原发性胃肠道间质瘤的多因素Cox模型分析

 目的　分析胃肠道间质瘤（GIST）的临床特征、治疗效果及其影响因素。方法　复习216例原发性GIST临床资料并加以随访进行Cox回归模型分析。结果　全组1、2、3、4、5年生存率分别为94.4 ％（204／216）、90.2 ％（129／143）、88.3 ％（68／77）、87.5 %（35／40）和85.0 %（17／20）。年龄、发生部位、完整切除、肿瘤是否破裂、辅助治疗、是否复发、肿瘤病理核分裂象、最大径等因素对GIST患者预后生存率的影响有显著性意义（P＜0.05）;并且随着影响因素变量值增大,死亡的风险值增高。其中完整切除对患者的预后起着决定性的作用。性别、CD117、是否活检、内镜黏膜是否糜烂、手术切缘等对预后生存率影响无显著性意义（P＞0.05）。术后辅助治疗可明显提高患者生存率,尤其对于高危险度患者。结论　GIST仍以外科治疗为主,其手术方式的选择更多取决于肿瘤的部位和大小,完整切除或扩大切除能提高生存率。年龄、发生部位、完整切除、肿瘤是否破裂、辅助治疗、术后是否复发、肿瘤病理核分裂象、最大径等是影响预后的重要因素,有利于指导临床规范化治疗。     

胃肠间质瘤68例

目的探讨胃肠道间质瘤（GIST）的临床特点、诊断、治疗及预后。方法回顾性分析68例GIST的临床病理及随访资料。结果GIST部位：胃41例，肠26例，大网膜1例。62例行外科手术切除，6例行姑息性切除。8例术后1年内复发再手术，未行辅助治疗。6例姑息术后患者及12例术后复发者给予甲磺酸伊马替尼200～600mg／d口服，患者获益率（CR＋PR＋SD）83-3％，获益者中位无进展生存期（TTP）超过14个月。结论GIST以胃及小肠多见，目前治疗仍以手术切除为主，手术切除辅以分子靶向药物甲磺酸伊马替尼，可延长患者生存期。     

胃肠间质瘤辅助治疗现状

胃肠间质瘤(gastrointestinal stromal tumor,GIST)是一类异质性肿瘤,生物学行为差异很大.肿瘤从小于1 cm到超过35 cm均有报道,其生物学行为也从近乎良性到高度恶性不尽相同[1].在靶向药物伊马替尼应用于GIST治疗之前,GIST完整切除后患者的5年生存率仅为50％左右,不完全切除患者的5年生存率小于10％,原发性GIST完整切除术后复发率约为40％～90％[2,3],尽管报道差异较大,但总体复发率仍偏高.术后中位复发时间为10～20个月[2,3].如何解决GIST切除术后的复发问题一直是GIST治疗领域的难点和热点.     

19例结直肠胃肠道间质瘤的外科治疗

目的:探讨结直肠的胃肠道间质瘤(gastrointestinal stromal tumors,GIST)外科治疗效果及其影响因素.方法:对我院1990年1月至2004年3月首次治疗的19例结直肠GIST临床资料和病理切片(含免疫组织化学检查)重新复核并加以随访,分析手术切除的效果以及影响手术疗效的因素.结果:手术者中位生存时间为60.0个月,术后1、3、5年生存率分别为100%、79.3%和69.4%.非扩大切除术者(即肿瘤局部切除和肿瘤及所在器官切除)与扩大切除术者比较,差异有显著性(P=0.001).完全切除术患者的生存率与肿瘤大小、病理类型、核分裂和复发转移有关;但多因素COX回归分析显示,术后生存率仅与肿瘤大小、核分裂和复发转移相关(P＜0.05).结论:结直肠GIST仍以外科治疗为主,原则上行局部完全切除即可.     

49例胃肠间质瘤的治疗及预后

目的探讨胃肠间质瘤（GIST）的治疗方法及预后因素。方法收集1990年7月至2007年7月收治的49例GIST患者的完整临床资料并进行分析。结果手术治疗47例,2例不能手术者及11例术后危险分级为恶性者口服伊马替尼治疗。术后服药者5年总体生存率64．7％,单纯服药者2年生存率为50．0％。免疫指标阳性率与肿瘤发生部位及恶性程度不相关（P〉0．05）。结论手术切除是GIST最主要的治疗手段,伊马替尼治疗是不可切除或转移的GIST患者的最佳选择,合理治疗及充分认识相关影响因素可以提高GIST的预后。     

影响胃肠间质瘤患者预后的相关临床病理因素分析

目的分析影响胃肠间质瘤(GIST)患者预后的相关临床病理因素,为GIST的临床治疗提供参考。方法选取2013年1月至2015年10月柳州市中医医院普通外科收治的300例GIST患者,所有患者均行手术治疗,且于术后行病理和免疫组化检测,对其临床病理资料进行回顾性分析及随访,采用Cox风险模型分析影响GIST患者术后3年生存情况的临床病理因素。结果 GIST患者3年生存率有差异的指标包括肿瘤切除情况、切缘阳性情况、有无破裂、有无转移、核分裂数、Ki-67指数、NIH分级和术后甲磺酸伊马替尼服用与否及服用疗程(P0.05);Cox风险模型结果显示,肿瘤切除不完整、切缘阳性、肿瘤破裂、肿瘤转移、核分裂数增多、Ki-67指数5%、NIH分级高危险性、术后未进行靶向治疗皆为影响GIST患者预后的独立危险因素(P0.05)。结论影响GIST患者预后的独立危险因素有切缘阳性、肿瘤破裂、肿瘤转移、核分裂数增多、Ki-67指数5%、NIH分级高危险性、术后未进行靶向治疗,临床治疗应结合各临床病理因素综合考虑,以准确判断患者的预后。     

影响胃肠间质瘤患者预后的相关临床病理因素分析

目的分析影响胃肠间质瘤(GIST)患者预后的相关临床病理因素,为GIST的临床治疗提供参考。方法选取2013年1月至2015年10月柳州市中医医院普通外科收治的300例GIST患者,所有患者均行手术治疗,且于术后行病理和免疫组化检测,对其临床病理资料进行回顾性分析及随访,采用Cox风险模型分析影响GIST患者术后3年生存情况的临床病理因素。结果GIST患者3年生存率有差异的指标包括肿瘤切除情况、切缘阳性情况、有无破裂、有无转移、核分裂数、Ki 67指数、NIH分级和术后甲磺酸伊马替尼服用与否及服用疗程(P<005);Cox风险模型结果显示,肿瘤切除不完整、切缘阳性、肿瘤破裂、肿瘤转移、核分裂数增多、Ki 67指数>5％、NIH分级高危险性、术后未进行靶向治疗皆为影响GIST患者预后的独立危险因素(P<005)。结论影响GIST患者预后的独立危险因素有切缘阳性、肿瘤破裂、肿瘤转移、核分裂数增多、Ki 67指数>5％、NIH分级高危险性、术后未进行靶向治疗,临床治疗应结合各临床病理因素综合考虑,以准确判断患者的预后。     

101例原发性腹膜后肿瘤外科治疗

目的探讨原发性腹膜后肿瘤的外科治疗。方法回顾性分析1992年来原发性腹膜后肿瘤手术切除101例，总结提高手术治疗效果的策略。结果其中良性肿瘤38例，恶性肿瘤63例，均经术后病理证实。肿瘤完整切除率71．29％。良性肿瘤的手术完整切除率高于恶性肿瘤，术中失血少，需要合并切除的脏器少，术后复发率相对低。全部病人无一例术中死亡。术后复发33例，再次手术19例。结论手术完整切除是腹膜后肿瘤治疗首选的方法，术前准备非常重要，对复发的肿瘤应该争取再次手术。     

胃肠间质瘤大小与预后

 目的 探讨胃肠间质瘤（GIST）原发肿瘤大小与预后的关系。方法 对该院1990年1月至2006年3月132例能完全切除的GIST患者的临床资料和病理切片（含免疫组织化学检查）重新复核并进行随访，分析原发肿瘤大小与预后的关系。结果 患者中位生存时间为66.0个月，术后2年和5年生存率分别为89.4 ％和70.9 ％。原发灶肿瘤完全切除术患者的生存率与其性别、肿瘤部位和大小、肿瘤性质、核分裂及复发转移有关；但多因素的Cox回归分析显示，术后生存率仅与肿瘤大小、肿瘤性质和复发转移相关（P＜0.05）。以2 cm为界比较生存率有统计学意义（P＜0.05），以5 cm为界比较生存率无统计学意义（P＞0.05）。结论 GIST仍以外科治疗为主，GIST原发灶大小是影响预后的独立高危因素，直径≥2 cm的患者应加强随诊。     

格列卫新辅助治疗胃肠间质瘤

目的 :探讨格列卫 (STI 5 71)术前用于胃肠间质瘤 (GIST)的新辅助治疗。方法 :晚期GIST 1例 ,剖腹探查未能够手术切除 ,采用格列卫 (40 0mg/日 )新辅助治疗 ,通过CT、再次手术所见和术后病理组织检查评价其疗效。结果 :经过格列卫治疗后 ,盆腔GIST肿块由 13 0cm× 10 0cm× 10 0cm缩小为 10 0cm× 9 0cm× 9 0cm ,即瘤体缩小了 38% ;再次进行手术获得成功 ,病理组织学检查可见肿瘤组织发生大片状坏死 ;未见明显毒副反应。术后随访 13个月 ,患者一般情况良好 ,仍然无病生存。结论 :格列卫可以用于GIST的新辅助治疗 ,能够使肿瘤降期 ,便于完整切除。     

A case of duodenal gastrointestinal stromal tumor treated by pancreas-sparing partial duodenectomy

An 79-year-old man admitted our hospital for abdominal mass. Computed tomography showed a tumor measuring about 10 cm in diameter without any metastasis lesion and any sings of local infiltration. Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the third portion of the duodenum, and biopsy revealed tumor cells stained positive for c-kit. These findings were consistent with a GIST and we performed a partial resection of the duodenum sparing the pancreas. Gastrointestinal stromal tumors (GIST) were mainly located in the stomach and the small intestine. Duodenal localization is rare. Surgical approach for GISTs should basically be a partial resection. However, for GISTs located in the duodenum, the partial resection was sometimes difficult and pancreaticoduodenectomy (PD) may be needed, depending on the tumor size and the location of the tumor close to the papilla Vater. Since GIST grew expansively, rarely involving lymph nodes, PD may be an excessive procedure to treat the disease. For this reason pancreas-sparing partial duodenectomy has been introduced for the treatment of duodenal GIST.     

胃肠道间质瘤肝转移患者肝转移和预后的影响因素分析--基于SEER数据库的回顾性研究

目的探讨胃肠道间质瘤肝转移患者肝转移和预后的影响因素。方法收集监测、流行病学、最终结果(SEER)数据库中2010-2015年的2684例胃肠道间质瘤患者的病历资料,根据是否发生肝转移分为肝转移组(191例)和非肝转移组(2493例),评估临床特征与胃肠道间质瘤肝转移及预后的关系。结果Logistic回归分析结果显示肿瘤分化差(OR=1.31,95%CI=1.09~1.59,P=0.005)、肿瘤大小﹥5 cm(OR=2.55,95%CI=1.78~3.65,P﹤0.01)和淋巴结转移(OR=2.39,95%CI=1.84~3.12,P﹤0.01)增加胃肠道间质瘤肝转移发生风险。肝转移患者生存时间明显短于非肝转移患者,差异有统计学意义(P﹤0.01)。肿瘤大小﹥5 cm(HR=1.881,95%CI=1.432~2.469,P=0.000)、淋巴结转移(HR=1.326,95%CI=1.031~1.706,P=0.028)、肝转移(HR=2.090,95%CI=1.615~2.703,P=0.000)是胃肠道间质瘤患者死亡风险较高的预后因素。亚组分析结果显示,原发部位在胃、种族为白种人和黑种人的胃肠道间质瘤肝转移患者的预后较差(P﹤0.05)。结论肿瘤分化差、肿瘤大小﹥5 cm、淋巴结转移是胃肠道间质瘤肝转移发生的易感因素;肿瘤大小﹥5 cm、淋巴结转移、肝转移为影响胃肠道间质瘤患者预后的危险因素;肝转移是原发部位在胃的胃间质瘤患者预后的危险因素,也是种族为白种人和黑种人的胃肠道间质瘤患者预后的危险因素。发生肝转移患者的总生存较差。对于发生肝转移的高危患者,在治疗和随访过程中应加强肝转移的相关检查,采取积极的综合治疗手段。     

胃肠道间质瘤淋巴结转移临床意义文献分析

目的探讨胃肠道间质瘤（GIST）淋巴结转移的临床意义。方法于PubMed及万方数据库检索1998年1月至2010年12月有关GIST淋巴结转移研究的文献,分析相关病例资料,总结GIST淋巴结转移的临床病理学特征、基因表达、GIST分期及GIST预后与淋巴结转移的关系。结果共收集到GIST淋巴结转移详细报告病例16例,男性6例,女性10例,中位年龄49．25岁;GIST发生于胃12例,小肠3例,食管1例;肿瘤细胞为梭形7例,上皮样3例,余6例呈以梭形为主的混合形状;7例进行了基因检测。结论发生于胃、肿瘤分级为高危组、细胞形态为梭形细胞的GIST容易发生淋巴结转移,基因突变与其存在某种相关性。但其临床意义仍不清楚。     

A case of amelanotic anorectal malignant melanoma mimicking gastrointestinal stromal tumor

A 56-year-old female patient was admitted, complaining of hematochezia. She was preoperatively diagnosed with poorly-differentiated carcinoma of anorectum with metastases in the lung and mesorectal lymph nodes, and underwent abdominoperineal resection of the rectum. The immunohistochemistry of the rectal tumor showed positive for vimentin and c-kit, and negative for AE1/AE3, S-100, a-SMA, LCA and CD34, which was compatible with gastrointestinal stromal tumor (GIST). Regardless of the administration of imatinib mesylate, multiple metastases in the brain, bone, adrenal glands and inguinal lymph node proceeded in a short term. An excisional biopsy of the inguinal lymph node was performed and immunohistochemistry of the specimen showed positive for S-100, melan-A, HMB45 and tyrosinase. Therefore, we concluded that amelanotic anorectal melanoma (AMM) metastasized to the lymph node, and rechecked the immuno histochemistry of the anorectal tumor. The anorectal tumor showed positive for melan-A, HMB45 and tyrosinase, but negative for S-100. As far as we know, there are few reports of AMM with S-100 negative and c-kit positive. In such cases, making a differential diagnosis between AMM and GIST of the anorectal region can be very confusing.     

胃肠道间质瘤术后复发转移的治疗

  胃肠间质瘤（GIST）是消化道最常见的间叶组织来源的肿瘤。手术虽然是GIST的主要治疗方法，但不能治愈复发转移的GIST。如NCCN建议，复发转移的GIST应首选伊马替尼（STI571）。晚期和复发转移的GIST患者应该长期服用STI571，直到患者出现耐药而不能控制肿瘤。虽然复发转移再手术的效果很差，几乎100％会再复发转移，但病变能切除时或在能观察的病变在STI571治疗后一旦取得最大疗效反应时仍要外科手术或建议手术。关于STI571的新辅助和辅助治疗的试验正在研究中。另一种多靶点的酪氨酸激酶抑制剂SU11248正在临床试验中，对STI571无效或耐药的患者中约65 %获益。总之，合理的治疗方法和治疗时机对减少GIST复发转移、有效地控制疾病、提高生活质量以及生存率至关重要。     

Imatinib mesylate acts in metastatic or unresectable gastrointestinal stromal tumor by targeting KIT receptors--a review

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. This tumor is resistant to conventional chemotherapy and radiotherapy. Although surgery has been the only effective treatment for GIST to date, it is not enough to manage metastatic GIST. Imatinib mesylate, a KIT tyrosine kinase inhibitor, is an oral agent that has been found to have a dramatic antitumor effect on metastatic GIST with either wild-type or mutant KIT. Although imatinib mesylate has been used in GIST treatment for several years, its use marks a new era of molecular targeting therapy. While several issues remain, they should be clarified by the current clinical trials and associated laboratory studies.     

Three cases of giant rectal gastrointestinal stromal tumor

The frequency of rectal gastrointestinal stromal tumor (GIST) is relatively low. We have experienced three cases of giant rectal GIST. Case 1 was treated with sunitinib after imatinib failed by Stevens-Johnson syndrome as neoadjuvant therapy. Case 2 was treated with imatinib as neoadjuvant therapy. These neoadjuvant therapies had no effect on tumor size. All patients underwent an abdominoperineal resection. The mean major axis was 11 .7 cm. Immnohistochemical staining showed that CD34 and KIT were positive. The term of follow-up is short, but no recurrences have been found in all cases. It has been reported that imatinib as neoadjuvant therapy is useful for radical resection in cases of giant rectal GIST. Furthermore, neoadjuvant therapy seems to be one of the treatment options for locally advanced rectal GIST. However, in cases of GIST patients not responding to imatinib, we should perform a surgical resection immediately.     

STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications

Mutations in the c-KIT receptor occur somatically in many sporadic Gastrointestinal Stromal Tumors (GIST), and similar mutations have been identified at the germline level in kindreds with multiple GISTs. These mutations activate the tyrosine kinase activity of c-KIT and induce constitutive signaling. To investigate the function of activated c-KIT in GIST, we established a human GIST cell line, GIST882, which expresses an activating KIT mutation (K642E) in the first part of the cytoplasmic split tyrosine kinase domain. Notably, the K642E substitution is encoded by a homozygous exon 13 missense mutation, and, therefore, GIST882 cells do not express native KIT. GIST882 c-KIT protein is constitutively tyrosine phosphorylated, but tyrosine phosphorylation was rapidly and completely abolished after incubating the cells with the selective tyrosine kinase inhibitor STI571. Furthermore, GIST882 cells evidenced decreased proliferation and the onset of apoptotic cell death after prolonged incubation with STI571. Similar results were obtained after administering STI571 to a primary GIST cell culture that expressed a c-KIT exon 11 juxtamembrane mutation (K558NP). These cell-culture-based studies support an important role for c-KIT signaling in GIST and suggest therapeutic potential for STI571 in patients afflicted by this chemoresistant tumor.     

Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Long-term survival of patients with metastatic disease has only been observed in patients with completely resected disease. Recently, the tyrosine kinase inhibitor imatinib has been found to yield responses in the majority of patients with metastatic GIST suggesting improved resectability in responding patients. Combined treatment approaches including resective surgery after imatinib treatment in patients with advanced metastatic disease have rarely been explored. We report a series of 90 patients with metastatic GIST in whom treatment with imatinib enabled 12 patients with mostly recurrent and extensive disease to be considered for resection of residual disease. In 11 of these patients, complete resection could be achieved. Viable tumor cells were found in all but one resected specimens suggesting that despite favorable radiological or clinical responses, imatinib is unlikely to induce pathological complete responses. Until more mature data from prospective trials are available, these data suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST. Further trials investigating a combined surgical and pre/postoperative treatment with imatinib in patients with advanced metastatic GIST are warranted.     

Clinico-Pathological Characteristics and Mutational Analysis of Gastrointestinal Stromal Tumors from India: A Single Institution Experience

Background: Gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal neoplasm of gastrointestinal tract. The incidence of GIST in India is not known and its treatment strategy in our country is largely derived from studies in other global populations. Some of the most important features of this type of cancer include its size, site of origin, mitotic index, histology and Immunohistochemistry. In this report we have studied these parameters in the Indian GIST patients presenting at our center. Additionally, we have also studied the mutational spectrum of these GISTs by next generation sequencing. Methods: Thirty one Indian patients of GIST were enrolled in this study and information regarding age, gender, tumor location and size was collected from their records. Immunohistochemistry studies were performed by the pathologist. Mutational analysis of these samples was performed by next generation sequencing. Results and Discussion: The most common site of GIST occurrence in our study was stomach. The tumor size for all 31 patients ranged between 0.6 cms to 20 cms. A spindle-cell pattern was present in 24 out of 31 of the cases. 29 out of 31 subjects were positive for CD117 expression. C-KIT was the most highly mutated gene indentified in our patients. Apart from these findings we observed many similarities as well as dissimilarities between the results of our study and literature published previously. Conclusions: The dissimilarities in the results of our study and published literature could be attributed to the genetic or ethnic differences that exist between the Indian population and other global populations. The results of our study warrant a need to conduct studies of GIST in a much larger population of India. Such large scale studies may also help in better treatment and/or prevention of GIST in developing countries like India.