胃肠间质瘤个体化治疗策略的探讨

胃肠间质瘤（GIST）是最常见的胃肠道间叶源性肿瘤,多见于胃和小肠,GIST多具有恶性潜能,生物学行为可以从良性到高度恶性不等。GIST的预后与肿瘤的发病部位、瘤体大小、核分裂数以及肿瘤是否破裂密切相关,伊马替尼辅助治疗明显延长了GIST患者的生存时间。近年对于GIST患者实施个体化治疗的理念也得到了越来越多的重视,本文就GIST个体化治疗的策略研究进行阐述。     

Perforation of the colon by invading recurrent gastrointestinal stromal tumors during sunitinib treatment

The molecular targets of sunitinib are receptor tyrosine kinases （RTKs）, and this drug has also been known to exert blocking effects on the activation of KIT, which is similar to the mechanism of action of imatinib. Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. We report here a 70-year-old patient diagnosed with a recurrent gastrointestinal stromal tumor （GIST）, which invaded the transverse colon and led to a perforation during sunitinib treatment. A computed tomography scan and 3-dimensional reconstruction showed necrosis of the recurrent hepatic mass and perforation of the invaded transverse colon. After percutaneous drainage of the intraperitoneal abscess, antibiotic treatment and restricted diet, the condition of the patient improved. The present case is the first to report that sunitinib, which is administered to treat GIST resistant to imatinib, can cause unexpected colon perforation and subsequent peritonitis.     

Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor： A case report

Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor STI571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.     

Treatment of patients with advanced gastrointestinal stromal tumor of small bowel： Implications of imatinib mesylate

AIM: To examine the impact of imatinib mesylate (Glivec) on patient survival and response and its safety,and the correlation of the response rate with the kit gene mutation status. METHODS: Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS: Advanced small bowel GIST patients treated with Glivec had substantially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant). CONCLUSION: Glivec significantly prolongs the post-recurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients with advanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.     

小肠间质瘤的临床特征、诊断与治疗措施

近年来,随着对小肠疾病检出方法的不断完善,对小肠疾病的诊断有了进一步的认识;本文通过比较各种用于小肠肿瘤检出的方法(包括消化道造影、腹部CT、DSA、内窥镜检查、腹部核素扫描、PET等),基本确立小肠间质瘤的诊断流程。再结合临床特征、病理学、以及免疫组化检查,最终确诊小肠间质瘤。手术切除是目前最有效的治疗方法,对于高度怀疑小肠间质瘤的患者,应尽早手术探查;此外,对于不可切除的、复发的、已有转移的间质瘤患者可用伊马替尼治疗。     

Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn's disease

We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the first report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.     

Giant gastrointestinal stromal tumor in the esophagus

We report a case of a 74-year-old woman with an esophageal gastrointestinal stromal tumor (GIST). Endoscopic examination suggested a submucosal tumor in the middle-lower thoracic esophagus. Computed tomography showed a solid mass 95 × 56 × 44 mm in size, suggesting an esophageal mesenchymal tumor. Endoscopic ultrasonography-guided fine-needle aspiration biopsy was positive for c-kit and CD34, and negative for both S-100 and desmin, on immunohistochemical examination, confirming this to be a GIST. The patient underwent transthoracic esophagectomy with esophageal reconstruction using a gastric tube through the subcutaneous route. The tumor was completely resected, and there was no lymph node metastasis. The pathological examination confirmed the tumor to be at high risk for recurrence because of its size and the presence of necrosis. We are carefully following the patient conservatively with no adjuvant chemotherapy such as imatinib mesylate.     

Unusual combination of paraneoplastic manifestations in a patient with metastatic gastrointestinal stromal tumor (GIST)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Activating mutations in tyrosine kinase receptors KIT or platelet-derived growth factor receptor alpha (PDGFRA) are the main mechanisms causing the disease. Patients generally present with non-specific symptoms, while a number of tumors are discovered incidentally and may be metastatic at the time of diagnosis. Aggressive GISTs have a defined pattern of metastasis to the liver or throughout the abdomen, or both. Though GISTs rarely present systemic or isolated paraneoplastic reactions, a few cases have been reported in the literature. We present the case of a 54-year-old patient with metastatic GIST at diagnosis and the emergence of paraneoplastic manifestations during follow-up.     

小肠间质瘤74例临床诊断分析

目的 总结小肠间质瘤(SIST)的临床特征,评价多种影像、内镜诊断方法 对SIST的诊断价值.方法 收集2004年7月至2009年6月经手术或内镜病理确诊的SIST患者74例,回顾性分析患者的临床资料、影像学(小肠造影、腹部B超、螺旋CT)和双气囊小肠镜等检查结果 .将SIST按其生物学行为分为极低度、低度、中度及高度危险性4级,并对SIST的病理特点及与螺旋CT表现间的关系进行分析.结果 SIST发病部位最常见于空肠,共43例(58.1%),其次是十二指肠17例(23%),回肠10例(13.5%).94.6%(70/74)的患者有临床症状,最常见的为消化道出血,共46例(67.2%),腹痛23例(31.1%).各种影像及内镜检查中螺旋CT诊断率和诊断符合率最高,分别为100%和72.1%.74例SIST病灶中,极低度危险性14例(18.9%)、低度危险性21例(28.4%)、中度危险性15例(20.3%)、高度危险性24例(32.4%).螺旋CT检查有助于判断SIST的危险性.结论 SIST起病隐匿,早期诊断困难.螺旋CT检查无创、方便、可靠,并有助于对肿瘤的危险度及预后进行预测,可作为目前SIST首选的检查手段.     

Interventional digital subtraction angiography for small bowel gastrointestinal stromal tumors with bleeding

AIM: To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography (DSA) for bleeding small bowel gastrointestinal stromal tumors (GISTs).METHODS: Between January 2006 and December 2013, small bowel tumors in 25 consecutive patients undergoing emergency interventional DSA were histopathologically confirmed as GIST after surgical resection. The medical records of these patients and the effects of interventional DSA and the presentation and management of the condition were retrospectively reviewed.RESULTS: Of the 25 patients with an age range from 34- to 70-year-old (mean: 54 ± 12 years), 8 were male and 17 were female. Obscure gastrointestinal bleeding, including tarry or bloody stool and intermittent melena, was observed in all cases, and one case also involved hematemesis. Nineteen patients required acute blood transfusion. There were a total of 28 small bowel tumors detected by DSA. Among these, 20 were located in the jejunum and 8 were located in the ileum. The DSA characteristics of the GISTs included a hypervascular mass of well-defined, homogeneous enhancement and early developed draining veins. One case involved a complication of intussusception of the small intestine that was discovered during surgery. No pseudoaneurysms, arteriovenous malformations or fistulae, or arterial rupture were observed. The completely excised size was approximately 1.20 to 5.50 cm (mean: 3.05 ± 1.25 cm) in maximum diameter based on measurements after the resection. There were ulcerations (n = 8), erosions (n = 10), hyperemia and edema (n = 10) on the intra-luminal side of the tumors. Eight tumors in patients with a large amount of blood loss were treated with transcatheter arterial embolization with gelfoam particles during interventional DSA.CONCLUSION: Emergency interventional DSA is a useful imaging option for locating and diagnosing small bowel GISTs in patients with bleeding, and is an effective treatment modality.     

伊马替尼治疗胃肠间质瘤并瘢痕疙瘩增生一例

甲磺酸伊马替尼是一种选择性酪氨酸激酶抑制剂,能在细胞水平上抑制bcr-abl、PDGF受体、SCF、c-Kit等受体的酪氨酸激酶,抑制细胞增殖、诱导细胞凋亡,是治疗胃肠道间质瘤一线药物。最常见的不良反应有水肿、皮疹、疲劳、恶心、中性粒细胞减少,但其促进患者瘢痕疙瘩增生尚未有报道,现报道如下。     

Gastric gastrointestinal stromal tumor with synchronous metastasis to the esophagus: case report and review of the literature

We report a patient with synchronous gastrointestinal stromal tumors (GISTs) of the stomach and esophagus. The gastric GIST was larger than that in the esophagus, and no direct connection between the two lesions was seen microscopically. Based on molecular analysis, both lesions had the same c-kit mutation on exon 11, with deletion of codon 557–558. Analysis of normal gastric tissue showed no mutations. The gastric GIST was the primary lesion, and the esophageal tumor was thought to suggest a hematogenous metastasis. A liver metastasis in S6 appeared 6 months after surgery. Imatinib mesylate has been an effective treatment for liver metastasis at follow-up of 2 years.     

内镜黏膜下剥离术治疗胃肠道间质瘤的安全性及疗效观察

目的评价内镜黏膜剥离术治疗胃肠道间质瘤的安全性和疗效。方法回顾性分析22例确诊为胃肠道间质瘤行内镜黏膜下剥离术治疗的患者资料,包括患者的基本情况、病变部位、大小、临床表现、治疗经过以及病理结果等,统计并发症发生情况及术后随访结果。结果22例患者均顺利完成ESD治疗,病变直径在0．8～4．0cm,均一次性完整切除病变,手术时间（自黏膜下注射开始至完整剥离病变的时间）在35～150min,平均64．5min,术中创面均有少量出血,经氩离子凝固术、电活检钳凝固治疗或金属夹闭合创面止血成功,有4例术中并发穿孔,穿孔发生率18．1％（4／22）,应用金属夹夹闭缝合穿孔,术后经胃肠减压、质子泵抑制剂抑酸、抗炎等治疗后,其中3例腹胀缓解,余1例腹胀严重者追加经腹壁穿刺排气后缓解。22例患者均未出现严重的术后出血,内镜黏膜下剥离术治疗后住院3～10d,平均4．5d,穿孔患者术后1个月胃镜复查见穿孔均闭合,所有患者接受随访3～18个月,未见病变残留和复发。结论内镜黏膜下剥离术治疗胃肠道间质瘤是安全和有效的,虽然出血和穿孔仍是其主要的并发症,但经积极地对症治疗后可以治愈。     

A gastrointestinal stromal tumor of the duodenum masquerading as a pancreatic head tumor

Gastrointestinal stromal tumor （GIST） represents the most common kind of mesenchymal tumor that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor showing CD117 （c-kit protein） positivity at immunohistochemistry. Throughout the whole length of the gastrointestinal tract, GIST arises most commonly from the stomach followed by the small intestine, the colorectum, and the esophagus. Only 3%-5% of GISTs occur in the duodenum, and especially, if GIST arises from the C loop of the duodenum, it can be difficult to differentiate from the pancreas head mass because of its anatomical proximity. Here, we report a case of duodenal GIST, which was assessed as a pancreatic head tumor preoperatively.     

Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn＇s disease

We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the first report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.     

胃肠道间质瘤生物学特性对临床实践的指导意义

目的总结胃肠道间质瘤(gastrointestinal stromal tumor,GIST)的生物学特性,进一步指导临床诊治。方法回顾性分析2004年1月~2008年12月经病理证实的73例GIST的临床资料,包括好发部位、恶性程度、临床表现、组织学特点、治疗及预后,阐述其生物学特性。结果本组GIST好发于胃(74%)及小肠(14%),特别是胃底(44%)及胃体(39%)。恶性程度较低的间质瘤容易出现腹痛,胃底间质瘤较易发生呕血。外科手术是根治GIST的主要方式,内镜下切除有望成为新的重要治疗方式。结论对GIST生物学特性的分析有利于更好地指导临床。     

Clinicopathological and immunohistochemical analysis of gastrointestinal stromal tumor

AIM: To investigate the dinicopathological features of gastrointestinal stromal tumor (GIST) and to study the reference indexes for malignancy. METHODS: Fifty-two cases of primary GIST were distinguished from a group of gastrointestinal mesenchymal tumors using a panel of antibodies such as CD117 and CD34 by immunohistochemical SP method. Their biological behaviors were analyzed using the expression of p21WAF1 and Bax in 52 cases of GIST. RESULTS: Grossly, the tumor size was between 1.5 cm and 13 cm (mean: 5.5 cm). Focal areas of hemorrhage, necrosis, or small cyst formation could be seen. Microscopically, the tumor was composed of spindle cells (20 cases), epithelioid cells (20 cases) and mixed cells (12 cases). Immunohistochemically, CD117 and CD34 showed diffuse strong positive expressions, the positive rates were 98.1% and 92.3%. SMA, S-100, NSE, NF and MBP showed focal positive expressions, the positive rates were 48.1%, 28.8%, 25%, 21.2% and 42.3% respectively. Vimentins were all positive desmin and CgA were all negative. In normal adult stomach and intestine, the immunoreactive staining for CD117 and CD34 showed immunoreactive interstitial cells of Cajal in myenteric neuroplexus. Among the 52 cases of GIST, 27 were positive for p21WAF1 (51.9%), 29 for Bax (55.8%). The expression of p21WAF1 and Bax had no significent difference with the localization, size, histological subtype of GIST, but had a significent difference with the histological grade (P = 0.000, respectively). p21WAF1 expression had a positive correlation to Bax expression (r = 0.461, P = 0.001,κ= 0.459). CONCLUSION: GIST has complicated arrangements and various cell types. Positivity of CD117 and CD34 is the most valuable factor in diagnosing GIST. Expression of p21WAF and Bax plays an important role in potential malignancy and malignancy rather than in benign GIST. p21WAF1 and Bax may be used as the markers in the assessment of GIST malignant potential.     

Segmental duodenectomy for gastrointestinal stromal tumor of the duodenum

AIM: To evaluate the results of segmental duodenectomy (SD) and pancreaticoduodenectomy (PD) for duodenal gastrointestinal stromal tumor (GIST) and help clinicians with surgical management. METHODS: All patients who underwent surgery for non-metastatic GIST of the duodenum in a single institution since 2000 were prospectively followed up. Seven patients (median age 51 years, range: 41-73 years) were enrolled: five underwent SD and two underwent PD. RESULTS: All the patients had a complete resection (R0), wi...     

A ruptured large extraluminal ileal gastrointestinal stromal tumor causing hemoperitoneum

We describe an 87-year-old woman with a large ileal gastrointestinal stromal tumor （GIST） causing hemoperitoneum. A CT scan demonstrated a large heterogeneous mass measuring about 13 cm × 11 cm in the pelvis and hemoperitoneum, with a non-uniform enhancement pattern. The mass was diagnosed as a GIST originating from the gastrointestinal tract. She underwent an urgent laparotomy and an ileal GIST with a rupture was found 130 cm from the anal to the Treitz’s ligament. Hemoperitoneum caused by ileal GIST rupture is a rare condition. Bleeding in the large tumor leading to rupture of the capsule might cause hemoperitoneum in the present case.