Clinical presentations of gastric small gastrointestinal stromal tumors mimics functional dyspepsia symptoms

AIM: To explore whether clinical presentations of gastric small gastrointestinal tumors(GISTs) mimics gastrointestinal dyspepsia symptoms.METHODS: The endosonographic data of 167 patients who underwent endoscopic submucosal dissection at the Tianjin Medical University General Hospital, China between 2009 and 2011 were analyzed. GISTs and leiomyomas had a similar intragastric distribution and similar locations within the gastric wall. Therefore, patients with GISTs were chosen as the study group and those with leiomyomas were chosen as the control group. Dyspepsia symptom questionnaires were used to investigate and compare the gastrointestinal symptoms of patients with GISTs and those with gastric leiomyomas before and after endoscopic submucosal dissection(ESD). The questionnaires evaluated symptoms such as epigastric pain, heartburn, regurgitation, epigastric discomfort, nausea and vomiting, abdominal bloating, and eructation. Symptoms were assessed using a four-point scoring scale.RESULTS: GISTs were the most common gastric submucosal lesion(67 cases, 40.12%), followed by leiomyomas(38 cases, 22.75%). Both groups were similar in terms of gender distribution(P = 0.49), intragastric location(P = 0.525), and originating layer within the gastric wall(P = 0.449), but leiomyomas were more commonly found in the proximal fundus(P < 0.05). Overall, 94.2% of the patients with small GISTs and 93.5% of those with gastric leiomyomas experienced some dyspepsia; however, total symptom scores were significantly lower in the GIST group than in the leiomyoma group(1.34 ± 1.27 vs 2.20 ± 1.70, P < 0.05). Each component of the symptom score demonstrated a statistically significant improvement in the GIST patients after ESD(P < 0.05), including epigastric pain(0.80 ± 0.90 vs 0.13 ± 0.46), heartburn(0.63 ± 1.08 vs 0.13 ± 0.41), regurgitation(0.55 ± 0.87 vs 0.22 ± 0.57), epigastric discomfort(0.70 ± 0.98 vs 0.32 ± 0.47), nausea and vomiting(0.27 ± 0.62 vs 0.05 ± 0.21), abdominal bloating(0.70 ± 0.90 vs 0.27 ± 0.49), and eructation(0.36 ± 0.61 vs 0.21 ± 0.46). For leiomyoma patients, symptoms such as heartburn, nausea, vomiting, and eructation improved after treatment; however, these improvements were not statistically significant(P > 0.05). Thus, the pathophysiology of dyspepsia symptoms may be different between the two groups. CONCLUSION: Symptoms of gastric small GISTs may mimic those of functional dyspepsia. An alternative diagnosis should be considered in patients with functional dyspepsia and treatment failure.

Interventional digital subtraction angiography for small bowel gastrointestinal stromal tumors with bleeding

AIM:To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography(DSA)for bleeding small bowel gastrointestinal stromal tumors(GISTs).METHODS:Between January 2006 and December2013,small bowel tumors in 25 consecutive patients undergoing emergency interventional DSA were histopathologically confirmed as GIST after surgical resection.The medical records of these patients and the effects of interventional DSA and the presentation and management of the condition were retrospectively reviewed.RESULTS:Of the 25 patients with an age range from34-to 70-year-old(mean:54±12 years),8 were male and 17 were female.Obscure gastrointestinal bleeding,including tarry or bloody stool and intermittent melena,was observed in all cases,and one case also involved hematemesis.Nineteen patients required acute blood transfusion.There were a total of 28 small bowel tumors detected by DSA.Among these,20 were located in the jejunum and 8 were located in the ileum.The DSA characteristics of the GISTs included a hypervascular mass of well-defined,homogeneous enhancement and early developed draining veins.One case involved a complication of intussusception of the small intestine that was discovered during surgery.No pseudoaneurysms,arteriovenous malformations or fistulae,or arterial rupture were observed.The completely excised size was approximately 1.20 to 5.50 cm(mean:3.05±1.25 cm)in maximum diameter based on measurements after the resection.There were ulcerations(n=8),erosions(n=10),hyperemia and edema(n=10)on the intra-luminal side of the tumors.Eight tumors in patients with a large amount of blood loss were treated with transcatheter arterial embolization with gelfoam particles during interventional DSA.CONCLUSION:Emergency interventional DSA is a useful imaging option for locating and diagnosing small bowel GISTs in patients with bleeding,and is an effective treatment modality.

Efficacy of endoscopic ultrasound in the evaluation of small gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)with a diameter of<2 cm are called small GISTs.Currently,endoscopic ultrasound(EUS)is widely used as a regular followup method for GISTs,which can also provide a preliminary basis for judging the malignancy potential of lesions.However,there are no studies on the accuracy of EUS to assess the malignant potential of small GISTs.AIM To evaluate the efficacy of EUS in the diagnosis and risk assessment of small GISTs.METHODS We collected data from patients with small GISTs who were admitted to Shengjing Hospital of China Medical University between October 2014 and July 2019.The accurate diagnosis and risk classifications of patients were based on the pathological assessment according to the modified National Institute of Health criteria after endoscopic resection or laparoscopic surgery.Preoperative EUS features(marginal irregularity,cystic changes,homogeneity,ulceration,and strong echogenic foci)were retrospectively analyzed.The assessment results based on EUS features were compared with the pathological features.RESULTS A total of 256 patients(69 men and 187 women)were enrolled.Pathological results included 232,16,7,and 1 very low-,low-,intermediate-,and high-risk cases,respectively.The most frequent tumor location was the gastric fundus(78.1%),and mitoses were calculated as>5/50 high power field in 8(3.1%)patients.Marginal irregularity,ulceration,strong echo foci,and heterogeneity were detected in 1(0.4%),2(0.8%),22(8.6%),and 67(65.1%)patients,respectively.However,cystic changes were not detected.Tumor size was positively correlated with the mitotic index(P<0.001).Receiver operating curve analysis identified 1.48 cm as the best cut-off value to predict malignant potential(95%confidence interval:0.824–0.956).EUS heterogeneity with tumor diameters>1.48 cm was associated with higher risk classification(P<0.05).CONCLUSION Small GISTs(diameters>1.48 cm)with positive EUS features should receive intensive surveillance or undergo endoscopic surgery.EUS and dissection are efficient diagnostic and therapeutic approaches for small GISTs.

Delayed-release oral mesalamine tablet mimicking a small jejunal gastrointestinal stromal tumor:A case report

BACKGROUND Enteric-coated medications are supposed to pass intact through the gastric environment and to release the drug content into the small intestine or the colon.Before dissolution of the enteric coating,they may appear hyperdense on computed tomography(CT).Unfortunately,few reports have been published on this topic so far.In this case report,the hyperdense appearance on contrastenhanced CT of an enteric-coated mesalamine tablet was initially misinterpreted as a jejunal gastrointestinal stromal tumor(GIST).CASE SUMMARY An asymptomatic 81-year-old male patient,who had undergone laparoscopic right nephrectomy four years earlier for stage 1 renal carcinoma,was diagnosed with a jejunal GIST at the 4-year follow-up thoraco-abdominal CT scan.He was referred to our hub hospital for gastroenterological evaluation,and subsequently underwent 18-fluorodeoxyglucose positron emission tomography,abdominal magnetic resonance imaging,and video capsule endoscopy.None of these examinations detected any lesion of the small intestine.After reviewing all the CT images in a multidisciplinary setting,the panel estimated that the hyperdense jejunal image was consistent with a tablet rather than a GIST.The tablet was an 800 mg delayed-release enteric-coated oral mesalamine tablet(Asacol®),which had been prescribed for non-specific colitis,while not informing the hospital physicians.CONCLUSION Delayed-release oral mesalamine(Asacol®),like other enteric-coated medications,can appear as a hyperdense image on a CT scan,mimicking a small intestinal GIST.Therefore,adetailed knowledge of the patients’medications and a multidisciplinary review of the images areessential.

Long-term outcomes of endoscopic resection for small(≤4.0cm) gastric gastrointestinal stromal tumors originating from the muscularis propria layer

AIM To evaluate the long-term efficacy of endoscopic resection(ER) for small(≤ 4.0 cm) gastric gastrointestinal stromal tumors(GISTs) originating from the muscularis propria layer.METHODS Between June 2005 and February 2015, we retrospectively analyzed 229 consecutive patients with gastric MP-GISTs who underwent ER with a follow-up at least 36 mo. The main outcome measurements included complete resection rate, complications, and long-term follow-up outcomes.RESULTS ER included endoscopic muscularis excavation in 179 cases, endoscopic full-thickness resection in 32 cases, and submucosal tunneling endoscopic resection in 18 cases. The median size of GISTs was 1.90 cm. Of the 229 GISTs, 147 were very low risk, 72 were low risk, 8 were intermediate risk, and 2 were high risk. Shortterm outcomes showed the complete resection rate was 96.5%, and 8 patients(3.5%) had complications. Of the 8 patients with complications, only one patient required surgical intervention. Long-term outcomes showed 225 patients were actively followed-up until composition of this manuscript. The remaining 4 patients were lost because of unrelated death. During the follow-up period(median, 57 mo), no residual, recurrent lesions, or distant metastasis were detected in any patients. Binary logistic regression analysis showed tumor size was a risk factor associated with a high mitotic index(≥ 5/50 HPF) of GISTs(P = 0.002).CONCLUSION ER seems to be an effective and safe method for gastric MP-GISTs ≤ 4.0 cm, and, for some intermediate or high risk GISTs, adjuvant therapy and/or additional surgery might be required to reduce the risk of recurrence or metastasis.

Prognositic factors and clinicopathologic characteristics of small gastrointestinal stromal tumor of the stomach:a retrospective analysis of 31 cases in one center

Objective:To analyze the clinicopathologic characteristics and prognostic factors of small gastrointestinal stromal tumor(GIST) of the stomach.Methods:A total of 31 small gastric GIST patients,including 10 males and 21 females,with a median age of 58 years(37-81 years),who underwent surgery at any time from 1999 to 2012 were included in this study.The clinical records of the patients were analyzed retrospectively.Results:Abdominal discomfort and pain(10 cases,32.3%,respectively) were the two most common complaints among the patients.All patients received surgery,11 received gastric wedge resection,11 received subtotal gastrectomy,5 received laparoscopic gastric wedge resection,and 4 received endoscopic submucosal dissection.No severe adverse complication was observed.A total of 29 patients(93.5%) were followed up.During the follow-up,2 patients were found to exhibit tumor recurrence,and 1 patient had liver metastases.One patient died of tumor progression,while another died of another malignant tumor.Median progression free survival(PFS) time was 120.3 months,and median overall survival(OS) time was 130.4 months.Conclusion:Small gastric GIST has better prognosis.Surgery is the best choice for therapy.Micro-invasive procedures are safe and effective for elective patients.Tumor necrosis,tumor bleeding,and muscle invasion are potential prognostic factors of small gastric GIST.

Clinical course of suspected small gastrointestinal stromal tumors in the stomach

BACKGROUND Gastric subepithelial lesions are frequently encountered during endoscopic examinations,and the majority of them are small and asymptomatic.Among these lesions,gastrointestinal stromal tumors(GISTs)are the major concern for patients and clinicians owing to their malignant potentials.Although previous guidelines suggested periodic surveillance for such small(≤20 mm)lesions,several patients and clinicians have still requested or prescribed repeated examinations or radical resection,posing extra medical burdens and risks.AIM To describe the clinical course of suspected small gastric GISTs and provide further evidence for surveillance strategy for tumor therapy.METHODS This single-center,retrospective study was conducted at West China Hospital,Sichuan University.Consecutive patients with suspected small gastric GISTs were reviewed from November 2004 to November 2018.GIST was suspected according to endoscopic ultrasonography features:hypoechoic lesions from muscularis propria or muscularis mucosa.Eligible patients with suspected small(≤20 mm)GISTs were included for analysis.Patients’demographic data,lesions’characteristics,and follow-up medical records were collected.RESULTS A total of 383 patients(male/female,121/262;mean age,54 years)with 410 suspected small gastric GISTs(1 lesion in 362 patients,2 lesions in 16,3 lesions in4,and 4 lesions in 1)were included for analysis.The most common location was gastric fundus(56.6%),followed by body(29.0%),cardia(12.2%),and antrum(2.2%).After a median follow-up of 28 mo(interquartile range,16-48;range,3-156),402 lesions(98.0%)showed no changes in size,and size of 8 lesions(2.0%)was increased(mean increment,10 mm).Of the 8 lesions with size increment,endoscopic or surgical resection was performed in 6 patients(5 GISTs and 1 leiomyoma).For other 2 remaining patients,unroofing biopsy or endoscopic ultrasound-guided fine-needle aspiration was carried out(2 GISTs),while no further change in size was noted over a period of 62-64 mo.CONCLUSION The majority of suspected small(≤20 mm)gastric GISTs had no size increment during follow-up.Regular endoscopic follow-up without pathological diagnosis may be highly helpful for such small gastric subepithelial lesions.

Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn’s disease

We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the f irst report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.

Small gastrointestinal stromal tumor concomitant with early gastric cancer:A case report

术语胃肠的基质肿瘤(大意) 与锭子或上皮样细胞与免疫从胃肠道的墙产生特征地被定义为间充质的肿瘤的主要的组为 CD117 的组织化学的反应抗体。以前的研究表明在大意的细胞与酷氨酸激酶活动(称为的 c 工具包) 表示生长因素受体，它是 c 工具包 proto-oncogene 的产品。为大意的最特定、实际的诊断标准是：免疫组织化学地决定了 c 工具包(CD117 ) 表示；有丝分裂的分数；并且肿瘤尺寸。有早胃的癌症的小大意伴随物很少临床上被遇到。此处，我们报导了与早胃的癌症(环状体房间类型) 的一种 IIc 类型伴随物的 esophagogastroduodenoscopy 检测的 1.1 厘米的大意的一个案例。它在平淡的物理健康检查期间被检测。到我们的知识，这是有早胃的癌症的一种环状体房间类型的小大意伴随物的第一份报告。

Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: Implications of imatinib mesylate

瞄准：检验 imatinib 的影响耐心的幸存和反应和它的安全上的 mesylate (Glivec ) ，和反应的关联与工具包基因变化地位评价。方法：74 中的 33 个(44.6%) 在药品切除术以后并且不开发了复发的胃肠的基质肿瘤(大意) 病人与 Glivec 对待的小肠是被分类组 A 病人。与 Glivec 对待的 22 个先进的小肠大意病人作为组 B 病人被分类。Clinicopathological 特征，复发以后、全面的幸存率被比较。在组 B 病人的每个肿瘤为工具包或导出血小板的生长因素高山的变化被调查哈(PDGFRA ) 。变化类型与临床的结果被相关。在组 B 病人的 Glivec 的反肿瘤效果和安全也被估计。结果：与 Glivec 对待的先进的小肠大意病人比没与 Glivec 对待的那些有 substatntially 更长的复发以后的幸存和更高全面的幸存率。15 个病人的一个总数有部分回答(PR )(67.8%) 。c 工具包的激活的变化在 19 个测试病人中的 16 个被发现，没有 PDGFRA 异种被识别。在有在 11 个工具包变化上怀有前的大意的 13 个病人，部分反应率(PR ) 是 69.3% ，而有在 9 工具包变化上包含前的肿瘤的三个病人中的二个有 66.7% 的全面反应率(ORR )( 不重要) 。结论：Glivec 显著地与先进大意延长亚洲病人的复发以后、全面的幸存。Glivec 导致持续客观回答在多于有先进的小肠大意的亚洲病人的一半。11 上的工具包前的激活的变化在绝大多数大意是可检测的。在 11 个变化上处于为其大意在 9 上有工具包前的病人和前的 PR 率没有差别。

Gastric IgG4-related disease mimicking a gastrointestinal stromal tumor in a child: A case report

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.

Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor: A case report

Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor STI571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

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.

Perforation of metastatic melanoma to the small bowel with simultaneous gastrointestinal stromal tumor

The gastrointestinal tract (GIT) is a common site of metastases for malignant melanoma. These metastatic tumors are often asymptomatic. We describe a case of a 58-year-old male who presented with a sudden onset of generalized abdominal pain. The patient's past medical history was significant for lentigo melanoma of the right cheek. Laparotomy was performed and two segments ofsmall bowel, one with a perforated tumor, the other with a non-perforated tumor, were removed. Histology and immunohistochemical staining revealed the perforated tumor to be a metastatic malignant melanoma and the non-perforated tumor was found to be a gastrointestinal stromal tumor (GIST). The patient was discharged 7 d postoperatively. To the best of our knowledge, this is the first reported case in the literature of a simultaneous metastatic malignant melanoma and a GIST. Surgical intervention is warranted in patients with symptomatic GIT metastases to improve the quality of life or in those patients with surgical emergencies.

Systemic therapy in gastrointestinal stromal tumors

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.

Primary Extra-Gastrointestinal Stromal Tumor (GIST) arising from mesentery of small bowel and presenting as abdominal mass: A rare entity

Introduction: Majority of mesenchymal tumors of gastrointestinal tract are Gastrointestinal Stromal Tumor (GIST). It is, however, a rare tumor, accounting for less than 1% of primary gastrointestinal (GI) neoplasms. Though, these tumors are refractory to conventional chemotherapy or radiotherapy but show a good response to targeted adjuvant chemotherapy with tyrosine kinase inhibitors following surgical resection. Case Report: we report here a case of primary Extra-GIST tumor arising from mesentry of small bowel near duodeno-jejunal junction in a 69 years old male patient. The patient presented with a palpable mass in upper abdomen for past 15 days. On examination, a non-tender mobile lump of size around 17 × 10 cm, with bosselated surface and firm in consistency was palpable involving epigastric, left hypochondrium and umbilical region. Contrast enhanced computed tomography of abdomen revealed a heterogenous mesentric mass. On surgical intervention a mass was found involving mesentery near dudenojejunal junction without involvement of gastrointestinal tract. Complete surgical resection of the tumor was done and adjuvant chemotherapy with Imatinib mesylate was started as HPE revealing GIST with mitotic index of >10/50 HPF and 17 × 10 cm size placed the patient in high risk category. Patient was discharged on 12th of post-operative day with advice of regular follow-up. Conclusion: GIST occurrence is not restricted to bowel but can involve unusual sites also. The mainstay of treatment remains surgical resection with adequate margin. In cases where tumour has malignant potential (high mitotic figures on histopathology) adjuvent treatment with tyrosine kinase may prevent or delay relapse.

TATA-box-binding protein-associated factor 15 is a novel biomarker that promotes cell proliferation and migration in gastrointestinal stromal tumor

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.

Relationship between multi-slice computed tomography features and pathological risk stratification assessment in gastric gastrointestinal stromal tumors

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.

Optical second-harmonic generation imaging for identifying gastrointestinal stromal tumors

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.

Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors:A case report

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.