甲磺酸伊马替尼治疗高危胃肠间质瘤预后的研究

目的探讨靶向药物甲磺酸伊马替尼对高危胃肠间质瘤(GIST)患者预后的影响。方法回顾性分析2008年1月~2013年5月手术治疗的97例原发高危GIST患者的临床病理及术后随访资料。结果 97例患者中男性51例,女性46例,平均年龄57岁。肿瘤位于小肠(45.3%)、胃(42.3%)、结直肠(12.4%)。其中术后随访89例,中位随访时间33(6~96)个月,复发率43.8%(39例),死亡率20.2%(18例)。1,3和5年生存率分别为94.1%,83.2%和64.3%。术后43例服用甲磺酸伊马替尼,中位时间为28(9~74)个月。单因素和多因素预后分析显示,术后是否服用甲磺酸伊马替尼辅助治疗是影响预后的独立危险因素(P<0.05)。结论术后给予靶向药物甲磺酸伊马替尼辅助治疗可明显改善原发高危GIST患者的预后。     

胃肠道间质瘤术后复发因素分析及药物治疗

目的探讨胃肠道间质瘤的术后复发因素和药物治疗。方法选取2012年12月至2016年9月我院收治并手术的52例胃肠道间质瘤患者。术后均予以伊马替尼400 mg/d治疗,其中先后有21例出现病灶复发,对比分析复发因素,10例给予增加伊马替尼剂量(伊马替尼组),达600 mg/d,11例改为口服舒尼替尼50 mg/d(舒尼替尼组),比较两组病灶范围、不良反应以及总生存率。结果肿瘤直径超过10 cm,未能达到R0根治,核分裂像大于10/50HRF以及高危患者,术后复发率明显增高。治疗上增加伊马替尼剂量(伊马替尼组),病灶范围未见明显缩小,且大部分患者出现药物毒性,而舒尼替尼组病灶范围部分缩小或消失,且总生存率高于伊马替尼组(P<0.05)。结论肿瘤的大小、根治程度、核分裂像以及危险度等级均是胃肠间质瘤术后复发的独立危险因素,而术后常规剂量应用伊马替尼仍有复发时,应及时更换二线药物舒尼替尼。     

2010 ASCO年会胃肠道间质瘤研究进展对临床实践的启示

基因分型实现伊马替尼个体化辅助治疗胃肠道间质瘤 2007年ASCO年会首次报告了伊马替尼辅助治疗胃肠道间质瘤（GIST）的随机对照ACOSOGZ9001研究结果,即伊马替尼辅助治疗1年可改善肿瘤直径〉3cm的GIST患者的术后无复发生存（RFS）率。c—kit（一种原癌基因）／血小板衍生生长因子受体A（PDGFRA）基因突变状态可以预测伊马替尼治疗晚期GIST的疗效,     

伊马替尼治疗术后复发和转移性胃肠间质瘤11例疗效观察

胃肠间质瘤（GIST）是消化道最常见的间叶源性肿瘤,其主要治疗方法是手术,但术后极易复发或转移,术后如何进一步治疗是目前的难点。伊马替尼（Imatinib）的商品名是格列卫（Gleevec）,是对GIST有效的分子靶向药物,为术后复发、转移的患者提供了新的治疗手段。本文探讨伊马替尼对于术后复发和（或）转移性GIST的治疗效果,现报道如下。     

胃肠道间质瘤术后肝转移的临床分析

目的探讨胃肠间质瘤术后肝转移的治疗策略。方法回顾性分析2010年4月至2014年4月收治的16例GIST术后肝转移患者的临床资料、消融治疗及生存情况。结果 9例患者(56.3%)依然存活,其中5例(31.3%)无瘤生存,4例(25.0%)带瘤生存;1年、2年生存率分别为81.3%和56.3%。7例患者进行了微波消融,所有患者均接受伊马替尼400~600 mg/d治疗,耐药改用舒尼替尼治疗。随访期内微波消融组、未消融组中位生存时间分别为25.4、15.7个月。结论对于GIST术后肝转移病例应该首选靶向治疗,靶向治疗联合消融治疗可能是GIST术后肝转移的较佳治疗模式。     

伊马替尼停药后复发胃肠道间质瘤的临床特征与KIT/PDGFR基因突变分析

目的 探讨转移性胃肠道间质肿瘤(GIST)患者术后伊马替尼辅助治疗过程中,停药与复发的关系,以及KIT第11外显子突变的患者复发后,对伊马替尼的敏感性研究和预后监测. 方法 对GIST患者复发前后临床特征进行分析比较;利用免疫组织化学的方法 辅助诊断和分析复发前后CD117,CD34等GIST细胞标志物的表达情况;采用基因测序的方法 进行KIT/PDGFR基因突变检测. 结果GIST患者术后,规范伊马替尼治疗3年,停药后1年余腹部包块证实为GIST复发;患者KIT 基因第11外显子检测出有缺失突变：c.1667_1672delAGTGGA,提示该患者仍然对伊马替尼敏感;对于诊断GIST,DOG1比CD34更敏感. 结论 伊马替尼的连续用药延长无进展生存时间及延缓GIST复发,DOG1具有比CD34更好的敏感性,更加适合作为GIST的诊断标记物.     

甲磺酸伊马替尼新辅助治疗胃肠间质瘤的应用进展

胃肠间质瘤（gastrointestinal stromal tumor，GIST）仅占胃肠道恶性肿瘤的2％，但因术后复发再行切除术后的复发率仍高达100％，且对放化疗极度不敏感，使其成为治疗的难点。而靶向治疗药物甲磺酸伊马替尼应用于GIST的治疗仅5年的历史，就产生了较好效果。新辅助治疗是近年来探讨越来越多的一种新的治疗方法，是指患者在手术或放疗前所进行的化疗。现就伊马替尼新辅助治疗GIST的有关问题综述如下。     

胃肠道间质瘤的治疗现状

胃肠道间质瘤是一类起源于胃肠道间叶组织的肿瘤。目前治疗方法主要包括手术治疗和药物治疗。在药物治疗中,伊马替尼治疗不可切除/转移/复发GIST疗效显著,使得伊马替尼辅助治疗的应用日益受到重视。     

肿瘤治疗药物Mastinib的Ⅱ期临床试验结束

2012年2月1日。法国AB Science制药公司宣布其在研的肿瘤治疗药物Masitinib用于对伊马替尼耐药的胃肠道间质瘤（GIST）患者的Ⅱ期临床试验取得积极结果。这项试验的受试者为不可手术的局部晚期或转移性GIST患者．且之前在接受伊马替尼治疗期间出现疾病恶化。试验显示．Masitinib治疗组患者在接受治疗18个月后和2年后的生存率均显著高于舒尼替尼对照组。     

舒尼替尼对胃肠道间质瘤患者二线治疗的临床观察

目的 探讨二线药物舒尼替尼治疗胃肠道间质瘤(GIST)的疗效及安全性.方法 回顾性分析经病理组织和免疫组化确诊的GIST患者32例,所有的患者均用二线药物舒尼替尼治疗,37.5 mg·d-1口服,连续给药服用.观察评估舒尼替尼的不良反应及患者的生存时间.结果 舒尼替尼治疗GIST的不良反应轻微,且均可控制.32例患者接受舒尼替尼治疗的时间为3~72个月,中位治疗时间为24个月.获得完全缓解(CR)1例,部分缓解(PR)7例,稳定期(SD)16例,进展(PD)8例,有效率25.0%,疾病控制率75.0%.32例患者中,中位随访时间为96周,中位无进展生存期(PFS)为55周,中位总生存时间(OS)为96周.结论 舒尼替尼治疗伊马替尼耐药进展的GIST疗效可靠,不良反应轻微,安全可控.     

胃间质瘤临床病理因素与预后分析

目的探讨胃间质瘤（gasric stromal tumor,GST）的临床病理因素和预后。方法回顾性分析解放军总医院2005年7月—2013年9月手术治疗的有完整记录103例GST的临床资料。结果 103例随访1～84个月,平均27个月,总体1、3、5年生存率分别为95%、89%、80%,中位生存期68个月。单因素分析显示肿瘤部位、是否破裂、Fletcher风险分级、Ki-67指数、是否R0切除和术后是否应用伊马替尼与GST预后相关（P〈0.05）;多因素分析显示是否R0切除是影响GST预后的独立危险因素（P〈0.05）。结论 GST预后与肿瘤生长部位等多种因素相关,能否R0切除是影响其预后的重要因素。     

介入治疗在提高中晚期肝癌二期切除率中的疗效及意义

目的探讨中晚期原发性肝癌（HCC）经门静脉、肝动脉双重介入治疗使肿瘤缩小后切除的疗效及意义。方法30例中晚期肝癌患者（肿瘤直径8．0～20．0cm，平均10．2cm）在超声引导下行门静脉化疗及经皮穿刺肝动脉化疗栓塞（TACE），观察肝功能，AFP，各肝叶体积及不良反应，并择期手术切除肿瘤。结果手术前肿瘤平均直径缩小至4．9cm，末次TACE距手术时间为1～3个月，平均1．6个月。25例AFP阳性中9例转正常。30例患者中，行肝段、联合肝段或肝部分切除25例，左半肝切除4例，左外叶切除1例。切除肿瘤中各有60％～100％坏死，其中12例100％坏死。1、3、5年生年率分别为80％、68％、59％。结论术前经门静脉、肝动脉双重介入治疗可为一期不能切除的中晚期肝癌患者提供二期手术机会，提高手术的安全性，对预防转移、延迟复发、改善预后有肯定意义。     

Vascular resection in pancreaticoduodenectomy: is it worthwhile?

Pancreaticoduodenectomy (PD) is the gold standard treatment for cancer of pancreatic head in all the cases that are supposed to be resectable. Although the overall survival depends on many heterogeneous factors, the main aim of the treatment must be to achieve a R0 resection with microscopically and macroscopically free margins. As in recent reports vascular involvement does not represent anymore a technical limit, it is mandatory pointing out whether or not vascular resection modifies overall survival and if that is the case vascular invasion should not be considered as an exclusion criterion but as part of a standard resection. The review analysis demonstrated a progressive trend of inversion in the treatment of head pancreatic cancer over the last years. Recently, provided that a R0 resection may be performed, a more aggressive surgical approach has led to consider the possibility of venous and arterial resections. The basis for this new approach has been that the superior mesenteric vein or spleno-portal mesenteric vein invasion is not a measure of the tumor malignancy but merely a consequence of the tumor location. On the contrary, the controversial results in terms of overall survival and local recurrences achieved with major arterial resections are more likely due to a biological aggressivity than to the tumor site. The "artery first" technique seems to be the most promising approach to the problem although it needs further trials to determine whether or not this approach may be beneficial for patients in terms of overall survival and local recurrences.     

大肠癌肝转移同期手术联合化疗的临床价值

目的 探究大肠癌肝转移同期手术联合化疗的有效途径及临床价值。方法 回顾性分析同期联合手术切除原发癌及转移癌,经肝动脉门静脉双置泵栓塞灌注化疗,局部注射无水酒精及热电疗法综合性治疗结直肠癌肝转移46例临床资料。结果 本组46例大肠癌患者原发癌均获切除,其中同期切除肝转移癌21例,6例复发,4例再次手术切除。25例不能切除的转移性肝癌,行肝动脉门静脉双置泵栓塞灌注化疗,无水酒精注射和热电疗法。肿瘤直径平均缩小50％,其中4例因肿瘤缩小行二期手术切除。1、2、3年生存率分别为:切除组分别为95.2％、81％、57.1％。明显高于置泵组的64％、44％、32％(P<0.01)。结论 大肠癌肝转移同期联合手术切除加肝动脉门静脉双置泵栓塞灌注化疗,是一种首选而有效的治疗方法。不能切除肝转移癌者,只要切除原发肿瘤,肝动脉门静脉双置泵栓塞灌注化疗,可延长病人生存期,改善预后。     

DCC and TS protein expression in resected gastric cancer: A Hellenic Cooperative Oncology Group Study

There is a high risk of relapse after resection of gastric cancer. We studied the prognostic significance of the deleted colorectal cancer (DCC) gene and thymidylate synthase (TS) protein expression after resection of gastric cancer. Protein expression in the primary tumor of 146 patients with serosal and/or lymph node involvement was studied immunohistochemically by using anti-DCC and anti-TS monoclonal antibodies. DCC expression was found in 69.9%, while low TS staining intensity (0+,1+) and focal staining (<25% of tumor cells stained) were found in 44.6% and 33.8%, respectively. Overall survival (OS) was significantly longer in patients with DCC (p=0.014) negative tumors. TS expression was not an independent prognostic factor. Lack of DCC expression was associated with significantly longer cause-specific survival (CSS) (p=0.040) after curative resection. In conclusion, DCC expression is an independent prognostic factor in patients undergoing resection of gastric cancer while TS expression was not associated with the prognosis in our study.     

原发性小肠肿瘤60例临床分析

目的 探讨原发性小肠肿瘤的临床特点、诊断及治疗方法.方法 回顾分析60例原发性小肠肿瘤从肿瘤的发病部位、病理、临床表现、诊断及治疗.结果 术前经内窥镜、X线、B超及CT等检查,术前确诊率（25.0%,15/60）明显低于术后确诊率（75.0%,45/60）（Х^2=9.145,P＜0.01）;好发部位：十二指肠20例（33.3%）,空肠13例（21.6%）,回肠27例（45.5%）;60例均经手术证实诊断,良性肿瘤18例（30.0%）,明显低于恶性肿瘤的42例（70.0%）（Х^2=8.215,P＜0.01）;腺癌22例（36.0%）,明显高于其它性质肿瘤[15例（25.0%）、5例（8.3%）、2例（3.3%）、2例（3.3%）、1例（1.6%）、3例（3.3%）、4例（6.6%）、3例（3.3%）、3例（3.3%）]（Х^2=3.89、8.89、9.152、9.162、10.23、9.012、8.999、9.042、9.111,均P＜0.05）;良性肿瘤行局部肠壁或肠段切除,恶性肿瘤行根治性切除.结论 原发性小肠肿瘤的临床表现缺乏特异性,手术切除是主要的治疗手段.     

Treatment of hepatocellular carcinoma.

Treatment options have largely been selected according to empirical criteria, such as the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic deterioration and taking into account the local technological and economic resources. There are virtually no controlled studies comparing the efficacy of the available treatments, and the substantial heterogeneity of survival between control groups does not allow us to obtain therapeutic evaluation by comparing results of separate trials. The reassessment of treatment outcomes on the basis of intention-to-treat analysis yielded less encouraging figures. Hepatic resection is the primary option for the few patients with a hepatocellular carcinoma arising in a normal liver with well-preserved hepatic function and for patients with a single tumor, compensated cirrhosis and low portal hypertension who are not candidable to liver transplantation. The latter is the best treatment modality for patients with a solitary tumor <5 cm in diameter or patients with less than three tumors <3 cm, resulting in a 5-year survival of 75%. Locoregional ablative treatments are curative options for patients with a "resectable" tumor who cannot be offered transplantation or hepatic resection. The 5-year survival is approximately 50% but it copes with a high risk of tumor recurrence. Patients with advanced tumor disease cannot be offered curative treatments but only symptomatic treatments.     

Identification of bladder cancer patients at risk for recurrence or progression: an immunohistochemical study based on the expression of metallothionein

Despite similarities in tumor stage and grade the individual outcome of bladder cancer patients is not predictable. The ideal tool for treatment stratification has not yet been found. Metallothionein (MT) overexpression is correlated with poor tumor differentiation, resistance to chemotherapy, and impaired survival in different malignancies. The clinical relevance of MT expression for defining patients at high risk for recurrence or progression was assessed. MT was detected immunohistochemically and evaluated semiquantitively in tumor specimens of 103 male and 19 female patients (transsurethral resection: n = 94, cystectomy: n = 28). Mean age of the patients was 68 (38-87) yr. According to histopathological features, three groups were distinguished for further analysis (pTa-1G1-2, pTis/pT1G3, and muscle invasive tumors). A cutoff value of 50% immunoreactive cells was used for further analysis. The 5-yr tumor specific survival rate was significantly lower in patients with high MT expression (32 vs. 72%). Accordingly, impaired 5-yr recurrence (90 vs. 58%), and progression rates (78 vs. 54%) were associated with high MT expression. All patients suffering from pTis and pT1G3 tumors with MT expression above the cutoff value showed recurrence within less than 40 mo, whereas 26% of those patients with MT expression below the cutoff value remained long-term recurrence free. Long term progression free survival was detected in 75% of pT1G3 patients with MT expression below the cutoff value. In contrast, 68% of pT1G3 tumor patients with MT expression above the cutoff value progressed, all within the first 12 mo after initial tumor resection. A correlation between high MT expression and prognosis was demonstrated especially in pT1G3 and pTis tumors, where >50% MT expression was linked to shorter tumor-specific survival and increased recurrence/progression rates. Thus, MT expression seems to be a promising marker for further risk stratification in the clinical treatment of bladder cancer patients.     

盆腔脏器切除术治疗复发直肠癌的效果观察

目的:探讨盆腔脏器切除术治疗复发直肠癌的效果。方法:回顾性分析1990年9月～2007年5月54例直肠癌术后复发患者的临床资料,其中42例再次手术,手术组中盆腔脏器切除术20例、姑息性复发病灶切除术22例,12例行非手术治疗。结果:姑息手术与非手术患者5年生存率分别为13.6%及0%,盆腔脏器切除术患者的5年生存率为40.0%,且均获得R0切除(肿瘤周围及切缘镜下未见癌残留)。结论:盆腔脏器切除术是治疗复发直肠癌的有效方法,严格选择病例,掌握手术适应证,确保获得R0切除,是获得满意疗效、减少术后并发症的关键。