Preoperative diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration

AIM： to evaluate the role of endoscopic ultrasonographyguided fine needle aspiration （EUS-FNA） in the preoperative diagnosis of gastrointestinal stromal tumor （GIST）.
METHODS： From September 2002 to June 2006, Fiftythree consecutive EUS-FNAs of GI tract subepithelial hypoechoic tumors with continuity to proper muscle layer suspected as GIST by standard EUS were evaluated prospectively. The reference standards for the final diagnosis were surgery （n = 31）, or clinical follow-up （n = 22）. Additionally, immunophenotyping of specimens obtained by EUS-FNA and surgical resection specimens were compared.
RESULTS： In 2 cases puncture was not performed because of anatomical problems. The collection rate of adequate specimens from the GI tract subepithelial hypoechoic tumor with continuity to proper muscle layer was 82% （42/51）. The diagnostic rate for the tumor less than 2 cm, 2 to 4 cm, and 4 cm or more were 71% （15/21）, 86% （18/21）, and 100% （9/9）,respectively. In 29 surgically resected cases, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of EUS-FNA using immunohistochemical analysis of GIST were 100%（24/24）, 80% （4/5）, 96% （24/25）, 100% （4/4）, and 97% （28/29）, respectively. No major complications were encountered.
CONCLUSION： EUS-FNA with immunohistochemical analysis is a safe and accurate method in the pretherapeutic diagnosis of GIST. It should be taken into consideration in decision making, especially in early diagnosis following minimal invasive surgery for GIST.     

CT和超声内镜诊断胃肠道间质瘤的现状

胃肠道间质瘤是原发于胃肠道和腹部的间叶源性肿瘤,绝大多数存在c-Kit基因突变。内镜检查胃肠道间质瘤有一定困难,而CT和超声内镜结合有助于胃肠道间质瘤的定位和良、恶性的判断,对指导临床治疗和估计预后有一定的价值。     

Clinical implications of doubling time of gastrointestinal submucosal tumors

AIM To evaluate the efficacy of doubling time(DT) of gastrointestinal submucosal tumors(GIST).METHODS From April 1987 through November 2012, a total of 323 patients were given a final histopathological diagnosis of GISTs on surgical resection or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA) in Kitasato University East Hospital or Kitasato University Hospital. We studied 53 of these patients(34 with resected tumors and 19 with unresected tumors) whose tumors could be measured on EUS on at least two successive occasions. The histopathological diagnosis was GIST in 34 patients, leiomyoma in 5, schwannoma in 3, ectopic pancreas in 1, hamartoma in 1, cyst in 1, Brunner's adenoma in 1, and spindle-cell tumor in 7. We retrospectively calculated the DT of GISTs on the basis of the time course of EUS findings to estimate the growth rate of such tumors.RESULTS The DT was 17.2 mo for GIST, as compared with 231.2 mo for leiomyoma, 104.7 mo for schwannoma, 274.9mo for ectopic pancreas, 61.2 mo for hamartoma, 49.0 mo for cyst, and 134.7 mo for Brunner's adenoma. The GISTs were divided into risk classes on the basis of tumor diameters and mitotic figures(Fletcher's classification). The classification was extremely low risk or low risk in 28 patients, intermediate risk in 3, and high risk in 3. DT of GIST according to risk was 24.0 mo for extremely low-risk plus low-risk GIST, 17.1 mo for intermediate-risk GIST, and 3.9 mo for high-risk GIST. DT of GIST was significantly shorter than that of leiomyoma plus schwannoma(P 0.05), and DT of high-risk GIST was significantly shorter than that of extremely low-risk plus low-risk GIST(P 0.05).CONCLUSION For GIST, a higher risk grade was associated with a significantly shorter DT. Small SMTs should initially be followed up within 6 mo after detection.     

胃肠道间质瘤治疗新方法的探讨

目的探讨胃镜与腹腔镜双镜联合、内镜黏膜下挖除术(endoscopic submucosal excavation,ESE)及内镜黏膜下隧道肿瘤切除术(submucosal tunneling endoscopic resection,STER)治疗胃肠道间质瘤(GIST)的效果和安全性。方法经胃(肠)镜、超声内镜及病理学、免疫组化证实GIST患者86例,对其中53例患者采用ESE、29例患者采用胃镜与腹腔镜双镜联合、4例患者采用STER法进行瘤体切除。结果 ESE、双镜联合及STER治疗的所有患者均完整切除瘤体,术后风险评估极低危56例、低危17例、中危8例、高危5例。三种方法均无术中及术后迟发性出血、剧烈腹痛等并发症,瘤体位于贲门者切除后患者贲门功能保持良好,术后随访无反流性食管炎等并发症。术后随访有1例中危GIST患者因术后未服用格列卫发生盆腔转移,其他患者无远处转移及复发。结论胃镜与腹腔镜双镜联合技术、ESE及STER是治疗胃肠道间质瘤的微创、安全、有效的新方法。     

Mucosal-incision assisted biopsy for suspected gastric gastrointestinal stromal tumors

To evaluate the diagnostic yield of the procedure, mucosal-incision assisted biopsy (MIAB), for the histological diagnosis of gastric gastrointestinal stromal tumor (GIST), we performed a retrospective review of the 27 patients with suspected gastric GIST who underwent MIAB in our hospitals. Tissue samples obtained by MIAB were sufficient to make a histological diagnosis (diagnostic MIAB) in 23 out of the 27 patients, where the lesions had intraluminal growth patterns. Alternatively, the samples were insufficient (non-diagnosticMIAB) in remaining 4 patients, three of whom had gastric submucosal tumor with extraluminal growth patterns. Although endoscopic ultrasound and fine needle aspiration is the gold standard for obtaining tissue specimens for histological and cytological analysis of suspected gastric GISTs, MIAB can be used as an alternative method for obtaining biopsy specimens of lesions with an intraluminal growth pattern.     

胃肠道间质瘤的影像学表现及临床价值

胃肠道间质瘤是消化道常见的间叶源性肿瘤,术前极易与其他间叶源性的消化道肿瘤混淆,目前影像学检查在该疾病的诊断与鉴别诊断方面占有重要的地位。此文着重探讨胃肠道间质瘤的影像学特征,并比较分析各种影像学检查的优缺点,阐述影像学检查对诊断胃肠道间质瘤的价值。     

内镜超声引导下细针穿刺结合免疫组织化学鉴别上消化道固有肌层肿瘤

目的探讨内镜超声引导下细针穿刺结合免疫组织化学检查在鉴别上消化道固有肌层肿瘤起源中的作用。方法选择经内镜发现并由内镜超声检查证实直径大于25mm的上消化道固有肌层病变患者35例，内镜超声检查明确病变的大小、形态、位置，并观察有无周围脏器转移。在内镜超声导引下对病变行细针穿刺，对取材分别进行HE、CD117，CD34和肌动蛋白（SMA）染色。结果35例患者中，31例患者取得了足够的组织，经免疫组化染色，诊断为间质瘤21例，平滑肌瘤10例。与术后诊断比较超声内镜结合免疫组织化学检查的敏感性为88．6％，特异性为100％。无一例患者出现不良反应。结论内镜超声引导下细针穿刺结合免疫组织化学检查是鉴别上消化道固有肌层肿瘤安全有效的方法。     

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。     

Resected tumor seeding in stomach wall due to endoscopic ultrasonography-guided fine needle aspiration of pancreatic adenocarcinoma

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a useful and relatively safe tool for the diagnosis and staging of pancreatic cancer. However, there have recently been several reports of tumor seeding after EUS-FNA of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and the stage of the cancer was T3N0M0. The patient underwent surgery with curative intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The patient underwent surgical resection of the gastric tumor with curative intent. The pathological result of the resected gastric specimen was adenocarcinoma with a perfectly matched mucin special stain result with the previously resected pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA which was surgically resected and inspected pathologically.     

胃肠道间质瘤的临床特征及治疗进展

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是胃肠道最常见的间叶性肿瘤,近年来随着分子生物学、组织病理学和临床医学的研究进展,对其认识不断加深.传统手术与分子靶向药物相结合对GIST的治疗显得尤为重要,以伊马替尼和舒尼替尼等药物为代表的多靶点和多激酶抑制剂在治疗不可切除及复发性GIST中更是受到高度关注.本文主要对该病的基因分析、病理组化特点、手术及辅助治疗相关进展作一综述.     

Endoscopic management of gastrointestinal smooth muscle tumor

AIM: To systematically evaluate the efficacy and safety of endoscopic resection of gastrointestinal smooth muscle tumors (SMTs, including leiomyoma and leiomyosarcoma) and to review our preliminary experiences on endoscopic diagnosis of gastrointestinal SMTs. METHODS: A total of 69 patients with gastrointestinal SMT underwent routine endoscopy in our department. Endoscopic ultrasonography (EUS) was also performed in 9 cases of gastrointestinal SMT. The sessile submucosal gastrointestinal SMTs with the base smaller than 2 cm in diameter were resected by "pushing" technique or "grasping and pushing" technique while the pedunculated SMTs were resected by polypectomy. For those SMTs originating from muscularis propria or with the base size ≥ 2 cm, ordinary biopsy technique was performed in tumors with ulcers while the "Digging" technique was performed in those without ulcers. RESULTS: 54 cases of leiomyoma and 15 cases of leiomyosarcoma were identified. In them, 19 cases of submucosal leiomyoma were resected by "pushing" technique and 10 cases were removed by "grasping and pushing" technique. Three cases pedunculated submucosal leiomyoma were resected by polypectomy. No severe complications developed during or after the procedure. No recurrence was observed. The diagnostic accuracy of ordinary and the "Digging" biopsy technique was 90.0% and 94.1%, respectively. CONCLUSION: Endoscopic resection is a safe and effective treatment for leiomyomas with the base size ≤2 cm. The "digging" biopsy technique would be a good option for histologic diagnosis of SMTs.     

Impact of Franseen needle on rapid onsite evaluation and histological examination following endoscopic ultrasonography-guided tissue acquisition in patients with splenic malignant lymphoma

Rapid onsite evaluation (ROSE) following endoscopic ultrasonography (EUS)-guided fine-needle aspiration contributes to the establishment of a diagnosis for various organs. Newly designed three-plane symmetric needles for EUS-guided fine-needle biopsy (EUS-FNB), such as the Franseen needle, have been developed to enable histological core tissue acquisition. However, EUS-guided tissue acquisition for hypervascular splenic lesions remains challenging. Tissue acquisition in cases of splenic malignant lymphoma by using a conventional needle with multiple strokes and suction may result in indeterminate ROSE due to blood contamination and tiny fragments of lymphoma tissue, whereas EUS-FNB by using the Franseen needle with a minimal number of strokes with suction demonstrates qualified specimens for the ROSE as well as histological examination. For splenic malignant lymphomas, EUS-FNB by using the Franseen needle with a limited number of strokes may facilitate qualified specimen acquisition.     

食管贲门部间质瘤和平滑肌瘤内镜超声图像的计算机分析

目的 寻找食管、贲门部间质瘤和平滑肌瘤EUS图像的差别.方法 选取经免疫组化确诊的食管、贲门部间质瘤13例和平滑肌瘤11例的EUS图像,利用计算机分析病变处和黏膜下层图像的灰度值信息,包括灰度值离散度和灰度平均值,并校正病变处的灰度平均值.结果 间质瘤的校对后灰度平均值为0.285,平滑肌瘤为0.185;间质瘤的灰度值离散度的平均值为8.14,平滑肌瘤为4.59.t检验分析校对后的灰度平均值和灰度值离散度,P均＜0.05,差异有显著意义.结论 食管、贲门部间质瘤EUS的回声强于平滑肌瘤,并且回声更不均匀.     

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.     

内镜下胃壁全层切除术对胃间质瘤的治疗价值研究

目的初步探讨内镜下胃壁全层切除术（EFTR）对胃间质瘤治疗的价值。方法2010年1月至2011年7月对33例病灶大、位于固有肌深层胃间质瘤行内镜下胃壁全层切除术治疗,观察疗效及安全性,并与同期行内镜黏膜下切除术（ESD）治疗的34例胃间质瘤病例在有效性、安全性、手术复杂程度等方面进行比较。结果33例EFTR治疗的病例中,2例因病灶过大未能完成手术,其余均顺利切除病灶,术后恢复良好,随访12个月无复发。与ESD治疗病例相比,手术切除率（93．9％比100％）、并发症发生率（6．5％比2．9％）、术后3d平均体温[（37．2±0．4）℃比（37．0±0．4）℃]及血常规白细胞总数[（8．5±8．0）×10^9／L比（6．1±1．7）×10^9／L]、术后恢复时间[（6．1±2．1）d比（5．2±2．8）d],差异均无统计学意义。EFTR组术中钛夹使用个数[（7．0±3．5）比（4．9±3．1）,t=2．55,P〈0．05]及术后禁食天数[（3．4±1．5）d比（2．0±1．0）d,t=4．36,P〈0．05]明显多于ESD组。结论EFTR对胃问质瘤的治疗是安全、有效的,与ESD术式比较EFTR手术风险并未明显增加,但作为ESD手术的扩展,EYrR手术更为复杂。     

胃肠道间质瘤110例临床诊治分析

目的 研究胃肠道间质瘤(gastrointestinal stromaltumor,GIST)的临床特点、治疗方法和预后.方法 对2002年2月至2008年7月110例经手术后病理确诊为GIST患者的临床资料进行回顾性分析.结果 所有患者的GIST主要起源于胃(50.9%)和小肠(31.8%),103例(93.6%)有临床症状.最常见的临床表现为消化道出血、腹痛和腹部肿块.手术病理结果发现良性14例(1 2.7%),交界性37例(33.6%),恶性59例(53.6%).免疫组化检测CD117、CD34的阳性率分别为98.2%(108/110)和77.3%(85/110).81.8%的患者进行了根治性的手术切除.15例手术时已转移的GIST和6例复发的GIST行伊马替尼治疗,15例可评估,临床获益率80.0%.结论 GIST临床表现缺乏特异性,确诊须依赖大体标本或免疫组化病理结果,CD117对诊断有重要价值.肿瘤的完整切除是主要治疗方法,分子靶向药物伊马替尼能延长晚期GIST患者的生存期.     

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.     

Endoscopic enucleation of gastrointestinal stromal tumors of the stomach： Report of five cases

Gastrointestinal stromal tumor （GIST） of the stomach was treated by endoscopic enucleation in five patients. They were three men and two woman, aged 36-56 years. Tumors located in the cardia were completely enucleated endoscopically without any serious complication. The largest diameter of removed tumors ranged from 1.2 to 2.5 cm. Histopathological diagnosis was GIST with low risk of malignancy （mitotic index 〈 5/50 high power field） in all cases. The patients were disease-free for 10.5-42.2 mo after endoscopic enucleation.     

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.