表皮生长因子受体在乳腺癌中的研究进展

近几十年,在分子肿瘤的研究中发现一些能够促进肿瘤生长、存活的分子,为肿瘤的治疗带来了新的希望.表皮生长因子受体是最早发现的对抑制肿瘤具有重要意义的分子之一,大约50％的三阴性乳腺癌和炎性乳腺癌都过度表达表皮生长因子受体.表皮生长因子受体及其下游通路可以促进上皮问质转化、肿瘤细胞迁移以及肿瘤浸润.此外,由于凋亡信号转导的发生针对表皮生长因子受体治疗可以提高三阴性乳腺癌细胞化疗的敏感性.研究表明,表皮生长因子受体靶向治疗可能对三阴性乳腺癌和炎性乳腺癌的治疗具有重要作用.     

食管胃结合部肿瘤的治疗

目前,食管胃结合部肿瘤的发病率逐年上升,且预后较差。手术仍是最有效的治疗方法,但单纯手术的效果并不理想。术前放化疗是西方国家治疗食管胃结合部肿瘤的标准治疗方案,而东方国家更倾向于使用围术期化疗方案,靶向治疗的出现将为食管胃结合部肿瘤病人带来新的希望。我们通过分析多个临床实验,结合最新研究进展,分析和探讨食管胃结合部肿瘤的治疗方式。     

从“单打独斗”到“合作共赢”：论多学科团队在食管胃结合部腺癌诊治中的现状和展望

由于食管胃结合部腺癌特殊的肿瘤部位和生物学行为,其治疗模式也由传统的完全外科医师主导、手术治疗为先向包括胸外科、肿瘤内科、放疗科、麻醉科等在内的多学科团队合作的综合治疗发生转变。腔镜技术的发展使腹腔镜和胸腔镜共同治疗食管胃结合部腺癌将逐渐成为可能,加速康复外科理念则有望进一步推动食管胃结合部腺癌手术的微创化。同时,新辅...     

食管胃结合部腺癌保功能手术的现状和发展

食管胃结合部腺癌是消化系统常见肿瘤,其发生率呈进行性上升。传统经腹食管裂孔路径的食管胃结合部腺癌根治手术多采用全胃切除术。随着早期病人的比例增加,保功能手术观念的发展及更多的研究数据支持,近端胃切除术在早期食管胃结合部腺癌中越来越得到重视。食管胃结合部腺癌的近端胃切除术的两个重要研究方向：一是食管胃结合部腺癌的适应证研究,主要涉及淋巴结转移、切缘要求等;二是消化道重建的术式选择研究,主要基于增加残胃的容受、重建结构屏障或压力屏障、加速胃排空三个基本原理进行重建术式的设计。笔者希望通过对两个研究方向的探讨,为食管胃结合部腺癌保功能手术的发展提供一些方向。     

食管胃结合部腺癌外科治疗现状与争议

食管胃结合部腺癌的发病率在全球范围内呈上升趋势。由于肿瘤位于食管和胃的结合部,因此,有关手术方式、淋巴结清扫、食管和胃的切除范围、微创技术应用等问题尚未达成共识,存在争议。但手术仍然应该重视术前分期和分型的准确性,遵循恶性肿瘤根治手术的基本原则,合理选择规范化和个体化治疗策略。未来食管胃结合部腺癌的诊治将需要通过多学科协作的模式来共同完成。     

曲妥珠单抗联合化疗与单纯化疗治疗HER2阳性的晚期胃癌或食管胃结合部腺癌：一个3期开放随机对照试验（TOGA）

曲妥珠单抗为拮抗人上皮生长因子受体2（HER2）的单克隆抗体。TOGA是一项由24个国家的122个医疗中心共同参与的3期开放随机对照试验,该试验旨在探讨曲妥珠单抗联合化疗治疗HER2阳性的晚期胃癌或食管胃结合部腺癌的效果。研究对象为经免疫组化或荧光原位杂交基因扩增方法确定存在HER2高表达的晚期胃癌或食管胃结合部腺癌患者,     

脂联素分子受体3在转化生长因子-β介导的食管-胃交界腺癌发生和转移中的临床意义

目的:观察脂联素分子受体3(PAQR3)在食管-胃交界腺癌组织中的表达并探讨其临床意义,特别是PAQR3表达水平与转化生长因子-β(TGF-β)通路介导肿瘤转移的相关性。方法:采用免疫组织化学检测180例食管-胃交界腺癌(Siewert Ⅱ型)手术组织标本中肿瘤组织及配对的癌旁正常组织中PAQR3、TGF-β、p-Sm...     

Ⅱ型和Ⅲ型食管胃结合部腺癌诊疗的研究进展

Ⅱ型和Ⅲ型食管胃结合部腺癌是一种特殊类型癌,兼具食管癌与胃癌特点,其在分期、分型及诊疗方式上存在诸多争论.目前公认的分型方法是Siewert分型,尚缺乏独立的TNM分期,其发病原因与胃食管反流、幽门螺杆菌感染、Barrett食管密切相关,治疗上以根治性手术联合围手术期放化疗、靶向治疗等在内的综合治疗为主.     

不同结果判定标准下胃食管结合部癌人表皮生长因子受体2的表达及其与临床病理特征的关系

目的对比在不同的结果判定标准下胃食管结合部癌中人表皮生长因子受体2（HER2）的表达情况及其与临床病理学因素的关系。方法回顾性分析2009年1—12月间北京大学肿瘤医院外科收治的127例胃食管结合部癌患者的临床资料．并对手术标本进行免疫组织化学（免疫组化）染色。结果采用新的和传统的HER2免疫组化判定标准、HER2阳性表达率均为15．0％（19／127）,强阳性率则分别为10．2％（13／127）和6．3％（8／127）（P=0．26）。单因素分析显示．HER2表达与胃食管结合部癌肿瘤分化程度和Lauren分型有关：多因素分析则显示,肿瘤分化程度和TNM分期是影响HER2在胃食管结合部癌表达的独立因素（均P〈0．05）。结论新旧两种免疫组化判定标准下HER2的阳性率并无差异;HER2在胃食管结合部癌中的表达与临床病理特征关系密切。     

MRI动态增强扫描在食管胃结合部腺癌上界定位中的应用

目的:探讨MRI动态增强扫描在食管胃结合部腺癌上界定位中的临床意义。方法:回顾性分析2018年7月至2019年8月郑州大学附属肿瘤医院收治并行手术治疗的73例食管胃结合部腺癌患者的临床资料,所有患者均于术前1周内行MRI检查。首先在患者的T 2WI和扩散加权成像及动态增强图像上了解肿瘤的部位、大小、形态、信...     

手术入路对食管胃结合部腺癌生存预后的影响

目的:评价经胸入路与经腹入路手术治疗SiewertⅡ/Ⅲ型食管胃结合部腺癌的临床疗效.方法:回顾分析2004年1月至2014年11月手术治疗的168例SiewertⅡ/Ⅲ型胃食管结合部腺癌患者的临床资料,对其人群特征、手术并发症、总生存率及生存预后的影响因素进行分析.结果:两组临床资料具有可比性,经胸入路组较经腹入路组...     

Molecular targeted agents for gastric and gastroesophageal junction cancer

Despite recent improvements in surgical techniques and chemotherapy, advanced cancers of the stomach and gastroesophageal junction (GEJ) continue to have poor clinical outcomes. However, molecules intimately related to cancer cell proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. Target molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways are considered to be promising candidates for molecular targeted therapy for gastric and GEJ cancer. In this review we focus on the recent developments in targeting relevant pathways in these types of cancer.     

HER2 Expression in Carcinomas of the True Cardia (Siewert Type II Esophagogastric Junction Carcinoma)

Objectives

To evaluate the HER2 status in patients with Siewert type II esophagogastric junction carcinoma.

Background

Trastuzumab is now approved for use in the treatment of human epidermal growth factor receptor 2 (HER2)-positive unresectable metastatic gastric or esophagogastric junction (EGJ) carcinoma. Several studies have evaluated HER2 status in EGJ carcinoma, but none has addressed the implication of HER2 positivity in patients with Siewert type II EGJ carcinoma.

Methods

We retrospectively evaluated the frequency of HER2 positivity in a large single-center cohort of 208 patients with Siewert type II tumors. The relations between HER2 expression and the outcomes and other clinicopathologic features were examined.

Results

Overall, 18.2 % (38/208) of patients in our cohort had HER2-positive tumors. HER2 positivity was associated only with differentiated carcinomas. The 5-year overall survival (OS) rate was 58.7 %. The 5-year OS rates in the patient groups with HER2-negative and HER2-positive tumors were 61.2 and 48.5 %, respectively. There was no significant difference between the groups. Recurrence in the liver was observed in 23.7 % patients of the HER2-positive group and 7.6 % patients of the HER2-negative group. Multivariate analysis to identify the risk factors for liver recurrence revealed only HER2 positivity (p = 0.0155) as an independent predictive factor.

Conclusions

HER2 positivity is a powerful predictor of liver recurrence in patients with Siewert type II EGJ carcinoma. Use of trastuzumab in combination with chemotherapy in an adjuvant setting can be a potentially useful therapeutic strategy to prevent hepatic recurrence in patients with resectable EGJ adenocarcinoma showing HER2 overexpression.     

Individualized surgical strategies for cancer of the esophagogastric junction

Due to their borderline location between the stomach and esophagus the optimal surgical strategy for patients with adenocarcinoma of the esophagogastric junction is controversial. Irrespective of the surgical approach a complete removal of the primary tumor and its lymphatic drainage has to be the primary goal of surgical treatment of such tumors. Based on the experience with surgical resection of more than 1000 patients with adenocarcinoma of the esophagogastric junction we recommend an individualized surgical strategy guided by tumor stage and topographic location of the tumor center or tumor mass. This requires detailed preoperative staging and classification of tumors arising in the vicinity of the esophagogastric junction into adenocarcinoma of the distal esophagus (AEG Type I Tumors), true carcinoma of the gastric cardia (AEG Type II Tumors) and subcardial gastric carcinoma infiltrating the esophagogastric junction (AEG Type III Tumors). In patients with Type I Tumors transthoracic esophagectomy offers no survival benefit over radical transmediastinal esophagectomy, but is associated with higher morbidity. In patients with Type II or Type III tumors an extended total gastrectomy results in equal or superior survival and less postoperative mortality than a more extended esophagogastrectomy. In patients with early tumors, staged as uT1 on preoperative endosonography, a limited resection of the proximal stomach, cardia and distal esophagus with interposition of a pedicled isoperistaltic jejunal segment allows a complete tumor removal with adequate lymphadenectomy and offers excellent functional results. Multimodal treatment protocols with neoadjuvant chemotherapy or combined radiochemotherapy followed by surgical resection appear to markedly improve the prognosis in patients with locally advanced tumors who respond to preoperative treatment. With this tailored approach extensive preoperative staging becomes mandatory for an adequate selection of the appropriate therapeutic concept.     

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??Surgical treatment of adenocarcinoma of esophagogastric junction LI Guo-li, MAO Qi. Department of Surgery, Jinling Hospital,Nanjing University School of Medicine,Nanjing 210002,China
Corresponding author: LI Guo-li, E-mail:drguoli@yahoo.com.cn
Abstract Recently adenocarcinoma of esophagogastric junction has attracted extensive attention for the significant increasing of its incidence. Besides tumour nodemetastasis (TNM) stage and histological subtype, more attention should be paid to the localization of the tumour, which mainly affects the direction of neoplasm metastasis ---to thoracic cavity, abdomen cavity, or both of them involved. The extent of ectomy should also be influenced by the metastatic direction.To adenocarcinomas of esophagogastric junction of different localization, the surgeons should take advisable operative approach, excisional scope, reconstructive style and adjunctive therapy according to preoperative diagnosis.     

提高对食管胃结合部肿瘤的认识

食管胃结合部肿瘤、尤其是食管胃结合部腺癌的发病率正在逐年增高.该部位肿瘤在解剖、生理及病理等方面都存在着特殊性,国内及国际学者对该部位肿瘤的治疗尚未达成共识,故目前亦无一致认同的治疗规范.因此,我们有必要提高对该区域肿瘤的进一步认识,寻找更加合理、可行的治疗策略.     

The significance of c-erb B-2 and p53 immunoreactivity in patients with adenocarcinoma of the esophagus.

OBJECTIVE: Studies in breast cancer suggest that p53 and c-erb B2 protein overexpression are predictive of outcome. The authors determined whether these molecular markers correlated with treatment response and survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. METHOD: Immunostaining for p53 and c-erb B2 was performed on paraffin-embedded specimens from 42 patients with esophageal adenocarcinoma. All patients received neoadjuvant chemotherapy (cisplatin and fluorouracil [5-FU] x 3 cycles) and irradiation (4500 rads) followed by resection. RESULTS: In this cohort of patients, 79% (33/42) were positive for p53, and 43% (18/42) were positive for c-erb B2. p53 positivity correlated with residual disease in the resection specimen but not with disease-free survival. Although c-erb B2 negatively correlated with residual disease after resection and a 5-year survival of 10%, c-erb B2 positivity was associated with a 5-year actuarial survival of 60%. CONCLUSIONS: Although p53 protein overexpression is commonly observed in adenocarcinoma of the esophagus, its prognostic value appears limited. In contrast, c-erb B2 protein expression predicts a favorable response to therapy and improved survival.     

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内镜黏膜下剥离术(endoscopic submucosal dissection,ESD)作为一种治疗早期胃癌新技术,同样适用于治疗食管胃结合部(esophagogastric junction,EGJ)的浅表癌。ESD治疗食管胃结合部腺癌(adenocarcinoma of the esophagogastric junction,AEG)及EGJ处癌前病变,与外科剖腹手术及内镜黏膜切除术(endoscopic mucosal resection,EMR)等内镜治疗方法相比,具有明显优势。但ESD治疗EGJ处病变,手术难度较高,手术时间更长,手术并发症发生率更高,对操作者的技术要求较高。     

转移性结直肠癌抗EGFR治疗耐药机制研究进展

转移性结直肠癌（mCRC）是结直肠癌进展的晚期阶段,治疗选择多样,但患者预后通常不佳。表皮生长因子受体（EGFR）信号通路在mCRC的发展中扮演核心角色,涉及多个关键分子。EGFR异常活化与肿瘤生长、转移及治疗耐药紧密相关。因此,EGFR靶向治疗对mCRC至关重要,但治疗耐药常常导致治疗失败,且分子机制复杂。在此,笔者综述mCRC抗EGFR治疗耐药的相关分子机制及干预研究进展,为深入理解抗EGFR耐药机制,优化治疗策略提供参考。