Surgical Resection of Gastrointestinal Stromal Tumors After Treatment with Imatinib

Background Surgical resection of gastrointestinal stromal tumors (GISTs) has been the most effective therapy for these rare tumors. Imatinib has been introduced as systemic therapy for locally advanced and metastatic GIST. In this study, the surgical resection rates and long-term outcomes of patients treated with preoperative imatinib for locally advanced primary, recurrent, or metastatic GISTs were evaluated. Methods Patients were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. Results Forty-six patients underwent surgery after treatment with imatinib. Eleven were treated for locally advanced primary GISTs for a median of 11.9 months, followed by complete surgical resection. All eleven were alive at a median of 19.5 months, and ten were free of disease. Thirty-five patients were treated for recurrent or metastatic GIST. Of these, eleven underwent complete resection. Six of the eleven patients had recurrent disease at a median of 15.1 months. All eleven patients were alive at a median of 30.7 months. Patients with a partial radiographic tumor response to imatinib had significantly higher complete resection rates than patients with progressive disease (91% vs. 4%; P < .001). Of the 24 patients with incomplete resection, 18 initially responded to imatinib but were unable to undergo complete resection after they progressed before surgery. Conclusions Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs. Presented in part at the Annual Meeting of the Society of Surgical Oncology, Atlanta, GA, March 2005.     

Rhabdomyosarcomatous differentiation in gastrointestinal stromal tumors after tyrosine kinase inhibitor therapy: a novel form of tumor progression

Approximately 80% of advanced metastatic gastrointestinal stromal tumors (GISTs) respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib mesylate. However, the majority of patients suffer disease progression at a median of 2 years due to drug resistance. In general, progressing GISTs retain their typical morphology. Herein, we report 5 cases of progressing metastatic GIST with heterologous rhabdomyoblastic differentiation after TKI treatment. Histologic, immunohistochemical, and mutational analyses were performed on histologically classic GISTs and components with rhabdomyoblastic differentiation. There were 3 men and 2 women (ranging from 35 to 66 y of age). Three tumors were localized at presentation (2 stomach and 1 small bowel) and 2 presented with metastases. All localized primary tumors were high risk. Two tumors showed spindle cell morphology and 3 were epithelioid, including 1 with marked pleomorphism. After resection of the 3 localized primary tumors, intra-abdominal (2 patients) and liver (1 patient) metastases developed. All patients were treated with imatinib and showed partial clinical responses (4 patient) or stable disease (1 patient). Four patients subsequently progressed; 2 patients were treated with sunitinib after progression with minor responses. Four patients underwent surgical debulking. At last follow-up (range: 20 to 87 mo), 2 patients died of disease, 2 were alive with metastatic disease resistant to TKIs, and 1 was alive without evidence of disease. In all cases, rhabdomyoblastic differentiation was identified adjacent to areas with classic GIST morphology in at least 1 metastatic site; in 1 case, the primary tumor (after treatment with TKIs) showed heterologous differentiation. The rhabdomyoblastic components showed strong and diffuse positivity for desmin and expressed myogenin, whereas KIT was negative in the rhabdomyoblastic component in all cases. Primary KIT mutations were detected in both the conventional GIST and rhabdomyoblastic components from all patients: KIT exon 11 mutations in 4 cases and a platelet-derived growth factor receptor alpha gene exon 18 deletion in 1 case. No secondary mutations of the type associated with TKI resistance were identified in the rhabdomyoblastic areas. This is the first report of rhabdomyoblastic differentiation occurring in GISTs that progressed on TKI therapy. It is associated with loss of KIT expression, but retention of the receptor tyrosine kinase mutation of the precursor GIST. The rhabdomyoblastic differentiation can represent a diagnostic pitfall. The molecular mechanisms for this form of TKI-resistant clonal evolution remain to be determined.     

Combined surgical and molecular therapy: the gastrointestinal stromal tumor model

OBJECTIVE: This review describes the pathologic and epidemiologic features of gastrointestinal stromal tumor (GIST) as well as the contemporary management of this tumor. The integration of surgery and treatment with targeted molecular agents in the treatment of GIST is highlighted. SUMMARY BACKGROUND DATA: GIST is the most common mesenchymal tumor of the gastrointestinal tract. Its cellular origin from the interstitial cell of Cajal and distinctness from smooth muscles tumors were only recently appreciated. The discovery of the centrality of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST. METHODS: We conducted a review of the English literature on GIST. The pathology, epidemiology, diagnosis, and treatment of this tumor are summarized with particular emphasis on recent developments in the field. RESULTS: GIST is a rare tumor that usually arises from the stomach or small intestine. It is characterized by immunohistochemical staining for KIT. Treatment of primary localized tumors is surgical. The benefit of adjuvant treatment with the KIT tyrosine kinase inhibitor imatinib is the subject of investigation. The treatment of unresectable, recurrent, or metastatic GIST is primarily imatinib treatment. The integration of surgery or ablative modalities is often employed, particularly when all disease is amenable to gross resection or destruction, or when GIST becomes resistant to imatinib. Newer tyrosine kinase inhibitors, such as sunitinib are the subject of ongoing investigation. CONCLUSIONS: The treatment paradigm for GIST has required the integration of surgery and molecular therapy and this will likely serve as a paradigm for the treatment of other solid tumors as targeted agents are developed.     

Analysis of Prognostic Factors Impacting Oncologic Outcomes After Neoadjuvant Tyrosine Kinase Inhibitor Therapy for Gastrointestinal Stromal Tumors

Background

Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown.

Methods

Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records.

Results

Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3–1,611) days for primary and 537 (range 4–3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS.

Conclusions

Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.     

Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor

INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. Nearly all tumors have an activating mutation in the KIT or, less often, PDGFRalpha, gene. Therapy with tyrosine kinase inhibitors benefits over 80% of patients with advanced GIST, but most patients eventually develop drug resistance. METHODS: Forty patients with metastatic GIST were treated with tyrosine kinase inhibitors and then underwent surgical resection. Based on the growth of their tumors by serial radiologic imaging, patients were categorized at the time of operation as having responsive disease, focal resistance (1 tumor growing), or multifocal resistance (more than 1 tumor growing). Patients were followed for a median of 15 months (range, 6-46 months) after surgery. RESULTS: Initially, molecular therapy achieved stable disease or a partial response in all but 1 patient. Surgery was performed after a median of 15 months, and there were no perioperative deaths. After operation, the 20 patients with responsive disease had a 2-year progression-free survival of 61% and 2-year overall survival of 100%. In contrast, the 13 patients with focal resistance progressed after surgery at a median of 12 months and the 2-year overall survival was 36%. There were 7 patients with multifocal resistance and they progressed postoperatively at a median of 3 months and had a 1-year overall survival of 36%. CONCLUSION: Selected patients with metastatic GIST who have responsive disease or focal resistance to tyrosine kinase inhibitor therapy may benefit from elective surgical resection. Surgery for patients with metastatic GIST who have multifocal resistance is generally not indicated, and these patients should be considered for clinical trials of new systemic agents.     

Surgical treatment of gastrointestinal stromal tumors in the imatinib (STI-571) era

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors that are characterized by constitutive overexpression of the tyrosine kinase receptor KIT (CD117). Imatinib mesylate is a selective inhibitor of tyrosine kinase-mediated activity. This study reports a single-institution experience of surgical resection and the use of imatinib in the treatment of GIST. METHODS: A retrospective review from 1995 to 2002 identified 57 patients (M:F, 29:28; median age, 61 years) with GIST who were treated at the University of Chicago. Twenty-eight patients underwent exploratory surgery with curative intent; 29 patients were referred for treatment of metastatic disease after surgery at outside institutions. Twenty-nine patients were treated with oral imatinib for either metastatic disease (n=26 patients) or in the adjuvant setting after complete resection (n=3 patients). RESULTS: Resections were performed in 53 patients, and metastatic disease was identified in 17 patients at the time of exploratory surgery. Immunohistochemical staining for CD117 was positive in 96% of patients. A size larger than 5 cm, a mitotic rate larger than 1/10 high-power field, and tumor necrosis predicted recurrence in patients after resection. The median follow-up period was 18 months (range, 4-81 months). Twenty-three patients (40%) are alive without disease; 22 patients (39%) are alive with disease; 7 patients died, and 5 patients are lost to follow-up. Among the 26 patients with metastatic disease who were treated with imatinib, 5 deaths have occurred, and disease stabilization or tumor regression was observed initially in 22 patients, with a median duration of response of 19 months. CONCLUSIONS: Complete surgical extirpation remains the only curative treatment of GIST. Imatinib-targeted therapy of metastatic disease yields encouraging clinical responses. The true efficacy of imatinib in this setting, as induction therapy or as an adjuvant treatment in patients with GIST, is unknown pending the completion of ongoing prospective trials.     

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%).     

Staged surgical approach for metastatic GIST,how far should we go? Case report

IntroductionGastrointestinal stromal tumor (GIST) is an uncommon mesenchymal neoplasm that commonly arises from the stomach and proximal small intestine but can develop in any part of the gastrointestinal tract. The disease can range from primary localized to an advanced metastatic unresectable disease in up to 30% of patients. Usually, metastasis involves the liver, peritoneum, and occasionally the lungs. The current standard treatment of localized resectable tumors is complete oncological resection, while advanced metastatic GISTs treatment remains contentious.Case presentationWe report a case of a 34 years old pregnant female presenting with a 3 days history of multiple episodes of hematemesis and melena. Laboratory investigations were unremarkable except for severe anemia (Hgb 4.4 g/dL). After further investigations a diagnosis of duodenal GIST (DGIST) with liver metastasis was made. She received and showed good response to neoadjuvant Imatinib therapy, which was followed by a successful 2-stage surgery in the form of extended right hepatectomy and Whipple procedure with a good survival.Clinical dissectionThe evolution of Imatinib had a tremendous impact on surgery in metastatic GIST even in initially unresectable cases, thereby providing a better survival. However, the duration of neoadjuvant Imatinib course and the matter of resistance are still unclear those necessitating the use of different agents or the surgical approach.ConclusionAlthough with the advancements in surgical approaches and perioperative care, liver resection might be a curative option. The role of surgery in advanced GIST remains a controversial matter that needs critical selection of cases based on further future research.     

Optimizing Surgical and Imatinib Therapy for the Treatment of Gastrointestinal Stromal Tumors

Introduction

The discovery of activating KIT and PDGFRα mutations in gastrointestinal stromal tumors (GISTs) represented a milestone as it allowed clinicians to use tyrosine kinase inhibitors, like imatinib, to treat this sarcoma. Although surgery remains the only potentially curative treatment, patients who undergo complete resection may still experience local recurrence or distant metastases. Therapeutic strategies that combine surgical resection and adjuvant imatinib may represent the best treatment to maximize patient outcomes. In addition to the use of imatinib in the adjuvant and metastatic settings, neoadjuvant imatinib, employed as a cytoreductive therapy, can decrease tumor volume, increase the probability of complete resection, and may reduce surgery-related morbidities. Thus, selected patients with metastatic disease may be treated with a combination of preoperative imatinib and metastasectomy. However, it is critical that patients with GIST be evaluated by a multidisciplinary team to coordinate surgery and targeted therapy in order to maximize clinical outcomes.

Discussion

Following a systematic literature review, we describe the presentation, diagnosis, and treatment of GIST, with a discussion of the risk assessment for imatinib therapy. The application of surgical options, combined with adjuvant/neoadjuvant or perioperative imatinib, and their potential impact on survival for patients with primary, recurrent, or metastatic GIST are discussed.     

Preoperative Imatinib Treatment in Patients With Advanced Gastrointestinal Stromal Tumors: Patient Experiences and Systematic Review of 563 Patients

Preoperative IM therapy for GIST is now a research focus. Due to the low incidence of the disease, there are few RCTs on the preoperative treatment for advanced GIST, let alone relevant meta-analysis. Efficacy of this therapy and targeting population are still undetermined. Therefore, the first part of this article is composed of a controlled retrospective study and demonstrates that preoperative therapy with IM can significantly improve the outcome of advanced GIST. In the second part of the paper, we further investigated what portion of advanced GIST patients benefit more from the therapy, based on a meta-analysis. As the disease is relatively rare, we involved 563 cases in the meta-analysis, much higher than in the controlled clinical studies (51 cases). The objective of this paper is to investigate effects of surgical resection on imatinib-treated advanced GIST. Twenty-two consecutive advanced GIST patients (Group A) with preoperative IM treatment were compared to 29 patients (Group B) who underwent initial tumor resection during the same period. Subsequently, a systematic review of 563 patients was applied to identify the benefit of the advanced GIST patients receiving imatinib before surgery. Compared with Group B, less patients in Group A underwent multivisceral resection (18.2% versus 48.3%, P = 0.026) or suffered tumor rupture at time of surgery (0% versus 17.2%, P = 0.04). The 3-year estimated progression-free survival of Group A (94.4%) was also superior to that of Group B (61.4%; P = 0.045). Subsequent meta-analysis indicated that primarily unresectable patients had higher complete resection and 2-year PFS rates than recurrent/metastasis patients (P = 0.005 and 0.20, respectively); (b) stable disease (SD) patients had better outcome in resection including resectability rate (P < 0.0001), PFS (P < 0.00001) and OS (P = 0.0008) than progressive disease (PD) patients; (c) in recurrent/metastatic PD patients, surgery played a minor role, because they had a higher bulky residual disease rate (P = 0.0005) and higher progression risk (P < 0.00001) within 2 years after surgery. Preoperative IM treatment improves prognosis of advanced GISTs. Among recurrent/metastatic patients, postimatinib surgery may benefit those who have SD after IM treatment but not those resistant to IM.Key words: Gastrointestinal stromal tumors, Imatinib, Targeted therapy, Surgical resectionGastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasia of the digestive tract, with a worldwide incidence of approximately 15 per 1 million people. Between 15% and 50% of GISTs are advanced at the time of diagnosis.¹ Historically, owing to the low response rate of GISTs to conventional chemotherapy or radiation therapy (overall response rate < 5%),² surgery was the only recognized treatment for GIST before the advent of imatinib. However, surgery has historically had poor outcomes, so surgery alone is seldom sufficient for advanced GIST. Even if patients with locally advanced GIST undergo complete resection, tumor recurrence occurs frequently, and the 5-year survival can be as low as 54%. In patients with locally nonresectable, recurrent or metastatic disease, the outcomes are even poorer, with a median survival of 12–19 months and a 5-year survival rate of < 5–10%.³In 2000, imatinib mesylate (IM), a tyrosine kinase inhibitor, was first reported to have been used in one patient with metastatic GIST, and it achieved remarkable success.⁴ Currently, IM is the first-line palliative treatment for advanced GIST.^5,6 Nevertheless, although IM confers clinical benefits to more than 80% of patients with advanced disease, complete response to IM therapy is restricted to a few patients. Furthermore, while the majority of patients initially benefit from IM, the development of resistance to the drug still limits long-term IM use. Clinical trials have shown that two-thirds of the patients with metastatic disease who use IM develop progression, with a median progression-free survival (PFS) of approximately 20 to 24 months.⁷ These flaws in IM treatment led us to investigate the value of potential multimodal approaches combining surgery and IM therapy. Several multi-institutional trials have described the successful use of postoperative IM treatment,^8,9 which was approved for adjuvant treatment of patients with primary GIST in December 2008 by the US Food and Drug Administration (FDA). In addition, surgery following primary IM treatment is feasible in advanced GIST.^10,11 However, limited by low case numbers, most of these studies have been based on the results of isolated cases or small joint institutions, and they do not include randomized controlled clinical trials. Therefore, little is known about the exact effects of postimatinib surgical resection on outcomes of patients with locally advanced primary, recurrent or metastatic GIST. In the present study, we retrospectively analyzed the outcomes of patients with advanced GISTs who received preoperative IM treatment at our institution and compared their outcomes with the prognostic results of patients with high-risk GIST (according to the NIH risk stratification system¹²) who did not receive preoperative IM. Then, we performed a meta-analysis in which we further divided advanced patients into an unresectable and a metastasis group or a stable disease and a progressive disease group to identify which portion of the advanced patients benefit more from the surgery following IM therapy. By combining our findings with the results of our meta-analysis, we evaluated the role of postimatinib surgical intervention in patients with advanced GISTs.     

如何更好地联合外科手术与靶向药物治疗胃肠间质瘤

对于原发性局限性胃肠间质瘤（GIST）．外科手术结合术后伊马替尼辅助治疗已成为中高危患者的治疗共识。而对于一些手术切除困难、部位特殊或需要联合脏器切除的原发局限性GIST．术前伊马替尼治疗可以使肿瘤降期而降低手术风险．提高切除率．甚至保留脏器功能。而对于进展期GIST,靶向药物是治疗的首选,外科手术干预尽管在一些回顾性的病例分析中显示出一定的效果．但仍缺乏前瞻性对照试验的证据支持。如何在两类患者中更好地结合靶向治疗和外科手术已成为GIST综合治疗实施的关键。     

Cardiac Angiosarcoma Management and Outcomes: 20-Year Single-institution Experience

Purpose

To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS).

Methods

This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival.

Results

Data from 18 patients (78?% male) were reviewed. Sixteen patients (89?%) had AS originating in the right atrium. At diagnosis, eight patients (44?%) had localized/locally advanced disease and ten patients (56?%) had metastatic disease. Initial treatment strategies included resection (44?%), chemotherapy (39?%), and radiotherapy (11?%). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12?months. Median overall survival (OS) was 13?months for the entire cohort; median OS was 19.5?months for those presenting with localized/locally advanced AS and 6?months for those with metastatic disease at presentation (p?=?0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5?months, p?=?0.01).

Conclusions

Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression.     

Role of Surgery Combined with Kinase Inhibition in the Management of Gastrointestinal Stromal Tumor (GIST)

Background  

Surgery is the standard treatment for primary, gastrointestinal stromal tumor (GIST); however, surgical resection often is not curative, particularly in large GIST. Five years after complete removal of their tumor, approximately half of treated patients relapse. Imatinib, an oral tyrosine kinase inhibitor (TKI), is first-line treatment in patients with metastatic or unresectable GIST. It has resulted in durable objective responses or stable disease in 84% of patients and is well tolerated. The efficacy of imatinib in advanced GIST has created interest in a variety of potential multimodal approaches to management that combine surgery with systemic therapy.     

Population-Based Epidemiology and Mortality of Small Malignant Gastrointestinal Stromal Tumors in the USA

Background and Aims

Gastrointestinal stromal tumors (GISTs) have significant variability in size and malignant behavior. Our current understanding is limited to pathological analyses, autopsy studies, and small case series. The aim of the current study is to define the risk factors, incidence, and mortality rates of GIST <2 cm in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database.

Methods

Patients with histologically confirmed malignant GIST <2 cm were studied from 2001 to 2011. GIST was defined by GI tumor site codes and GIST-specific histology codes.

Results

We identified 378 patients with GIST <2 cm. The average age at diagnosis was 64.0 years with equal sex distribution. The most common tumor location was the stomach (62.2 %), followed by the small intestine (23.3 %), colon (5.6 %), and rectum (3.4 %). Most patients had localized disease (79.4 %), but 11.4 % had regional/distant metastatic disease. The annual incidence rate was 4.2 per 10,000,000 (10M). This was the highest among Blacks (7.6 per 10M). Among patients with GIST and no additional cancers, the 5-year GIST-specific mortality was 12.9 %. Moreover, there was a significantly increased 5-year GIST-specific mortality in those patients who had regionally advanced (34.0 %) or metastatic GIST (34.3 %), as compared to those patients with localized GIST (5.6 %).

Conclusions

This study represents the first population-based analysis of malignant GIST <2 cm. While quite rare, these tumors have an underappreciated disease-specific mortality. Further studies are needed to define the underlying reasons for the identified racial differences, to develop novel risk assessment schema for patients with these small tumors, and to determine appropriate indications for resection and/or medical therapy.

     

Giant GIST of the mesocolon: report of a case

Gastrointestinal stromal tumors are rare neoplasms arising from mesenchymal cells of the gastrointestinal tract, that strongly express a class III receptor tyrosine kinase, called KIT, due to some mutations in the KIT proto-oncogene. Two thirds of GISTs are found in the stomach, 20% to 50% in the small bowel (one third in the duodenum), and 5% to 15% in colon and rectum; GISTs, however, may rarely be found also in the oesophagus, omentum, mesentery or the retroperitoneum. Their treatment is strictly surgical, and only R0 resection can achieve good RESULTS: Treatment with Imatinib seems to be promising in case of unresectable or metastatic GIST, even if some trials are studying its effects after curative resection. GIST of the mesocolon are rare, and as in the other locations, require extensive surgery. The Autohrs report a case of giant malignant GIST arising from transverse mesocolon, treated by en-bloc resection of the tumor with a segment of transverse colon and great omentum.     

Gastrointestinale Stromatumoren (GIST)

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. GIST occur predominantly in the stomach and less frequently in the extraduodenal small bowel, the colon, and the rectum; rarely, GIST can be found in the esophagus and the duodenum. Due to their biological behavior, the primary treatment goal for localized primary GIST is complete resection, without the need for lymphadenectomy or wide resection margins. Thus, gastric wedge resections and segmental resections of the small bowel are the most common surgical procedures for treating primary GIST. Surgical therapy of extensive primary tumors or of metastatic or recurrent GIST should be integrated into a multimodal therapeutic concept that includes targeted therapy with tyrosine kinase inhibitors, such as imatinib.     

Gastrointestinal stromal tumor (GIST)--medical rarities?

Although their overall incidence is low, GISTs are distinctive subgroup of gastrointestinal mesenchymal tumors which express CD117 or platelet derived growth factor receptor alpha (PDGFRA). Considered as rare digestive cancers, tumors like schwannomas, neurofibromas, gastrointestinal leiomiomas are now reclassified as GIST based on immunohistochemistry studies. GIST are more frequent in stomach (40-70%), small bowel (20-40%), colon (5-15%), meanwhile locations such as mesentery, omentum, retro peritoneum in less of 5%. 10 GIST patients were surgically managed during 2004-2009. 5 gastric and 5 small bowel GIST. Most with symptomatic disease: palpable tumor, abdominal pain, anemia, fatigue, superior digestive hemorrhage or occlusion. Imagistic diagnosis consisted of: barium swallow, abdominal sonography, CT and PET-CT. Confirmation was made by hystopathological exam and immunohistochemistry. All patients had more or less wide surgical resections. For some patients there was also a specific adjuvant treatment. All patients survived after surgery. The principle of surgery for GIST is RO resection of the tumor. Tumor rupture or R1 resection of the primary tumor has a negative impact on disease free survival. Some patients (great volume tumors, R1 or R2 resection) had adjuvant treatment. Imatinib mesylate and derivates showed a significant improvement of recurrence free survival with one condition: permanent treatment. Surgery remains the mainstay of treatment in patients with localized, resectable GIST. Recurrence rate of 17-21% and 5 years survival rate of 48-70%, even in resectable GIST, impose an adjuvant treatment.     

Surgical Outcomes of Gastrointestinal Sarcoma Including Gastrointestinal Stromal Tumors: A Population-based Examination

Introduction The surgical approaches and outcomes for gastrointestinal sarcoma are determined largely from single institutional series. Objective We sought to determine patient outcomes after different surgical approaches for gastrointestinal sarcomas, including gastrointestinal stromal tumors (GIST), utilizing a large prospective cancer registry. Material and Methods The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1991 to 2002. Results Overall, 1873 gastrointestinal mesenchymal tumors were identified in the SEER data set, with 82% GIST and 18% smooth muscle neoplasms. Surgery was performed in 83% of the cohort. Median survival was 68 months for complete resection (CR), 51 months for partial resection (PR), and 10 months for no resection (NR) (P < 0.001 each category). Outcomes within the CR group were equivalent for wedge or total organ removal. Median survival rates for localized, regionally advanced, and metastatic disease were 97, 35, and 18 months, respectively, after CR, and in all cases significantly improved relative to patients not undergoing resection. Median survival rates in patients treated after 2000 have substantially improved in this cohort, possibly reflecting the impact of imatinib on overall population-based survival. Multivariate analysis identified organ, histologic grade, surgical resection, and date of surgery (pre-2000 or post-2000) as independent predictors of survival. Conclusions: The outcomes after surgical therapy for gastrointestinal sarcomas, including GIST, support the operative goal of a complete resection. Improved outcomes after 2000 indicate the potential benefit of newer therapies, including imatinib.     

伊马替尼耐药的复发转移性胃肠道间质瘤再手术的作用

目的 探讨复发转移性胃肠道间质瘤伊马替尼治疗耐药后手术干预的作用价值.方法 回顾分析2005年1月至2011年12月期间15例完全切除原发病灶后出现转移复发、接受伊马替尼治疗后出现耐药患者的临床病理资料、手术及生存情况.结果 7例患者（46.7%）依然存活,其中3例（20%）无瘤生存,4例（26.7%）带瘤生存;有1例患者失访（6.7%）;耐药后的中位生存时间为32个月,1年、2年生存率分别为85.6%和58.2%.9例患者耐药后进行了手术,其中8例患者肿瘤完全切除,1例为减瘤手术;其余6例患者则是接受伊马替尼600 mg/d或改用索坦治疗.生存分析显示,手术干预组总生存期优于未手术者（P=0.041）,中位生存时间分别为44.0个月及19.5个月.结论 对伊马替尼耐药的复发或转移性胃肠道间质瘤患者进行手术干预可能提高患者的总体生存时间,改善患者的预后.     

原发性胃肠道间质瘤73例的外科治疗

目的 探讨原发性胃肠道间质瘤(GIST)的外科治疗方法及预后.方法 回顾性分析1997年4月至2007年12月手术切除治疗的73例原发性GIST的临床病理资料和治疗方法,并对其预后进行评价.结果 73例GIST施行肿瘤完全切除者68例(其中12例在腹腔镜下完成肿瘤切除术),行肿瘤不完全切除仅取活检者5例,两组生存率差异有统计学意义(P=0.000).66例获随访的患者1、3、5年总体生存率分别为91.0%、78.2%、74.1%,根据肿瘤直径和核分裂象计数分级的肿瘤恶性程度风险分级与术后生存率密切相关(P=0.002),极低度及低度风险组与高度风险组间生存率差异有统计学意义(P<0.05).结论 应高度重视原发性GIST的初次手术治疗,积极行肿瘤完全切除以提高疗效,对肿瘤恶性程度风险较高者需扩大切除范围,应强调腹腔镜下GIST切除术适应证的选择和肿瘤完全切除.