Gastrointestinal Stromal Tumors: Current Diagnosis, Biologic Behavior, and Management

Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The majority of GISTs are immunohistochemically positive for c-kit protein (CD117) and CD34. GISTs express a heterogeneous clinical course not easily predicted by standard pathological means. The most important prognostic factors are size >5 cm, tumor necrosis, infiltration and metastasis to other sites, mitotic count >1–5 per 10 high-powered fields, and most recently, mutation in the c-kit gene. Surgical resection remains the mainstay of treatment, as chemotherapy and radiation are ineffective. Long-term follow-up is imperative, as recurrence rates are high.     

Small,spontaneously ruptured gastrointestinal stromal tumor in the small intestine causing hemoperitoneum: A case report

IntroductionGastrointestinal stromal tumors (GISTs) are clinically asymptomatic until they reach a significant size; therefore, GISTs that are 2 cm or less are typically asymptomatic. Patients with symptomatic GISTs typically present with abdominal pain, gastrointestinal bleeding, or a palpable mass but rarely present with hemoperitoneum.Presentation of caseA 72-year-old Japanese man presented to us with acute onset abdominal pain. Physical examination showed peritoneal irritation in the lower abdomen. Findings of abdominal computed tomography were suggestive of hemoperitoneum; therefore, urgent surgery was performed. Approximately 1500 ml of blood in the abdominal cavity was removed. A small, ruptured mass was found in the middle of the small intestine, and partial resection of the small intestine, including the mass, was performed. The resected tumor was 2 cm in size and exhibited an exophytic growth pattern. Immunohistochemical staining revealed that the tumor was positive for KIT and CD34; therefore, a final diagnosis of GIST was made. Treatment with imatinib at 400 mg per day was started from postoperative month 1. The patient is doing well without recurrence 5 months after surgery.DiscussionEven small GISTs in the small intestine can spontaneously rupture and cause hemoperitoneum. Moreover, when a patient presents with sudden abdominal pain and hemoperitoneum without an evident mass on imaging, clinicians should be aware of the possibility of bleeding from a small GIST in the small intestine.ConclusionWe present an extremely rare case of a patient with a small, spontaneously ruptured GIST in the small intestine, resulting in hemoperitoneum.     

Secondary c-kit Mutation in a Recurrent Gastrointestinal Stromal Tumor Under Long-Term Treatment with Imatinib Mesylate: Report of a Case

Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the c-kit receptor gene, which are targets for imatinib mesylate. However, imatinib resistance is an increasing clinical problem. We herein present such a case with a recurrent GIST, in association with the development of a secondary mutation in the c-kit gene. A 67-year-old man, who had a GIST of the stomach with multiple liver metastases, underwent a partial gastrectomy, distal pancreatectomy, and partial hepatectomy. After surgery, he was treated with imatinib. However, during the approximately 4-year treatment period, a recurrence of the GIST in the liver was detected, for which a partial hepatectomy was again performed. The primary GIST constitutively had a deletion mutation in exon 11. In addition, the recurrent hepatic tumor developed a secondary point mutation (Val654Ala) in exon 13, which may be responsible for the imatinib resistance.     

胃间质瘤临床诊治和预后分析:附35例报告

目的:探讨胃间质瘤的临床特点,诊治经验和预后。方法:回顾性分析我院诊治的35例胃GIST病人的临床资料,并对临床特点、诊断、治疗以及预后进行报道,探讨该病复发转移的特点及影响预后的因素。结果:术前诊断正确率为68.6%肿瘤,中位直径7.0(1.5～14.0)cm。行胃楔形切除9例,胃部分切除23例,全胃切除3例;术后服用甲磺酸伊马替尼9例。CD117(+)100%,CD34(+)90.9%,Vim(+)79.3%,SMA(+)42.9%,S-100(+)26.9%。术后有6例出现复发转移,其中1例进行了再次手术。2例出现肝转移,3例后腹膜转移,1例腹腔广泛转移;2例死亡,4例带瘤生存。单因素分析发现,肿瘤直径≥5 cm、核分裂象≥5/50 HPF以及高危病人为胃GIST复发转移的预测因素。结论:胃GIST高危病人术后出现复发或转移的可能性大,即使出现复发、转移,也应积极再次手术,同时高危和复发转移者应配合甲磺酸伊马替尼辅助治疗。     

Transanal approach after preoperative imatinib treatment of a rectal gastrointestinal stromal tumors with external anal sphincter invasion: A case report

Introduction and importanceRectal gastrointestinal stromal tumors (GISTs) are rare, and preserving anorectal function can be challenging. We report the case of a patient with rectal GIST with external anal sphincter invasion, treated via the laparoscopic and transanal approaches.Case presentationA 61-year-old man with locally advanced GIST in the right anterolateral wall of the lower rectum was examined. Lower endoscopy revealed a 50-mm submucosal tumor located 4 cm from the anal verge. On immunohistochemistry, the biopsy specimen tested positive for CD34 and C-KIT, and the patient was diagnosed with GIST. Abdominal magnetic resonance imaging (MRI) revealed external anal sphincter infiltration. Because of the large tumor size and proximity to the anal verge, preserving the anus was challenging, and colorectal resection was avoided. Instead, neoadjuvant therapy with imatinib was administered to facilitate local resection of the tumor. Post-treatment MRI showed a reduction in tumor size (30 × 20 × 30 mm), and surgery was performed. We identified an appropriate resection line for diplomatic sphincter resection of the infiltrated area by laparoscopy alone. Thus, we performed a hybrid surgery using the laparoscopic and transanal approaches. The patient had an unremarkable postoperative course and was discharged on postoperative day 23.Clinical discussionNo study has reported cases of rectal GIST with external anal sphincter invasion wherein anal function was preserved. Here, imatinib was administered preoperatively, and hybrid surgery was performed using the transanal and laparoscopic approaches.ConclusionPreoperative treatment and surgery preserved anorectal function in a patient with a massive rectal GIST.     

Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature

Gastrointestinal stromal tumors (GISTs), specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are rare in children and young adults, and their clinicopathologic and molecular genetic profile is incompletely understood. In this study, we analyzed 44 gastric GISTs occurring by the age of 21 years. There were 32 females and 12 males, youngest of whom were a 5-year-old boy and an 8-year-old girl. All but 1 of 25 patients under the age of 16 were girls. The patients most commonly received medical attention because of chronic, insidious gastrointestinal bleeding with anemia, less commonly with acute GI bleeding. Only 1 patient had Carney triad with pulmonary chondroma. None of the patients had family members with GIST. The tumors measured from 1.5 to 24 cm (median, 5.6 cm). A total of 21 tumors with specified location were in the antrum and 8 were in the gastric body. Histologically, 26 tumors were composed of epithelioid cells, 12 of spindle cells, and 6 of combination thereof. Mitotic activity varied form 0 to 65/50 HPF (median, 5/50). All but one of the 24 tumors tested were KIT-positive, and 20 were CD34-positive. Eleven patients developed liver or abdominal metastases, and 6 of them died of tumor surviving 5.5 to 35.5 years (median, 16 years) after the first surgery; three of these tumors had a low mitotic activity and size <10 cm. Twenty-one patients were alive with no evidence for disease 7 to 41 years (median, 17 years) after the first surgery. None of the 13 tumors examined (7 of them 8- to 16-year-old females) had KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as typically seen in adult GISTs. Gastric GISTs in children have mainly epithelioid morphology, often occur in antrum, and have a somewhat unpredictable but slow course of disease. Their pathogenesis may differ from that of adult GISTs because no KIT or PDGFRA mutations were found; connection with Carney triad seems infrequent despite demographic and histologic similarities.     

NOD2 mutations predict the risk for surgery in pediatric-onset Crohn's disease

Backgroud/Purpose

Three common mutations of the NOD2/CARD15 gene have been associated with Crohn disease (CD), ileal disease location, and fibrostenotic behavior. The aim of this study was to investigate the effect of these mutations on disease manifestation and the risk of surgery in a cohort of German childhood-onset CD patients.

Methods

Genotyping for the NOD2 mutations p.Arg702Trp, p.Gly908Arg, and p.1007fs was performed in 171 CD children (onset of disease <17 years; mean 11.8 years) and in 253 controls. NOD2 mutation status was correlated with the need for surgery during childhood.

Results

Seventy-eight children (45.6%) were carriers of at least 1 NOD2 mutation versus 36 (14.2%) in the control group (P < .0001). NOD2 mutations were highly associated with CD and stricturing behavior (P < .0001), with the p.1007fs mutation also conferring a risk for isolated ileal disease (P = .003). Thirty-two children (18.7%) needed an intestinal resection with a significant association between the need of surgery and NOD2 carrier status. Surgery occurred at an earlier stage of disease in children with p.1007fs mutations.

Conclusions

In children with pediatric-onset CD, the need for surgical therapy younger than 17 years is associated with the NOD2 genotype. Genetic testing therefore may identify children with CD who are at risk.     

Exophytic gastrointestinal stromal tumor of the stomach. Report of two cases

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Most GISTs occur in the stomach (60-70%). Their diagnosis is established immunohistochemically and reveals that the tumor cells are immunoreactive for the antigens CD117 and CD34. The infiltration of the adjacent organs, the large tumor size (>5cm) and the mitosis count of the cells (>5/50 CHPFs) are typical characteristics of GIST malignancy. GISTs rarely infiltrate adjacent organs and usually push them back. The clinical behaviour of GISTs is highly variable and tumor size mitotic rate and location are prognostic determinants.The biologic behaviour of GIST is variable. The majority were previously thought to be benign due to their characteristically bland histopathologic features. However, it is becoming increasingly clear that with long follow-up, virtually all GISTs have the potential for malignant behaviour, even those 2 cm or less with bland histologic features. Thus, it is not appropriate to define any GIST as "benign" per se.We present two cases of exophytic gastric GIST which were recently treated successfully in our Clinic with “wedge” gastric resection. The margins were negative and there was neither rupture of the tumor, nor spillage.     

Multiple jejunal gastrointestinal stromal tumors and Neurofibromatosis type 1: A rare association

Introduction and importanceThe association between gastrointestinal stromal tumor (GIST), mesenchymal tumor arising from the interstitial cells of cajal and Neurofibromatosis type 1 (NF1), an autosomal dominant disease has been reported in the literature. GIST in NF1 patients are multiple and located in the small intestine. Tumorigenesis in NF1 associated GIST is different to that of sporadic GIST and hence the treatment. Here we report a rare case of an NF1 patient with multiple jejunal GISTs.Case presentationWe here present a rare case of a 57-year-old male diagnosed with NF1 30 years back, presented in our emergency department with complaints of black, tarry stools later diagnosed to have multiple GIST in jejunum. Contrast enhanced computed tomography (CECT) of the abdomen showed a large 10.1 × 7.33 × 6.2 cm heterogeneous, exophytic, solid mass with cystic areas originating from the jejunum. The microscopic examination of the specimen showed spindle shaped tumor cells while immunohistochemistry showed CD117 (c-KIT) and DOG-1 positivity. The primary treatment was complete surgical excision of the tumor.Clinical discussionThe incidence of GISTs in NF1 patient is around 6–7%; however, concomitant presence of multiple GISTs is rare. CECT of abdomen along with histopathological and immunohistochemistry studies are diagnostic. The management of GIST includes surgical and adjuvant therapy methods based on the tumorigenesis and recurrent risk stratification.ConclusionEarly clinical suspicion and imaging aids in early detection of the tumor in patients with NF1 presenting with gastrointestinal symptoms. Postoperatively, screening for recurrence with radiology is of utmost importance.     

Gastrointestinale Stromatumoren

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the gastrointestinal tract. The standard therapy is complete surgical resection with safety margins of 1–2 cm. Intraoperative rupture of the tumor capsule must be avoided because this carries a very high risk of tumor spread. A lymph node dissection is not routinely indicated as lymph node metastases very rarely occur with GIST. Smaller GISTs can normally be removed laparoscopically according to the rules of tumor surgery. Depending on the size of the tumor, the mitosis index and the localization of the primary tumor, the risk of recurrence after potentially curative resection is considerable in many cases. Patients with intermediate and high risks according to Miettinen’s classification should receive adjuvant treatment with the tyrosine kinase inhibitor imatinib. Exceptions are those patients whose tumors exhibit the mutation D842V in exon18 of the PDGFRA gene. According to current European Society for Medical Oncology (ESMO) guidelines this therapy should be continued for 3 years. This leads to a significant improvement in progression-free survival compared to a 1-year therapy, and more important to an improvement in overall survival.     

Gastrointestinal Stromal Tumor of the Rectum: An Analysis of Seven Cases

Purpose Gastrointestinal stromal tumors (GISTs) rarely originate in the rectum. We investigated the clinicopathologic characteristics of rectal GISTs. Methods We analyzed the medical records of seven patients who underwent surgery for GIST of the rectum between 1998 and 2003. Results There were two men and five women with a median age of 55 years (range, 41–72 years) at the time of diagnosis. The median follow-up period was 23 months (range, 7–75 months). The chief symptoms were hematochezia, constipation, and anal pain. All patients underwent curative resection; in the form of abdominoperineal resection in five patients, transanal excision in one, and Hartmann's operation with prostatectomy in one. The median tumor size was 6.6 cm (range, 1–12 cm). Four patients received adjuvant radiation therapy. Local recurrence developed in two patients; 54 months and 23 months after surgery, respectively. Conclusion The common symptoms of rectal GIST were the same as those of other rectal tumors. Curative surgical resection should be done, but further studies are necessary to investigate better adjuvant treatment strategies for patients with rectal GISTs     

复发转移胃肠道间质瘤治疗策略

胃肠道间质瘤（GIST）的检出率逐年升高。大多数GIST可行手术切除，单纯手术后约70％～84％会出现复发转移，术后中位复发转移时间约为2年。中位生存期只有1年左右。伊马替尼应用于GIST治疗可延长至5年。然而，约一半以上的复发转移GIST患者应用药物半年以上后最终出现耐药，故如何合理安排此类患者治疗模式成为当前最迫切的需求。本文从复发转移GIST患者的评估、合理用药、手术干预、药物治疗失败后补救措施、患者依从性管理等方面介绍治疗策略。     

Predicting Recurrence and Progression of Noninvasive Papillary Bladder Cancer at Initial Presentation Based on Quantitative Gene Expression Profiles

Background

Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified.

Objective

To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach.

Design, setting, and participants

Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n = 16), recurrence without progression (n = 16), and progression to carcinoma in situ or invasive disease (n = 16).

Measurements

Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation.

Results and limitations

CCND3 (p = 0.003) and HRAS (p = 0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97% and 63%, respectively. HRAS (p < 0.001), E2F1 (p = 0.017), BIRC5/Survivin (p = 0.038), and VEGFR2 (p = 0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81% sensitivity and 94% specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed.

Conclusions

Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.     

Primary large gastrointestinal stromal tumor of the liver: Report of a case

A 30-year-old man was diagnosed to have a large intra-abdominal tumor in 1999. A histological examination of a resected liver specimen from an operation in 2002 revealed a gastrointestinal stromal tumor (GIST), diagnosed based on positive immunostaining for CD34 and c-kit. Two years after the operation, new lesions developed in the residual liver and the lesser curvature of the stomach. An immunohistological examination of both specimens showed the features of a GIST, thus matching those of the first histological examination of the liver GIST. While there were no mutations at exon 11 of c-kit in the liver GISTs resected in 2002 and 2004, the gastric lesion had a mutation at P577L (CCT to CTT) at exon 11. Therefore, the liver GIST and the gastric lesion were diagnosed to be independent. The patient already has survived for more than 9 years after receiving surgery three times and with administration of imatinib.     

磷酸化血小板源生长因子受体α和C—kit在胃肠道和胃肠道外间质瘤的表达及其临床意义

目的探讨磷酸化血小板源生长因子受体α（P—PDGFR—α）在胃肠道间质瘤（GIST）和胃肠道外GIST（EGIST）的表达及临床意义，为进一步提高GIST和EGIST的病理诊断、病理分型及临床治疗提供依据。方法用免疫组织化学方法检测28例CD117阳性和13例CD117阴性的GIST和EGIST间质瘤组织中P—PDGFR-α的表达，并且用PCR直接测序的方法检测41例GISTC—kiI基因外显子9、11、13、17和P—PDGFR-α外显子12、18突变。结果P—PDGFR-α在CD117阴性的GIST表达（69．2％）显著高于在CD117阳性的GIST表达（7．1％）（P〈0．05）；P—PDGFR-α在上皮型GIST的表达（27．3％）和混合型GIST的表达（63．3％）均显著高于在梭型细胞型GIST的表达（9％）（P〈0．05）；CD117在梭型细胞型GIST的表达（53．6％）明显高于在上皮型GIST（7．1％）和混合型GIST（39．3％）的表达（P〈0．05）。在28例CD117阳性GIST中，19例有c—kit基因的突变，其中15例在外显子11有突变，4例在外显子13有突变，13例CD117阴性GIST中无C—kit基因突变：11例PDGFR-α阳性的GIST中4例有PDGFR-α基因的突变．均发生在外显子18。结论P—PDGFR-α为CD117阴性GIST的病理诊断、病理分型和临床治疗进一步提供了可靠的依据。PDGFR-α基因突变后引起产物蛋白的磷酸化可能是CD117阴性的GIST发生的重要分子基础和生物学行为。     

直肠间质瘤19例的诊断与治疗

目的探讨直肠间质瘤的临床、病理特点及合理治疗方法.方法对1986年6月至2005年2月收治的19例直肠间质瘤患者的临床、病理学及治疗等临床资料进行回顾性分析.结果19例中男11例,女8例,平均年龄53.5岁.19例患者诊断均经手术及病理证实.组织学形态以梭形细胞为主,CD117、CD34阳性率分别为100%及74%.高侵袭危险度5例,中侵袭危险度3例,低侵袭危险度4例,极低侵袭危险度7例.结论直肠间质瘤少见,多数倾向于低度恶性生物学行为.治疗以外科手术切除为主.术前获得病理诊断以及术式的选择存在一定困难.对肿瘤直径＜3cm的低侵袭危险度病例,应经肛门行局部切除术.     

Surgical Outcomes of Patients with Gastrointestinal Stromal Tumors in the Era of Targeted Drug Therapy

Background  The discovery of the c-KIT mutation and the advent of targeted drug therapy with imatinib mesylate have revolutionized the management of gastrointestinal stromal tumors (GISTs). The outcome of patients with surgically treated GISTs treated in the era of targeted drug therapy was assessed and factors associated with adverse outcomes determined. Materials and Methods  Patients with GISTs requiring surgery at a tertiary care center from 2002 to 2007 were reviewed and prognostic factors determined. Results  Forty patients were surgically treated for GISTs. The median age at presentation was 59 years. The stomach (55%) was the main site of primary disease. The median tumor size was 7 cm. Eleven (28%) patients had metastatic disease at presentation. Surgery was undertaken in all patients with curative intent. Multi-organ resection was required in 10 (25%) patients. Imatinib mesylate was administered postoperatively in 68% of cases. Median follow-up was 24 months. There was a 40% recurrence rate with 63% undergoing repeat surgical resection. The peritoneum and liver were the main sites of recurrent disease. The 5-year disease-specific survival and disease-free survival (DFS) were 65% and 35%, respectively. High mitotic rate (P = 0.017) and tumor size greater than 10 cm (P = 0.009) were the only prognostically significant adverse factors of DFS on multivariate analysis, independent of imatinib mesylate treatment. Conclusion  Aggressive surgical treatment and follow-up of GISTs, combined with targeted drug therapy, leads to long-term DFS survival. Tumor recurrence is independently associated with a high tumor mitotic rate and size greater than 10 cm, despite the use of adjuvant targeted drug therapy.     

Gastrointestinal stromal tumors (GIST) of the stomach as a cause of upper gastrointestinal bleeding

Gastrointestinal stromal tumors (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor containing spindle cells (less commonly epitheloid cells or rarely both) and showing CD 117 (c-kit protein) positivity in more than 95% of cases. Although they may arise throughout the gut, the commonest site are stomach (60-70%), small intestine (20-30%), colorectum (5%) and esophagus (up to 5%). Rarely, GISTs develop in the retroperitoneum, omentum or mesentery. GIST originates from the intestinal cell of Cajal (ICC). ICCs are located in and around the myenteric plexus and are thought to function as intestinal pacemaker cells. Historicaly, GIST were often misclassified as leiomyomas or leiomyosarcomas. Subsequently, it has been determined that GISTs have distinct ultrastructural features and immunophenotypical markers compared with smooth muscle and smooth muscle tumors. GIST predominantly occur in middle aged and older patients, with no significant difference in the sex incidence. Data from the recent population study suggest an incidence of about 10-22 cases per million persons per year. Clinical presentation of GIST varies widely, and depends on tumor size and location. GISTs that caused symptoms tended to be larger with an average size of 6cm versus 2cm for asymptomatic GISTs. Symptoms are most commonly related to mass effect or bleeding. GISTs can grow very large before producing symptoms. Commonest symptom of gastric GIST is manifest or occult bleeding. Abudant, life-threateting bleeding that require urgent surgery is rare. For patient with primary, localized, nonmetastatic GIST, complete surgical resection represents the only chance for cure. Lymhadenectomy is not necessary, because lymph node metastasis is very rare. The 5 year survival rate in patients with resected primary GISTs ranges from 48-65%. Conventional chemotherapy and radiation therapy is ineffective in the treatment of GIST. Imatinib mesilate (a tyrosine kinase inhibitor) was confirmed to be effective against metastatic or unresectable GISTs.     

Predicting the Antitumor Effects of STI571 by Analysis of c-kit Gene Mutations in Gastrointestinal Stromal Tumors of the Stomach: Report of a Case

We report a case of a large gastrointestinal stromal tumor (GIST), greater than 5 cm in diameter, in the stomach. Microscopically, high levels of mitosis were observed, indicative of a high-grade malignancy. We analyzed the c-kit gene mutations by a replication competent retrovirus assay and DNA sequencing, which revealed a c-kit mutation in exon 11. Liver metastases were detected 7 months after surgery. Patients with an exon 11 mutation of the c-kit gene are reported to have a high response to STI571 (imatinib mesylate, Glivec). Accordingly, a 1-month course of STI571 treatment clearly changed the characterization of the metastatic tumors radiographically. Thus, it may be important to analyze c-kit gene mutations in patients presenting with GISTs to predict the effectiveness of STI571 in suppressing GISTs, especially tumors thought to have malignant potential.     

Surgical management of GIST in the era of Gleevec

The diagnostic and treatment options for patients with GIST have evolved rapidly with the discovery of uncontrolled KIT tyrosine kinase and Gleevec that selectively inhibits Kit. Gleevec has already revolutionized the treatment of patients with metastatic disease and is also currently being tested as an adjuvant therapy after the resection of primary GIST. But the majority of responses are limited to partial responses and secondary resistances are emerging. These observations suggest that initial surgical resection remains a vital component of the treatment for patients with primary resectable cKIT+ GISTs and raises the question of secondary surgery after Gleevec. The objective of secondary surgery is to obtain a complete remission when the response to Gleevec is maximum. Surgery should be discussed between 6 and 12 months treatment when no additional improvement is observed on 2 consecutive CT scan. Three subgroups may benefit from secondary surgery: primary unresectable tumors amenable to surgery with Gleevec even in case of complete response, huge necrotic masses before expected complication, local re-progressions. Gleevec should also be discussed when a functionnal benefit can be expected by a tumor size decrease. Surgery is being evaluated in the other responding patients. The majority of responses being limited to partial responses, best indications of surgery are when complete resection may be expected (< 10%).