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1.
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.  相似文献   

2.

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.  相似文献   

3.
酪氨酸激酶抑制剂联合手术治疗转移性胃肠间质瘤   总被引:1,自引:0,他引:1  
目的 探讨酪氨酸激酶抑制剂(TKI)甲磺酸伊马替尼或舒尼替尼联合手术治疗晚期转移性胃肠间质瘤(GIST)的临床疗效.方法 回顾分析中山大学附属第一医院2007年6月至2009年12月接受TKI治疗后进行手术治疗的转移性GIST患者临床病理资料.结果 共计15例转移性GIST患者在TKI治疗后接受肿瘤切除手术.术前TKI治疗反应分别为疾病控制6例(40.0%),局限性进展4例(26.7%),全面性进展5例(33.3%).手术相关并发症发生率20.0%.全组患者中位无进展生存期18.7个月.其中疾病控制和局限性进展组患者术后无进展中位生存期25.0个月,全面性进展组则仅为3.0个月(P<0.01);疾病控制和局限性进展组患者至今仍全部存活,而全面性进展组患者中位总生存期为10.5个月(P<0.01).结论 靶向治疗后,疾病控制或局限性进展的晚期转移性GIST患者行手术治疗安全有效,而全面性进展患者手术治疗不能改善其预后,应谨慎选择.  相似文献   

4.
The diagnosis of gastrointestinal stromal tumor (GIST) relies on a combination of the following criteria: anatomic location, typical histopathology, and the presence of CD 117-antigen (the tyrosine kinase receptor, c-kit) or CD 34-antigen. Imatinib mesylate, a specific tyrosine kinase inhibitor, is highly efficient against locally advanced or metastatic GIST. We report a case of unresectable duodenal GIST, which we were able to resect with curative intent after down-staging treatment with a dosage of imatinib 400 mg daily for 8 months. We performed Whipple's procedure combined with en bloc resection of the right kidney and adrenal gland. The patient was recurrence free at his 24-month follow-up examination. Down-staging treatment may be worthwhile in selected patients, but further prospective studies of imatinib in this setting are necessary. We think that imatinib should be continued postoperatively, as the risk of recurrence in these patients may be high.  相似文献   

5.
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。  相似文献   

6.

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.  相似文献   

7.
Imatinib is a tyrosine kinase inhibitor directed against the KIT and the PDGF-alpha receptors. Imatinib has proven efficacy in the treatment of metastatic GIST with a response rate achieving 70%, but treatment with imatinib alone is not curative. The median progression-free survival is about 2 years. In locally advanced GIST, primary treatment with imatinib proved to be safe and feasible in several cohort studies. The goal of any curatively intended surgical treatment for GIST is R0 resection. Therefore, neoadjuvant treatment with imatinib can be recommended if tumor-free margin resection is doubtful. After R0 resection of GISTs with intermediate or high risk of relapse, preliminary data indicate that imatinib administered for at least 1 year reduces the risk of relapse and may improve the prognosis. However, no mature survival data from randomized studies have been published thus far. Therefore adjuvant treatment with imatinib is not yet approved nor is it a standard of care at this stage. The inclusion of patients with intermediate- and high-risk resected GIST into clinical studies is strongly recommended.  相似文献   

8.
Background Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined. Methods One hundred nineteen patients with metastatic GIST diagnosed prior to July 1, 1998 (approximately 2 years prior to the use of imatinib for GIST) were identified from an institutional database of patients with pathologically confirmed GIST. Mutational analysis was performed in cases with available tissue. The log rank test and Cox regression models were used to assess prognostic factors. Results Median survival was 19 months with a 41% 2-year survival and a 25% 5-year survival. Resection of metastatic GIST was performed in 81 patients (68%), while 50 (42%) received conventional chemotherapy. Twelve patients (10%) were eventually started on imatinib. Primary tumor size <10 cm, <5 mitoses/50 HPF in the primary tumor, epithelioid morphology, longer disease-free interval, and surgical resection were independent predictors of improved survival on multivariate analysis. Mutational status did not predict outcome. In patients who underwent resection, the 2 year survival was 53%, and negative microscopic margins also independently predicted improved survival. Conclusions Treatment with imatinib appears to improve 2-year survival of metastatic GIST by approximately 20% when compared to surgery alone. The combination of imatinib and surgery for the treatment of metastatic GIST therefore warrants investigation. An erratum to this article can be found at  相似文献   

9.
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.  相似文献   

10.
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.  相似文献   

11.
Gastrointestinal stroma tumors (GIST), an abdominal stroma entity, are characterized by a gain-in-function mutation in the c-kit proto-oncogen (CD117). Initial treatment should aim at complete removal of the primary tumor (R0 resection), which almost never develops lymphatic metastases. Distant metastatic spread mainly involves the peritoneal cavity and the liver. In patients with metastatic disease, treatment with the tyrosine kinase inhibitor imatinib mesylate is indicated and very effective. Systemic chemotherapy and external beam radiation must be considered ineffective. Patients requiring multivisceral resection for primary tumor removal quickly develop tumor recurrence and could benefit from preoperative treatment with imatinib. To assess the response to treatment, 18F-FDG positron emission tomography or gadolinium-enhanced magnetic resonance imaging have proven helpful, as the conventional criteria of tumor shrinkage according to WHO standards are rarely met. Primary tumors are classified into four risk categories according to size and mitotic activity. The possible advantages of adjuvant treatment are currently under investigation through international randomized trials. Patients who develop extensive remission of metastatic disease should be evaluated individually for resection of the tumor remnants. Even the resection of single progressive lesions (newly developed mutations) should be considered in carefully selected patients if the remaining tumor can be controlled by continued imatinib treatment.  相似文献   

12.
Surgery for gastrointestinal stromal tumour in the post-imatinib era   总被引:3,自引:0,他引:3  
Gastrointestinal stromal tumour (GIST) is a rare tumour. Historically, surgery has been the only effective treatment. The prognosis of patients with gastrointestinal stromal tumour is poor. Even after apparently 'curative' surgical resection more than 50% of patients relapse. The development of an effective novel targeted therapy against GIST (imatinib mesylate) is a success story of molecular biology that has dramatically altered the management of patients with these tumours. However, as follow up of patients who have initially responded to imatinib has increased, it has become evident that such hopes of cure were premature because responses to imatinib are of limited duration. Unresolved issues include the role of imatinib as an induction (neo-adjuvant) therapy prior to surgery, or as adjuvant treatment after surgery, the role of surgery in patients with a differential or partial response and the role of surgery in patients with isolated metastatic disease. In the present paper the biology and natural history of GIST are reviewed, and the complexities of surgical management that exist in the context of an effective, but not curative, biological therapy, are addressed.  相似文献   

13.
Gastrointestinal stromal tumours   总被引:16,自引:0,他引:16  
BACKGROUND: Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumours of the gastrointestinal tract. GISTs express a growth factor receptor with tyrosine kinase activity, termed KIT. Mutations of KIT are common in malignant GISTs and lead to constitutional activation of tyrosine kinase function, which causes cellular proliferation and resistance to apoptosis. GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease. METHODS: A Medline literature search was preformed to locate all articles relating to gastrointestinal tumours, GISTs, KIT and imatinib. RESULTS AND CONCLUSIONS: The 5-year survival rate after complete resection of GISTs is approximately 50 per cent. The median duration of survival for patients with a metastatic GIST is approximately 20 months, and 9-12 months for patients with local recurrence. Phase II trials have investigated the effect of imatinib on irresectable or metastatic GISTs. In these trials more than 50 per cent of patients responded to imatinib within a few months and approximately 12 per cent had disease progression. Uptake of [(18)F]fluoro-2-deoxy-D-glucose demonstrated by positron emission tomography has been found to be reduced after starting imatinib. The potential for cure and the optimal length of treatment is currently unknown. Imatinib is the first effective systemic therapy for metastatic and locally irresectable GISTs. Large multi-institutional clinical trials to investigate the efficacy of imatinib as adjuvant or neoadjuvant therapy for GISTs are now required.  相似文献   

14.
目的探讨手术对于伊马替尼治疗后晚期胃肠道间质瘤(GIST)患者的临床疗效。方法回顾性分析13例术前予以伊马替尼治疗,然后接受手术切除的晚期GIST患者的临床资料。结果13例伊马替尼治疗后手术切除的患者中,有3例为局部晚期原发肿瘤,10例为复发或转移患者。治疗有效(RD组)的5例中有4例、疾病进展(PD组)的8例中有1例共计5例(38.5%)患者肿瘤获得完全切除。RD组无疾病进展生存(PFS)为24.8个月,PD组的PFS为2.8个月,两组比较,差异有统计学意义(P〈0.01)。RD组和PD组患者的总生存率比较,差异无统计学意义(P〉0.05)。结论在对伊马替尼治疗有效的晚期GIST患者中,伊马替尼治疗后再行外科手术切除是可行的。  相似文献   

15.
目的评估延长伊马替尼辅助治疗时间对中高度复发风险胃肠间质瘤(GIST)患者无复发生存率与安全性的影响。方法回顾性分析北京大学肿瘤医院消化肿瘤内科自2004年3月至2009年5月接受伊马替尼辅助治疗、且随访时间均在3年以上的101例中高度复发风险GIST患者的临床和随访资料。伊马替尼治疗情况:3例因不良反应服药不足1年后停药;24例服药1年后停药:21例患者服药2年后停药;18例患者服药3年后停药;8例患者服药3年余仍继续治疗中:27例患者服药超过4年。结果中位随访时间60个月(95%CI:57.9~62.1个月),19例患者出现肿瘤复发,其中5例于辅助治疗过程中出现复发,14例为终止辅助治疗后出现复发。伊马替尼停药至肿瘤复发的中位时间为12.0个月(95%CI:9.6~14.4个月),再次给予伊马替尼治疗均获得肿瘤控制。53例辅助治疗时间3年或3年以上者5年无复发生存率为93.9%,明显优于不足3年的48例患者(68.0%,P〈0.01)。其中,3年以上者与3年者5年无复发生存率分别为97.1%和86.6%,差异无统计学意义(P〉0.05)。除乏力发生率有所增加外,辅助治疗时间3年以上者总体不良反应发生率并未明显增加(P〉0.05)。结论延长伊马替尼辅助治疗时间超过3年有望进一步延长中高度复发风险GIST术后的无复发生存期,且其不良反应并未显著增多。  相似文献   

16.
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.  相似文献   

17.
目的 探讨同时性胃肠道间质瘤(gastrointestinal stromal tumor,GIST)肝转移行同期切除原发肿瘤和肝转移瘤的手术疗效.方法 回顾性分析7例GIST同时性肝转移同期手术病人的临床资料.结果 7例病人中男5例,女2例;中位年龄52(43~67)岁.原发肿瘤部位分布为:胃2例,小肠5例.全组接受手术切除,无明显并发症,1例病人术后2个月死于肝内复发,1例术后8个月肝内复发者服用伊马替尼,肿瘤进展得到控制.其余病人在随访1年期间未见肿瘤复发或转移.结论 同期手术切除对于合适的同时性GIST肝转移瘤病人安全、有效.  相似文献   

18.
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.  相似文献   

19.
Gastrointestinal stromal tumor (GIST) is a neoplasm of the gastrointestinal tract, mesentery, or omentum that expresses the protein-tyrosine kinase KIT (CD117) and is the most common mesenchymal tumor arising at these sites. Surgical resection is the first-line intervention for operable GISTs, particularly localized primary tumors, and it was historically the only effective treatment. However, more than half of all GIST patients present with locally advanced, recurrent, or metastatic disease. The 5-year survival rate ranges from 50% to 65% after complete resection of a localized primary GIST and decreases to approximately 35% for patients with advanced disease who undergo complete surgical resection. A total of 40% to 90% of all GIST surgical patients subsequently have postoperative recurrence or metastasis. Imatinib is a potent, specific inhibitor of KIT that has demonstrated significant activity and tolerability in the treatment of malignant unresectable or metastatic GIST, inducing tumor shrinkage of 50% or more or stabilizing disease in most patients. A key strategy for prolonging the survival of patients with GIST is to improve the outcome of surgery. It is possible that the adjuvant and neoadjuvant use of imatinib (e.g., rendering initially inoperable tumors resectable) in the overall management approach to advanced GIST may contribute to surgeons success in attaining this objective.  相似文献   

20.
目的探讨胃肠间质瘤(GIST)不同危险程度、不同部位以及不同方案治疗患者的预后。方法回顾性总结2006年1月至2010年12月间在天津医科大学附属肿瘤医院接受伊马替尼治疗的156例成人GIST患者的临床资料。依据改良的NIH危险度分级,30例患者纳入中危组:126例患者纳人高危组,其中67例为晚期GIST(复发转移或病情进展)。肿瘤原发于胃78例,非胃(小肠、结直肠、肠系膜及腹膜后)78例。全组均接受口服伊马替尼400mg/d的治疗,其中根治术后口服伊马替尼89例(根治术后辅助治疗组);另67例为晚期GIST(复发转移或病情进展)患者中,根治术后肿瘤进展后口服伊马替尼26例(根治术后进展治疗组),姑息术后口服伊马替尼27例,未手术而单纯服用伊马替尼14例。比较原发肿瘤不同危险程度、不同部位以及不同治疗方法患者的生存情况。结果全组156例患者对伊马替尼治疗的总体耐受性良好。全组均获得随访,随访时间9~56(中位时间27)月,1、2、3年总体生存率(OS)分别为96%、81%和71%。高危组1、2、3年0s分别为95%、77%和65%,中危组均为100%,两组差异有统计学意义(P=0.001)。肿瘤原发于胃组患者1、2、3年0s分别为97%、90%和84%;肿瘤原发非胃组患者1、2、3年OS分别为95%、69%和52%,两组差异有统计学意义(P=0.000)。根治术后辅助治疗组患者1、2、3年OS分别为98%、95%和90%。晚期GIST患者1、2、3年OS分别为91%、58%和43%;其中根治术后进展治疗组分别为92%、74%和56%,姑息术后治疗组分别为92%、51%和21%,未手术治疗组分别为77%、27%和0;前组的预后明显优于后两组(P=0.000)。结论高危GIST和肿瘤位于非胃以及晚期患者的预后不佳。根治性手术及应用伊马替尼能够改善晚期GIST患者的预后。  相似文献   

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