Assessment of gastrointestinal stromal tumors with computed tomography following treatment with imatinib mesylate

AIM： To evaluate and characterize the patterns of disease progression of metastatic or unresectable gastrointestinal stromal tumor （GIST） treated with imatinib mesylate, and to determine the prognostic significance associated with disease progression. METHODS： Clinical data and computed tomography （CT） images were retrospectively reviewed in 17 GIST patients who were treated with imatinib mesylate from October 2002 to October 2006. Apart from using size measurement for evaluation of tumor response [Response Evaluation Criteria in Solid Tumors （RECIST） criteria], patterns of CT changes during treatment were evaluated and correlated with clinical data. RESULTS： There were eight non-responders and nine responders. Five patterns of CT change during treatment were found： focal progression （FP）, generalized progression （GP）, generalized cystic change （GC）, new cystic lesion （NC） and new solid lesion （NS）. At the end of study, all non-responders showed GP, whereas responders showed cystic change （GC and NC） and response according to RECIST criteria. Overall survival was significantly better in patients with cystic change or response within the RECIST criteria compared with GP patients （P = 0.0271）. CONCLUSION： Various patterns of CT change in patients with GIST who responded to imatinib mesylate were demonstrated, and might determine the prognosis of the disease. A combination of RECIST criteria and pattern of CT change are proposed for response evaluation in GIST.     

Imatinib mesylate neoadjuvant treatment for rectal malignant gastrointestinal stromal tumor

Surgical treatments including radical resection and local excision remain the main treatment for primary rectal gastrointestinal stromal tumors （GISTs）. However, since patients with high-grade rectal GISTs have a higher risk of tumor recurrence and a shorter life expectancy, neoadjuvant treatment is necessary. In this case report, the efficacy of imatinib mesylate （IM） as a neoadjuvant therapy was assessed in an old man with malignant rectal GIST. The patient received IM preoperative treatment for a short period of one and a half months; at the end of the IM treatment, computed tomography scanning showed a markedly reduced tumor size and cystic changes of the tissue. At that time, a function sphincter-sparing surgery was performed. The histological examination of the resected specimen detected no tumor cells, but residual blood vessels and scattered inflammatory lymphocytes. After surgery, the patient has been followed up without additional IM treatment and remained disease-free for 57 mo. This case indicates that IM neoadjuvant therapy can dramatically improve the prognosis of rectal malignant GIST.     

Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate： A case report

Gastrointestinal stromal tumors （GISTs） are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, coexistance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma （MM） with GIST.     

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor （GIST）. Computed tomography （CT） and magnetic resonance imaging （MRI） 107 mo after the operation, revealed a cystic mass （14 cm in diameter） and a solid mass （9 cm in diameter） in the right and left lobes of the liver, respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate （IM） treatment, 400 mg/day orally. Following the IM treatment for a period of 35 mo, the patient underwent partial hepatectomy （S4 ＋ S5）. The effect of IM on the metastatic lesions was interpreted as pathologic complete response （CR）. Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.     

胃肠道间质瘤4例报道

间质瘤主要发生在胃肠道,指在光镜下主要由梭形细胞和上皮样细胞构成,某些免疫组化阳性的肿瘤。本文对4例胃肠道间质瘤手术病人的临床表现、影像学特点、肿瘤大小等进行总结。     

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。     

Laparoscopic resection of gastric gastrointestinal stromal tumors presenting as left adrenal tumors

Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal malignancies. They are rarely seen near the urinary tract. In a literature review, only one case of GIST presenting as a left adrenal tumor was reported. We report two documented cases of gastric GISTs mimicking left adrenal tumors which were successfully treated with pure laparoscopic adrenalectomy and wedge resection of the stomach by excising the tumor from the stomach with serial firing of endoscopic gastrointestinal staplers. The surgical margins were clear, and the patients recovered smoothly. No adjuvant therapy with imatinib was prescribed. During the surveillance for 9 mo and 44 mo respectively, no tumor recurrence and metastasis were documented. Laparoscopic tumor excision, when adhering to the principles of surgical oncology, seems feasible and the prognosis is favorable for such tumors.     

胃的胃肠间质瘤114例

目的:总结发生于胃的胃肠间质瘤(GISTs)的临床病理特征、诊治及预后.方法:回顾分析2005-1/2010-9华中科技大学同济医学院附属协和医院普通外科收治的114例胃GISTs患者的临床病理资料.结果:胃GISTs最常见于贲门胃底部(53.5%)和胃体部(36.8%),常见的临床表现包括消化道出血与腹部胀痛.内镜超声与CT在术前诊断方面准确率较高,确诊则需要病理组织学与免疫组织化学检查.除1例患者外其余均行手术完整切除,免疫组织化学示CD117阳性率98.2%(112/114),CD34阳性92.1%(105/114).术后随访3-68mo(平均随访26.2mo),共有24例服用甲磺酸伊马替尼治疗,本组98例随访患者5年生存率为100%,无瘤生存率达到98.0%.结论:胃GISTs临床表现没有特异性,内镜超声与CT是术前有效的诊断方法.手术仍是胃GISTs治疗的主要方法,术后给予靶向治疗可显著改善患者预后.     

Gastrointestinal stromal tumor of the anus

Abstract. We report a rare case of gastrointestinal tumor of the anus with an unusual presentation as a perianal lipoma. A 65-year-old man presented with a 2-month history of a painless perianal lump clinically resembling a perianal lipoma. Endoanal ultrasonography revealed a 3x3 cm² mass in the intersphincteric plane. Following initial excision of the lesion, histological analysis revealed a stromal lesion comprising fascicles of spindle cells with a mitotic count of 4 per 50x high power field. Immunohistochemical analysis displayed positive reactivity for CD34 with focal staining for CD117; S100, smooth muscle actin and desmin were not expressed. No evidence of local or distant metastatic disease was found on computed tomography of the abdomen and pelvis. The patient subsequently underwent abdominoperineal resection. The resected specimen contained a mural nodule measuring 0.7 cm, located 5 cm from the distal margin and 2 mm from the radial margin. Histological analysis confirmed a stromal tumor composed of spindle cells with mitoses up to 2 per 10x high power field. The patients recovery was uneventful and he was free of recurrence at the 1-year follow-up. Gastrointestinal stromal tumors of the anal canal are an extremely rare occurrence, and may mimic benign perianal lesions. Tumor size and mitotic count are the most important factors in prognosticating outcome. Oncologic resection and protracted follow-up must factor in their predilection for late recurrence and metastatic spread. The role of adjuvant therapy with STI571 here remains to be clearly defined.     

Current update on molecular cytogenetics,diagnosis and management of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract and are thought to arise from precursors of the interstitial cells of Cajal. GISTs can arise anywhere in the GI tract, but most commonly originate from the stomach and small intestine. The majority of GISTs occur as a result of activating mutations in two receptor protein tyrosine kinases: KIT and/or platelet-derived growth factor receptor-α. Mutational analyses allow for predicting patient prognosis and treatment response. Clinical presentations can vary from no symptoms, typical in the case of small incidentally found tumors, to GI bleeding, abdominal discomfort, and ulcer-related symptoms when the tumor is enlarged. Imaging plays a critical role in the diagnosis and management of these tumors with multiphasic computed tomography serving as the imaging modality of choice. Magnetic resonance imaging and positron emission tomography-computed tomography can serve as imaging adjuncts in lesion characterization, especially with liver metastases, and subsequent staging and assessment for treatment response or recurrence. Surgical resection is the preferred management for small GISTs, while tyrosine kinase inhibitors − imatinib mesylate and sunitinib malate − serve as crucial molecular-targeted therapies for locally advanced and metastatic GISTs. This review article highlights the clinical presentation, pathology and molecular cytogenetics, imaging features, and current management of GISTs.     

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。     

Gastrointestinal stromal tumor of the stomach with a giant abscess penetrating the gastric lumen

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. In large GISTs, cystic degeneration, necrosis and focal hemorrhage that occur inside the tumor can result in gastrointestinal bleeding. We describe a case of a 74-year old male with GIST of the stomach accompanied with a giant abscess that penetrated the gastric lumen. The patient experienced undiagnosed fever for two months prior to hospitalization. Gastrointestinal endoscopy, X-ray series and computed tomography of the patient’s abdomen revealed a gastric submucosal tumor in the fornix, with a fistula to the gastric lumen that was inundated with a great deal of pus. The mass was diagnosed as a GIST from biopsy specimens. The patient was treated by endoscopic drainage of the abscess and intravenous administration of antibiotics. Eventually, a partial gastrectomy was performed. He was also administered Imanitib mesylate as adjuvant therapy. He was followed up for 2 years and no metastasis or recurrence was recognized at the follow- up examinations. This is the first report of a patient with clearly diagnosed GIST with endoscopic evidence of an abscess penetrating into the gastric lumen.     

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.     

Early detection of response to imatinib therapy for gastrointestinal stromal tumor by using 18F-FDG-positron emission tomography and computed tomography imaging

A 41-year old female with metastatic gastrointestinal stromal tumor was referred to 18F-FDG-positron emission tomography and computed tomography （PET/CT） scan before and after one-month treatment with imatinib （Glivec, Gleevec, Novartis, Basel, Switzerland）, a tyrosine kinase inhibitor （400 mg/d）. Metabolic response was evaluated before and after one month of therapy. The decrease of the maximum standardised uptake value （SUV） was 79% （from 9.8 to 2.1）. Positron emission tomography demonstrated complete metabolic response after one-month of imatinib treatment. Additionally, the previous lesion was compared with the coronal computerized tomographic image. There was no difference in the size of the tumor before and after therapy according to CT images. However, metabolic activity was inhibited. 18F-FDG-PEr is a valuable method for the detection of response to one-month imatinib treatment in patients with gastrointestinal stromal tumors.     

Gastrointestinal stromal tumor and mitosis, pay attention

The difference between stages I and III of gastric gastrointestinal stromal tumor depends principally on the number of mitosis. According with TNM classification, the presence in the tumor of high mitotic rate determines the upgrading. Many studies exposed different count techniques in evaluating the number of mitosis. An international standardized method to assess mitotic rate is needed.     

Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients

AIM: To investigate the efficacy and safety of imatinib dose escalation in Chinese patients with advanced gastrointestinal stromal tumor (GIST).METHODS: Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled in this study. Patients received imatinib with dose escalation to 600 mg/d, and further dose escalation to 800 mg/d if imatinib 600 mg/d failed. Progression-free survival, overall survival, clinical efficacy, c-kit/PDGFRA genotype and safety were evaluated.RESULTS: 52 patients were enrolled in this study. For the 47 evaluable patients receiving imatinib (600 mg/d), the disease control rate was 40.4%, and the median progression-free survival for all patients was 17 wk (95% CI: 3.9-30.1). The median overall survival after dose escalation was 81 wk (95% CI: 36.2-125.8). Adverse events, mainly edema, fatigue, granulocytopenia and skin rash were tolerable. However, further dose escalation (800 mg/d) in 14 cases was ineffective, with disease progression and severe adverse events. Among 30 cases examined for gene mutations, patients with exon 9 mutations experienced a better progression-free survival of 47 wk.CONCLUSION: Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.     

Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach

Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract. It may coexist with other type of cancers, and if so, the tumors usually involve the stomach. The most common associated cancers are gastrointestinal carcinomas. We report a 65-year-old woman with a history of gastric gastrointestinal stromal tumor who had undergone subtotal segmental gastrectomy. New polypoid lesions were detected on a follow-up gastroscopy one year later. The lesions were biopsied and found to be carcinoid tumors. There was serum hypergastrinemia, and type 1 gastric carcinoid tumor was diagnosed. A total gastrectomy was performed. Pathologic examination revealed both carcinoid tumors and a recurrent gastrointestinal stromal tumor.     

Modern treatment of gastric gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial cells of Cajal have been identified as the key molecular step in GIST carcinogenesis. Although many patients are asymptomatic, the most common associated symptoms include: abdominal pain, dyspepsia, gastric outlet obstruction, and anorexia. Rarely, GIST can perforate causing life-threatening hemoperitoneum. Most are ultimately diagnosed on cross-sectional imaging studies (i.e., computed tomography and/or magnetic resonance imaging in combination with upper endoscopy. Endoscopic ultrasonographic localization of these tumors within the smooth muscle layer and acquisition of neoplastic spindle cells harboring mutations in the c-KIT gene is pathognomonic. Curative treatment requires a complete gross resection of the tumor. Both open and minimally invasive operations have been shown to reduce recurrence rates and improve long-term survival. While there is considerable debate over whether GIST can be benign neoplasms, we believe that all GIST have malignant potential, but vary in their propensity to recur after resection and metastasize to distant organ sites. Prognostic factors include location, size (i.e., > 5 cm), grade (> 5-10 mitoses per 50 high power fields and specific mutational events that are still being defined. Adjuvant therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to reduce the risk of recurrence after one year of therapy. Treatment of locally-advanced or borderline resectable gastric GIST with neoadjuvant imatinib has been shown to induce regression in a minority of patients and stabilization in the majority of cases. This treatment strategy potentially reduces the need for more extensive surgical resections and increases the number of patients eligible for curative therapy. The modern surgical treatment of gastric GIST combines the novel use of targeted therapy and aggressive minimally invasive surgical procedures to provide effective treatment for this lethal, but rare gastrointestinal malignancy.