.It brings a challenge to diagnosis because it is asymptomatic clinically.It is well known that tumor development...Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors arising in the digest tract.It brings a challenge to diagnosis because it is asymptomatic clinically.It is well known that tumor development is often accompanied by the changes in the morphology of collagen fibers.Nowadays,an emerging optical imaging technique,second-harmonic generation(SHG),can directly identify collagen fibers without staining due to its noncentrosymmetric properties.Therefore,in this study,we attempt to assess the feasibility of SHG imaging for detecting GISTs by monitoring the morphological changes of collagen fibers in tumor microenvironment.We found that collagen alterations occurred obviously in the GISTs by comparing with normal tissues,and furthermore,two morphological features from SHG images were extracted to quantitatively assess the morphological difference of collagen fibers between normal muscular layer and GISTs by means of automated image analysis.Quantitative analyses show a significant difference in the two collagen features.This study demonstrates the potential of SHG imaging as an adjunctive diagnostic tool for label-free identification 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 Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.Tyrosine kinase inhibitors,such as imatinib,have been used as first-line therapy for the treatment ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.Tyrosine kinase inhibitors,such as imatinib,have been used as first-line therapy for the treatment of GISTs.Although these drugs have achieved considerable efficacy in some patients,reports of resistance and recurrence have emerged.Extracellular signal-regulated kinase 1/2(ERK1/2)protein,as a member of the mitogen-activated protein kinase(MAPK)family,is a core molecule of this signaling pathway.Nowadays,research reports on the important clinical and prognostic value of phosphorylated-ERK(P-ERK)and phosphorylated-MAPK/ERK kinase(P-MEK)proteins closely related to raf kinase inhibitor protein(RKIP)have gradually emerged in digestive tract tumors such as gastric cancer,colon cancer,and pancreatic cancer.However,literature on the expression of these downstream proteins combined with RKIP in GIST is scarce.This study will focus on this aspect and search for answers to the problem.AIM To detect the expression of RKIP,P-ERK,and P-MEK protein in GIST and to analyze their relationship with clinicopathological characteristics and prognosis of this disease.Try to establish a new prognosis evaluation model using RKIP and PERK in combination with analysis and its prognosis evaluation efficacy.METHODS The research object of our experiment was 66 pathologically diagnosed GIST patients with complete clinical and follow-up information.These patients received surgical treatment at China Medical University Affiliated Hospital from January 2015 to January 2020.Immunohistochemical method was used to detect the expression of RKIP,PERK,and P-MEK proteins in GIST tissue samples from these patients.Kaplan-Meier method was used to calculate the survival rate of 63 patients with complete follow-up data.A Nomogram was used to represent the new prognostic evaluation model.The Cox multivariate regression analysis was conducted separately for each set of risk evaluation factors,based on two risk classification systems[the new risk grade model vs the modified National Institutes of Health(NIH)2008 risk classification system].Receiver operating characteristic(ROC)curves were used for evaluating the accuracy and efficiency of the two prognostic evaluation systems.RESULTS In GIST tissues,RKIP protein showed positive expression in the cytoplasm and cell membrane,appearing as brownish-yellow or brown granules.The expression of RKIP was related to GIST tumor size,NIH grade,and mucosal invasion.P-ERK protein exhibited heterogeneous distribution in GIST cells,mainly in the cytoplasm,with occasional presence in the nucleus,and appeared as brownish-yellow granules,and the expression of P-ERK protein was associated with GIST tumor size,mitotic count,mucosal invasion,and NIH grade.Meanwhile,RKIP protein expression was negatively correlated with P-ERK expression.The results in COX multivariate regression analysis showed that RKIP protein expression was not an independent risk factor for tumor prognosis.However,RKIP combined with P-ERK protein expression were identified as independent risk factors for prognosis with statistical significance.Furthermore,we establish a new prognosis evaluation model using RKIP and P-ERK in combination and obtained the nomogram of the new prognosis evaluation model.ROC curve analysis also showed that the new evaluation model had better prognostic performance than the modified NIH 2008 risk classification system.CONCLUSION Our experimental results showed that the expression of RKIP and P-ERK proteins in GIST was associated with tumor size,NIH 2008 staging,and tumor invasion,and P-ERK expression was also related to mitotic count.The expression of the two proteins had a certain negative correlation.The combined expression of RKIP and P-ERK proteins can serve as an independent risk factor for predicting the prognosis of GIST patients.The new risk assessment model incorporating RKIP and P-ERK has superior evaluation efficacy and is worth further practical application to validate.展开更多
BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GI...BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.展开更多
Background and Objective: To investigate the histopathological characteristics and immunohistochemistry of gastrointestinal stromal tumors (GIST). Immunohistochemistry (IHC) refers to the expression and meaning of CD1...Background and Objective: To investigate the histopathological characteristics and immunohistochemistry of gastrointestinal stromal tumors (GIST). Immunohistochemistry (IHC) refers to the expression and meaning of CD117, DOG-1, CD34. Methods: Sixty-six gastrointestinal stromal tumor (GIST) samples with complete clinical data and definite clinicopathological diagnosis were collected from the Seventh Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022. Retrospective analysis was performed on the pathological data of 66 patients with GIST, and the histopathology and IHC were analyzed and summarized. Results: Among the 66 cases, 46, 14, 1, 5 were found in the stomach, small intestine, large intestine, and gastroenteral area. There were 45 cases (97%), 11 cases (79%), 1 case (100%), 5 cases (100%) in order of fusiform cell type. There were 1 case (3%), 2 cases (14%), 0 case, 0 case of upper dermatiform;Mixed type in 0 case, 1 case (7%), 0 case, 0 case;CD117 positive 66 cases (100%), DOG-1 positive 66 cases (100%), CD34 positive 61 cases (92%), CD117 and/or CD34 negative 5 cases (8%);CD34, CD117 and DOG-1 were negative simultaneously in 0 case. 19 cases (28%) were positive for SMA and 7 cases (11%) were positive for S-100. Conclusion: Fusiform cell type is the common type of GIST, followed by epithelioid type and mixed type, but the tumor sites are different, and the comparison cases are not completely the same. CD117, DOG-1 and CD34 are high surface in GIST, and the combination of SMA, S-100 and histomorphology can be used to diagnose most GIST.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare tumors of the gastrointestinal tract accounting for less than 1%of all gut tumors.GISTs occurring in the rectum are extremely rare,and these usually present at...BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare tumors of the gastrointestinal tract accounting for less than 1%of all gut tumors.GISTs occurring in the rectum are extremely rare,and these usually present at an advanced stage compared with other sites.CASE SUMMARY A 60-year-old male who presented with features of sensations of rectal tenesmus was referred to our department with a mass in the lower rectum that was detected during a routine checkup.Colonoscopy,transrectal ultrasound,perianal magnetic resonance imaging and ultrasonic contrast were used to diagnose the rectum GIST,and then the patient underwent complete transanal resection using the ultrasonic scalpel.The patient was discharged ten days after the operation and was defined as low risk.Therefore,he had no need to receive subsequent adjuvant therapies,and he had not suffered any anal dysfunction or had any evidence of recurrence at follow up.CONCLUSION Surgical resection with histologically negative margins is the standard curative treatment for rectal GISTs.Appropriate surgical techniques based on the location,size,and resectability of the tumor should attract great attention from clinicians.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 Gastrointestinal stromal tumor(GIST)is a rare gastrointestinal mesenchymal tumor with potential malignancy.Once the tumor ruptures,regardless of tumor size and mitotic number,it can be identified into a hig...BACKGROUND Gastrointestinal stromal tumor(GIST)is a rare gastrointestinal mesenchymal tumor with potential malignancy.Once the tumor ruptures,regardless of tumor size and mitotic number,it can be identified into a high-risk group.It is of great significance for the diagnosis,treatment,and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor.AIM To identify the factors associated with GIST rupture and pathological risk.METHODS A cohort of 50 patients with GISTs,as confirmed by postoperative pathology,was selected from our hospital.Clinicopathological and computed tomography data of the patients were collected.Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade.RESULTS Pathological risk grade,tumor diameter,tumor morphology,internal necrosis,gas-liquid interface,and Ki-67 index exhibited significant associations with GIST rupture(P<0.05).Gender,tumor diameter,tumor rupture,and Ki-67 index were found to be correlated with pathological risk grade of GIST(P<0.05).Multifactorial logistic regression analysis revealed that male gender and tumor diameter≥10 cm were independent predictors of a high pathological risk grade of GIST[odds ratio(OR)=11.12,95%confidence interval(95%CI):1.81-68.52,P=0.01;OR=22.96,95%CI:2.19-240.93,P=0.01].Tumor diameter≥10 cm,irregular shape,internal necrosis,gas-liquid interface,and Ki-67 index≥10 were identified as independent predictors of a high risk of GIST rupture(OR=9.67,95%CI:2.15-43.56,P=0.01;OR=35.44,95%CI:4.01-313.38,P<0.01;OR=18.75,95%CI:3.40-103.34,P<0.01;OR=27.00,95%CI:3.10-235.02,P<0.01;OR=4.43,95%CI:1.10-17.92,P=0.04).CONCLUSION Tumor diameter,tumor morphology,internal necrosis,gas-liquid,and Ki-67 index are associated with GIST rupture,while gender and tumor diameter are linked to the pathological risk of GIST.These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most frequent mesenchymal tumors of gastrointestinal tract.The most common sites of metastases are the liver and the peritoneum,whereas breast metastases from G...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most frequent mesenchymal tumors of gastrointestinal tract.The most common sites of metastases are the liver and the peritoneum,whereas breast metastases from GIST are extremely rare.We present a second case of GIST breast metastasis.CASE SUMMARY We found a case of breast metastasis from rectum GIST.A 55-year-old female patient presented with rectum tumor with multiply liver lesions and metastasis in the right breast.Abdominal-perineal extirpation of rectum was performed,histology and immunohistochemistry study showed GIST,mixed type with CD117 and DOG-1 positive staining.The patient was taking imatinib 400 mg for 22 mo with stable disease.Because of growth of the breast metastasis the treatment was changed twice:The dose of imatinib was doubled with further progression in the breast lesion and then the patient was receiving sunitinib for 26 mo with partial response in the right breast and stable disease in the liver lesions.The breast lesion increased and right breast resection was done–surgery on local progression,the liver metastases were stable.Histology and immunohistochemistry studies revealed GIST metastasis,CD 117 and DOG 1 positive with KIT exon 11 mutation.After surgery the patient resumed imatinib.Until now the patient has been taking imatinib 400 mg for 19 mo without progression,last follow up was in November 2022.CONCLUSION GISTs breast metastases are extremely rare,we described the second case.At the same time second primary tumors have been reported frequently in patients diagnosed with GISTs and breast cancer is one of the most common second primary tumors in patients with GISTs.That is why it is very important to distinguish primary from metastatic breast lesions.Surgery on local progression made it possible to resume less toxic treatment.展开更多
BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and c...BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype of GISTs.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common malignant subepithelial lesions(SELs) of the gastrointestinal tract. They originate from the interstitial cells of Cajal located within the muscle layer and a...Gastrointestinal stromal tumors(GISTs) are the most common malignant subepithelial lesions(SELs) of the gastrointestinal tract. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Pathologically, diagnosis of a GIST relies on morphology and immunohistochemistry [KIT and/or discovered on gastrointestinal stromal tumor 1(DOG1) is generally positive]. The prognosis of this disease is associated with the tumor size and mitotic index. The standard treatment of a GIST without metastasis is surgical resection. A GIST with metastasis is usually only treated by tyrosine kinase inhibitors without radical cure; thus, early diagnosis is the only way to improve its prognosis. However, a GIST is usually detected as a SEL during endoscopy, and many benign and malignant conditions may manifest as SELs. Conventional endoscopic biopsy is difficult for tumors without ulceration. Most SELs have therefore been managed without a histological diagnosis. However, a favorable prognosis of a GIST is associated with early histological diagnosis and R0 resection. Endoscopic ultrasonography(EUS) and EUS-guided fine needle aspiration(EUSFNA) are critical for an accurate diagnosis of SELs. EUSFNA is safe and effective in enabling an early histological diagnosis and adequate treatment. This review outlines the current evidence for the diagnosis and management of GISTs, with an emphasis on early management of small SELs.展开更多
In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST tho...In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST (2017 edition) was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.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
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.
文摘BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric patients.To our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child.We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based approaches.Therefore,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary surgery.CASE SUMMARY The patient suffered from epigastric pain for several days.Panendoscopy and computed tomography scan revealed a submucosal tumor.Differential diagnoses included GIST,leiomyoma,teratoma,and mucinous adenocarcinoma.However,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease.CONCLUSION We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical 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 National Natural Science Foundation of China,No.81870453.
文摘BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.
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 the National Natural Science Foundation of China(Grant Nos.82171991 and 82172800)Joint Funds for the Innovation of Science and Technology of Fujian Province(Grant No.2019Y9101)+1 种基金Fujian Major Scientific and Technological Special Project for"Social Development"(No.2020YZ016002)Special Funds of the Central Government Guiding Local Science and Technology Development(No.2020L3008).
文摘Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors arising in the digest tract.It brings a challenge to diagnosis because it is asymptomatic clinically.It is well known that tumor development is often accompanied by the changes in the morphology of collagen fibers.Nowadays,an emerging optical imaging technique,second-harmonic generation(SHG),can directly identify collagen fibers without staining due to its noncentrosymmetric properties.Therefore,in this study,we attempt to assess the feasibility of SHG imaging for detecting GISTs by monitoring the morphological changes of collagen fibers in tumor microenvironment.We found that collagen alterations occurred obviously in the GISTs by comparing with normal tissues,and furthermore,two morphological features from SHG images were extracted to quantitatively assess the morphological difference of collagen fibers between normal muscular layer and GISTs by means of automated image analysis.Quantitative analyses show a significant difference in the two collagen features.This study demonstrates the potential of SHG imaging as an adjunctive diagnostic tool for label-free identification 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.
基金Natural Science Foundation of Liaoning Province,No.2020-MS-148。
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.Tyrosine kinase inhibitors,such as imatinib,have been used as first-line therapy for the treatment of GISTs.Although these drugs have achieved considerable efficacy in some patients,reports of resistance and recurrence have emerged.Extracellular signal-regulated kinase 1/2(ERK1/2)protein,as a member of the mitogen-activated protein kinase(MAPK)family,is a core molecule of this signaling pathway.Nowadays,research reports on the important clinical and prognostic value of phosphorylated-ERK(P-ERK)and phosphorylated-MAPK/ERK kinase(P-MEK)proteins closely related to raf kinase inhibitor protein(RKIP)have gradually emerged in digestive tract tumors such as gastric cancer,colon cancer,and pancreatic cancer.However,literature on the expression of these downstream proteins combined with RKIP in GIST is scarce.This study will focus on this aspect and search for answers to the problem.AIM To detect the expression of RKIP,P-ERK,and P-MEK protein in GIST and to analyze their relationship with clinicopathological characteristics and prognosis of this disease.Try to establish a new prognosis evaluation model using RKIP and PERK in combination with analysis and its prognosis evaluation efficacy.METHODS The research object of our experiment was 66 pathologically diagnosed GIST patients with complete clinical and follow-up information.These patients received surgical treatment at China Medical University Affiliated Hospital from January 2015 to January 2020.Immunohistochemical method was used to detect the expression of RKIP,PERK,and P-MEK proteins in GIST tissue samples from these patients.Kaplan-Meier method was used to calculate the survival rate of 63 patients with complete follow-up data.A Nomogram was used to represent the new prognostic evaluation model.The Cox multivariate regression analysis was conducted separately for each set of risk evaluation factors,based on two risk classification systems[the new risk grade model vs the modified National Institutes of Health(NIH)2008 risk classification system].Receiver operating characteristic(ROC)curves were used for evaluating the accuracy and efficiency of the two prognostic evaluation systems.RESULTS In GIST tissues,RKIP protein showed positive expression in the cytoplasm and cell membrane,appearing as brownish-yellow or brown granules.The expression of RKIP was related to GIST tumor size,NIH grade,and mucosal invasion.P-ERK protein exhibited heterogeneous distribution in GIST cells,mainly in the cytoplasm,with occasional presence in the nucleus,and appeared as brownish-yellow granules,and the expression of P-ERK protein was associated with GIST tumor size,mitotic count,mucosal invasion,and NIH grade.Meanwhile,RKIP protein expression was negatively correlated with P-ERK expression.The results in COX multivariate regression analysis showed that RKIP protein expression was not an independent risk factor for tumor prognosis.However,RKIP combined with P-ERK protein expression were identified as independent risk factors for prognosis with statistical significance.Furthermore,we establish a new prognosis evaluation model using RKIP and P-ERK in combination and obtained the nomogram of the new prognosis evaluation model.ROC curve analysis also showed that the new evaluation model had better prognostic performance than the modified NIH 2008 risk classification system.CONCLUSION Our experimental results showed that the expression of RKIP and P-ERK proteins in GIST was associated with tumor size,NIH 2008 staging,and tumor invasion,and P-ERK expression was also related to mitotic count.The expression of the two proteins had a certain negative correlation.The combined expression of RKIP and P-ERK proteins can serve as an independent risk factor for predicting the prognosis of GIST patients.The new risk assessment model incorporating RKIP and P-ERK has superior evaluation efficacy and is worth further practical application to validate.
文摘BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.
文摘Background and Objective: To investigate the histopathological characteristics and immunohistochemistry of gastrointestinal stromal tumors (GIST). Immunohistochemistry (IHC) refers to the expression and meaning of CD117, DOG-1, CD34. Methods: Sixty-six gastrointestinal stromal tumor (GIST) samples with complete clinical data and definite clinicopathological diagnosis were collected from the Seventh Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022. Retrospective analysis was performed on the pathological data of 66 patients with GIST, and the histopathology and IHC were analyzed and summarized. Results: Among the 66 cases, 46, 14, 1, 5 were found in the stomach, small intestine, large intestine, and gastroenteral area. There were 45 cases (97%), 11 cases (79%), 1 case (100%), 5 cases (100%) in order of fusiform cell type. There were 1 case (3%), 2 cases (14%), 0 case, 0 case of upper dermatiform;Mixed type in 0 case, 1 case (7%), 0 case, 0 case;CD117 positive 66 cases (100%), DOG-1 positive 66 cases (100%), CD34 positive 61 cases (92%), CD117 and/or CD34 negative 5 cases (8%);CD34, CD117 and DOG-1 were negative simultaneously in 0 case. 19 cases (28%) were positive for SMA and 7 cases (11%) were positive for S-100. Conclusion: Fusiform cell type is the common type of GIST, followed by epithelioid type and mixed type, but the tumor sites are different, and the comparison cases are not completely the same. CD117, DOG-1 and CD34 are high surface in GIST, and the combination of SMA, S-100 and histomorphology can be used to diagnose most GIST.
基金Supported by National Nature Science Foundation of China,No.82004374the second round of construction project for the National Traditional Chinese Medicine Academic School Inheritance Studio+1 种基金the three-year action project for Shanghai to further accelerate the inheritance innovation and development of traditional Chinese medicine,No.ZY[2021-2023]-0209Shanghai"Rising Stars of Medical Talents"Youth Development Program,Youth Medical Talents–Specialist Program,No.[2021]-099.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare tumors of the gastrointestinal tract accounting for less than 1%of all gut tumors.GISTs occurring in the rectum are extremely rare,and these usually present at an advanced stage compared with other sites.CASE SUMMARY A 60-year-old male who presented with features of sensations of rectal tenesmus was referred to our department with a mass in the lower rectum that was detected during a routine checkup.Colonoscopy,transrectal ultrasound,perianal magnetic resonance imaging and ultrasonic contrast were used to diagnose the rectum GIST,and then the patient underwent complete transanal resection using the ultrasonic scalpel.The patient was discharged ten days after the operation and was defined as low risk.Therefore,he had no need to receive subsequent adjuvant therapies,and he had not suffered any anal dysfunction or had any evidence of recurrence at follow up.CONCLUSION Surgical resection with histologically negative margins is the standard curative treatment for rectal GISTs.Appropriate surgical techniques based on the location,size,and resectability of the tumor should attract great attention from clinicians.
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.
文摘BACKGROUND Gastrointestinal stromal tumor(GIST)is a rare gastrointestinal mesenchymal tumor with potential malignancy.Once the tumor ruptures,regardless of tumor size and mitotic number,it can be identified into a high-risk group.It is of great significance for the diagnosis,treatment,and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor.AIM To identify the factors associated with GIST rupture and pathological risk.METHODS A cohort of 50 patients with GISTs,as confirmed by postoperative pathology,was selected from our hospital.Clinicopathological and computed tomography data of the patients were collected.Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade.RESULTS Pathological risk grade,tumor diameter,tumor morphology,internal necrosis,gas-liquid interface,and Ki-67 index exhibited significant associations with GIST rupture(P<0.05).Gender,tumor diameter,tumor rupture,and Ki-67 index were found to be correlated with pathological risk grade of GIST(P<0.05).Multifactorial logistic regression analysis revealed that male gender and tumor diameter≥10 cm were independent predictors of a high pathological risk grade of GIST[odds ratio(OR)=11.12,95%confidence interval(95%CI):1.81-68.52,P=0.01;OR=22.96,95%CI:2.19-240.93,P=0.01].Tumor diameter≥10 cm,irregular shape,internal necrosis,gas-liquid interface,and Ki-67 index≥10 were identified as independent predictors of a high risk of GIST rupture(OR=9.67,95%CI:2.15-43.56,P=0.01;OR=35.44,95%CI:4.01-313.38,P<0.01;OR=18.75,95%CI:3.40-103.34,P<0.01;OR=27.00,95%CI:3.10-235.02,P<0.01;OR=4.43,95%CI:1.10-17.92,P=0.04).CONCLUSION Tumor diameter,tumor morphology,internal necrosis,gas-liquid,and Ki-67 index are associated with GIST rupture,while gender and tumor diameter are linked to the pathological risk of GIST.These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most frequent mesenchymal tumors of gastrointestinal tract.The most common sites of metastases are the liver and the peritoneum,whereas breast metastases from GIST are extremely rare.We present a second case of GIST breast metastasis.CASE SUMMARY We found a case of breast metastasis from rectum GIST.A 55-year-old female patient presented with rectum tumor with multiply liver lesions and metastasis in the right breast.Abdominal-perineal extirpation of rectum was performed,histology and immunohistochemistry study showed GIST,mixed type with CD117 and DOG-1 positive staining.The patient was taking imatinib 400 mg for 22 mo with stable disease.Because of growth of the breast metastasis the treatment was changed twice:The dose of imatinib was doubled with further progression in the breast lesion and then the patient was receiving sunitinib for 26 mo with partial response in the right breast and stable disease in the liver lesions.The breast lesion increased and right breast resection was done–surgery on local progression,the liver metastases were stable.Histology and immunohistochemistry studies revealed GIST metastasis,CD 117 and DOG 1 positive with KIT exon 11 mutation.After surgery the patient resumed imatinib.Until now the patient has been taking imatinib 400 mg for 19 mo without progression,last follow up was in November 2022.CONCLUSION GISTs breast metastases are extremely rare,we described the second case.At the same time second primary tumors have been reported frequently in patients diagnosed with GISTs and breast cancer is one of the most common second primary tumors in patients with GISTs.That is why it is very important to distinguish primary from metastatic breast lesions.Surgery on local progression made it possible to resume less toxic treatment.
基金Supported by the National Natural Science Foundation of China Program Grant,No.82203108China Postdoctoral Science Foundation,No.2022M722275+1 种基金Beijing Bethune Charitable Foundation,No.WCJZL202105Beijing Xisike Clinical Oncology Research Foundation,No.Y-zai2021/zd-0185。
文摘BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype of GISTs.
文摘Gastrointestinal stromal tumors(GISTs) are the most common malignant subepithelial lesions(SELs) of the gastrointestinal tract. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Pathologically, diagnosis of a GIST relies on morphology and immunohistochemistry [KIT and/or discovered on gastrointestinal stromal tumor 1(DOG1) is generally positive]. The prognosis of this disease is associated with the tumor size and mitotic index. The standard treatment of a GIST without metastasis is surgical resection. A GIST with metastasis is usually only treated by tyrosine kinase inhibitors without radical cure; thus, early diagnosis is the only way to improve its prognosis. However, a GIST is usually detected as a SEL during endoscopy, and many benign and malignant conditions may manifest as SELs. Conventional endoscopic biopsy is difficult for tumors without ulceration. Most SELs have therefore been managed without a histological diagnosis. However, a favorable prognosis of a GIST is associated with early histological diagnosis and R0 resection. Endoscopic ultrasonography(EUS) and EUS-guided fine needle aspiration(EUSFNA) are critical for an accurate diagnosis of SELs. EUSFNA is safe and effective in enabling an early histological diagnosis and adequate treatment. This review outlines the current evidence for the diagnosis and management of GISTs, with an emphasis on early management of small SELs.
文摘In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST (2017 edition) was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.
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.