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.

Genetic alteration and mutation profiling of circulating cell-free tumor DNA(cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs) have been recognized as a biologically distinctive type of tumor,different from smooth muscle and neural tumors of the gastrointestinal tract.The identification of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the efficacy of cancer therapy by matching targeted drugs to specific mutations.Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A(PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by the KIT gene.Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs,yet the prevalence and size of subpopulations remain largely unexplored.Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods,such as polymerase chain reaction(PCR) target amplification technology,is hampered by the high abundance of wildtype alleles,which limit the sensitivity of detection of these minor mutant alleles.This is especially true in the case of mutant tumor DNA derived "driver" and "drug-resistant" alleles that are present in the circulating cell-free tumor DNA(cfDNA) in the peripheral blood circulation of GIST patients.So-called "liquid biopsy" allows for the dynamic monitoring of the patients' tumor status during treatment using minimally invasive sampling.New methodologies,such as a technology that employs a xenonucleic acid(XNA) clamping probe to block the PCR amplification of wild-type templates,have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA.These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs.

Rare rectal gastrointestinal stromal tumor case:A case report and review of the literature

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.

Targeted therapy of gastrointestinal stromal tumours

Gastrointestinal stromal tumours(GISTs) are mesen-chymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majo-rity of the tumours stain positively for the CD-117(KIT) and discovered on GIST-1(DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy(tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs.

Therapeutic targets in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs) are the most common type of mesenchymal tumor of the gastrointestinal tract. The tumorigenesis of GISTs is driven by gain-of-function mutations in KIT or plateletderived growth factor receptor α(PDGFRA),resultingin constitutive activation of the tyrosine kinase and its downstream signaling pathways. Oncogenic KIT or PDGFRA mutations are compelling therapeutic targets for the treatment of GISTs,and the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GISTs. However,most GIST patients develop clinical resistance to imatinib and other tyrosine kinase inhibitors. Five mechanisms of resistance have been characterized:(1) acquisition of a secondary point mutation in KIT or PDGFRA;(2) genomic amplification of KIT;(3) activation of an alternative receptor tyrosine kinase;(4) loss of KIT oncoprotein expression; and(5) wild-type GIST. Currently,sunitinib is used as a secondline treatment for patients after imatinib failure,and regorafenib has been approved for patients whose disease is progressing on both imatinib and sunitinib. Phase Ⅱ/Ⅲ trials are currently in progress to evaluate novel inhibitors and immunotherapies targeting KIT,its downstream effectors such as phosphatidylinositol 3-kinase,protein kinase B and mammalian target of rapamycin,heat shock protein 90,and histone deacetylase inhibitor. Other candidate targets have been identified,including ETV1,AXL,insulin-like growth factor 1 receptor,KRAS,FAS receptor,protein kinase c theta,ANO1(DOG1),CDC37,and aurora kinase A. These candidates warrant clinical evaluation as novel therapeutic targets in GIST.

The Clinical Study of Multigene Combination Test to Guide Chemotherapy Combined with Targeted Therapy in Patients with Advanced Gastrointestinal Tumors

Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.

Current clinical management of gastrointestinal stromal tumor

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.

Rectal gastrointestinal stromal tumors:Imaging features with clinical and pathological correlation

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.

Chinese consensus guidelines for diagnosis and management of gastrointestinal stromal tumor

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.

Endoscopic therapy for gastric stromal tumors originating from the muscularis propria

AIM:To explore endoscopic therapy methods for gastric stromal tumors originating from the muscularis propria.METHODS:For 69 cases diagnosed as gastric stromal tumors originating from the muscularis propria,three types of endoscopic therapy were selected,based on the size of the tumor.These methods included endoscopic ligation and resection(ELR),endoscopic submucosal excavation(ESE) and endoscopic full-thickness resection(EFR).The wound surface and the perforation of the gastric wall were closed with metal clips.Immunohistostaining for CD34,CD117,Dog-1,S-100 and smooth muscle actin(SMA) was performed on the resected tumors.RESULTS:A total of 38 cases in which the tumor size was less than 1.2 cm were treated with ELR;three cases were complicated by perforation,and the perforations were closed with metal clips.Additionally,18 cases in which the tumor size was more than 1.5 cm were treated with ESE,and no perforation occurred.Finally,13 cases in which the tumor size was more than 2.0 cm were treated with EFR;all of the cases were complicated by artificial perforation,and all of the perforations were closed with metal clips.All of the 69 cases recovered with medical treatment,and none required surgical operation.Immunohistostaining demonstrated that among all of the 69 gastric stromal tumors diagnosed by gastroscopy,12 cases were gastric leiomyomas(SMA-positive),and the other 57 cases were gastric stromal tumors.CONCLUSION:Gastric stromal tumors originating from the muscularis propria can be treated successfully with endoscopic techniques,which could replace certain surgical operations and should be considered for further application.

Current research and treatment for gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.

Prognostic factors of primary gastrointestinal stromal tumors： a cohort study based on high-volume centers

Objective： We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors（GISTs）.Methods： Data from 2,570 consecutive GIST patients from four medical centers in China（January2001–December 2015） were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors.Results： Of the included patients, 1,375（53.5%） were male, and the patient age range was 18 to 95（median, 58）years. The tumors were mostly found in the stomach（64.5%）, small intestine（25.1%） and colorectal region（5.1%）.At the time of diagnosis, the median tumor size was 4.0（range： 0.1–55.0） cm, and the median mitotic index per 50 high power fields（HPFs） was 3（range： 0–254）. Of the 2,168 resected patients, 2,009（92.7%） received curative resection. According to the modified National Institutes of Health（NIH） classification, 21.9%, 28.9%, 14.1% and35.1% were very low-, low-, intermediate-and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1（DOG-1）, 8.0% for S-100, 31.0% for smooth muscle actin（SMA） and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib（P〈0.001）, whereas intermediate-risk patients did not（P=0.954）.Conclusions： Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors

The most common digestive system(DS)cancers,including tumors of the gastrointestinal tract(GIT)such as colorectal cancer(CRC),gastric cancer(GC)and esophageal cancer(EC)as well as tumors of DS accessory organs such as pancreatic and liver cancer,are responsible for more than one-third of all cancerrelated deaths worldwide,despite the progress that has been achieved in anticancer therapy.Due to these limitations in treatment strategies,oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity.These studies led to new molecular target-driven therapeutic approaches.Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3(B7-H3)among the most common cancers of the GIT,including CRC,GC,and EC,whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal.This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms,and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways,such as Janus kinase 2/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B,extracellular signal-regulated kinase,and nuclear factor-κB.B7-H3 exerts an important role in progression,metastasis and resistance to anticancer therapy in these tumors.In addition,the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response.Accordingly,it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response,impaired tumor progression,invasion,angiogenesis,and metastasis and decreased resistance to anticancer therapy.Finally,the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis.In this review,we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.

Current treatment strategies and future perspectives for gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are mesenchymal tumors that originate from the gastrointestinal tract,mostly from the stomach.GISTs are derived from the myenteric interstitial cells of Cajal and are caused by several mutations in the c-kit and platelet-derived growth factor receptor genes.Clinically,GISTs are detected by endoscopic and imaging findings and are diagnosed by immunostaining.Surgery is the first line of treatment,and if the tumor is relatively small,minimally invasive surgery such as laparoscopy is performed.In recent years,neoadjuvant therapy has been administered to patients with GISTs that are suspected of having a large size or infiltration to other organs.Postoperative adjuvant imatinib is the standard therapy for high-risk GISTs.It is important to assess the risk of recurrence after GIST resection.However,the effect of tyrosine kinase inhibitor use will vary by the mutation of c-kit genes and the site of mutation.Furthermore,information regarding gene mutation is indispensable when considering the treatment policy for recurrent GISTs.This article reviews the clinicopathological characteristics of GISTs along with the minimally invasive and multidisciplinary treatment options available for these tumors.The future perspectives for diagnostic and treatment approaches for these tumors have also been discussed.

Clinical outcomes of gastrointestinal stromal tumor in southern Thailand

AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients.

Gastrointestinal stromal tumor metastasis at the site of a totally implantable venous access port insertion:A rare case report

BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.

Prognostic Factors of Gastrointestinal Stromal Tumors： A Single Institutional Retrospective Experience with Surgical Management over 20 Years

OBJECTIVE To analyze the pathological features and prognosis factors of gastrointestinal stromal tumor （GIST） after primary resection. METHODS Medical records of the diagnosis, surgery, and follow-up of 327 patients with GISTs who underwent surgery between 1988 and 2007 were retrospectively reviewed. The predic-tive factors for the survival of these patients were identi. ed using multivariate analysis. RESULTS In the 327 tumors, 152 （46.5%） were located in the stomach, 89 （27.2%） in the small intestine, 33 （10.1%） in the colon and rectum, and 43 （13.1%） in other sites including the omentum and mesentery. The 3-year and 5-year overall survival rates of the 327 GIST patients were 74.4% and 62.7%, respectively, and univariate survival analysis demonstrated that factors, such as tumor size, mitotic index, NIH categories, Ki-67 index, tumor location, surgical margins, tumor bleeding, and tumor necrosis have significant effect on survival of the patients （P 〈 0.05）. Multivariate analysis demonstrated that the NIH categories, surgical margins, and Ki-67 index were independent prognostic factors for the survival rate. In the group of patients with postoperative recurrence or metastasis, the median survival time of patients who did not receive imatinib treatment was 30 months and that of patients who received imatinib treatment was 59 months. Their 5-year survival rates were 16.4% and 39.4%, respectively, and the difference was statistically significant （P = 0.017）. CONCLUSION Complete resection is the .rst choice of treat-ment for GISTs. It is reasonable to evaluate the prognosis of resect-able GISTs and guide the adjunctive therapy with NIH categories and Ki-67 index. Imatinib treatment can signi.cantly increase the survival rate of patients with recurrent and metastatic GISTs.

Gastrointestinal Stromal Tumors in the 21^stCentury

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal lesions accounting for only 0.2% of all gastrointestinal neoplasms. These tumors arise from the interstitial cells of Cajal, with mutations described in proto-oncogenes such as KIT, PDGFRA, DOG-1, and SDH. The majority of these lesions are asymptomatic, thus the true incidence remains unknown. While patients typically undergo initial endoscopy, CT scan and/or MRI, findings are often nonspecific and require a biopsy to identify the tumor. As such, immunohistochemical evaluation is the gold-standard for the accurate diagnosis of GIST. Though surgical excision remains the gold-standard for curative management, the discovery of imatinib, a tyrosine kinase inhibitor (TKI), has revolutionized the treatment of GIST in the 21st?century as a “prototype” of molecular targeted therapy for solid tumors. Risk assessment for recurrence divides these tumors into low and high-risk categories. In the latter, a role for adjuvant therapy with TKI confers a significantly better prognosis than previously observed. However, secondary mutations conferring drug resistance remain an ongoing challenge for management, as few alternative treatment options are available for patients intolerant/refractory to TKI therapy. In this review, we summarize the epidemiology, molecular pathogenesis, clinical presentation, diagnosis, pathology features, management options, and prognostic features of GISTs.

Familial gastrointestinal stromal tumors with KIT germline mutation in a Chinese family:A case report

BACKGROUND Familial gastrointestinal stromal tumors(GISTs)is a rare autosomal dominant disorder characterized by an array of clinical manifestations.Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far.It is often characterized by a series of manifestations,such as multiple lesions and hyperpigmentation.However,the effect of imatinib treatment in these patients is still uncertain.CASE SUMMARY Here,we report two patients(father and daughter)in a Chinese family(for the first time)with germline KIT mutation,and described their pathology,genetics and clinical manifestations.A 25-year-old Chinese woman went to hospital because of abdominal pain,and computed tomography showed multiple tumors in the small intestine.Small pigmented spots appeared on the skin within a few months after birth.Her father also had multiple pigmented spots and a history of multifocal GISTs.Multiple GISTs associated with diffuse interstitial Cajal cells(ICCs)hyperplasia were positive for CD117 and DOG-1.Gene sequencing revealed a germline mutation at codon 560 of exon 11(p.V560G)of KIT gene in these two patients.Imatinib therapy showed the long-lasting disease stability after resection.Remarkably,the hypopigmentation of the skin could also be observed.Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient.CONCLUSION Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia,germline KIT/PDGFRA mutation,hyperpigmentation and family history.

Results of the Management of Gastrointestinal Stromal Tumors (GIST): About 6 Cases at the Vichy Hospital Center (France)

The aim of our study was to analyze the results of surgical management of gastrointestinal stromal tumors (GIST) at the Vichy Hospital Center. Methodology: Between 2010 and 2020, the data of 6 patients operated at the Vichy Hospital Center for GIST were analyzed. The parameters studied were: age, sex, antecedents, discovery circumstances, imagery, surgical procedure, anatomopathological data, the follow-up and the morbidity-mortality. Results: There were 5 men and one woman with an average age of 72.16 years [58 - 80 years]. The average time of evolution was 8 months (0 - 14 months). The diagnosis was fortuitous in 2 cases. Atypical abdominal pain was the main symptom in 3 cases. One case was received in a clinical picture of peritoneal irritation syndrome. Echo-endoscopy with biopsy specimen histology made it possible to make the diagnosis in 5 cases and the surgical specimen in 1 case. The fusiform type was the predominant histological form. The stomach was the most common location. The average size of GISTs was 7.3 × 4 cm with a positive C Kit in all patients. Neoadjuvant chemotherapy was performed on one patient. Surgery was curative and was done laparoscopically on 4 patients. Adjuvant chemotherapy based on Imatinib at a rate of 400 mg/d in 3 patients was initiated. One patient presented a fistula of the esophagus-jejunal anastomosis on D6 post operation controlled by a drainage and an antibiotic therapy. Mortality was zero. During the surgery, all of the patients were followed up with surgeon, oncologist. Conclusion: GISTs are the most common mesenchymal tumors of the digestive tract with a preferential gastric location. Laparoscopic surgery, with advances in molecular biology and the introduction of targeted therapy has improved the management of these tumors in terms of morbidity and mortality.