甲磺酸伊马替尼致间质性肺炎1例并文献复习

目的 提高对甲磺酸伊马替尼所致间质性肺炎的认识,做到早期诊断和治疗,改善患者预后.方法 对北京大学首钢医院呼吸内科诊治的1例甲磺酸伊马替尼致间质性肺炎患者的临床资料进行回顾性分析,并进行相关文献复习.结果 患者女性,小肠间质瘤术后服用甲磺酸伊马替尼3个半月后出现水肿、呼吸困难,入院后胸部CT提示双肺弥漫分布的斑片影,BALF显示细胞总数升高(0.54×109/L),其中淋巴细胞56％.除外感染、自身免疫性疾病和其他药物因素,诊断甲磺酸伊马替尼导致的间质性肺炎,停止服用伊马替尼3周后患者呼吸困难无改善,后加用糖皮质激素治疗,激素治疗约2周后患者呼吸困难明显减轻,胸部CT双肺斑片影较前部分吸收,激素治疗4个月后复查胸部CT病变较前明显吸收,但遗留肺间质纤维化改变,停用激素治疗.随访患者未再服用甲磺酸伊马替尼,2年及5年后胸部CT较前无明显变化,3年后患者因小肠间质瘤复发再次手术切除.结论 服用甲磺酸伊马替尼后出现呼吸困难症状应考虑间质性肺炎可能,早期诊断、停药和应用糖皮质激素治疗可获得显著效果,停药后应长期随访患者基础疾病及肺部情况.通过这此例报道并进行文献复习有助于提高对甲磺酸伊马替尼所致间质性肺炎的认识.     

甲磺酸伊马替尼治疗120例慢性髓性白血病的临床研究

目的观察甲磺酸伊马替尼（IM）治疗Ph染色体阳性和（或）BCR／ABL基因阳性的慢性髓性白血病（CML）的疗效和安全性。方法对90例Ph染色体阳性和（或）BCR／ABL基因阳性CML慢性期（CP）患者,持续口服IM,400mg／d;30例CML疾病进展期（加速期／急变期）患者,持续口服IM,600mg／d。服药期间定期复查血常规、骨髓细胞学、染色体和（或）BCR／ABL基因等指标,并随访观察。结果（1）CML—CP患者总的完全血液学缓解率（CHR）、完全细胞遗传学缓解率（CCyR）和完全分子遗传学疗效（CMR）分别为73．3％（66／90）、66．7％（60／90）、54．4％（49／90）;治疗前是否接受过干扰素治疗对CHR、CCyR和CMR均无明显影响;服药前病程≤6个月的CMR优于〉6个月者。初次达到CHR的时间与首次达CCyR的时间、首次达CCyR的时间与BCR／ABL首次转阴时间之间均存在相关性,而初次达CHR的时间与BCR／ABL首次转阴时间则无明显相关性。（2）进展期CML患者的CHR、CCyR、CMR分别为43．3％（13／30）、25．9％（7／27）、25．0％（7／28）,总病死率为30．0％（9／30）。（3）年龄≤25岁患者的病死率高于〉25岁者,差异有统计学意义（P〈0．05）。（4）白细胞减少达Ⅲ级者有19例（16．0％）,发生于治疗后5～20周。血小板减少达Ⅲ级者有21例（18．0％）,发生于治疗后3～16周。主要的非血液系统毒性为双下肢水肿、骨痛和皮疹等,但均程度轻微。结论IM对初治CML及经干扰素治疗失败的CML有较高的CHR及CCyR且起效迅速,对CML—CP疗效显著优于进展期;不良反应程度轻微,患者易于耐受。     

甲磺酸伊马替尼治疗慢性粒细胞白血病54例近期疗效观察

目的 观察甲磺酸伊马替尼(imatinib)治疗慢性粒细胞白血病(CML)的近期疗效。方法 54例CML患者接受imatinib治疗,其中慢性期(CP)17例,加速期(AP)13例,急变期(BC)24例。imatinib用法：CP患者400mg／d,AP和BC患者600mg／d,均为餐后一次顿服。治疗前全面查体,查血象、骨髓象、Ph染色体和(或)bcr／abl融合基因。治疗期间第1个月每周查血象2次,1个月后每周或2周1次。每2～4周查一次肝、肾功能。待血液学取得完全缓解(CR)后择期复查骨髓、Ph染色体和(或)bcr／abl基因。根据血象和患者对药物耐受情况及时调整药物剂量。结果 经中位时间5个月(1～10个月)随访,17例CML CP期患者16例(94．1％)取得血液学CR,其中6例(35．2％)Ph染色体转阴;13例AP患者8例(61．5％)回到CP;24例BC患者9例(37．5％)回到CP。药物不良反应有造血功能抑制、眶周和下肢轻度水肿、全身肌肉关节酸痛和恶心、呕吐、低热(37．5～38℃)、皮疹、胆红素升高等。结论 imatinib对CML有较好近期疗效,其疗效以CP最好,AP其次,BC较差。远期疗效有待进一步观察。药物不良反应可以耐受。     

甲磺酸伊马替尼治疗晚期慢性粒细胞白血病致多浆膜腔积液2例

目的通过2例晚期慢性粒细胞白血病(CML)患者接受甲磺酸伊马替尼治疗后出现多浆膜腔积液的病例分析和文献复习,探讨甲磺酸伊马替尼在治疗晚期慢性粒细胞白血病中的安全性.方法对2例甲磺酸伊马替尼治疗晚期慢性粒细胞白血病的临床资料进行分析并结合文献复习使其在今后治疗中可能出现的不良反应引起重视.结果2例分别确诊为晚期慢性粒细胞白血病的患者接受甲磺酸伊马替尼治疗后,出现多浆膜腔积液.结论甲磺酸伊马替尼治疗晚期慢性粒细胞白血病时可能会出现严重的不良反应.     

甲磺酸伊马替尼治疗晚期慢性粒细胞白血病致多浆膜腔积液2例

目的:通过2例晚期慢性粒细胞白血病(CML)患者接受甲磺酸伊马替尼治疗后出现多浆膜腔积液的病例分析和文献复习,探讨甲磺酸伊马替尼在治疗晚期慢性粒细胞白血病中的安全性。方法:对2例甲磺酸伊马替尼治疗晚期慢性粒细胞白血病的临床资料进行分析并结合文献复习使其在今后治疗中可能出现的不良反应引起重视。结果:2例分别确诊为晚期慢性粒细胞白血病的患者接受甲磺酸伊马替尼治疗后,出现多浆膜腔积液。结论:甲磺酸伊马替尼治疗晚期慢性粒细胞白血病时可能会出现严重的不良反应。     

甲磺酸伊马替尼治疗进展期慢性髓细胞白血病14例疗效分析

慢性髓细胞白血病(CML)是起源于造血干细胞的恶性克隆性疾病,由于9号染色体的ABL基因与22号染色体的BCR基因相互易位形成BCR/ABL融合基因,表达P210蛋白,具有异常的酪氨酸激酶活性,激活细胞信号传导途径,促进细胞增殖,抑制细胞凋亡.     

甲磺酸伊马替尼治疗慢性粒细胞白血病附加异常Ph阳性克隆的预后意义

目的探讨甲磺酸伊马替尼（伊马替尼）治疗后慢性粒细胞白血病（CML）具有附加异常的Ph阳性克隆的演变及其预后意义。方法收集37例CML加速期和急变期患者的骨髓标本培养24h,G显带进行核型分析。结果伊马替尼治疗前患者的附加染色体种类主要有双Ph、＋8、i（17q）等,其次还有-Y、除i（17q）外17号的异常、inv（3q）等,以及少见的易位和其他异常。伊马替尼治疗后具有附加异常的Ph阳性克隆比例发生扩增、基本不变、比例下降、完全消失等4种形式的演变。24例加速期患者中有2例获得完全细胞遗传学缓解（CCyR）,13例急变期患者中2例获CCyR。附加异常克隆扩增／不变组的中位生存时间和无疾病进展时间显著短于比例下降／完全消失组（P〈0．05）。结论有附加染色体异常的Ph阳性CML患者伊马替尼治疗后附加异常克隆比例可以下降甚至完全消失,获得CCyR,并伴生存期延长。     

大剂量伊马替尼治疗慢性髓细胞白血病的临床观察

目的:评价大剂量(600mg/d以上)甲磺酸伊马替尼治疗慢性髓系白血病(CML)的疗效及安全性。方法:筛选28例接受大剂量格列卫治疗(600～800mg/d)的CML患者,疗程0.25～30.00个月,观察其疗效及毒副作用,并与之前接受常规剂量(300～400mg/d)格列卫时的情况比较。结果:10例(35.7%)患者达到并保持血液学完全缓解,13例(46.4%)患者达到血液学部分缓解,5例患者格列卫加量后病情仍进展;发生主要细胞遗传学反应5例(17.9%),次要细胞遗传学反应12例(42.9%);3例初始格列卫剂量为600mg/d的患者出现Ⅳ度不良反应,2例为血液学毒性,1例为剥脱性皮炎,其余25例患者中,9例发生Ⅲ度以下血液学毒性,1例发生Ⅳ度血液学毒性;非血液学不良反应均为Ⅲ度以下,主要有软组织水肿(7/28)、浆膜腔积液(5/28)、关节疼痛(2/28)以及消化道反应(3/28)。结论:大剂量格列卫对初治的、经羟基脲或IFN-α治疗失败的以及常规剂量格列卫疗效欠佳的各阶段CML均有较好疗效;对于曾接受常规剂量格列卫治疗的患者,大剂量格列卫不良反应轻微、多可耐受。     

两种生活质量评分对甲磺酸伊马替尼治疗胃肠间质瘤患者生活质量评价的可行性

目的探讨生活功能指数量表（FLIC量表）及KPS评分评价甲磺酸伊马替尼治疗胃肠间质瘤（GIST）患者生活质量变化的可行性。方法同时采用FLIC量表及KPS评分评价GIST患者接受伊马替尼治疗前及治疗过程中的生活质量。结果有症状患者治疗后KPS评分及FLIC量表得分明显提高（P〈0．01）。Ⅰ-Ⅱ级疲乏、腹泻、呕吐、肌肉疼痛不良反应使患者FLIC量表得分下降（P〈0．05）,KPS评分下降不明显;Ⅲ-Ⅳ级不良反应使患者FLIC量表得分及KPS评分均下降（P〈0．05）。治疗后病情进展初期KPS评分及FLIC得分下降不明显（P〉0．05）;死亡患者平均在临终前1个月KPS评分及FLIC得分骤然下降。结论FLIC量表及KPS评分均能评价甲磺酸伊马替尼治疗胃肠道间质瘤患者生活质量变化,FLIC量表较KPS评分有更高的敏感性。     

国产甲磺酸伊马替尼一线治疗慢性髓性白血病慢性期患者的临床效果及安全性分析

目的:分析国产甲磺酸伊马替尼(商品名:格尼可)治疗慢性髓性白血病慢性期(CML-CP)患者的临床疗效和安全性。方法:回顾性分析62例一线服用格尼可治疗的CML-CP患者的临床资料。根据患者Sokal预后风险评分、耐受情况适当调整伊马替尼剂量,即300～600 mg/d。分析患者用药3、6、12个月获得的最佳反应、分子生物学反应,采用χ²检验比较各Sokal积分组达到的最佳反应率,统计药物引起的不良反应。结果:62例接受格尼可治疗的CML-CP患者,治疗后3个月时完全血液学缓解(CHR)率为90.32%,BCR-ABL^IS≤10%为75.81%,分子学缓解为9.68%;治疗后6个月时CHR率为95.16%,BCR-ABL^IS≤1%为70.97%,分子学缓解为30.65%;治疗后12个月时所有患者达到CHR,50.00%的患者获得分子学缓解。按照Sokal评分将62例患者分为高危组7例、中危组19例和低危组36例,在治疗后3、6、12个月,3组最佳反应发生率比较均差异无统计学意义(χ²=5.49、3.8...     

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.     

Effect of sunitinib on metastatic gastrointestinal stromal tumor in patients with neurofibromatosis type 1： A case report

Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal malignancy of the gastrointestinal (GI) tract. In neurofibromatosis (NF), the increased incidence of tumor needs to be considered even in non-symptomatic individuals. Patients with neurofibromatosis NF type 1 have an increased risk of developing GI tumors including rare types such as GIST. We report a case of GIST in a 53-year-old male patient with neurofibromatosis. The patient was diagnosed with NF four years ago and his medical history revealed that he was hospitalized 5 times with a provisional diagnosis of massive lower gastrointestinal bleeding. GIST was diagnosed at explorative laparotomy and the tumor was 21 cm × 13 cm × 7 cm in size. Immunohistochemical examination showed that vimentin, actin and CD117 were positive. Computerized tomography showed peritoneal implants three months later. Imatinib mesylate (600 mg/d) was initiated. However, control computerized tomography revealed liver and omental metastasis. The dosage was elevated to 800 mg/d. Despite high dosage, the progression of the metastatic lesions continued in the liver and omentum. The patient started oral sunitinib malate (Sutent? Pfizer Inc, New York, NY, USA) 50 mg per day for 4 consecutive weeks, followed by 2 wk off per treatment cycle. The metastatic lesions in the liver and omentum were decreased in size after four courses, suggesting that sunitinib is also an effective treatment modality for metastatic GIST in NF patients.     

Rectal angiolipoma： A case report and review of literature

Angiolipoma is a rare vascular variant of the benign lipomatous tumors and is generally seen in subcutaneous tissues. We report a 70-year-old female with abdominal distension not related to rectal small polypoid mass with peduncule described as angiolipoma by histologically, and review the literature.     

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.     

Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors (GISTs). The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here, we report the clinicopathological features of our case, along with a review of the few cases present in the literature.     

伊马替尼治疗不能切除和（或）转移性胃肠道间质瘤的系统评价

目的系统评价伊马替尼治疗不能切除和（或）转移性胃肠道问质瘤的有效性和安全性。方法计算机检索PubMed（1989～2009．4）、EMbase（1989～2009．4）、Cochrane图书馆（2009年第3期）、CBM（1989～2009．4）、CNKI（1989～2009．4）、VIP（1989～2009．4）。同时手工检索其引文,以便发现新的可纳入文献。按Cochrane协作网推荐的方法进行系统评价。结果共纳入5个RCT,包括1845例患者。meta分析结果显示：与标准剂量组（400mg／d）相比,高剂量组（600mg／d或800rag／d）依马替尼虽然增加2年无疾病进展生存率[RR=1．15,95％CI=1．01～1．30,P=0．03],但在2年总生存率（RR=1．00,95％CI=0．92—1．08,P=0．93）、完全肿瘤反应率（RR=1．02,95％CI=0．66～1．59,P=0．93）、部分肿瘤反应率（RR=1．06,95％CI=0．96～1．17,P=0．28）方面两组相似。在安全性方面,高剂量组依马替尼增加了血液毒性反应（RR=1．08,95％CI=1．03—1,14,P=0．003）和各种非血液毒性反应（RR：1．18～2．07,95％CI=1．06～3．32,P均〈0．05）,特别是增加了3级以上毒性反应（RR=1．48,95％CI=1．33～1．65,P〈0．00001）。依马替尼间断治疗的患者出现疾病进展的风险明显增高（RR=0．27,95％CI=0．13～0．58,P〈0．05）,而生存质量未见改善（MD=3．50,95％CI=-11．17～18．17,P〉0．05）。结论对不能切除和（或）转移性的胃肠道间质瘤患者,增加剂量,病人未见明显临床获益;依马替尼治疗胃肠道间质瘤取得疗效后,应持续服药,以免引起疾病进展的风险增加。     

Imatinib-induced decompensated heart failure in an elderly patient with chronic myeloid leukemia: case report and literature review

Because it is safe and well tolerated, imatinib is a standard first-line therapy for chronic myeloid leukemia (CML). Although there have been sporadic reports of imatinib-induced cardiotoxicity, including left ventricle (LV) dysfunction and heart failure, the evidence for it is contradictory. Here, we reported a case of an 88-year-old male patient with CML developed decompensated heart failure following imatinib therapy. Four days after the initiation of imatinib, the patient developed orthopnea, edema and a pleural effusion accompanied by abdominal distension, nausea and vomiting. The chest X-ray film showed an enlarged cardiac profile. The echocardiogram demonstrated a decreased LV ejection fraction and enlarged left-side cardiac chambers. B-type natriuretic peptide concentrations were markedly increased. The patient recovered soon after the withdrawal of imatinib and introduction of comprehensive therapy for heart failure. Imatinib-induced cardiotoxicity in elderly patients is a potentially serious complication that merits further evaluation.     

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.